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Sample records for experimental acute ischemia

  1. [Effectiveness of various dopamine doses in acute myocardial ischemia complicated by cardiogenic shock (an experimental study)].

    Science.gov (United States)

    Kipshidze, N N; Korotkov, A A; Marsagishvili, L A; Prigolashvili, T Sh; Bokhua, M R

    1981-06-01

    The effect of various doses of dopamine on the values of cardiac contractile and hemodynamic function under conditions of acute two-hour ischemia complicated by cardiogenic shock was studied in 27 experiments on dogs. In a dose of 5 microgram/kg/min dopamine caused an optimum increase in cardiac productive capacity, reduction of peripheral resistance, adequate increase in coronary circulation and decrease in ST segment depression on the ECG. Infusion of 10 microgram/kg/min dopamine usually caused myocardial hyperfunction with an increase in total peripheral resistance and cardiac performance. Maximum dopamine doses (10 microgram/kg/min and more) were effective in the areactive form of cardiogenic shock. In longterm dopamine infusion it is necessary to establish continuous control over the hemodynamic parameters and the ECG to prevent aggravation of ischemia and for stage-by-stage reduction of the drug concentration and determination of the minimum maintenance dose.

  2. Acute bowel ischemia: CT findings

    International Nuclear Information System (INIS)

    Angelelli, Giuseppe; Scardapane, Arnaldo; Memeo, Maurizio; Stabile Ianora, Amato Antonio; Rotondo, Antonio

    2004-01-01

    Acute bowel ischemia represents one of the most dramatic abdominal emergencies and, despite the fact it is more and more frequently observed in clinical practice, its mortality rate remains very high. In recent years Computed Tomography (CT) has proved to be a valid diagnostic tool in the evaluation of patients with acute abdominal syndrome and in the visualization of early signs of bowel ischemia. This paper reviews the aetiological and pathophysiological aspects as well as a broad spectrum of CT findings of this clinical condition

  3. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

    Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion...... in the penumbra is recruited in the infarction process leading to a progressive growth of the infarct. The penumbra hence constitutes an important target for pharmacological treatment because of the existence of a therapeutic time window during which treatment with neuroprotective compounds may prevent...

  4. Revascularization for acute mesenteric ischemia.

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    Ryer, Evan J; Kalra, Manju; Oderich, Gustavo S; Duncan, Audra A; Gloviczki, Peter; Cha, Stephen; Bower, Thomas C

    2012-06-01

    Acute mesenteric ischemia (AMI) remains difficult to diagnose, carries a high rate of complications, and is associated with significant mortality. We evaluated our experience with AMI over the last 2 decades to evaluate changes in management and assess current outcomes. Data from consecutive patients who underwent arterial revascularization for AMI over a 20-year period (January 1990-January 2010) were retrospectively reviewed. Patient demographics, treatment modalities, and outcomes over the last decade (2000-2010) were compared with those of the preceding decade (1990-1999) previously reported. Over the last 2 decades, 93 patients with AMI underwent emergency arterial revascularization. Forty-five patients were treated during the 1990s and 48 during the 2000s. The majority of these patients were transferred from outside facilities. Patient demographics and risk factors were similar between the 2 decades with the exception that the more contemporary patients were significantly older (65.1 ± 14 vs 71.3 ± 14; P = .04). Etiology remained constant between the groups with in situ thrombosis being the most common followed by arterial embolus. The majority of patients were treated with open revascularization. Endovascular therapy alone or as a hybrid procedure was used in 11 total patients, eight of which were treated in the last 10 years. The use of second-look laparotomy was much more liberal in the last decade (80% vs 48%; P = .003) Thirty-day mortality was 27% in the 1990s and 17% during the 2000s (P = 0.28). Major adverse events occurred in 47% of patients with no difference between decades. There was no significant difference in outcomes between open and endovascular revascularization. On univariate analysis, elevated SVS comorbidity score, congestive heart failure, and chronic kidney disease predicted early death, while a history of chronic mesenteric ischemia appeared protective. On multivariate analysis, no factor independently predicted perioperative

  5. Experimental mesenteric ischemia. Radioisotopic diagnosis

    International Nuclear Information System (INIS)

    Alberti, Carlos; Dallaglio, Juan; Sarra, Luis; Obiols, Eugenio; Rodriguez Santos, Emilio; Delgado, Eduardo; Castelleti, Luis

    1995-01-01

    A non-invasive radionuclide technique with 99-Tc-DMP for the early diagnosis of small bowel infarction due to mesenteric artery compression, was evaluated. The usefulness of 99-Tc-DMP and critical pressure of mesenteric artery were demonstrated. The diagnosis was performed before one hour had passed from the beginning of the ischemia

  6. Endovascular Management of Acute Limb Ischemia.

    LENUS (Irish Health Repository)

    Hynes, Brian G

    2011-09-14

    Despite major advances in pharmacologic and endovascular therapies, acute limb ischemia (ALI) continues to result in significant morbidity and mortality. The incidence of ALI may be as high as 13-17 cases per 100,000 people per year, with mortality rates approaching 18% in some series. This review will address the contemporary endovascular management of ALI encompassing pharmacologic and percutaneous interventional treatment strategies.

  7. Acute mesenteric ischemia: a vascular emergency.

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    Klar, Ernst; Rahmanian, Parwis B; Bücker, Arno; Hauenstein, Karlheinz; Jauch, Karl-Walter; Luther, Bernd

    2012-04-01

    Acute mesenteric ischemia is still fatal in 50% to 70% of cases. This consensus paper was written with the participation of physicians from all of the involved specialties for the purpose of improving outcomes. Mesenteric ischemia must be recognized as a vascular emergency requiring rapid and efficient clinical evaluation and treatment. We reviewed pertinent literature that was retrieved by a PubMed search on the terms "mesenteric ischemia" AND "arterial" OR "venous" OR "clinical presentation" OR "diagnosis" OR "therapy" OR "surgery" OR " interventional radiology." Our review also took account of the existing guidelines of the American College of Cardiology/American Heart Association. Intensive discussions among the participating physicians, representing all of the specialties involved in the management of mesenteric ischemia, led to the creation of this interdisciplinary paper. Biphasic contrast-enhanced computerized tomography is the diagnostic tool of choice for the detection of arterial or venous occlusion. If non-occlusive mesenteric ischemia is suspected, angiography should be performed, with the option of intraarterial pharmacotherapy to induce local vasodilation. Endovascular techniques have become increasingly important in the treatment of arterial occlusion. Embolic central mesenteric artery occlusion requires surgical treatment; surgery is also needed in case of peritonitis. Portal-vein thrombosis can be treated by local thrombolysis through a transhepatically placed catheter. This should be done within 3 to 4 weeks of the event to prevent later complications of portal hypertension. Rapid diagnosis (within 4 to 6 hours of symptom onset) and interdisciplinary cooperation in the provision of treatment are required if the poor outcome of this condition is to be improved.

  8. Diagnostic Value of Procalcitonin Levels in Acute Mesenteric Ischemia

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    Yunus Karaca

    2015-09-01

    Full Text Available Background: Acute mesenteric ischemia (AMI is a potentially fatal disease. Difficulties in diagnosis make it essential to find early biomarkers. Aims: This study investigated the diagnostic value of procalcitonin (PCT levels in AMI. Study Design: Animal experimentation. Methods: Rats were divided into six groups of six animals each. In the experimental group, an experimental ischemia model was established by clamping the superior mesenteric artery from the aortic outflow tract. Blood and tissue specimens were collected from rats in the experimental mesenteric ischemia model at 30 min and 2 and 6 h, and these were compared with specimens from the respective control groups. PCT levels were compared at 30 min and 2 and 6 h. Results: PCT levels were 185.3 pg/mL in the control group and 219.3 pg/mL in the study group, 199.6 pg/mL in the control group and 243.9 pg/mL in the study group, and 201.9 pg/mL in the control group and 286.9 pg/mL in the study group, respectively, at 30 minute, 2 and 6 hours. Significant differences were determined between 6-h control group and ischemia group PCT levels (p=0.005. Conclusion: The absence of a significant increase in PCT levels in the early period, while a significant difference was detected in the later period (6 h, shows that PCT levels rise late in mesenteric ischemia and can be a marker in the late period.

  9. MR of experimental cerebral ischemia

    International Nuclear Information System (INIS)

    DeLaPaz, R.; Steinberg, G.; Rocklage, S.; Glover, G.H.

    1990-01-01

    This paper reports on MR imaging of cerebral ischemia and treatment with N-methyl-D-aspartate (NMDA) antagonists in an animal model. Forty-four New Zealand white rabbits underwent 1-hour transorbital ICA-MCA-ACA occlusion and pretreatment or immediate posttreatment with systemic dextromethorphan (DM, n = 14), dextrorphan (DX, n = 14), or normal saline (NS, n = 16). Serial MR studies (1.5 T) were performed 1--6 hours after occlusion with T1- and T2-weighted spinecho, IVIM (b = 1,352), gradient recalled acquisition in a steady-state, and chemical shift sequences (for magnetic susceptibility, T2* and T2') and DyDTPA-BMA intravenous contrast material (Salutar). Spatial correlation between MR findings, histologic findings (ischemic neuronal damage), and regional cerebral blood flow (microspheres) was done

  10. Purine Metabolism in Acute Cerebral Ischemia

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    Ye. V. Oreshnikov

    2008-01-01

    Full Text Available Objective: to study the specific features of purine metabolism in clinically significant acute cerebral ischemia. Subjects and materials. Three hundred and fifty patients with the acutest cerebral ischemic stroke were examined. The parameters of gas and electrolyte composition, acid-base balance, the levels of malonic dialdehyde, adenine, guanine, hypox-anthine, xanthine, and uric acid, and the activity of xanthine oxidase were determined in arterial and venous bloods and spinal fluid. Results. In ischemic stroke, hyperuricemia reflects the severity of cerebral metabolic disturbances, hemodynamic instability, hypercoagulation susceptiility, and the extent of neurological deficit. In ischemic stroke, hyperuri-corachia is accompanied by the higher spinal fluid levels of adenine, guanine, hypoxanthine, and xanthine and it is an indirect indicator of respiratory disorders of central genesis, systemic acidosis, hypercoagulation susceptibility, free radical oxidation activation, the intensity of a stressor response to cerebral ischemia, cerebral metabolic disturbances, the depth of reduced consciousness, and the severity of neurological deficit. Conclusion. The high venous blood activity of xanthine oxidase in ischemic stroke is associated with the better neurological parameters in all follow-up periods, the better early functional outcome, and lower mortality rates. Key words: hyperuricemia, stroke, xanthine oxidase, uric acid, cerebral ischemia.

  11. Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

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    Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

    2015-03-01

    Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

  12. Outcomes of lower extremity bypass performed for acute limb ischemia.

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    Baril, Donald T; Patel, Virendra I; Judelson, Dejah R; Goodney, Philip P; McPhee, James T; Hevelone, Nathanael D; Cronenwett, Jack L; Schanzer, Andres

    2013-10-01

    Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation, deterioration in renal function

  13. Magnetic resonance imaging in acute stage of cerebral ischemia

    International Nuclear Information System (INIS)

    Yamagata, Sen; Kikuchi, Haruhiko; Ihara, Ikuo

    1986-01-01

    The value of the nuclear magnetic resonance image (MRI) was investigated in the acute stage of experimental cerebral ischemia. The MRI system employed was designed for clinical use, and the superconducting magnet was operated at a field strength of 1.5 tesla. Ischemic insult was made by transorbital occlusion of the middle cerebral artery (MCA) permanently in 4 cats and temporarily in 2 cats. After MCA occlusion the regional cerebral blood flow (rCBF) was measured on the affected cortex, and 5 cats with rCBF below 10 ml/100 g/min and one with rCBF over 15 ml/100 g/min were studied. In the permanent occlusion group, MRI was performed every 2 hours from 4 to 12 hours after MCA occlusion and another MRI was carried out 20 min after gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA) intravenous administration. The earliest changes were found 6 to 8 hours after MCA occlusion on the spin echo image (repetition time = 1.4 sec, echo time = 70 msec) in 3 cats with severe ischemia. It was postulated that the ischemic lesion could be depicted less than 6 hours on more T 2 -weighted images. The increased intensity area was markedly enhanced with Gd-DTPA 12 hours after occlusion. In the recirculation group, the increased intensity area was observed on enhanced MRI in a cat with recirculation as early as one hour after MCA occlusion, although it was not found on the plain MRI. In the other cat with recirculation after 2 hours' occlusion, definite lesion was found in all parameter images without enhancement. The results suggest that changes in cerebral ischemia can be obtained on the MRI earlier than X-ray computed tomography, and that it may be possible to determine the severity of the ischemic brain injury by the MRI findings. (author)

  14. Ischemia modified albumin as laboratory marker of acute

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    Goran Miličević

    2009-02-01

    Full Text Available Daily clinical practice still lacks a marker of acute myocardial ischemia as compared with markers ofmyocardial necrosis. Ischemia modifed albumin (IMA has recently been proposed as a useful biochemicaltool for detection of ischemia – it is a test which determines the inability of N-terminal end ofalbumin to bind cobalt during ischemia. A strong relation between IMA and early myocardial ischemiahas been shown by several studies, in most of which percutaneous coronary intervention was used asa model of myocardial ischemia, where this test showed high sensitivity. IMA values raise during nextfew minutes after the ischemia has occured, and return back to normal levels within next six hours, butthe precise dynamics of its rise and fall are still unknown. Beside defining etiology of acute or sub-acutechest pain in patients with inconclusive electrocardiogram (ECG, in patients with “silent” myocardialischemia with ischemic changes in ECG or in patients with non-ischemic ECG changes during cardiacstress test, this promising marker could also be used as the earliest biochemical indicator of early developmentof myocardial infarction. Relatively low organ-specificity is a limitation of this test, becauseIMA levels are also raised during different ischemic conditions and diseases of other organs. If thisproblem is taken into consideration, IMA test shows good results in diagnosing myocardial ischemiadue to its high sensitivity.

  15. Acute testicular ischemia caused by incarcerated inguinal hernia.

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    Orth, Robert C; Towbin, Alexander J

    2012-02-01

    Acute testicular ischemia caused by an incarcerated inguinal hernia usually affects infants. There are few reports of diagnosis using US, and the effect of long-standing reducible hernias on testicular growth in infants and children is unknown. The objectives of this study were to determine the incidence of testicular ischemia secondary to an incarcerated inguinal hernia at scrotal sonography and to determine the effect on testicular size at diagnosis. A hospital database was used to locate scrotal sonography examinations documenting an inguinal hernia, and images were reviewed for signs of testicular ischemia. Testicular volumes were compared using the Wilcoxon signed rank test. A total of 147 patients were identified with an inguinal hernia (age 1 day to 23 years, average 6 years). Ten patients (6.8%) had associated testicular ischemia (age 3 weeks to 6 months, average 9 weeks) and showed a statistically significant increase in ipsilateral testicular size compared to the contralateral testicle (P = 0.012). Patients without testicular ischemia did not show a significant difference in testicular size, regardless of patient age. An incarcerated inguinal hernia should be considered as a cause of acute testicular ischemia in infants younger than 6 months of age.

  16. Acute limb ischemia in cancer patients: should we surgically intervene?

    LENUS (Irish Health Repository)

    Tsang, Julian S

    2012-02-01

    BACKGROUND: Cancer patients have an increased risk of venous thromboembolic events. Certain chemotherapeutic agents have also been associated with the development of thrombosis. Reported cases of acute arterial ischemic episodes in cancer patients are rare. METHODS: Patients who underwent surgery for acute limb ischemia associated with malignancy in a university teaching hospital over a 10-year period were identified. Patient demographics, cancer type, chemotherapy use, site of thromboembolism, treatment and outcome were recorded. RESULTS: Four hundred nineteen patients underwent surgical intervention for acute arterial ischemia, 16 of these patients (3.8%) had associated cancer. Commonest cancer sites were the urogenital tract (n = 5) and the lungs (n = 5). Eight patients (50%) had been recently diagnosed with cancer, and four (25%) of these cancers were incidental findings after presentation with acute limb ischemia. Four patients (25%) developed acute ischemia during chemotherapy. The superficial femoral artery was the most frequent site of occlusion (50%), followed by the brachial (18%) and popliteal (12%) arteries. All patients underwent thromboembolectomy, but two (12%) patients subsequently required a bypass procedure. Six patients (37%) had limb loss, and in-patient mortality was 12%. Histology revealed that all occlusions were due to thromboembolism, with no tumor cells identified. At follow-up, 44% of patients were found to be alive after 1 year. CONCLUSION: Cancer and chemotherapy can predispose patients to acute arterial ischemia. Unlike other reports that view this finding as a preterminal event most appropriately treated by palliative measures, in this series, early diagnosis and surgical intervention enabled limb salvage and patient survival.

  17. Acute coronary ischemia during alcohol withdrawal: a case report

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    Sriram Ganeshalingam

    2011-08-01

    Full Text Available Abstract Introduction The potential of alcohol withdrawal to cause acute coronary events is an area that needs the urgent attention of clinicians and researchers. Case presentation We report the case of a 52-year-old heavy-alcohol-using Sri Lankan man who developed electocardiogram changes suggestive of an acute coronary event during alcohol withdrawal. Despite the patient being asymptomatic, subsequent echocardiogram showed evidence of ischemic myocardial dysfunction. We review the literature on precipitation of myocardial ischemia during alcohol withdrawal and propose possible mechanisms. Conclusions Alcohol withdrawal is a commonly observed phenomenon in hospitals. However, the number of cases reported in the literature of acute coronary events occurring during withdrawal is few. Many cases of acute ischemia or sudden cardiac deaths may be attributed to other well known complications of delirium tremens. This is an area needing the urgent attention of clinicians and epidemiologists.

  18. Metabolomic profiling to characterize acute intestinal ischemia/reperfusion injury.

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    Rachel G Khadaroo

    Full Text Available Sepsis and septic shock are the leading causes of death in critically ill patients. Acute intestinal ischemia/reperfusion (AII/R is an adaptive response to shock. The high mortality rate from AII/R is due to the severity of the disease and, more importantly, the failure of timely diagnosis. The objective of this investigation is to use nuclear magnetic resonance (NMR analysis to characterize urine metabolomic profile of AII/R injury in a mouse model. Animals were exposed to sham, early (30 min or late (60 min acute intestinal ischemia by complete occlusion of the superior mesenteric artery, followed by 2 hrs of reperfusion. Urine was collected and analyzed by NMR spectroscopy. Urinary metabolite concentrations demonstrated that different profiles could be delineated based on the duration of the intestinal ischemia. Metabolites such as allantoin, creatinine, proline, and methylamine could be predictive of AII/R injury. Lactate, currently used for clinical diagnosis, was found not to significantly contribute to the classification model for either early or late ischemia. This study demonstrates that patterns of changes in urinary metabolites are effective at distinguishing AII/R progression in an animal model. This is a proof-of-concept study to further support examination of metabolites in the clinical diagnosis of intestinal ischemia reperfusion injury in patients. The discovery of a fingerprint metabolite profile of AII/R will be a major advancement in the diagnosis, treatment, and prevention of systemic injury in critically ill patients.

  19. Hyperbaric oxygen in skeletal muscle of rats submitted to total acute left hindlimb ischemia: A research report.

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    da Silva, Luis Gustavo Campos; Dalio, Marcelo Bellini; Joviliano, Edwaldo Edner; Feres, Omar; Piccinato, Carlos Eli

    2015-01-01

    Determine the effect of hyperbaric oxygen treatment in skeletal muscle of rats submitted to total acute left hindlimb ischemia. An experimental study was designed using 48 Wistar rats divided into four groups (n = 12): Control; Ischemia (I)--total hindlimb ischemia for 270 minutes; Hyperbaric oxygen treatment during ischemia (HBO2)--total hindlimb ischemia for 270 minutes and hyperbaric oxygen during the first 90 minutes; Pre-treatment with hyperbaric oxygen (PHBO2)--90 minutes of hyperbaric oxygen treatment before total hindlimb ischemia for 270 minutes. Skeletal muscle injury was evaluated by measuring levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total creatine phosphokinase (CPK); muscular malondialdehyde (MDA), muscular glycogen, and serum ischemia-modified albumin (IMA). AST was significantly higher in I, HBO2 and PHBO2 compared with control (P = .001). There was no difference in LDH. CPK was significantly higher in I, HBO2 and PHBO2, compared with control (p = .014). MDA was significantly higher in PHBO2, compared with other groups (p = .042). Glycogen was significantly decreased in I, HBO2 and PHBO2, compared with control (p < .001). Hyperbaric oxygen treatment in acute total hindlimb ischemia exerted no protective effect on muscle injury, regardless of time of application. When applied prior to installation of total ischemia, hyperbaric oxygen treatment aggravated muscle injury.

  20. Rat Experimental Model of Myocardial Ischemia/Reperfusion Injury: An Ethical Approach to Set up the Analgesic Management of Acute Post-Surgical Pain

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    Ciuffreda, Maria Chiara; Tolva, Valerio; Casana, Renato; Gnecchi, Massimiliano; Vanoli, Emilio; Spazzolini, Carla; Roughan, John; Calvillo, Laura

    2014-01-01

    Rationale During the past 30 years, myocardial ischemia/reperfusion injury in rodents became one of the most commonly used model in cardiovascular research. Appropriate pain-prevention appears critical since it may influence the outcome and the results obtained with this model. However, there are no proper guidelines for pain management in rats undergoing thoracic surgery. Accordingly, we evaluated three analgesic regimens in cardiac ischemia/reperfusion injury. This study was strongly focused on 3R’s ethic principles, in particular the principle of Reduction. Methods Rats undergoing surgery were treated with pre-surgical tramadol (45 mg/kg intra-peritoneal), or carprofen (5 mg/kg sub-cutaneous), or with pre-surgical administration of carprofen followed by 2 post-surgery tramadol injections (multi-modal group). We assessed behavioral signs of pain and made a subjective evaluation of stress and suffering one and two hours after surgery. Results Multi-modal treatment significantly reduced the number of signs of pain compared to carprofen alone at both the first hour (61±42 vs 123±47; pCarprofen alone was more effective at the second hour post-surgery when signs of pain reduced to 74±24 from 113±40 in the first hour (pcarprofen and tramadol groups, respectively (pcarprofen and tramadol was more effective in preventing pain during the second hour after surgery compared with both tramadol or carprofen. Our results suggest that the combination of carprofen and tramadol represent the best therapy to prevent animal pain after myocardial ischemia/reperfusion. We obtained our results accordingly with the ethical principle of Reduction. PMID:24756074

  1. Rat experimental model of myocardial ischemia/reperfusion injury: an ethical approach to set up the analgesic management of acute post-surgical pain.

    Directory of Open Access Journals (Sweden)

    Maria Chiara Ciuffreda

    Full Text Available RATIONALE: During the past 30 years, myocardial ischemia/reperfusion injury in rodents became one of the most commonly used model in cardiovascular research. Appropriate pain-prevention appears critical since it may influence the outcome and the results obtained with this model. However, there are no proper guidelines for pain management in rats undergoing thoracic surgery. Accordingly, we evaluated three analgesic regimens in cardiac ischemia/reperfusion injury. This study was strongly focused on 3R's ethic principles, in particular the principle of Reduction. METHODS: Rats undergoing surgery were treated with pre-surgical tramadol (45 mg/kg intra-peritoneal, or carprofen (5 mg/kg sub-cutaneous, or with pre-surgical administration of carprofen followed by 2 post-surgery tramadol injections (multi-modal group. We assessed behavioral signs of pain and made a subjective evaluation of stress and suffering one and two hours after surgery. RESULTS: Multi-modal treatment significantly reduced the number of signs of pain compared to carprofen alone at both the first hour (61±42 vs 123±47; p<0.05 and the second hour (43±21 vs 74±24; p<0.05 post-surgery. Tramadol alone appeared as effective as multi-modal treatment during the first hour, but signs of pain significantly increased one hour later (from 66±72 to 151±86, p<0.05. Carprofen alone was more effective at the second hour post-surgery when signs of pain reduced to 74±24 from 113±40 in the first hour (p<0.05. Stress behaviors during the second hour were observed in only 20% of rats in the multimodal group compared to 75% and 86% in the carprofen and tramadol groups, respectively (p<0.05. CONCLUSIONS: Multi-modal treatment with carprofen and tramadol was more effective in preventing pain during the second hour after surgery compared with both tramadol or carprofen. Our results suggest that the combination of carprofen and tramadol represent the best therapy to prevent animal pain after

  2. Acute hemifacial ischemia as a late complication of carotid stenting

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    Maurizio Domanin, MD

    2017-06-01

    Full Text Available Concerns about carotid artery stenting (CAS center primarily on procedural complications like acute occlusion, stroke, and long-term intrastent restenosis. External carotid artery (ECA thrombosis is observed during CAS follow-up, but it often remains asymptomatic or, at worst, results in jaw claudication. We report here a case of late occlusion of the ECA after CAS with symptoms of acute homolateral facial ischemia as well as pain, cyanosis, tongue numbness, and skin coldness. The patient was submitted to local thrombolysis and balloon angioplasty with regression of symptoms after recanalization. With this report, we add a caveat about blockage of the ECA ostium during CAS.

  3. Magnetic resonance imaging of experimental cerebral ischemia

    International Nuclear Information System (INIS)

    Kato, Hiroyuki; Kogure, Kyuya; Ohtomo, Hitoshi

    1986-01-01

    In the spectroscopic experiment on excised rat brain (cortex, white matter, hippocampus and thalamus for normal and ischemia-laden brain), T1 and T2 relaxation times and water content were determined. The ischemic insult was induced for 60 min by the method of Pulsinelli followed by 60 min of reperfusion. All of the T1, T2, and water content significantly increased in the ischemic tissue. Gray-white difference was evident in T1 and T1 was linearly correlated with the water content of the tissue. T2 way by far prolonged in the ischemic tissue compared with the increase in the water content, showing greater sensitivity of T2 for detection of ischemia. In the imaging experiment, coronal NMR imaging at 0.5 tesla was performed employing proton density-weighted saturation recovery (TR = 1.6 s, TE = 14 ms), T1-weighted inversion recovery (TR = 1.6 s, TI = 300 ms, TE = 14 ms) and T2-weighted spin echo (TR = 1.6 s, TE = 106 ms) pulse sequences. Spatial resolution of the images was excellent (0.3 - 0.5 mm) and the imaging of a gerbil brain clearly delineated anatomy separating cortex, white matter, hippocampus and thalamus. Hemispheric ischemia of a gerbil brain was detected as early as 30 min after occlusion of the carotid artery in T2-weighted images and the evolution of the lesion was clearly picturized in T1- and T2-weighted images. On the other hand. SR images were far less sensitive. Caluculated T1 and T2 relaxation times by the pixel-to-pixel computation indicated progress of the lesion and excellently correlated with the water content of the tissue (r = 0.892 and 0.744 for T1 and T2, respectively). (J.P.N.)

  4. Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

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    Jakub Bukowczan

    Full Text Available Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis.The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion.Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8 nmol/kg/dose was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula.Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food intake and

  5. Early CT findings in acute middle cerebral artery ischemia

    International Nuclear Information System (INIS)

    Mohamed, M.; Poniatowska, R.; Boguslawska, R.; Krawczyk, R.; Rejnowski, J.; Ryterski, J.; Tarrakowski, J.; Mendel, T.

    2004-01-01

    Stroke is characterized by a sudden onset of focal central neurological deficit, with symptoms lasting more than 24 hours, that can be fatal. The introduction of anti-coagulation treatments, together with continuous advances inneuroimaging techniques, have a positive impact, both on morbidity and mortality in stroke patients. It must be stressed, that 'therapeutic window' for fibrolytic treatment is up to 3 hours. The group consisted of 50 patients with clinical diagnosis of stroke, who met the following criteria: first ever, non-hemorrhagic stroke, middle cerebral artery territory involvement, first CT performed within 12 hours from the onset of symptoms, control CT, performed within 7 days, confirming signs of infarction in the distribution of middle cerebral artery. All CT were performed without contrast administration. First CT examinations were retrospectively studied for early evidence of ischemic changes, subsequently depicted as infarction in the control CT. Hyperdencemiddle cerebral artery sign (HMCAS), hypoattenuation of lentiform nucleus (ALN), loss of insular ribbon (LIR), hemispheric sulcus effacement (HES) were found as early abnormalities CT examinations continue to play a dominant role in the initial diagnosis of acute cerebral ischemia. Signs of early ischemia can be often detected within the first three hours from the onset, in the hyper acute phase. CT is used in evaluation of recent symptoms in acute phase and proper selection of patients for thrombolysis with significant therapeutic results. [author

  6. Acute mesenteric ischemia of arterial origin: importance of early revascularization.

    Science.gov (United States)

    Plumereau, F; Mucci, S; Le Naoures, P; Finel, J B; Hamy, A

    2015-02-01

    The goal of our study was to show that survival was better when early revascularization was performed rather than gastrointestinal resection in the management of acute mesenteric ischemia of arterial origin. The reports of patients managed in our center between January 2005 and May 2012 for acute mesenteric ischemia of arterial origin were analyzed retrospectively. Data on clinical, laboratory and radiologic findings, the interval before treatment, the operative findings and the surgical procedures were collected. Follow-up information included the postoperative course, and mortality at 48 h, 30 days and 1 year, the latter being compared between patients undergoing revascularization versus gastrointestinal resection. Of 43 patients treated during this period, 20 had gastrointestinal lesions deemed to be beyond all therapeutic resources, 13 were treated with gastrointestinal resection without revascularization, while 10 underwent early revascularization. There were no statistically significant differences found in the extent of involvement between the two groups (P=0.22). Mortality at 48 h, 30 days and 1 year was 8% (n=1), 30% (n=4) and 68% (n=8) in patients who underwent enterectomy vs. 0% (n=0), 0% (n=0) and 10% (n=1) in patients who underwent revascularization procedures. The difference at 1 year was statistically significant (P=0.02). At 1 year, two patients in the revascularized group had a short bowel syndrome vs. one in the non-revascularized group. Acute mesenteric ischemia of arterial origin is associated with high morbidity and mortality. Optimal management should include early revascularization. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  7. Silent ischemia in patients after the acute myocardial infarction

    International Nuclear Information System (INIS)

    Samarzija, M.

    1991-01-01

    The purpose of this study was to determine the frequency and importance of silent ischemia in patients (pts) after acute myocardial infarction (AMI) as well as to establish diagnostic and prognostic values of exercise stress test (EST), Holter (H) monitoring and thallium-201 (Tl) scintigraphy. All the tests were performed 2-4 months following the AMI. The criterion for diagnostic myocardial ischemia on EST and H is 1 mm or more of horizontal or down-sloping ST depression. Additional criteria for Holter imply that the ischemic episode should last one minute and be separated from other episodes by at least one minute. Planar thallium images were performed 5-10 minutes after the stress test; the delayed images were obtained after 3-6 hours. Visual and quantitative methods were employed in the analysis of Tl-scintigraphy. Scintigraphy was considered positive if exercise-induced perfusion defects showed redistribution. The study included 74 asymptomatic patients after the AMI. The patients were divided into two groups by results of quantitative Tl-scintigraphy: Group I - 44 pts with silent ischemia, Group II - 30 pts without ischemia. In Group I, out of 44 pts, 9 had a positive exercise stress test, 4 showed a painless ST depression on Holter and 7 had both tests positive, whereas 24 pts had only scintigraphy positive. In Group II one patient had positive EST and H. Sensitivity and specificity were determined by results of coronary arteriography performed on 33 pts: EST (Se=40%, Sp=80%), H (Se=21%, Sp=100%) and scintigraphy (Se=93%, Sp=80%). During the follow-up period lasting at least 12 months, in Group I 3 pts died, 1 developed a new myocardial infarction and 15 pts had painful ischemic occurrences. In Group II only 3 pts developed symptoms of angina pectoris. Tl-scintigraphy was the only non-invasive test showing significant correlation with the follow-up outcomes. The diagnostic and prognostic superiority of Tl-scintigraphy justifies its value as an initial

  8. Hemorheological changes in ischemia-reperfusion: an overview on our experimental surgical data.

    Science.gov (United States)

    Nemeth, Norbert; Furka, Istvan; Miko, Iren

    2014-01-01

    Blood vessel occlusions of various origin, depending on the duration and extension, result in tissue damage, causing ischemic or ischemia-reperfusion injuries. Necessary surgical clamping of vessels in vascular-, gastrointestinal or parenchymal organ surgery, flap preparation-transplantation in reconstructive surgery, as well as traumatological vascular occlusions, all present special aspects. Ischemia and reperfusion have effects on hemorheological state by numerous ways: besides the local metabolic and micro-environmental changes, by hemodynamic alterations, free-radical and inflammatory pathways, acute phase reactions and coagulation changes. These processes may be harmful for red blood cells, impairing their deformability and influencing their aggregation behavior. However, there are still many unsolved or non-completely answered questions on relation of hemorheology and ischemia-reperfusion. How do various organ (liver, kidney, small intestine) or limb ischemic-reperfusionic processes of different duration and temperature affect the hemorheological factors? What is the expected magnitude and dynamics of these alterations? Where is the border of irreversibility? How can hemorheological investigations be applied to experimental models using laboratory animals in respect of inter-species differences? This paper gives a summary on some of our research data on organ/tissue ischemia-reperfusion, hemorheology and microcirculation, related to surgical research and experimental microsurgery.

  9. Acute retinal ischemia caused by controlled low ocular perfusion pressure in a porcine model. Electrophysiological and histological characterisation

    DEFF Research Database (Denmark)

    Kyhn, Maria Voss; Warfvinge, Karin; Scherfig, Erik

    2009-01-01

    The purpose of this study was to establish, and characterize a porcine model of acute, controlled retinal ischemia. The controlled retinal ischemia was produced by clamping the ocular perfusion pressure (OPP) in the left eye to 5 mm Hg for 2 h. The OPP was defined as mean arterial blood pressure...... of the amplitudes obtained in the experimental, left eye, and the control, right eye. Quantitative histology was performed to measure the survival of ganglion cells, amacrine cells and horizontal cells 2-6 weeks after the ischemic insult. An OPP of 5 mm Hg for 2h induced significant reductions in the amplitudes...... the ischemic insult. This model seems to be suitable for investigations of therapeutic initiatives in diseases involving acute retinal ischemia....

  10. [Management of Acute Type A Dissection Complicated with Acute Mesenteric Ischemia].

    Science.gov (United States)

    Abe, Tomonobu; Usui, Akihiko

    2017-07-01

    Acute mesenteric ischemia as malperfusion syndrome associated with acute aortic dissection is a difficult situation. The incidence is approximately 3~4% in acute type A dissection. Traditionally, most of these patients underwent immediate simple central aortic repair expecting that mesenteric artery obstruction and intestinal ischemia would be resolved by simple central aortic repair. However, short term mortality has been reported very high in this strategy. With the aid of rapidly progressing imaging techniques and newer endovascular repair techniques, results seem to be improving in recent years. Newer management strategy include aggressive and patient specific revascularization to the mesenteric arteries, delayed central aortic repair, and meticulous intensive care. Diagnosis and management of this condition require high level of expertise. Cardiac surgeons, vascular surgeons, interventional radiologists, gastroenterologists, general surgeons, anesthesiologists, intensivists must corporate to save these patients' lives. Since this is a relatively rare condition, scientific evidence is insufficient to make robust recommendations. Further studies are warranted.

  11. Clinical effectiveness of percutaneous angioplasty for acute and chronic mesenteric ischemia: a six case series.

    Science.gov (United States)

    Jung, Yu Min; Jo, Yun Ju; Ahn, Sang Bong; Son, Byoung Kwan; Kim, Seong Hwan; Park, Young Sook; Bae, June Ho; Cho, Young Kwon

    2011-04-01

    Intestinal ischemia is divided into three categories, namely, acute mesenteric ischemia (AMI), chronic mesenteric ischemia (CMI), and colonic ischemia. AMI can result from arterial or venous thrombi, emboli, and vasoconstriction secondary to low-flow states. It is an urgent condition which can result in high mortality rate. The predominant causative factor of CMI is stenosis or occlusion of the mesenteric arterial circulation, and it is characterized by postprandial abdominal pain and weight loss. Surgery is the treatment of choice for intestinal ischemia. However, it has been recently reported that percutaneous transluminal angioplasty with stent placement and/or thrombolysis is an effective therapy in various types of mesenteric ischemia. We report six cases of mesenteric ischemia which were successfully treated by percutaneous angioplasty, and review the literature from South Korea.

  12. The Olson method for detection of acute myocardial ischemia in patients with coronary occlusion.

    Science.gov (United States)

    Lindow, Thomas; Olson, Charles W; Swenne, Cees A; Man, Sumche; Pahlm, Olle

    An automated ECG-based method may provide diagnostic support in the management of patients with acute coronary syndrome. The Olson method has previously proved to accurately identify the culprit artery in patients with acute coronary occlusion. The Olson method was applied to 360 patients without acute myocardial ischemia and 52 patients with acute coronary occlusion. This study establishes the normal variation of the Olson wall scores in patients without acute myocardial ischemia, which provides the basis for implementation of the Olson method for triage of patients with acute coronary syndrome. All patients with acute occlusion had Olson wall scores above the upper limit of normal. The Olson method can be used for ischemia detection with very high sensitivity. Future studies are needed to explore specificity in patients with non-ischemic ST elevation. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Tramadol Alleviates Myocardial Injury Induced by Acute Hindlimb Ischemia Reperfusion in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Takhtfooladi, Hamed Ashrafzadeh; Asl, Adel Haghighi Khiabanian [Department of Pathobiology, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Shahzamani, Mehran [Department of Cardiovascular Surgery, Isfahan University of Medical Sciences, Tehran (Iran, Islamic Republic of); Takhtfooladi, Mohammad Ashrafzadeh, E-mail: dr-ashrafzadeh@yahoo.com [Young Researchers and Elites Club, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Allahverdi, Amin [Department of Surgery, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Khansari, Mohammadreza [Department of Physiology, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of)

    2015-08-15

    Organ injury occurs not only during periods of ischemia but also during reperfusion. It is known that ischemia reperfusion (IR) causes both remote organ and local injuries. This study evaluated the effects of tramadol on the heart as a remote organ after acute hindlimb IR. Thirty healthy mature male Wistar rats were allocated randomly into three groups: Group I (sham), Group II (IR), and Group III (IR + tramadol). Ischemia was induced in anesthetized rats by left femoral artery clamping for 3 h, followed by 3 h of reperfusion. Tramadol (20 mg/kg, intravenous) was administered immediately prior to reperfusion. At the end of the reperfusion, animals were euthanized, and hearts were harvested for histological and biochemical examination. The levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were higher in Groups I and III than those in Group II (p < 0.05). In comparison with other groups, tissue malondialdehyde (MDA) levels in Group II were significantly increased (p < 0.05), and this increase was prevented by tramadol. Histopathological changes, including microscopic bleeding, edema, neutrophil infiltration, and necrosis, were scored. The total injuryscore in Group III was significantly decreased (p < 0.05) compared with Group II. From the histological and biochemical perspectives, treatment with tramadol alleviated the myocardial injuries induced by skeletal muscle IR in this experimental model.

  14. Hyperoxic preconditioning fails to confer additional protection against ischemia-reperfusion injury in acute diabetic rat heart.

    Science.gov (United States)

    Pourkhalili, Khalil; Hajizadeh, Sohrab; Akbari, Zahra; Dehaj, Mansour Esmaili; Akbarzadeh, Samad; Alizadeh, Alimohammad

    2012-01-01

    Experimental studies show that detrimental effects of ischemia-reperfusion (I/R) injury can be attenuated by hyperoxic preconditioning in normal hearts, however, there are few studies about hyperoxia effects in diseased myocardium. The present study was designed to assess the cardioprotective effects of hyperoxia pretreatment (≥ 95 % O2) in acute diabetic rat hearts. Normal and one week acute diabetic rats were either exposed to 60 (H60) and 180 (H180) min of hyperoxia or exposed to normal atmospheric air (21 % O2). Then hearts were isolated immediately and subjected to 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size, cardiomyocyte apoptosis, enzymes release and ischemia induced arrhythmias were determined. Heart of diabetic control rats had less infarct size and decreased LDH and CK-MB release compared to normal hearts. 60 and 180 min of hyperoxia reduced myocardial infarct size and enzymes release in normal hearts. 180 min of hyperoxia also decreased cardiomyocytes apoptosis in normal state. On the other hand, protective values of hyperoxia were not significantly different in diabetic hearts. Moreover, hyperoxia reduced severity of ventricular arrhythmias in normal rat hearts whereas; it did not confer any additional antiarrhythmic protection in diabetic hearts. These findings suggest that diabetic hearts are less susceptible to ischemia-induced arrhythmias and infarction. Hyperoxia greatly protects rat hearts against I/R injury in normal hearts, however, it could not provide added cardioprotective effects in acute phase of diabetes.

  15. Acute limb ischemia caused by incorrect deployment of a clip-based arterial closure device

    Directory of Open Access Journals (Sweden)

    Łukasz Dzieciuchowicz

    2016-04-01

    Full Text Available Failure of a vascular closure device most commonly results in a hemorrhage or pseudoaneurysm formation. In this paper a rare case of severe acute limb ischemia following incorrect deployment of a clip-based closure device (Starclose SE, Abbott Vascular in a 31-year-old woman is presented. Symptoms of acute limb ischemia occurred at the start of the ambulation, 6 h after completion of the procedure. Because of the severity of ischemia the patient was treated surgically, and limb perfusion was successfully restored. An attempt of closure of an inadvertently punctured narrow superficial femoral artery was identified as the cause of this complication.

  16. Assessment and diagnosis of acute bowel ischemia with multidetector computed tomography (MDCT)

    International Nuclear Information System (INIS)

    Sojka, B.; Gieszczyk-Paraniak, B.; Gibinska, J.; Konopka, M.

    2008-01-01

    Acute bowel ischemia (ABT) is a life-threatening condition which most often effects elderly patients. It requires an intensive treatment and quick diagnosis. Unfortunately ABI manifested not only by specific but also various nonspecific clinical or laboratory finding. The radiological symptoms of the bowel ischemia are also differentiated and often nonspecific while the specific findings are rather uncommon.That is why the knowledge of the bowel ischemia pathogenesis and possible CT findings is so important for the correct diagnosis. The our paper, we present the radiological findings of the acute bowel ischemia based on the analysis of the patients' abdominal -CT examination. The purpose of our study is to MDCT in patients with acute bowel ischemia. The material of this study consists of four computer tomography examinations - three of those an angio-CT and one abdominal - in patients with acute abdomen symptoms. The result revealed the mesenteric thrombosis in two cases, and mesenteric artery stenosis in one case. In one case, the thrombus was present in the abdominal aorta. In conclusion, we claim that the MDCT should be the modality of choice for the diagnosis of the acute bowel ischemia. (author)

  17. [Application of Ischemia Modified Albumin for Acute Ischemic Heart Disease in Forensic Science].

    Science.gov (United States)

    Wang, P; Zhu, Z L; Zhu, N; Yu, H; Yue, Q; Wang, X L; Feng, C M; Wang, C L; Zhang, G H

    2017-10-01

    To explore the application value and forensic significance of ischemia modified albumin (IMA) in pericardial fluid to diagnose sudden cardiac death. IMA level in pericardial fluid was detected in acute ischemic heart disease group ( n =36), acute myocardial infarction group ( n =6), cardiomyopathy group ( n =4) and control group ( n =15) by albumin cobalt binding method. The levels of IMA were compared among these groups. The best cut-off IMA value was estimated and the sensitivity and specificity of acute myocardial ischemia group was distinguished from control group by receiver operating characteristics (ROC) curve. The IMA level in acute ischemic heart disease group was significantly higher than that of control group ( P 0.05). The cut-off value for the identification of acute myocardial ischemia which obtained by ROC analysis was 40.65 U/mL. And the sensitivity and specificity for distinguishing acute ischemia cardiac disease was 60.0% and 80.5%, respectively. The IMA value in pericardial fluid can be a reference marker for the diagnosis of acute myocardial ischemia, which also can provide objective basis for the forensic identification of sudden cardiac death. Copyright© by the Editorial Department of Journal of Forensic Medicine

  18. Abdominal Aortic Dissection with Acute Mesenteric Ischemia in a Patient with Marfan Syndrome

    Directory of Open Access Journals (Sweden)

    Chii-Shyan Lay

    2006-07-01

    Full Text Available Marfan syndrome is an autosomal dominant inherited disorder of connective tissue, with various complications manifested primarily in the cardiovascular system. It potentially leads to aortic dissection and rupture, these being the major causes of death. We report a patient who complained of acute abdominal pain, which presented as acute mesenteric ischemia combined with abdominal aortic dissection. Echocardiography showed enlargement of the aortic root and mitral valve prolapse. Abdominal computed tomography scan revealed acute mesenteric ischemia due to abdominal aortic dissection. Finally, the patient underwent surgery of aortic root replacement and had a successful outcome. Therefore, we suggest that for optimal risk assessment and monitoring of patients with Marfan syndrome, both aortic stiffness and the diameter of the superior mesenteric vein compared with that of the superior mesenteric artery are useful screening methods to detect acute mesenteric ischemia secondary to abdominal aortic dissection. Early diagnosis and early treatment can decrease the high mortality rate of patients with Marfan syndrome.

  19. Aortic plaque rupture in the setting of acute lower limb ischemia.

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2012-02-01

    Acute aortic plaque rupture is an uncommon cause of acute lower limb ischemia. The authors report sequence computed tomographic imaging of a distal aortic plaque rupture in a young man with bilateral lower limb complications. Clinical awareness, prompt recognition and imaging, and appropriate treatment of this uncommon condition are necessary to improve patient outcomes.

  20. Autoradiographic analysis of iodoamphetamine redistribution in experimental brain ischemia

    International Nuclear Information System (INIS)

    Matsuda, H.; Tsuji, S.; Oba, H.; Shiba, K.; Terada, H.; Kinuya, K.; Mori, H.; Sumiya, H.; Hisada, K.

    1990-01-01

    The pathophysiologic significance of iodoamphetamine (IMP) redistribution was analyzed using a double radionuclide autoradiography technique in experimental brain ischemia in the rat. Within 4 hr after unilateral arterial occlusion, IMP almost completely redistributed at 150 min postinjection in the affected areas. At 2 min postinjection, both a remarkable decrease of IMP accumulation and histopathologic change of diminished staining were observed in these areas. The redistribution amplitude was higher in the affected hemisphere, especially in the regions surrounding the ischemic core than in the unaffected hemisphere. These findings were consistent with computer simulation studies of the time course of brain activity based on the standard diffusible tracer model. The results suggest that IMP redistribution in the ischemic area is due to differences of the temporal changes of the brain activity between the unaffected and affected areas and that it is a physical phenomenon (only flow related) rather than a biologic one

  1. Astragaloside IV for Experimental Focal Cerebral Ischemia: Preclinical Evidence and Possible Mechanisms

    Directory of Open Access Journals (Sweden)

    Hui-Lin Wang

    2017-01-01

    Full Text Available Astragaloside IV (AST-IV is a principal component of Radix Astragali seu Hedysari (Huangqi and exerts potential neuroprotection in experimental ischemic stroke. Here, we systematically assessed the effectiveness and possible mechanisms of AST-IV for experimental acute ischemic stroke. An electronic search in eight databases was conducted from inception to March 2016. The study quality score was evaluated using the CAMARADES. Rev Man 5.0 software was used for data analyses. Thirteen studies with 244 animals were identified. The study quality score of included studies ranged from 3/10 to 8/10. Eleven studies showed significant effects of AST-IV for ameliorating the neurological function score (P<0.05; seven studies for reducing the infarct volume (P<0.05; and three or two studies for reducing the brain water content and Evans blue leakage (P<0.05, respectively, compared with the control. The mechanisms of AST-IV for ischemic stroke are multiple such as antioxidative/nitration stress reaction, anti-inflammatory, and antiapoptosis. In conclusion, the findings of present study indicated that AST-IV could improve neurological deficits and infarct volume and reduce the blood-brain barrier permeability in experimental cerebral ischemia despite some methodological flaws. Thus, AST-IV exerted a possible neuroprotective effect during the cerebral ischemia/reperfusion injury largely through its antioxidant, anti-inflammatory, and antiapoptosis properties.

  2. Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep

    Directory of Open Access Journals (Sweden)

    Wolfgang Härtig

    2017-08-01

    Full Text Available As part of the extracellular matrix (ECM, perineuronal nets (PNs are polyanionic, chondroitin sulfate proteoglycan (CSPG-rich coatings of certain neurons, known to be affected in various neural diseases. Although these structures are considered as important parts of the neurovascular unit (NVU, their role during evolution of acute ischemic stroke and subsequent tissue damage is poorly understood and only a few preclinical studies analyzed PNs after acute ischemic stroke. By employing three models of experimental focal cerebral ischemia, this study was focused on histopathological alterations of PNs and concomitant vascular, glial and neuronal changes according to the NVU concept. We analyzed brain tissues obtained 1 day after ischemia onset from: (a mice after filament-based permanent middle cerebral artery occlusion (pMCAO; (b rats subjected to thromboembolic MACO; and (c sheep at 14 days after electrosurgically induced focal cerebral ischemia. Multiple fluorescence labeling was applied to explore simultaneous alterations of NVU and ECM. Serial mouse sections labeled with the net marker Wisteria floribunda agglutinin (WFA displayed largely decomposed and nearly erased PNs in infarcted neocortical areas that were demarcated by up-regulated immunoreactivity for vascular collagen IV (Coll IV. Subsequent semi-quantitative analyses in mice confirmed significantly decreased WFA-staining along the ischemic border zone and a relative decrease in the directly ischemia-affected neocortex. Triple fluorescence labeling throughout the three animal models revealed up-regulated Coll IV and decomposed PNs accompanied by activated astroglia and altered immunoreactivity for parvalbumin, a calcium-binding protein in fast-firing GABAergic neurons which are predominantly surrounded by neocortical PNs. Furthermore, ischemic neocortical areas in rodents simultaneously displayed less intense staining of WFA, aggrecan, the net components neurocan, versican and the

  3. MRI of experimental focal cerebral ischemia in sheep

    International Nuclear Information System (INIS)

    Foerschler, A.; Waldmin, D.; Gille, U.; Leipzig Univ.; Zimmer, C.

    2007-01-01

    Purpose: With respect to the specific characteristic of rete mirabile epidurale rostrale in sheep, the aim of this study was to investigate the use of time of flight (TOF) magnetic resonance angiography (MRA) to observe vascular anatomy and to validate MCA occlusion in a new model of experimental focal cerebral ischemia by permanent middle cerebral artery (MCA) occlusion in sheep (designed to study stroke therapy using autologous stem cells from umbilical cord blood). Furthermore, we wanted to assess the extent and natural time course of ischemic focal brain injury in sheep using functional and morphological magnetic resonance imaging (MRI). Materials and Method: 13 Merino sheep were examined. In 4 of the animals all, in 5 sheep 1 or 2 MCA branches were occluded and in 1 one case touched (sham operation). 4 controls did not undergo a surgical procedure. 23 MRI sessions were performed in 10 sheep. These sessions included T1, T2, T2 * sequences, diffusion-weighted imaging (DWI) and TOF MRA before and 2 - 46 days after the onset of stroke using a 1.5T clinical MR scanner. Corrosion casts of the cerebral arteries of 3 sheep were prepared and compared to MRA. Results: The MRA visualized the vessel anatomy or occlusion distal to the rete mirabile. Anatomical variants concerning the variant origin of the MCA and inconstant arteria choroidea rostralis and communicans rostralis were revealed. Sheep with occluded left MCA showed space occupying lesions with a drop in ADC values. Depending on the number of preserved MCA branches (0; 1; 2), highly significant (p < 0.001) differences in lesion size (21 ± 5.7; 13; 1.7 ± 1.3 ml) could be found. No indication of ischemia but minimal contusion damage was observed in the sham operated animal. (orig.)

  4. N-Acetylaspartate distribution in rat brain striatum during acute brain ischemia

    DEFF Research Database (Denmark)

    Sager, T.N.; Laursen, H; Fink-Jensen, A

    1999-01-01

    Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (1H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by 1H-MRS and how NAA......]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during...... normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA...

  5. Is chlormethiazole neuroprotective in experimental global cerebral ischemia? A microdialysis and behavioral study.

    Science.gov (United States)

    Thaminy, S; Reymann, J M; Heresbach, N; Allain, H; Lechat, P; Bentué-Ferrer, D

    1997-04-01

    Chlormethiazole, an anticonvulsive agent, has been shown to have a possible neuroprotective effect against cerebral ischemia. In addition, chlormethiazole inhibits methamphetamine-induced release of dopamine, protecting against this neurotransmitter's neurotoxicity. The aim of this work was to ascertain whether, in experimental cerebral ischemia, chlormethiazole administration attenuated the ischemia-induced rise of the extracellular concentration of aminergic neurotransmitters and whether it reduces ischemia-induced deficits in memory and learning. Histology for assessment of ischemic damage was a so included. The four-vessel occlusion rat model was used to induce global cerebral ischemia. Aminergic neurotransmitters and their metabolites in the striatal extracellular fluid obtained by microdialysis were assayed by high-performance liquid chromatography-electrochemical detection. The drug was administered either IP (50 mg/kg-1) or directly through the dialysis probe (30 microM) 80 min before ischemia. For the behavioral test and histology, the drug was given IP (100 mg/kg-1) 1 h postischemia. The results obtained did not demonstrate any statistically significant evidence that chlormethiazole has an effect on the ischemia-induced rise in extracellular dopamine and serotonin levels. There was also no variation in metabolite levels. Behavioral measures (learning, recall) were not changed appreciably by the treatment. We observed no significant cell protection in the hippocampus (CA1, CA1), striatum, and entorhinal cortex in animals treated with chlormethiazole. We conclude that, under our experimental conditions, chlormethiazole has little or no effect on the neurochemical, neurobehavioral, and histological consequences of global cerebral ischemia.

  6. Diagnosis of acute ischemia using dual energy CT after mechanical thrombectomy.

    Science.gov (United States)

    Gariani, Joanna; Cuvinciuc, Victor; Courvoisier, Delphine; Krauss, Bernhard; Mendes Pereira, Vitor; Sztajzel, Roman; Lovblad, Karl-Olof; Vargas, Maria Isabel

    2016-10-01

    To assess the performance of dual energy unenhanced CT in the detection of acute ischemia after mechanical thrombectomy. Retrospective study, approved by the local institutional review board, including all patients that underwent intra-arterial thrombectomy in our institution over a period of 2 years. The presence of acute ischemia and hemorrhage was evaluated by three readers. Sensitivity and specificity of the non-contrast CT weighted sum image (NCCT) and the virtual non-contrast reconstructed image (VNC) were estimated and compared using generalized estimating equations to account for the non-independence of regions in each patient. 58 patients (27 women and 31 men; mean age 70.4 years) were included in the study, yielding 580 regions of interest. Sensitivity and specificity in detecting acute ischemia were higher for all readers when using VNC, with a significant increase in sensitivity for two readers (pVNC images were superior in the identification of acute ischemia in comparison with NCCT. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  7. Acute administration of n-3 rich triglyceride emulsions provides cardioprotection in murine models after ischemia-reperfusion.

    Science.gov (United States)

    Zirpoli, Hylde; Abdillahi, Mariane; Quadri, Nosirudeen; Ananthakrishnan, Radha; Wang, Lingjie; Rosario, Rosa; Zhu, Zhengbin; Deckelbaum, Richard J; Ramasamy, Ravichandran

    2015-01-01

    Dietary n-3 fatty acids (FAs) may reduce cardiovascular disease risk. We questioned whether acute administration of n-3 rich triglyceride (TG) emulsions could preserve cardiac function and decrease injury after ischemia/reperfusion (I/R) insult. We used two different experimental models: in vivo, C57BL/6 mice were exposed to acute occlusion of the left anterior descending coronary artery (LAD), and ex-vivo, C57BL/6 murine hearts were perfused using Langendorff technique (LT). In the LAD model, mice treated with n-3 TG emulsion (1.5 g/kg body weight), immediately after ischemia and 1 h later during reperfusion, significantly reduced infarct size and maintained cardiac function (plevels, as a marker of injury, were significantly reduced by n-3 TG emulsion. To investigate the mechanisms by which n-3 FAs protects hearts from I/R injury, we investigated changes in key pathways linked to cardioprotection. In the ex-vivo model, we showed that n-3 FAs increased phosphorylation of AKT and GSK3β proteins (plevel and reduced an autophagy marker, Beclin-1 (pGSK3β inhibitor plus n-3 TG significantly inhibited LDH release. We conclude that acute n-3 TG injection during reperfusion provides cardioprotection. This may prove to be a novel acute adjunctive reperfusion therapy after treating patients with myocardial infarction.

  8. Imaging of acute mesenteric ischemia using multidetector CT and CT angiography in a porcine model.

    Science.gov (United States)

    Rosow, David E; Sahani, Dushyant; Strobel, Oliver; Kalva, Sanjeeva; Mino-Kenudson, Mari; Holalkere, Nagaraj S; Alsfasser, Guido; Saini, Sanjay; Lee, Susanna I; Mueller, Peter R; Fernández-del Castillo, Carlos; Warshaw, Andrew L; Thayer, Sarah P

    2005-12-01

    Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly facilitates the use of CT angiography (CTA) in the clinical setting. We sought to determine whether M.D.CT-CTA could accurately demonstrate vascular anatomy and capture the earliest stages of mesenteric ischemia in a porcine model. Pigs underwent embolization of branches of the superior mesenteric artery, then imaging by M.D.CT-CTA with three-dimensional reconstruction protocols. After scanning, diseased bowel segments were surgically resected and pathologically examined. Multidetector row CT and CT angiography reliably defined normal and occluded mesenteric vessels in the pig. It detected early changes of ischemia including poor arterial enhancement and venous dilatation, which were seen in all ischemic animals. The radiographic findings--compared with pathologic diagnoses-- predicted ischemia, with a positive predictive value of 92%. These results indicate that M.D.CT-CTA holds great promise for the early detection necessary for successful treatment of acute mesenteric ischemia.

  9. Molecular Mechanisms of Curcumin Renoprotection in Experimental Acute Renal Injury

    Directory of Open Access Journals (Sweden)

    Youling Fan

    2017-12-01

    Full Text Available As a highly perfused organ, the kidney is especially sensitive to ischemia and reperfusion. Ischemia-reperfusion (IR-induced acute kidney injury (AKI has a high incidence during the perioperative period in the clinic and is an important link in ischemic acute renal failure (IARF. Therefore, IR-induced AKI has important clinical significance and it is necessary to explore to develop drugs to prevent and alleviate IR-induced AKI. Curcumin [diferuloylmethane, 1,7-bis(4-hydroxy-3-methoxiphenyl-1,6-heptadiene-3,5-dione] is a polyphenol compound derived from Curcuma longa (turmeric and was shown to have a renoprotective effect on ischemia-reperfusion injury (IRI in a previous study. However, the specific mechanisms underlying the protective role of curcumin in IR-induced AKI are not completely understood. APPL1 is a protein coding gene that has been shown to be involved in the crosstalk between the adiponectin-signaling and insulin-signaling pathways. In the study, to investigate the molecular mechanisms of curcumin effects in kidney ischemia/reperfusion model, we observed the effect of curcumin in experimental models of IR-induced AKI and we found that curcumin treatment significantly increased the expression of APPL1 and inhibited the activation of Akt after IR treatment in the kidney. Our in vitro results showed that apoptosis of renal tubular epithelial cells was exacerbated with hypoxia-reoxygenation (HR treatment compared to sham control cells. Curcumin significantly decreased the rate of apoptosis in renal tubular epithelial cells with HR treatment. Moreover, knockdown of APPL1 activated Akt and subsequently aggravated apoptosis in HR-treated renal tubular epithelial cells. Conversely, inhibition of Akt directly reversed the effects of APPL1 knockdown. In summary, our study demonstrated that curcumin mediated upregulation of APPL1 protects against ischemia reperfusion induced AKI by inhibiting Akt phosphorylation.

  10. Pharmacologicalmodification of thegabaergicsystem as a potentialvariant of cerebral protection in acute cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Олександр Володимирович Тихоновський

    2015-10-01

    Full Text Available The aim is to study the possible impact of some derivatives of gamma-aminobutyric acid (GABA, piracetam, picamilon and Krebs cycle intermediates - succinate (as sodium salt on the pathobiochemical changes in the central nervous system, that occur under experimental playing of acute ischemic tissue damage of the cerebrum.Research methods: The study was conducted in 96 rats Wistar, who were on a standardized vivarium diet. Cerebral ischemia was caused by bond of the unilateral common carotid artery. All drugs were administered intraperitoneally once daily for 4 days after modeling of an acute cerebral ischemia after which animals were withdrawn from experiment. In the brain tissues concentrations of pyruvic, izocitric, dairy and apple acids were determined. The activity of antioxidant enzymes: catalase and superoxide dysmutaza. In addition, the brain tissues the contents of lipid peroxidation products were evaluated – diene conjugates and malonic dialdehyde. Level of brain energy production was judged by the content of the adenylic nucleotide and also phosphocreatine . The degree of destruction of the brain cells was assessed by activity of the enzyme lactate dehydrogenase in the blood and brain fraction of the creatine phosphokinase.Research results: As a result of studies, on the 4th day of ischemia a significant carbohydrate metabolism is detected, which is reflected in the sharp strengthening of anaerobic glycolysis and reduced activity of the Krebs cycle reactions, as evidenced by a significant increase in quantity of lactate and decrease in quantity of malate, isocitrate and pyruvate.A sharp strengthening of anaerobic glycolysis results in the accumulation of oxidized products and intermediates especially the latter product – lactic acid. Metabolic acidosis develops against the background of energy failure, which leads to activation of lipid peroxidation reactions. Courses appointment of the cyclic derivatives of GABA piracetam

  11. Ischemic preconditioning provides both acute and delayed protection against renal ischemia and reperfusion injury in mice.

    Science.gov (United States)

    Joo, Jin Deok; Kim, Mihwa; D'Agati, Vivette D; Lee, H Thomas

    2006-11-01

    Acute as well as delayed ischemic preconditioning (IPC) provides protection against cardiac and neuronal ischemia reperfusion (IR) injury. This study determined whether delayed preconditioning occurs in the kidney and further elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed renal IPC provided powerful protection against renal IR injury. Inhibition of Akt but not extracellular signal-regulated kinase phosphorylation prevented the protection that was afforded by acute IPC. Neither extracellular signal-regulated kinase nor Akt inhibition prevented protection that was afforded by delayed renal IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to scavenge free radicals prevented the protection that was provided by acute but not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin-sensitive G-proteins attenuated protection from both acute and delayed renal IPC. Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as heat-shock protein 27 synthesis, and the renal protective effects of delayed preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1-iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice. Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a selective A(1)AR antagonist failed to block preconditioning and acute and delayed preconditioning occurred in mice that lacked A(1)AR. Therefore, this study demonstrated that acute or delayed IPC provides renal protection against IR injury in mice but involves distinct signaling pathways.

  12. Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

    Science.gov (United States)

    Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

    2011-01-01

    The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

  13. Analysis of temporal dynamics in imagery during acute limb ischemia and reperfusion

    Science.gov (United States)

    Irvine, John M.; Regan, John; Spain, Tammy A.; Caruso, Joseph D.; Rodriquez, Maricela; Luthra, Rajiv; Forsberg, Jonathon; Crane, Nicole J.; Elster, Eric

    2014-03-01

    Ischemia and reperfusion injuries present major challenges for both military and civilian medicine. Improved methods for assessing the effects and predicting outcome could guide treatment decisions. Specific issues related to ischemia and reperfusion injury can include complications arising from tourniquet use, such as microvascular leakage in the limb, loss of muscle strength and systemic failures leading to hypotension and cardiac failure. Better methods for assessing the viability of limbs/tissues during ischemia and reducing complications arising from reperfusion are critical to improving clinical outcomes for at-risk patients. The purpose of this research is to develop and assess possible prediction models of outcome for acute limb ischemia using a pre-clinical model. Our model relies only on non-invasive imaging data acquired from an animal study. Outcome is measured by pathology and functional scores. We explore color, texture, and temporal features derived from both color and thermal motion imagery acquired during ischemia and reperfusion. The imagery features form the explanatory variables in a model for predicting outcome. Comparing model performance to outcome prediction based on direct observation of blood chemistry, blood gas, urinalysis, and physiological measurements provides a reference standard. Initial results show excellent performance for the imagery-base model, compared to predictions based direct measurements. This paper will present the models and supporting analysis, followed by recommendations for future investigations.

  14. Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

    Science.gov (United States)

    Schmiedt, C W; Brainard, B M; Hinson, W; Brown, S A; Brown, C A

    2016-01-01

    The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease. © The Author(s) 2015.

  15. Multi-detector CT features of acute intestinal ischemia and their prognostic correlations.

    Science.gov (United States)

    Moschetta, Marco; Telegrafo, Michele; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe

    2014-05-28

    Acute intestinal ischemia is an abdominal emergency occurring in nearly 1% of patients presenting with acute abdomen. The causes can be occlusive or non occlusive. Early diagnosis is important to improve survival rates. In most cases of late or missed diagnosis, the mortality rate from intestinal infarction is very high, with a reported value ranging from 60% to 90%. Multi-detector computed tomography (MDCT) is a fundamental imaging technique that must be promptly performed in all patients with suspected bowel ischemia. Thanks to the new dedicated reconstruction program, its diagnostic potential is much improved compared to the past and currently it is superior to that of any other noninvasive technique. The increased spatial and temporal resolution, high-quality multi-planar reconstructions, maximum intensity projections, vessel probe, surface-shaded volume rending and tissue transition projections make MDCT the gold standard for the diagnosis of intestinal ischemia, with reported sensitivity, specificity, positive and negative predictive values of 64%-93%, 92%-100%, 90%-100% and 94%-98%, respectively. MDCT contributes to appropriate treatment planning and provides important prognostic information thanks to its ability to define the nature and extent of the disease. The purpose of this review is to examine the diagnostic and prognostic role of MDCT in bowel ischemia with special regard to the state of art new reconstruction software.

  16. Effects of Chronic and Acute Zinc Supplementation on Myocardial Ischemia-Reperfusion Injury in Rats.

    Science.gov (United States)

    Ozyıldırım, Serhan; Baltaci, Abdulkerim Kasim; Sahna, Engin; Mogulkoc, Rasim

    2017-07-01

    The present study aims to explore the effects of chronic and acute zinc sulfate supplementation on myocardial ischemia-reperfusion injury in rats. The study registered 50 adult male rats which were divided into five groups in equal numbers as follows: group 1, normal control; group 2, sham; group 3, myocardial ischemia reperfusion (My/IR): the group which was fed on a normal diet and in which myocardial I/R was induced; group 4, myocardial ischemia reperfusion + chronic zinc: (5 mg/kg i.p. zinc sulfate for 15 days); and group 5, myocardial ischemia reperfusion + acute zinc: the group which was administered 15 mg/kg i.p. zinc sulfate an hour before the operation and in which myocardial I/R was induced. The collected blood and cardiac tissue samples were analyzed using spectrophotometric method to determine levels of MDA, as an indicator of tissue injury, and GSH, as an indicator of antioxidant activity. The highest plasma and heart tissue MDA levels were measured in group 3 (p zinc administration and markedly by chronic zinc supplementation.

  17. Acute administration of n-3 rich triglyceride emulsions provides cardioprotection in murine models after ischemia-reperfusion.

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    Hylde Zirpoli

    Full Text Available Dietary n-3 fatty acids (FAs may reduce cardiovascular disease risk. We questioned whether acute administration of n-3 rich triglyceride (TG emulsions could preserve cardiac function and decrease injury after ischemia/reperfusion (I/R insult. We used two different experimental models: in vivo, C57BL/6 mice were exposed to acute occlusion of the left anterior descending coronary artery (LAD, and ex-vivo, C57BL/6 murine hearts were perfused using Langendorff technique (LT. In the LAD model, mice treated with n-3 TG emulsion (1.5 g/kg body weight, immediately after ischemia and 1 h later during reperfusion, significantly reduced infarct size and maintained cardiac function (p<0.05. In the LT model, administration of n-3 TG emulsion (300 mg TG/100 ml during reperfusion significantly improved functional recovery (p<0.05. In both models, lactate dehydrogenase (LDH levels, as a marker of injury, were significantly reduced by n-3 TG emulsion. To investigate the mechanisms by which n-3 FAs protects hearts from I/R injury, we investigated changes in key pathways linked to cardioprotection. In the ex-vivo model, we showed that n-3 FAs increased phosphorylation of AKT and GSK3β proteins (p<0.05. Acute n-3 TG emulsion treatment also increased Bcl-2 protein level and reduced an autophagy marker, Beclin-1 (p<0.05. Additionally, cardioprotection by n-3 TG emulsion was linked to changes in PPARγ protein expression (p<0.05. Rosiglitazone and p-AKT inhibitor counteracted the positive effect of n-3 TG; GSK3β inhibitor plus n-3 TG significantly inhibited LDH release. We conclude that acute n-3 TG injection during reperfusion provides cardioprotection. This may prove to be a novel acute adjunctive reperfusion therapy after treating patients with myocardial infarction.

  18. Imaging of Acute Mesenteric Ischemia Using Multidetector CT and CT Angiography in a Porcine Model

    OpenAIRE

    Rosow, David E.; Sahani, Dushyant; Strobel, Oliver; Kalva, Sanjeeva; Mino-Kenudson, Mari; Holalkere, Nagaraj S.; Alsfasser, Guido; Saini, Sanjay; Lee, Susanna I.; Mueller, Peter R.; Castillo, Carlos Fernández-del; Warshaw, Andrew L.; Thayer, Sarah P.

    2005-01-01

    Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly f...

  19. Electrocardiographic scores of severity and acuteness of myocardial ischemia predict myocardial salvage in patients with anterior ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Fakhri, Yama; Sejersten, Maria; Schoos, Mikkel Malby

    2018-01-01

    inferior infarct locations. METHODS: In STEMI patients, the severity and acuteness scores were obtained from the admission ECG. Based on the ECG patients were assigned with severe or non-severe ischemia and acute or non-acute ischemia. Cardiac magnetic resonance (CMR) was performed 2-6days after primary...

  20. Persistent sciatic artery aneurysm: A rare cause of acute limb ischemia

    Directory of Open Access Journals (Sweden)

    Pranay Pawar

    2018-01-01

    Full Text Available Persistent sciatic artery (PSA is a rare but pertinent clinical entity that may pose a threat to the viability of the lower extremity. The incidence of PSA has been estimated to be between 0.01% and 0.05%. PSAs are prone to high incidence of aneurysm formation, thrombosis, distal embolization, and rupture. Early detection of a PSA as the main vascular supply to the lower limb helps in early surgery and avoids potential severe complications such as limb ischemia. We report a case of a female patient who was diagnosed with a case of lumbar disc compression and sciatica but had a PSA aneurysm with thrombosis and distal embolization leading to acute limb ischemia.

  1. Initial results from an agressive roentgenological and surgical approach to acute mesenteric ischemia.

    Science.gov (United States)

    Boley, S J; Sprayregan, S; Siegelman, S S; Veith, F J

    1977-12-01

    The 70% to 80% mortality rate of patients with acute mesenteric ischemia (AMI) has remained unchanged over the past 40 years. We report here the initial results using an aggressive approach to this problem. This included the earlier and more liberal use of angiography in patients at risk and the intra-arterial infusion of papaverine for the relief of superior mesenteric artery (SMA) vasoconstriction in both nonocclusive and occlusive forms of AMI. Of the first 50 patients managed by this approach, 35 (70%) had AMI demonstrated by SMA angiography, Nineteen (54%) of these 35 patients survived, including nine of 15 patients with nonocclusive mesenteric ischemia, seven of 16 with SMA embolus, two of three patients with SMA thrombosis, and the one patient with mesenteric venous thrombosis. Seventeen of the 19 survivors lost no bowel or had excision of less than 3 feet of small intestine.

  2. Improved CT-detection of acute bowel ischemia using frequency selective non-linear image blending.

    Science.gov (United States)

    Schneeweiss, Sven; Esser, Michael; Thaiss, Wolfgang; Boesmueller, Hans; Ditt, Hendrik; Nikolau, Konstantin; Horger, Marius

    2017-07-01

    Computed tomography (CT) as a fast and reliable diagnostic technique is the imaging modality of choice for acute bowel ischemia. However, diagnostic is often difficult mainly due to low attenuation differences between ischemic and perfused segments. To compare the diagnostic efficacy of a new post-processing tool based on frequency selective non-linear blending with that of conventional linear contrast-enhanced CT (CECT) image blending for the detection of bowel ischemia. Twenty-seven consecutive patients (19 women; mean age = 73.7 years, age range = 50-94 years) with acute bowel ischemia were scanned using multidetector CT (120 kV; 100-200 mAs). Pre-contrast and portal venous scans (65-70 s delay) were acquired. All patients underwent surgery for acute bowel ischemia and intraoperative diagnosis as well as histologic evaluation of explanted bowel segments was considered "gold standard." First, two radiologists read the conventional CECT images in which linear blending was adapted for optimal contrast, and second (three weeks later) the frequency selective non-linear blending (F-NLB) image. Attenuation values were compared, both in the involved and non-involved bowel segments creating ratios between unenhanced and CECT. The mean attenuation difference between ischemic and non-ischemic wall in the portal venous scan was 69.54 HU (reader 2 = 69.01 HU) higher for F-NLB compared with conventional CECT. Also, the attenuation ratio between contrast-enhanced and pre-contrast CT data for the non-ischemic walls showed significantly higher values for the F-NLB image (CECT: reader 1 = 2.11 (reader 2 = 3.36), F-NLB: reader 1 = 4.46 (reader 2 = 4.98)]. Sensitivity in detecting ischemic areas increased significantly for both readers using F-NLB (CECT: reader 1/2 = 53%/65% versus F-NLB: reader 1/2 = 62%/75%). Frequency selective non-linear blending improves detection of bowel ischemia compared with conventional CECT by increasing

  3. Quantified kidney echogenicity in mice with renal ischemia reperfusion injury: evaluation as a noninvasive biomarker of acute kidney injury.

    Science.gov (United States)

    Murata, Shinya; Sugiyama, Noriyuki; Maemura, Kentaro; Otsuki, Yoshinori

    2017-09-01

    The purpose is to evaluate quantified kidney echogenicity as a biomarker for the early diagnosis of acute kidney injury (AKI) and predicting progression to chronic kidney disease (CKD) in a mouse model of ischemia-reperfusion injury (IRI). Two separate protocols of murine models of IRI were used: (1) 10, 30, and 40 min of bilateral ischemia duration and (2) 45 and 60 min of unilateral ischemia duration. Renal echogenicity was measured with ultrasound and compared with serum creatinine or urine neutrophil gelatinase-associated lipocalin (NGAL) at various timepoints after IRI. In mice subjected to 10, 30, and 40 min of bilateral ischemia, renal echogenicity increased about 2 h after IRI for all ischemia times, earlier than serum creatinine or urine NGAL. In those subjected to 45 and 60 min of unilateral ischemia, 60 min of unilateral ischemia, which represents atrophic changes 28 days after IRI, resulted in a sustained high level of echogenicity and was significantly different 24 h after IRI, while 45 min of unilateral ischemia resulted in trivial levels of histological damage 28 days after IRI. Renal echogenicity might have the potential to be a biomarker for the early diagnosis of AKI and the prognosis of CKD.

  4. Experimental study of pulmonary thromboembolism ischemia-reperfusion injury in canine model

    International Nuclear Information System (INIS)

    Li Jianjun; Zhai Renyou; Zhang Dongpo; Huang Qiang; Yu Ping; Dai Dingke; Bao Na

    2009-01-01

    Objective: To establish a canine model of pulmonary thromboembolism ischemia- reperfusion injury (PTE IRI) that may be used for imaging study. Methods: Ten male and 10 female healthy mongrel canines with (18.6±0.8) kg/body weight, were used. A Swan-Ganz catheter was introduced into the right internal jugular vein via a preset percutaneous sheath using the Seldinger technique, and then was with further insertion the pulmonary artery. Balloon occlusion of the right inferior lobe pulmonary artery for 4 hours was followed by removing the catheter and ending with 4 hours of reperfusion. CT was performed before ischemia, 4 h after ischemia and 4 h after reperfusion. At last, dogs were killed and the bilateral inferior lung tissues were prepared for the examination by light and electronic microscopy. Results: All canine models were successfully developed pulmonary thromboembolism ischemia-reperfusion injury. The examination of CT, light and electron microscopy consistently indicated the presence of permeability pulmonary edema after reperfusion. Conclusions: A closed-chest canine model in vivo of pulmonary thromboembolism ischemia-reperfusion injury can be established with virtual pathophysiological process in human and be as well as for imaging experimental study. (authors)

  5. Accuracy of multidetector row computed tomography for the diagnosis of acute bowel ischemia in a non-selected study population

    International Nuclear Information System (INIS)

    Wiesner, Walter; Hauser, Andreas; Steinbrich, Wolfgang

    2004-01-01

    The diagnostic accuracy of multidetector row computed tomography for the prospective diagnosis of acute bowel ischemia in the daily clinical routine was analyzed. Two hundred ninety-one consecutive patients with an acute or subacute abdomen, examined by MDCT over a time period of 5 months, were included in the study. All original CT diagnoses made during the daily routine by radiological generalists were compared to the final diagnoses made by using all available medical information from endoscopies, surgical interventions, autopsies and follow-up. Finally, all CT examinations of patients with an initial CT diagnosis or a final diagnosis of bowel ischemia were reread by a radiologist specialized in abdominal imaging in order to analyze the CT findings and the reasons for initially false negative or false positive CT readings. Twenty-four patients out of 291 (8.2%) had acute bowel ischemia. The age of affected patients ranged from 50 to 94 years (mean age: 75.7 years). Eleven patients were male, and 13 female. Reasons for acute bowel ischemia were: arterio-occlusive (n=11), non-occlusive (n=5), strangulation (n=2), over-distension (n=3) and radiation (n=3). The prospective sensitivity, specificity, PPV and NPV of MDCT for the diagnosis of acute bowel ischemia in the daily routine were 79.17, 98.51, 90.48 and 98.15%. MDCT reaches a similarly high sensitivity in diagnosing acute bowel as angiography. Furthermore, it has the advantage of being helpful in most of its clinical differential diagnoses and of being less invasive with the consecutive possibility of being used earlier in the diagnostic process with all the resulting positive effects on the patients prognosis. Therefore, nowadays MDCT should probably be used as the first step imaging modality of choice in patients with suspected acute bowel ischemia. (orig.)

  6. Polyarteritis nodosa presenting as peripheral vascular disease and acute limb ischemia

    Directory of Open Access Journals (Sweden)

    A Shukla

    2017-01-01

    Full Text Available Acute limb ischemia and peripheral vascular disease (PVD are unusual presentations of polyarteritis nodosa (PAN. Here, we present a case with PVD of both lower limbs leading to foot claudication. Digital subtraction angiography showed narrowing, irregularity, and occlusion of both lower limb arteries with no involvement of the abdomen visceral arteries. Based on significant weight loss, diastolic blood pressure >90 mmHg, myalgia, testicular pain, and angiographic abnormalities in medium-sized arteries, he was diagnosed as having PAN. He was treated with corticosteroid and bolus intravenous cyclophosphamide following which he had prompt and near-complete recovery of the symptoms without any tissue loss.

  7. MR perfusion/diffusion-weighted imaging of acute ischemia in an animal model with PET correlation

    International Nuclear Information System (INIS)

    Pickens, D.R.; Dawson, R.C.; Votaw, J.R.; Lorenz, C.H.; Holburn, G.E.; Price, R.R.

    1990-01-01

    This paper evaluates acute cerebral ischemia in an animal model with MR perfusion/diffusion-sensitive pulse sequences and to compare the results with PET regional cerebral blood flow (rCBF) measurements. An embolizing agent was injected into the proximal middle cerebral artery (MCA) of a dog, and this was followed by DSA. Next, the animal was imaged in a 1.5-T MR system with perfusion/diffusion-sensitive spin-echo pulse sequence. Then, PET imaging was performed with H 2 O 15 at corresponding levels of the brain

  8. Single-cell resolution mapping of neuronal damage in acute focal cerebral ischemia using thallium autometallography.

    Science.gov (United States)

    Stöber, Franziska; Baldauf, Kathrin; Ziabreva, Iryna; Harhausen, Denise; Zille, Marietta; Neubert, Jenni; Reymann, Klaus G; Scheich, Henning; Dirnagl, Ulrich; Schröder, Ulrich H; Wunder, Andreas; Goldschmidt, Jürgen

    2014-01-01

    Neuronal damage shortly after onset or after brief episodes of cerebral ischemia has remained difficult to assess with clinical and preclinical imaging techniques as well as with microscopical methods. We here show, in rodent models of middle cerebral artery occlusion (MCAO), that neuronal damage in acute focal cerebral ischemia can be mapped with single-cell resolution using thallium autometallography (TlAMG), a histochemical technique for the detection of the K(+)-probe thallium (Tl(+)) in the brain. We intravenously injected rats and mice with thallium diethyldithiocarbamate (TlDDC), a lipophilic chelate complex that releases Tl(+) after crossing the blood-brain barrier. We found, within the territories of the affected arteries, areas of markedly reduced neuronal Tl(+) uptake in all animals at all time points studied ranging from 15 minutes to 24 hours after MCAO. In large lesions at early time points, areas with neuronal and astrocytic Tl(+) uptake below thresholds of detection were surrounded by putative penumbral zones with preserved but diminished Tl(+) uptake. At 24 hours, the areas of reduced Tl(+)uptake matched with areas delineated by established markers of neuronal damage. The results suggest the use of (201)TlDDC for preclinical and clinical single-photon emission computed tomography (SPECT) imaging of hyperacute alterations in brain K(+) metabolism and prediction of tissue viability in cerebral ischemia.

  9. Depolarization changes during acute myocardial ischemia by evaluation of QRS slopes: standard lead and vectorial approach.

    Science.gov (United States)

    Romero, Daniel; Ringborn, Michael; Laguna, Pablo; Pahlm, Olle; Pueyo, Esther

    2011-01-01

    Diagnosis and risk stratification of patients with acute coronary syndromes can be improved by adding information from the depolarization phase (QRS complex) to the conventionally used ST-T segment changes. In this study, ischemia-induced changes in the main three slopes of the QRS complex, upward ( ℑ(US)) and downward ( ℑ(DS) ) slopes of the R wave as well as the upward ( ℑ(TS)) slope of the terminal S wave, were evaluated as to represent a robust measure of pathological changes within the depolarization phase. From ECG recordings both in a resting state (control recordings) and during percutaneous coronary intervention (PCI)-induced transmural ischemia, we developed a method for quantification of ℑ(US), ℑ(DS), and ℑ(TS) that incorporates dynamic ECG normalization so as to improve the sensitivity in the detection of ischemia-induced changes. The same method was also applied on leads obtained by projection of QRS loops onto their dominant directions. We show that ℑ(US), ℑ(DS), and ℑ(TS) present high stability in the resting state, thus providing a stable reference for ischemia characterization. Maximum relative factors of change ( ℜ(ℑ)) during PCI were found in leads derived from the QRS loop, reaching 10.5 and 13.7 times their normal variations in the control for ℑ(US) and ℑ(DS), respectively. For standard leads, the relative factors of change were 6.01 and 9.31. The ℑ(TS) index presented a similar behavior to that of ℑ(DS). The timing for the occurrence of significant changes in ℑ(US) and ℑ(DS) varied with lead, ranging from 30 s to 2 min after initiation of coronary occlusion. In the present ischemia model, relative ℑ(DS) changes were smaller than ST changes in most leads, however with only modest correlation between the two indices, suggesting they present different information about the ischemic process. We conclude that QRS slopes offer a robust tool for evaluating depolarization changes during myocardial ischemia.

  10. Acute mesenteric ischemia: guidelines of the World Society of Emergency Surgery.

    Science.gov (United States)

    Bala, Miklosh; Kashuk, Jeffry; Moore, Ernest E; Kluger, Yoram; Biffl, Walter; Gomes, Carlos Augusto; Ben-Ishay, Offir; Rubinstein, Chen; Balogh, Zsolt J; Civil, Ian; Coccolini, Federico; Leppaniemi, Ari; Peitzman, Andrew; Ansaloni, Luca; Sugrue, Michael; Sartelli, Massimo; Di Saverio, Salomone; Fraga, Gustavo P; Catena, Fausto

    2017-01-01

    Acute mesenteric ischemia (AMI) is typically defined as a group of diseases characterized by an interruption of the blood supply to varying portions of the small intestine, leading to ischemia and secondary inflammatory changes. If untreated, this process will eventuate in life threatening intestinal necrosis. The incidence is low, estimated at 0.09-0.2% of all acute surgical admissions. Therefore, although the entity is an uncommon cause of abdominal pain, diligence is always required because if untreated, mortality has consistently been reported in the range of 50%. Early diagnosis and timely surgical intervention are the cornerstones of modern treatment and are essential to reduce the high mortality associated with this entity. The advent of endovascular approaches in parallel with modern imaging techniques may provide new options. Thus, we believe that a current position paper from World Society of Emergency Surgery (WSES) is warranted, in order to put forth the most recent and practical recommendations for diagnosis and treatment of AMI. This review will address the concepts of AMI with the aim of focusing on specific areas where early diagnosis and management hold the strongest potential for improving outcomes in this disease process. Some of the key points include the prompt use of CT angiography to establish the diagnosis, evaluation of the potential for revascularization to re-establish blood flow to ischemic bowel, resection of necrotic intestine, and use of damage control techniques when appropriate to allow for re-assessment of bowel viability prior to definitive anastomosis and abdominal closure.

  11. Identification of Reversible Disruption of the Human Blood-Brain Barrier Following Acute Ischemia.

    Science.gov (United States)

    Simpkins, Alexis N; Dias, Christian; Leigh, Richard

    2016-09-01

    Animal models of acute cerebral ischemia have demonstrated that diffuse blood-brain barrier (BBB) disruption can be reversible after early reperfusion. However, irreversible, focal BBB disruption in humans is associated with hemorrhagic transformation in patients receiving intravenous thrombolytic therapy. The goal of this study was to use a magnetic resonance imaging biomarker of BBB permeability to differentiate these 2 forms of BBB disruption. Acute stroke patients imaged with magnetic resonance imaging before, 2 hours after, and 24 hours after treatment with intravenous tissue-type plasminogen activator were included. The average BBB permeability of the acute ischemic region before and 2 hours after treatment was calculated using a T2* perfusion-weighted source images. Change in average permeability was compared with percent reperfusion using linear regression. Focal regions of maximal BBB permeability from the pretreatment magnetic resonance imaging were compared with the occurrence of parenchymal hematoma (PH) formation on the 24-hour magnetic resonance imaging scan using logistic regression. Signals indicating reversible BBB permeability were detected in 18/36 patients. Change in average BBB permeability correlated inversely with percent reperfusion (P=0.006), indicating that early reperfusion is associated with decreased BBB permeability, whereas sustained ischemia is associated with increased BBB disruption. Focal regions of maximal BBB permeability were significantly associated with subsequent formation of PH (P=0.013). This study demonstrates that diffuse, mild BBB disruption in the acutely ischemic human brain is reversible with reperfusion. This study also confirms prior findings that focal severe BBB disruption confers an increased risk of hemorrhagic transformation in patients treated with intravenous tissue-type plasminogen activator. © 2016 American Heart Association, Inc.

  12. An ischemia-guided approach for risk stratification in patients with acute coronary syndromes.

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    Pepine, C J

    2000-12-28

    The optimal management approach for patients with non-ST-segment elevation acute coronary syndromes continues to be an issue of debate. An ischemia-guided strategy appears to be effective as an alternative to either a very conservative "wait-and-see" approach or a very aggressive routine revascularization approach. The need for another approach is supported by the lack of conclusive evidence-based results favoring an early routine invasive treatment strategy. In the Thrombolysis in Myocardial Infarction (TIMI) IIIB trial, there were no differences in the incidence of death or myocardial infarction (MI) between patients treated with an early invasive approach and those treated with a conservative approach to treatment. Significantly worse outcomes were shown in patients assigned to an early invasive strategy in the Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) trial at 1-year follow-up (111 clinical events in the invasive group vs 85 in the conservative group; p = 0.05). Registry information, including that from the Organization to Assess Strategies for Ischemic Syndromes (OASIS), which included approximately 8,000 patients with unstable angina or suspected MI, has even suggested an excess hazard with a routine invasive approach. Patients with non-ST-segment elevation MI observed in the Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO)-IIB and Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trials also fared better with an ischemia-guided strategy. Even the recent FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC II) trial investigators had to be very selective relative to eliminating high-risk patients in the first week and treating with intense anti-ischemic therapy and 5-7 days of low-molecular-weight heparin therapy to show an advantage for assigned revascularization. A careful clinical evaluation with

  13. The effect of ozone and naringin on intestinal ischemia/reperfusion injury in an experimental model.

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    Isik, Arda; Peker, Kemal; Gursul, Cebrail; Sayar, Ilyas; Firat, Deniz; Yilmaz, Ismayil; Demiryilmaz, Ismail

    2015-09-01

    The aim of the study was to evaulate the effect of ozone and naringin on the intestine after intestinal ischemia-reperfusion(II/R) injury. Thirty five rats divided into 5 groups of 7 animals: control, II/R, ozone, naringin and naringin + ozone. Only laparotomy and exploration of the superior mesenteric artery (SMA) were done in control group. In the experimental groups, SAM was occluded for 1 h and reperfused for 1 h. 15 min after ischemia, ozone (25 μg/ml, 0.5 mg/kg), naringin (80 mg/kg) and naringin + ozone(80 mg/kg + 25 μg/ml, 0.5 mg/kg) were infused intraperitoneally to each groups. Ileum tissues were harvested to determine intestinal mucosal injury and oxidative stress markers. For SMA occlusion, different than literature, silk suture binding was used. Oxidative stress markers were significantly low in experimental groups compared with II/R group (p < 0.05). Histopathologically, the injury score was significantly low at experimental groups compared with II/R group (p < 0.05). The lowest injury score was encountered at naringine + ozone group. Ozone alone or combined with naringin has a protective effect for mesenteric ischemia. Instead of using instruments such as clamps in the II/R rat model, silk binding may be used safely. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  14. Neuro-Glio-Vascular Complexes of the Brain After Acute Ischemia

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    A. S. Stepanov

    2017-01-01

    Full Text Available The purpose of the study is to compare the structural and functional state of neuro-glio-vascular microstructural complexes of the somatosensory cortex (SSC, CA1 of the hippocampus and amygdala of the brain of white rats under normal conditions and after acute ischemia caused by a 20-minute occlusion of common carotid arteries.Materials and methods. In this experiment, neurons, astrocytes, endotheliocytes, pericytes, basal membrane of the microvessels were studied in the normal (n=5 and the reperfusion period (1, 3, 7, 14, 21 and 30 days, n=30 using electron and fluorescence microscopy (DAPI staining. The morphometric analysis was carried out using the ImageJ 1.46 software.Results. During the recovery period after ischemia was noted reactive (edema-swelling, tinctorial properties of cells and compensatory-restoration (hyperplasia, hypertrophy, proliferation, increased transcytosis changes in neuro-glia-vascular complexes. After ischemia, the number of neurons decreased (by 8.7%—55,3%, and the glial cell count 2—3 fold increased. Increasing neuroglial index (NGI was accompanied by: 1 the emergence of microvessels with numerous branched processes of pericytes, 2 the complication of the spatial organization of basal membranes, and 3 the structural features of activation of transcytosis processes (large number of caveolae, smooth and clathrin vesicles, large vesicles in pericytes and endothelial cells.Conclusion.These findings indicate the compensatory-restoration changes in the components of neuro-gliovascular complexes SSC, CA1 of the hippocampus and amygdala of white rat’s brain after a 20-minute occlusion of the common carotid arteries. The most complete implementation of mechanisms for the protection and repair of damaged neurons occurs in the SSC and amygdala exhibiting high NGI values.

  15. Bilateral Persistent Sciatic Arteries Complicated with Acute Left Lower Limb Ischemia

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    Hsuan-Yin Wu

    2007-12-01

    Full Text Available Persistent sciatic artery (PSA is a rare congenital malformation. In the early embryonic stage, the sciatic artery is the major blood supply for the lower limb bulb and is later replaced by the iliofemoral artery as the limb develops. Its failure to regress, sometimes associated with femoral arterial hypoplasia, and therefore becoming the dominant inflow to the lower extremity is called PSA. This anomaly is often associated with a higher rate of aneurysm formation or thromboembolic complications causing lower extremity ischemia. Here, we describe a 79-year-old male patient who presented with acute left lower extremity ischemia. He was treated initially with conventional embolectomy through inguinal and popliteal incisions. The bilateral PSA with thrombosed aneurysms was not identified at first on computed tomographic angiography. It was later diagnosed intraoperatively due to the discontinuity of the superficial femoral artery and popliteal artery found with embolectomy catheter, and was managed successfully with ePTFE graft bypass. Careful interpretation of the imaging study may be helpful in preoperative diagnosis.

  16. Acute myocardial infarctation in patients with critical ischemia underwent lower limb revascularization

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    Esdras Marques Lins

    2013-12-01

    Full Text Available BACKGROUND: Atherosclerosis is the main cause of peripheral artery occlusive disease (PAOD of the lower limbs. Patients with PAOD often also have obstructive atherosclerosis in other arterial sites, mainly the coronary arteries. This means that patients who undergo infrainguinal bypass to treat critical ischemia have a higher risk of AMI. There are, however, few reports in the literature that have assessed this risk properly. OBJECTIVE: The aim of this study was to determine the incidence of acute myocardial infarction in patients who underwent infrainguinal bypass to treat critical ischemia of the lower limbs caused by PAOD. MATERIAL AND METHODS: A total of 64 patients who underwent 82 infrainguinal bypass operations, from February 2011 to July 2012 were studied. All patients had electrocardiograms and troponin I blood assays during the postoperative period (within 72 hours. RESULTS: There were abnormal ECG findings and elevated blood troponin I levels suggestive of AMI in five (6% of the 82 operations performed. All five had conventional surgery. The incidence of AMI as a proportion of the 52 conventional surgery cases was 9.6%. Two patients died. CONCLUSION: There was a 6% AMI incidence among patients who underwent infrainguinal bypass due to PAOD. Considering only cases operated using conventional surgery, the incidence of AMI was 9.6%.

  17. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

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    Nathalie Le Clef

    Full Text Available Acute kidney injury (AKI is an underestimated, yet important risk factor for development of chronic kidney disease (CKD. Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD. Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

  18. I-FABP as biomarker for the early diagnosis of acute mesenteric ischemia and resultant lung injury.

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    Rachel G Khadaroo

    Full Text Available Acute mesenteric ischemia (AMI is a life-threatening condition that can result in multiple organ injury and death. A timely diagnosis and treatment would have a significant impact on the morbidity and mortality in high-risk patient population. The purpose of this study was to investigate if intestinal fatty acid binding protein (I-FABP and α-defensins can be used as biomarkers for early AMI and resultant lung injury. C57BL/6 mice were subjected to intestinal ischemia by occlusion of the superior mesenteric artery. A time course of intestinal ischemia from 0.5 to 3 h was performed and followed by reperfusion for 2 h. Additional mice were treated with N-acetyl-cysteine (NAC at 300 mg/kg given intraperitoneally prior to reperfusion. AMI resulted in severe intestinal injury characterized by neutrophil infiltrate, myeloperoxidase (MPO levels, cytokine/chemokine levels, and tissue histopathology. Pathologic signs of ischemia were evident at 1 h, and by 3 h of ischemia, the full thickness of the intestine mucosa had areas of coagulative necrosis. It was noted that the levels of α-defensins in intestinal tissue peaked at 1 h and I-FABP in plasma peaked at 3 h after AMI. Intestinal ischemia also resulted in lung injury in a time-dependent manner. Pretreatment with NAC decreased the levels of intestinal α-defensins and plasma I-FABP, as well as lung MPO and cytokines. In summary, the concentrations of intestinal α-defensins and plasma I-FABP predicted intestinal ischemia prior to pathological evidence of ischemia and I-FABP directly correlated with resultant lung injury. The antioxidant NAC reduced intestinal and lung injury induced by AMI, suggesting a role for oxidants in the mechanism for distant organ injury. I-FABP and α-defensins are promising biomarkers, and may guide the treatment with antioxidant in early intestinal and distal organ injury.

  19. Is prolonged cold ischemia a contraindication to using kidneys from acute kidney injury donors?

    Science.gov (United States)

    Orlando, Giuseppe; Khan, Muhammad A; El-Hennawy, Hany; Farney, Alan C; Rogers, Jeffrey; Reeves-Daniel, Amber; Gautreaux, Michael D; Doares, William; Kaczmorski, Scott; Stratta, Robert J

    2018-03-01

    To determine the impact of prolonged cold ischemia time (CIT) on the outcome of acute kidney injury (AKI) renal grafts, we therefore performed a single-center retrospective analysis in adult patients receiving kidney transplantation (KT) from AKI donors. Outcomes were stratified according to duration of CIT. A total of 118 patients receiving AKI grafts were enrolled. Based on CIT, patients were stratified as follows: (i) 20 hours (P = NS). In the nine patients with CIT >40 hours, the 4-year DCGS rate was 100%. We conclude that prolonged CIT in AKI grafts may not adversely influence outcomes and so discard of AKI kidneys because of projected long CIT is not warranted when donors are wisely triaged. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Assessment of ischemia in acute central retinal vein occlusion from inner retinal reflectivity on spectral domain optical coherence tomography

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    Browning DJ

    2016-12-01

    Full Text Available David J Browning, Omar S Punjabi, Chong Lee Department of Ophthalmology, Charlotte Eye, Ear, Nose and Throat Associates, P.A., Charlotte, NC, USA Purpose: To determine the relationship between different spectral domain optical coherence tomography (SD-OCT signs of retinal ischemia in acute central retinal vein occlusion (CRVO and whether they predict anterior segment neovascularization (ASNV.Design: Retrospective, observational study.Subjects: Thirty-nine consecutive patients with acute CRVO and 12 months of follow-up.Methods: We graded baseline SD-OCTs for increased reflectivity of the inner retina, loss of definition of inner retinal layers, presence of a prominent middle-limiting membrane (p-MLM sign, and presence of paracentral acute middle maculopathy (PAMM. Graders were masked with respect to all clinical information.Results: The intraclass correlation coefficients (ICCs of grading–regrading by graders 1 and 2 were 0.8104, 95% confidence interval (CI (0.6686, 0.8956, and 0.7986, 95% CI (0.6475, 0.8892, respectively. The intragrader coefficients of repeatability (COR for graders 1 and 2 were 0.94 and 0.92, respectively. The ICC of graders 1 compared with 2 was 0.8039, 95% CI (0.6544, 0.8916. The intergrader COR was 0.80. SD-OCT grades of baseline ischemia were not associated with baseline visual acuity (VA, central subfield mean thickness (CSMT, or relative afferent pupillary defect; 12-month VA, CSMT, change in VA, change in CSMT, number of antivascular endothelial growth factor injections or corticosteroid injections, or proportion of eyes developing ASNV. SD-OCT grades of ischemia did not correlate with the proportion of eyes having the p-MLM sign or PAMM. PAMM and p-MLM are milder signs of ischemia than increased reflectivity of the inner retinal layers. Eyes with PAMM can evolve, losing PAMM and gaining the p-MLM sign.Conclusion: Grading of ischemia from SD-OCT in acute CRVO was repeatable within graders and reproducible across

  1. Acute mesenteric ischemia and hepatic infarction after treatment of ectopic Cushing's syndrome.

    Science.gov (United States)

    Takayasu, Shinobu; Murasawa, Shingo; Yamagata, Satoshi; Kageyama, Kazunori; Nigawara, Takeshi; Watanuki, Yutaka; Kimura, Daisuke; Tsushima, Takao; Sakamoto, Yoshiyuki; Hakamada, Kenichi; Terui, Ken; Daimon, Makoto

    2017-01-01

    Patients with Cushing's syndrome and excess exogenous glucocorticoids have an increased risk for venous thromboembolism, as well as arterial thrombi. The patients are at high risk of thromboembolic events, especially during active disease and even in cases of remission and after surgery in Cushing's syndrome and withdrawal state in glucocorticoid users. We present a case of Cushing's syndrome caused by adrenocorticotropic hormone-secreting lung carcinoid tumor. Our patient developed acute mesenteric ischemia after video-assisted thoracoscopic surgery despite administration of sufficient glucocorticoid and thromboprophylaxis in the perioperative period. In addition, our patient developed hepatic infarction after surgical resection of the intestine. Then, the patient was supported by total parenteral nutrition. Our case report highlights the risk of microthrombi, which occurred in our patient after treatment of ectopic Cushing's syndrome. Guidelines on thromboprophylaxis and/or antiplatelet therapy for Cushing's syndrome are acutely needed. The present case showed acute mesenteric thromboembolism and hepatic infarction after treatment of ectopic Cushing's syndrome.Patients with Cushing's syndrome are at increased risk for thromboembolic events and increased morbidity and mortality.An increase in thromboembolic risk has been observed during active disease, even in cases of remission and postoperatively in Cushing's syndrome.Thromboprophylaxis and antiplatelet therapy should be considered in treatment of glucocorticoid excess or glucocorticoid withdrawal.

  2. Acute sleep deprivation preconditions the heart against ischemia/ reperfusion injury: the role of central GABA-A receptors.

    Science.gov (United States)

    Parsa, Hoda; Imani, Alireza; Faghihi, Mahdieh; Riahi, Esmail; Badavi, Mohammad; Shakoori, Abbas; Rastegar, Tayebeh; Aghajani, Marjan; Rajani, Sulail Fatima

    2017-11-01

    Central γ-aminobutyric acid (GABA) neurotransmission modulates cardiovascular functions and sleep. Acute sleep deprivation (ASD) affects functions of various body organs via different mechanisms. Here, we evaluated the effect of ASD on cardiac ischemia/reperfusion injury (IRI), and studied the role of GABA-A receptor inhibition in central nucleus of amygdala (CeA) by assessing nitric oxide (NO) and oxidative stress. The CeA in sixty male Wistar rats was cannulated for saline or bicuculline (GABA-A receptor antagonist) administration. All animals underwent 30 min of coronary occlusion (ischemia), followed by 2 hr reperfusion (IR). The five experimental groups (n=12) included are as follows: IR: received saline; BIC+IR: received Bicuculline; MLP+IR: received saline, followed by the placement of animals in an aquarium with multiple large platforms; ASD+IR: underwent ASD in an aquarium with multiple small platforms; and BIC+ASD+IR: received bicuculline prior to ASD. Bicuculline administration increased the malondialdehyde levels and infarct size, and decreased the NO metabolites levels and endothelial nitric oxide synthase (eNOS) gene expression in infarcted and non-infarcted areas in comparison to IR group. ASD reduced malondialdehyde levels and infarct size and increased NO metabolites, corticosterone levels and eNOS expression in infarcted and non-infarcted areas as compared to the IR group. Levels of malondialdehyde were increased while levels of NO metabolites, corticosterone and eNOS expression in infarcted and non-infarcted areas were reduced in the BIC+ASD+IR as compared to the ASD+IR group. Blockade of GABA-A receptors in the CeA abolishes ASD-induced cardioprotection by suppressing oxidative stress and NO production.

  3. Acute sleep deprivation preconditions the heart against ischemia/ reperfusion injury: the role of central GABA-A receptors

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    Hoda Parsa

    2017-11-01

    Full Text Available Objective(s: Central γ-aminobutyric acid (GABA neurotransmission modulates cardiovascular functions and sleep. Acute sleep deprivation (ASD affects functions of various body organs via different mechanisms. Here, we evaluated the effect of ASD on cardiac ischemia/reperfusion injury (IRI, and studied the role of GABA-A receptor inhibition in central nucleus of amygdala (CeA by assessing nitric oxide (NO and oxidative stress. Materials and Methods: The CeA in sixty male Wistar rats was cannulated for saline or bicuculline (GABA-A receptor antagonist administration. All animals underwent 30 min of coronary occlusion (ischemia, followed by 2 hr reperfusion (IR. The five experimental groups (n=12 included are as follows: IR: received saline; BIC+IR: received Bicuculline; MLP+IR: received saline, followed by the placement of animals in an aquarium with multiple large platforms; ASD+IR: underwent ASD in an aquarium with multiple small platforms; and BIC+ASD+IR: received bicuculline prior to ASD. Results: Bicuculline administration increased the malondialdehyde levels and infarct size, and decreased the NO metabolites levels and endothelial nitric oxide synthase (eNOS gene expression in infarcted and non-infarcted areas in comparison to IR group. ASD reduced malondialdehyde levels and infarct size and increased NO metabolites, corticosterone levels and eNOS expression in infarcted and non-infarcted areas as compared to the IR group. Levels of malondialdehyde were increased while levels of NO metabolites, corticosterone and eNOS expression in infarcted and non-infarcted areas were reduced in the BIC+ASD+IR as compared to the ASD+IR group. Conclusion: Blockade of GABA-A receptors in the CeA abolishes ASD-induced cardioprotection by suppressing oxidative stress and NO production.

  4. S3226, a novel NHE3 inhibitor, attenuates ischemia-induced acute renal failure in rats.

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    Hropot, M; Juretschke, H P; Langer, K H; Schwark, J R

    2001-12-01

    Acute renal failure (ARF) remains a major problem in clinical nephrology characterized by sudden loss of the kidney function due to ischemia, trauma, and/or nephrotoxic drugs. The current therapy of ARF is symptomatic with mortality rates exceeding 50%. The aim of this study was to investigate the effects of an intravenous infusion of S3226 (3-[2-(3-guanidino-2-methyl-3-oxopropenyl)-5-methyl-phenyl]-N-isopropylidene-2-methyl-acrylamide dihydrochloride), a selective Na+/H+ exchange subtype 3 (NHE3) blocker, in ischemia-induced ARF in rats. In a second series of experiments cytosolic pH (pHi) changes in the kidney during ARF were continuously measured by means of nuclear magnetic resonance spectroscopy (MRS). ARF was induced by bilateral occlusion of renal arteries for 40 minutes in three groups of anaesthetized Wistar rats. Control rats (N = 12) were infused with saline (6.25 mL/kg over 30 min) before occlusion and the compound groups (each N = 12) were infused with S3226 at a dose of 20 mg/kg over 30 minutes either before initiation of ischemia or immediately after release of clamps. Plasma creatinine (PCr), creatinine clearance (CCr), urine volume, sodium, and potassium excretion were determined up to seven days after release of clamps. In the second series of experiments in anaesthetized rats the left kidney was exposed by flank incision and fixed in a non-magnetic device. An inflatable cuff was positioned around the pedicle to induce ischemia without removing animals from the magnet. A double-tuned 1H-31P home-built surface coil was placed above the exposed kidney for the detection of pHi. At day 1 after ischemia CCr in the control group was significantly lower as compared to S3226-treated animals (control 0.30 +/- 0.05 vs. before 0.90 +/- 0.26 and reperfusion 0.83 +/- 0.15 mL/min/kg, respectively). PCr increased from 18 +/- 0.1 micromol/L before occlusion to 245 +/- 7 micromol/L in the control. The increase in PCr was significantly lower in the S3226 treated

  5. Prevention of subsequent exercise-induced periinfarct ischemia by emergency coronary angioplasty in acute myocardial infarction: comparison with intracoronary streptokinase

    International Nuclear Information System (INIS)

    Fung, A.Y.; Lai, P.; Juni, J.E.; Bourdillon, P.D.; Walton, J.A. Jr.; Laufer, N.; Buda, A.J.; Pitt, B.; O'Neill, W.W.

    1986-01-01

    To compare the efficacy of emergency percutaneous transluminal coronary angioplasty and intracoronary streptokinase in preventing exercise-induced periinfarct ischemia, 28 patients presenting within 12 hours of the onset of symptoms of acute myocardial infarction were prospectively randomized. Of these, 14 patients were treated with emergency angioplasty and 14 patients received intracoronary streptokinase. Recatheterization and submaximal exercise thallium-201 single photon emission computed tomography were performed before hospital discharge. Periinfarct ischemia was defined as a reversible thallium defect adjacent to a fixed defect assessed qualitatively. Successful reperfusion was achieved in 86% of patients treated with emergency angioplasty and 86% of patients treated with intracoronary streptokinase (p = NS). Residual stenosis of the infarct-related coronary artery shown at predischarge angiography was 43.8 +/- 31.4% for the angioplasty group and 75.0 +/- 15.6% for the streptokinase group (p less than 0.05). Of the angioplasty group, 9% developed exercise-induced periinfarct ischemia compared with 60% of the streptokinase group (p less than 0.05). Thus, patients with acute myocardial infarction treated with emergency angioplasty had significantly less severe residual coronary stenosis and exercise-induced periinfarct ischemia than did those treated with intracoronary streptokinase. These results suggest further application of coronary angioplasty in the management of acute myocardial infarction

  6. Pathophysiological studies of experimental brain edema and cerebral ischemia using MRI/S

    International Nuclear Information System (INIS)

    Naruse, Shoji; Higuchi, Toshihiro; Horikawa, Yoshiharu; Tanaka, Chuzo; Hirakawa, Kimiyoshi

    1987-01-01

    Pathophysiological changes in experimental brain edema and cerebral ischemia were examined by the in vivo 1 H- and 31 P-NMR method. Two types of experimental brain edema were induced in rats by cold injury and by triethyltin (TET) intoxication. Experimental cerebral ischemia was induced in rats by the four-vessel occlusion method. During the course of these pathological conditions, the 1 H-MRIs and 31 P-NMR spectra were measured sequentially with a single NMR spectrometer (4.8 tesla, 9 cm bore magnet). In the cold-injury edema, high-intensity lesions were detected in the gray and white matters of the injured hemisphere by means of SE images with a long Te 3 hours after the injury. The intensity reached its maximum 16 to 24 hours after the injury, and then returned to normal 7 days later. These high-intensity lesions indicated an increase in the T2 value in the edematous tissue. There were no changes in the 31 P-NMR spectra during the course of edema formation and absorption. In the TET-induced edema, high-intensity lesions were also detected in the bilateral white matter by means of SE images with a long Te from the 3rd day up to the 7th day during the injection of TET. These high-intensity lesions subsided 42 days after the discontinuance of injecting TET. There were no changes in the 31 P-NMR spectra during the whole course of TET-induced edema. In the cerebral ischemia, no remarkable changes in the MRI were detected in either SE or IR images during the ischemic and recirculated periods. However, dynamic changes in the 31 P-NMR spectra were detected during the course of cerebral ischemia. In the pre-ischemic period, the peaks of the ATP, PCr, phosphodiesters (PDE), Pi, and phosphomonoesters (PME) were detected. After the induction of ischemia, the ATP and PCr peaks decreased, while one Pi peak increased rapidly. (J.P.N.)

  7. Pathophysiological studies of experimental brain edema and cerebral ischemia using MRI/S

    Energy Technology Data Exchange (ETDEWEB)

    Naruse, S; Higuchi, T; Horikawa, Y; Tanaka, C; Hirakawa, K

    1987-02-01

    Pathophysiological changes in experimental brain edema and cerebral ischemia were examined by the in vivo /sup 1/H- and /sup 31/P-NMR method. Two types of experimental brain edema were induced in rats by cold injury and by triethyltin (TET) intoxication. Experimental cerebral ischemia was induced in rats by the four-vessel occlusion method. During the course of these pathological conditions, the /sup 1/H-MRIs and /sup 31/P-NMR spectra were measured sequentially with a single NMR spectrometer (4.8 tesla, 9 cm bore magnet). In the cold-injury edema, high-intensity lesions were detected in the gray and white matters of the injured hemisphere by means of SE images with a long Te 3 hours after the injury. The intensity reached its maximum 16 to 24 hours after the injury, and then returned to normal 7 days later. These high-intensity lesions indicated an increase in the T2 value in the edematous tissue. There were no changes in the /sup 31/P-NMR spectra during the course of edema formation and absorption. In the TET-induced edema, high-intensity lesions were also detected in the bilateral white matter by means of SE images with a long Te from the 3rd day up to the 7th day during the injection of TET. These high-intensity lesions subsided 42 days after the discontinuance of injecting TET. There were no changes in the /sup 31/P-NMR spectra during the whole course of TET-induced edema. In the cerebral ischemia, no remarkable changes in the MRI were detected in either SE or IR images during the ischemic and recirculated periods. However, dynamic changes in the /sup 31/P-NMR spectra were detected during the course of cerebral ischemia. In the pre-ischemic period, the peaks of the ATP, PCr, phosphodiesters (PDE), Pi, and phosphomonoesters (PME) were detected. After the induction of ischemia, the ATP and PCr peaks decreased, while one Pi peak increased rapidly.

  8. Sodium Hypochlorite-Modified Hemosorbents in the Treatment of Limb Ischemia-Reperfusion Syndrome: Experimental Study

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    V. I. Sergiyenko

    2007-01-01

    Full Text Available Objective: to enhance the efficiency of treatment for limb ischemia-reperfusion syndrome in an experiment, by using the modified hemosorbents that have oxidative properties.Materials and methods. The investigation was conducted on 94 mongrel male dogs divided into 3 groups: 1 intact animals (n=20; 2 animals treated with hemocarboperfusion on the standard sorbent CKH-1K (n=36; 3 animals received hemocarboperfusion on sodium hypochloride-modified sorbent CKH-1K (n=38. A model of acute ischemia-reperfusion syndrome was created by the method of V. D. Pasechnikov et al. Partial oxygen tension (pO2 was determined by pin polarography. The levels of vasoactive eicosanoids were measured by enzyme immunoassay.Results. In the animals with leg ischemia syndrome, there is a significant pO2 reduction in the muscles of the hip and shin, which does not completely recover after reperfusion. Standard CKN-1K sorbent hemocarboperfusion reduces pO2 as compared with the reperfusion period while the use of modified CKH-1K hemosorbent increased pO2 in the study hind limb muscles to the level observed in intact animals. The development of ischemia and reperfusion is accompanied by the elevated levels of inflammatory mediators that have vasoconstrictive properties (thromboxane B2, endothelin-1, leukotrienes C4/D4/E4 and the lower concentration of the vasodilator prostacyclin. Standard CKN-1K sorbent hemocarboperfusion results in a further increase in the concentrations of thromboxane B2 and leukotrienes C4/D4/E4, a decrease in the concentration of endothelin-1, and an elevation of the levels of prostacyclin and prostaglandin E2. When sodium hypochlorite-modified CKN-1K sorbent hemocarboperfusion is employed, the concentrations of thromboxane B2, endothelin-1, and leukotrienes C4/D4/E4 decrease, and the level of prostacyclin increases.Conclusion. Hemocarboperfusion used in the treatment of leg ischemia-reperfusion syndrome leads to restoration of tissue oxygenation and

  9. [Application of continuous renal replacement therapy in the treatment of myonephropathic metabolic syndrome caused by acute lower extremity ischemia].

    Science.gov (United States)

    Sun, Jianping; Wang, Tengke; Zhang, Jinglan

    2014-09-16

    To summarize the experiences of using continuous renal replacement therapy in the treatment of myonephropathic metabolic syndrome caused by acute lower limb ischemia. Retrospective study of patients diagnosed acute lower limb ischemia with surgical treatment between January 2008 and December 2013, among which 22 patients with myonephropathic metabolic syndrome received continuous renal replacement therapy. Summarize the change tendency of myoglobin, urine volume and serum creatinine levels during treatment and analysis the condition changes and prognosis of the patients. Among them, 2 patients were amputated and two died after surgery. The major causes of death were acute renal failure, metabolic acidosis, circulation failure and liver failure, etc. Myoglobin was significantly higher at Day 1 after surgery than that was before surgery (P metabolic syndrome, early targeted continuous renal replacement therapy may decrease the serum concentrations of myoglobin and CK, improve urine volume, maintain homeostasis, prevent renal function deterioration and improve the prognosis of patients. And it is highly recommended.

  10. Protective Effect Of Bosentan In Experimental Cerebral Ischemia-Reperfusion Injury

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    Eser Ataş

    2013-02-01

    Full Text Available OBJECTIVE: In cerebral ischemia, there are many factors that start the events leading to cell death. These factors contain free radical production, excitotoxicity, sodium and calcium flow disruption, enzymatic changes, stimulation of the inflamatuar process, the activation of platelets and leukocytes, delayed coagulation, endothelial dysfunction and endothelin (ET release. Bosentan is the competitive antagonist of endothelin receptors; ETA and ETB. The aim of this study is to determine whether the protective effects of bosentan in experimental cerebral ischemia reperfusion injury. MATERIAL and METHODS: In this study, after ischemia-reperfusion procedure, bosentan molecule was regularly given to rats for 5 days. The brain tissues of decapitated rats were histopathologically examined. The levels of oxidant and antioxidant were determined in these brain tissues. RESULTS: It was observed that antioxidant levels and histopathological examinations were in rats given bosentan better than control group rats. CONCLUSION: In conclusion, this study has showed that bosentan may be an agent which could reduce negative effects resulting from neuronal death associated with ischemic stroke.

  11. Carbonic anhydrase inhibitor attenuates ischemia-reperfusion induced acute lung injury.

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    Chou-Chin Lan

    Full Text Available Ischemia-reperfusion (IR-induced acute lung injury (ALI is implicated in several clinical conditions including lung transplantation, cardiopulmonary bypass surgery, re-expansion of collapsed lung from pneumothorax or pleural effusion and etc. IR-induced ALI remains a challenge in the current treatment. Carbonic anhydrase has important physiological function and influences on transport of CO2. Some investigators suggest that CO2 influences lung injury. Therefore, carbonic anhydrase should have the role in ALI. This study was undertaken to define the effect of a carbonic anhydrase inhibitor, acetazolamide (AZA, in IR-induced ALI, that was conducted in a rat model of isolated-perfused lung with 30 minutes of ischemia and 90 minutes of reperfusion. The animals were divided into six groups (n = 6 per group: sham, sham + AZA 200 mg/kg body weight (BW, IR, IR + AZA 100 mg/kg BW, IR + AZA 200 mg/kg BW and IR+ AZA 400 mg/kg BW. IR caused significant pulmonary micro-vascular hyper-permeability, pulmonary edema, pulmonary hypertension, neutrophilic sequestration, and an increase in the expression of pro-inflammatory cytokines. Increases in carbonic anhydrase expression and perfusate pCO2 levels were noted, while decreased Na-K-ATPase expression was noted after IR. Administration of 200mg/kg BW and 400mg/kg BW AZA significantly suppressed the expression of pro-inflammatory cytokines (TNF-α, IL-1, IL-6 and IL-17 and attenuated IR-induced lung injury, represented by decreases in pulmonary hyper-permeability, pulmonary edema, pulmonary hypertension and neutrophilic sequestration. AZA attenuated IR-induced lung injury, associated with decreases in carbonic anhydrase expression and pCO2 levels, as well as restoration of Na-K-ATPase expression.

  12. Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.

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    Lan Chen

    Full Text Available OBJECTIVES: Transient receptor potential vanilloid 1 (TRPV1 -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of renal function under pathophysiological conditions. Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R-induced acute kidney injury (AKI. However, it is unknown whether inhibition of these channels is detrimental in AKI or not. We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist, capsazepine (TRPV1 antagonist and using Trpv1-/- mice. METHODS AND RESULTS: Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion. Mice were pretreated with capsaicin (0.3 mg/kg body weight or capsazepine (50 mg/kg body weight. Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL abundance and Ly-6B.2 positive polymorphonuclear inflammatory cells in injured kidneys. Neither capsazepine nor deficiency of TRPV1 did deteriorate renal function or histology after AKI. Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE or epoxyeicosatrienoic acids (EETs are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI. CONCLUSIONS: Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli.

  13. The novel guanylhydrazone CPSI-2364 ameliorates ischemia reperfusion injury after experimental small bowel transplantation.

    Science.gov (United States)

    Websky, Martin von; Fujishiro, Jun; Ohsawa, Ichiro; Praktiknjo, Michael; Wehner, Sven; Abu-Elmagd, Kareem; Kitamura, Koji; Kalff, Joerg C; Schaefer, Nico; Pech, Thomas

    2013-06-15

    Resident macrophages within the tunica muscularis are known to play a crucial role in initiating severe inflammation in response to ischemia reperfusion injury after intestinal transplantation contributing to graft dysmotility, bacterial translocation, and possibly, acute rejection. The p38 mitogen-activated protein kinase is a key player in the signaling of proinflammatory cytokine synthesis in macrophages. Therefore, we investigated the effects of CPSI-2364, an apparent macrophage-specific inhibitor of the p38 mitogen-activated protein kinase pathway in an isogenic intestinal rat transplantation model. Recipient and donor animals were treated perioperatively with CPSI-2364 (1 mg/kg, intravenously) or vehicle solution. Nontransplanted animals served as control. Animals were killed 30 min, 3 hr, and 18 hr after reperfusion. CPSI-2364 treatment resulted in significantly less leukocyte infiltration and significantly improved graft motor function (18 hr). Messenger RNA expression of proinflammatory cytokines (interleukin 6) and kinetic active mediators (NO) was reduced by CPSI-2364 in the early phase after transplantation. Histologic evaluation revealed the protective effects of CPSI-2364 treatment by a significantly less destruction of mucosal integrity at all time points. Perioperative treatment with CPSI-2364 improves graft motor function through impaired inflammatory responses to ischemia reperfusion injury by inhibition of proinflammatory cytokines and suppression of nitric oxide production in macrophages. CPSI-2364 presents as a promising complementary pharmacological approach preventing postoperative dysmotility for clinical intestinal transplantation.

  14. Acute myocardial ischemia after aortic valve replacement: A comprehensive diagnostic evaluation using dynamic multislice spiral computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Lembcke, Alexander [Department of Radiology, Charite-Universitaetsmedizin Berlin, Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Berlin (Germany)]. E-mail: alexander.lembcke@gmx.de; Hein, Patrick A. [Department of Radiology, Charite-Universitaetsmedizin Berlin, Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Berlin (Germany); Enzweiler, Christian N.H. [Department of Radiology, Charite-Universitaetsmedizin Berlin, Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Berlin (Germany); Hoffmann, Udo [Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Klessen, Christian [Department of Radiology, Charite-Universitaetsmedizin Berlin, Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Berlin (Germany); Dohmen, Pascal M. [Department of Cardiovascular Surgery, Charite-Universitaetsmedizin Berlin, Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Berlin (Germany)

    2006-03-15

    We describe the case of a 72-year-old man presenting with endocarditis and clinical signs of acute myocardial ischemia after biological aortic valve replacement. A comprehensive cardiac dynamic multislice spiral computed tomography demonstrated: (1) an endocarditic vegetation of the aortic valve; (2) a subvalvular leakage feeding a paravalvular pseudoaneurysm based on an aortic root abscess with subsequent compromise of the systolic blood flow in the left main coronary artery and the resulting myocardial perfusion deficit.

  15. Acute myocardial ischemia after aortic valve replacement: A comprehensive diagnostic evaluation using dynamic multislice spiral computed tomography

    International Nuclear Information System (INIS)

    Lembcke, Alexander; Hein, Patrick A.; Enzweiler, Christian N.H.; Hoffmann, Udo; Klessen, Christian; Dohmen, Pascal M.

    2006-01-01

    We describe the case of a 72-year-old man presenting with endocarditis and clinical signs of acute myocardial ischemia after biological aortic valve replacement. A comprehensive cardiac dynamic multislice spiral computed tomography demonstrated: (1) an endocarditic vegetation of the aortic valve; (2) a subvalvular leakage feeding a paravalvular pseudoaneurysm based on an aortic root abscess with subsequent compromise of the systolic blood flow in the left main coronary artery and the resulting myocardial perfusion deficit

  16. Endovascular Therapy as a Primary Revascularization Modality in Acute Mesenteric Ischemia

    International Nuclear Information System (INIS)

    Kärkkäinen, Jussi M.; Lehtimäki, Tiina T.; Saari, Petri; Hartikainen, Juha; Rantanen, Tuomo; Paajanen, Hannu; Manninen, Hannu

    2015-01-01

    PurposeTo evaluate endovascular therapy (EVT) as the primary revascularization method for acute mesenteric ischemia (AMI).MethodsA retrospective review was performed on all consecutive patients treated for AMI during a 5-year period (January 2009 to December 2013). EVT was attempted in all patients referred for emergent revascularization. Surgical revascularization was performed selectively after failure of EVT. Patient characteristics, clinical presentation, and outcomes were studied. Failures and complications of EVT were recorded.ResultsFifty patients, aged 79 ± 9 years (mean ± SD), out of 66 consecutive patients with AMI secondary to embolic or thrombotic obstruction of the superior mesenteric artery were referred for revascularization. The etiology of AMI was embolism in 18 (36 %) and thrombosis in 32 (64 %) patients. EVT was technically successful in 44 (88 %) patients. Mortality after successful or failed EVT was 32 %. The rates of emergency laparotomy, bowel resection, and EVT-related complication were 40, 34, and 10 %, respectively. Three out of six patients with failure of EVT were treated with surgical bypass. EVT failure did not significantly affect survival.ConclusionsEVT is feasible in most cases of AMI, with favorable patient outcome and acceptable complication rate

  17. Endovascular Therapy as a Primary Revascularization Modality in Acute Mesenteric Ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Kärkkäinen, Jussi M., E-mail: jkarkkai@gmail.com [Kuopio University Hospital, Heart Center (Finland); Lehtimäki, Tiina T., E-mail: tiina.lehtimaki@kuh.fi; Saari, Petri, E-mail: petri.saari@kuh.fi [Kuopio University Hospital, Department of Clinical Radiology (Finland); Hartikainen, Juha, E-mail: juha.hartikainen@kuh.fi [Kuopio University Hospital, Heart Center (Finland); Rantanen, Tuomo, E-mail: tuomo.rantanen@kuh.fi; Paajanen, Hannu, E-mail: hannu.paajanen@kuh.fi [Kuopio University Hospital, Department of Gastrointestinal Surgery (Finland); Manninen, Hannu, E-mail: hannu.manninen@kuh.fi [Kuopio University Hospital, Department of Clinical Radiology (Finland)

    2015-10-15

    PurposeTo evaluate endovascular therapy (EVT) as the primary revascularization method for acute mesenteric ischemia (AMI).MethodsA retrospective review was performed on all consecutive patients treated for AMI during a 5-year period (January 2009 to December 2013). EVT was attempted in all patients referred for emergent revascularization. Surgical revascularization was performed selectively after failure of EVT. Patient characteristics, clinical presentation, and outcomes were studied. Failures and complications of EVT were recorded.ResultsFifty patients, aged 79 ± 9 years (mean ± SD), out of 66 consecutive patients with AMI secondary to embolic or thrombotic obstruction of the superior mesenteric artery were referred for revascularization. The etiology of AMI was embolism in 18 (36 %) and thrombosis in 32 (64 %) patients. EVT was technically successful in 44 (88 %) patients. Mortality after successful or failed EVT was 32 %. The rates of emergency laparotomy, bowel resection, and EVT-related complication were 40, 34, and 10 %, respectively. Three out of six patients with failure of EVT were treated with surgical bypass. EVT failure did not significantly affect survival.ConclusionsEVT is feasible in most cases of AMI, with favorable patient outcome and acceptable complication rate.

  18. The use of intraperitoneal xenon for early diagnosis of acute mesenteric ischemia

    International Nuclear Information System (INIS)

    Gharagozloo, F.; Bulkley, G.B.; Zuidema, G.D.; O'Mara, C.S.; Alderson, P.O.

    1984-01-01

    We evaluated the technique of intraperitoneal use of xenon Xe 133, previously described for the diagnosis of early intestinal strangulation obstruction in rats and dogs, for the recognition of acute mesenteric vascular occlusion in these animals. 133 Xe was injected intraperitoneally into five groups of six rats: control, sham operation, superior mesenteric artery (SMA) ligation, superior mesenteric vein ligation, and portal vein ligation. Residual gamma-activity was monitored by external counting and camera imaging. At 30 minutes after injection, the activity was significantly higher in the rats from the three groups with vascular ligation than in the control and sham operation animals (P less than 0.001). gamma-Camera images reflected these findings, with positive images only in the rats that underwent vascular ligation. ''Blinded'' readings of the 30 sets of scans confirmed the diagnostic accuracy of the images. Results were essentially the same in a second series of experiments in eight control dogs and six dogs with balloon occlusion of the SMA. Concentrations of isotope in ischemic intestine ranged from 10(3) to 10(5) times the levels in adjacent normal bowel. These levels and the positive images appeared early, prior to the development of tissue necrosis. The intraperitoneal use of 133 Xe therefore continues to show promise for the recognition of patients with early intestinal ischemia

  19. The use of intraperitoneal xenon for early diagnosis of acute mesenteric ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Gharagozloo, F.; Bulkley, G.B.; Zuidema, G.D.; O' Mara, C.S.; Alderson, P.O.

    1984-04-01

    We evaluated the technique of intraperitoneal use of xenon Xe 133, previously described for the diagnosis of early intestinal strangulation obstruction in rats and dogs, for the recognition of acute mesenteric vascular occlusion in these animals. /sup 133/Xe was injected intraperitoneally into five groups of six rats: control, sham operation, superior mesenteric artery (SMA) ligation, superior mesenteric vein ligation, and portal vein ligation. Residual gamma-activity was monitored by external counting and camera imaging. At 30 minutes after injection, the activity was significantly higher in the rats from the three groups with vascular ligation than in the control and sham operation animals (P less than 0.001). gamma-Camera images reflected these findings, with positive images only in the rats that underwent vascular ligation. ''Blinded'' readings of the 30 sets of scans confirmed the diagnostic accuracy of the images. Results were essentially the same in a second series of experiments in eight control dogs and six dogs with balloon occlusion of the SMA. Concentrations of isotope in ischemic intestine ranged from 10(3) to 10(5) times the levels in adjacent normal bowel. These levels and the positive images appeared early, prior to the development of tissue necrosis. The intraperitoneal use of /sup 133/Xe therefore continues to show promise for the recognition of patients with early intestinal ischemia.

  20. Dexamethasone Protects Against Tourniquet-Induced Acute Ischemia-Reperfusion Injury in Mouse Hindlimb

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    Ryan M. Corrick

    2018-03-01

    Full Text Available Extremity injuries with hemorrhage have been a significant cause of death in civilian medicine and on the battlefield. The use of a tourniquet as an intervention is necessary for treatment to an injured limb; however, the tourniquet and subsequent release results in serious acute ischemia-reperfusion (IR injury in the skeletal muscle and neuromuscular junction (NMJ. Much evidence demonstrates that inflammation is an important factor to cause acute IR injury. To find effective therapeutic interventions for tourniquet-induced acute IR injuries, our current study investigated effect of dexamethasone, an anti-inflammatory drug, on tourniquet-induced acute IR injury in mouse hindlimb. In C57/BL6 mice, a tourniquet was placed on unilateral hindlimb (left hindlimb at the hip joint for 3 h, and then released for 24 h to induce IR. Three hours of tourniquet and 24 h of release (24-h IR caused gastrocnemius muscle injuries including rupture of the muscle sarcolemma and necrosis (42.8 ± 2.3% for infarct size of the gastrocnemius muscle. In the NMJ, motor nerve terminals disappeared, and endplate potentials were undetectable in 24-h IR mice. There was no gastrocnemius muscle contraction in 24-h IR mice. Western blot data showed that inflammatory cytokines (TNFα and IL-1β were increased in the gastrocnemius muscle after 24-h IR. Treatment with dexamethasone at the beginning of reperfusion (1 mg/kg, i.p. significantly inhibited expression of TNFα and IL-1β, reduced rupture of the muscle sarcolemma and infarct size (24.8 ± 2.0%, and improved direct muscle stimulation-induced gastrocnemius muscle contraction in 24-h IR mice. However, this anti-inflammatory drug did not improve NMJ morphology and function, and sciatic nerve-stimulated skeletal muscle contraction in 24-h IR mice. The data suggest that one-time treatment with dexamethasone at the beginning of reperfusion only reduced structural and functional impairments of the skeletal muscle but not the

  1. Whole brain CT perfusion in acute anterior circulation ischemia: coverage size matters

    International Nuclear Information System (INIS)

    Emmer, B.J.; Rijkee, M.; Walderveen, M.A.A. van; Niesten, J.M.; Velthuis, B.K.; Wermer, M.J.H.

    2014-01-01

    Our aim was to compare infarct core volume on whole brain CT perfusion (CTP) with several limited coverage sizes (i.e., 3, 4, 6, and 8 cm), as currently used in routine clinical practice. In total, 40 acute ischemic stroke patients with non-contrast CT (NCCT) and CTP imaging of anterior circulation ischemia were included. Imaging was performed using a 320-multislice CT. Average volumes of infarct core of all simulated partial coverage sizes were calculated. Infarct core volume of each partial brain coverage was compared with infarct core volume of whole brain coverage and expressed using a percentage. To determine the optimal starting position for each simulated CTP coverage, the percentage of infarct coverage was calculated for every possible starting position of the simulated partial coverage in relation to Alberta Stroke Program Early CT Score in Acute Stroke Triage (ASPECTS 1) level. Whole brain CTP coverage further increased the percentage of infarct core volume depicted by 10 % as compared to the 8-cm coverage when the bottom slice was positioned at the ASPECTS 1 level. Optimization of the position of the region of interest (ROI) in 3 cm, 4 cm, and 8 cm improved the percentage of infarct depicted by 4 % for the 8-cm, 7 % for the 4-cm, and 13 % for the 3-cm coverage size. This study shows that whole brain CTP is the optimal coverage for CTP with a substantial improvement in accuracy in quantifying infarct core size. In addition, our results suggest that the optimal position of the ROI in limited coverage depends on the size of the coverage. (orig.)

  2. Whole brain CT perfusion in acute anterior circulation ischemia: coverage size matters

    Energy Technology Data Exchange (ETDEWEB)

    Emmer, B.J. [Erasmus Medical Centre, Department of Radiology, Postbus 2040, Rotterdam (Netherlands); Rijkee, M.; Walderveen, M.A.A. van [Leiden University Medical Centre, Department of Radiology, Leiden (Netherlands); Niesten, J.M.; Velthuis, B.K. [University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Wermer, M.J.H. [Leiden University Medical Centre, Department of Neurology, Leiden (Netherlands)

    2014-12-15

    Our aim was to compare infarct core volume on whole brain CT perfusion (CTP) with several limited coverage sizes (i.e., 3, 4, 6, and 8 cm), as currently used in routine clinical practice. In total, 40 acute ischemic stroke patients with non-contrast CT (NCCT) and CTP imaging of anterior circulation ischemia were included. Imaging was performed using a 320-multislice CT. Average volumes of infarct core of all simulated partial coverage sizes were calculated. Infarct core volume of each partial brain coverage was compared with infarct core volume of whole brain coverage and expressed using a percentage. To determine the optimal starting position for each simulated CTP coverage, the percentage of infarct coverage was calculated for every possible starting position of the simulated partial coverage in relation to Alberta Stroke Program Early CT Score in Acute Stroke Triage (ASPECTS 1) level. Whole brain CTP coverage further increased the percentage of infarct core volume depicted by 10 % as compared to the 8-cm coverage when the bottom slice was positioned at the ASPECTS 1 level. Optimization of the position of the region of interest (ROI) in 3 cm, 4 cm, and 8 cm improved the percentage of infarct depicted by 4 % for the 8-cm, 7 % for the 4-cm, and 13 % for the 3-cm coverage size. This study shows that whole brain CTP is the optimal coverage for CTP with a substantial improvement in accuracy in quantifying infarct core size. In addition, our results suggest that the optimal position of the ROI in limited coverage depends on the size of the coverage. (orig.)

  3. Arctigenin: A two-edged sword in ischemia/reperfusion induced acute kidney injury.

    Science.gov (United States)

    Han, Feng; Xia, Xin-Xin; Dou, Meng; Wang, Yu-Xiang; Xue, Wu-Jun; Ding, Xiao-Ming; Zheng, Jin; Ding, Chen-Guang; Tian, Pu-Xun

    2018-04-27

    Arctigenin (ATG) is one of the main active substances in fruit derived from Arctium lappa L. Previous studies have reported that ATG have antitumor, neuroprotective, antioxidant, antifibrosis and anti-inflammatory functions. However, the actions of ATG in kidney with acute injury following ischemia/ reperfusion (I/R) is still uncertain. In our study, mice were subjected to kidney I/R by having the kidney pedicles clamped and administered with vehicle or ATG (1, 3 or 9 mg/kg/d) via oral gavage for 7 consecutive days prior to I/R. Notably, ATG aggravated kidney I/R injury with the concentration increases. Multiple biochemical assays and histological examination showed ATG significantly alleviated the inflammatory response as reflected by a decreased expression of proinflammatory cytokine, TLR4/MyD88, and NF-κB, along with the infiltration of CD68 + macrophage and CD11b + Gr1 + neutrophil in the kidneys. Meanwhile, ATG alleviated I/R-induced oxidative stress proved by increasing kidney manganese superoxide dismutase and glutathione peroxidase activity but reducing levels of malonaldehyde and inducible nitric oxide synthase. On the contrary, apoptosis was significantly increased in kidneys of ATG-treated mice compared with vehicle-treated controls, especially in tubular cells. There were increased numbers of TUNEL positive cells and increased Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9 expression. The current study demonstrates that pretreatment of ATG aggravates I/R induced acute kidney injury by increasing apoptosis of tubular cells despite reducing infiltrating inflammatory cells and proinflammatory cytokine. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  4. Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

    Directory of Open Access Journals (Sweden)

    Zygmunt Warzecha

    2017-04-01

    Full Text Available Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Results: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

  5. [Acute limb ischemia from the general surgeon's point of view. How much knowledge of vascular surgery is necessary?].

    Science.gov (United States)

    Kopp, R; Weidenhagen, R; Hornung, H; Jauch, K W; Lauterjung, L

    2003-12-01

    The diagnosis of acute peripheral ischemia can be obtained based on clinical presentation, inspection, and palpation of the affected extremity. Unfractionated heparin as a single shot is immediately given followed by continuous infusion when diagnosis is clinically evident and contraindications are excluded. Thromboembolectomy using a Fogarty catheter is immediately performed in patients with evidence of arterial embolization and signs of advanced ischemia (TASC IIb/III) followed by intraoperative angiography. Patients with evidence of arterial thrombosis require urgent angiography followed by thrombectomy and probably subsequent endovascular or surgical interventions and vascular reconstruction. For patients with moderate ischemia (TASC IIa), initial diagnostic angiography is recommended followed by primary thrombectomy with subsequent intraoperative angiography and immediate endovascular or operative treatment of remaining vascular problems. As an alternative therapeutic option initial catheter-guided local thrombolysis can be performed in selected patients with the intention of subsequent limb revascularization or unmasking relevant vessel alterations leading to specific endovascular or surgically performed vascular reconstruction. Possible development of muscle ischemia because of increased compartment pressure should be considered and fasciotomy performed when indicated. Primary amputation of the severely ischemic limb after initial thrombectomy might be recommended in patients with life-threatening organ failure related to muscle necrosis.

  6. Protective effect of active perfusion in porcine models of acute myocardial ischemia

    Science.gov (United States)

    Feng, Zanxiang; Mao, Zhifu; Dong, Shengjun; Liu, Baohui

    2016-01-01

    Mortality rates associated with off-pump coronary artery bypass (CAB) are relatively high, as the majority of patients requiring CAB are at a high risk for cardiac events. The present study aimed to establish porcine models of acute myocardial ischemia, and evaluate the protective role of shunt and active perfusion. A total of 30 pigs were randomly assigned to five groups, as follows: i) Sham (control); ii) A1 (shunt; stenosis rate, 55%); iii) A2 (shunt; stenosis rate, 75%); iv) B1 (active perfusion; stenosis rate, 55%); and v) B2 (active perfusion; stenosis rate, 75%) groups. Aortic pressure (P0), left anterior descending coronary pressure (P1), and coronary effective perfusion pressure (P1/P0) were measured. The expression levels of tumor necrosis factor-α (TNF-α), cardiac troponin (cTnI), creatine kinase-myocardial band (CK-MB), interleukin (IL)-6, IL-10, B-cell lymphoma 2 (Bcl-2), and caspase-3 were detected using enzyme-linked immunosorbent assay or western blotting. The myocardial apoptosis rate was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Ischemia models with stenosis rates of 55 and 75% were successfully constructed following suturing of the descending artery. Compared with the control, the 55 and 75% stenosis groups demonstrated significantly decreased P1/P0, increased expression levels of TNF-α, cTnI, CK-MB, IL-6, IL-10 and caspase-3, an increased rate of myocardial apoptosis, and a decreased expression level of anti-apoptotic protein, Bcl-2. At 30 min following successful establishment of the model (ST segment elevation to 1 mm), group B demonstrated significantly increased P1/P0, decreased expression levels of TNF-α, cTnI, CK-MB, IL-6, IL-10 and caspase-3, a decreased rate of myocardial apoptosis, and an increased expression level of anti-apoptotic protein, Bcl-2. Furthermore, the current study indicated that active perfusion was more efficacious in maintaining myocardial perfusion and alleviating

  7. Pathophysiology of brain ischemia as it relates to the therapy of acute ischemic stroke

    DEFF Research Database (Denmark)

    Lassen, N A

    1990-01-01

    Current knowledge of the pathophysiology of cerebral ischemia, summarized in the present study, predicts that neurological deficits caused by moderate ischemia (flows in the penumbral range between 23 and 10 ml/100 g/min) are reversible provided flow is restored within 3-4 h of onset. It also...

  8. Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Lin

    2009-03-01

    Full Text Available Hsiao-Wen Lin, E-Jian LeeNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, TaiwanAbstract: Melatonin (N-acetyl-5-methoxy-tryptamine, a naturally occurring indole produced mainly by the pineal gland, is a well known antioxidant. Stroke (cerebral ischemia is the second leading cause of death worldwide. To date, however, effective and safe treatment for stroke remains unavailable. Melatonin is both lipid- and water-soluble and readily crosses the blood–brain barrier (BBB. Increasing evidence has shown that, in animal stroke models, administering melatonin significantly reduces infarct volume, edema, and oxidative damage and improves electrophysiological and behavioral performance. Here, we reviewed studies that assess effects of melatonin on cerebral ischemia in acute, sub-acute, and chronic stages. In addition to its potent antioxidant properties, melatonin exerts antiapoptotic, antiexcitotoxic, anti-inflammatory effects and promotes mitochondrial functions in animals with cerebral ischemia. Given that melatonin shows almost no toxicity to humans and possesses multifaceted protective capacity against cerebral ischemia, it is valuable to consider using melatonin in clinical trials on patients suffering from stroke.Keywords: cerebral ischemia, melatonin, stroke, neuroprotection

  9. Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model.

    Directory of Open Access Journals (Sweden)

    Chung-Kan Peng

    Full Text Available Lung ischemia reperfusion injury (LIRI is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75% diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS, proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF. The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway.

  10. Dynamics of markers of markers of acute kidney injury when using epidural block during resection under warm ischemia

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2017-01-01

    Full Text Available Objective: to investigate the time course of changes in the early biomarkers of acute kidney injury in patients with clinically localized cancer during partial nephrectomy, as electively indicated, under thermal ischemia with prior epidural block.Materials and methods. To analyze the nephroprotective effect of an epidural block in kidney resection with warm ischemia, markers of acute kidney injury (cystatin C, interleukin 18, NGAL, L-FABP and KIM-1 were studied by ELISA in the blood and urine of 35 patients with local cancer with an epidural block (main group and 37 patients with local cancer without an epidural block (control group before surgery and 40 min after its beginning and on days 1 and 3 of the postoperative period. All patients were divided into 2 groups by the levels of cystatin C in the blood serum: 1000 ng/ml and lower, and over 1000 ng/ml.Results. Epidural block during the perioperative period in kidney resection with warm ischemia for patients with local cancer had an obvious nephroprotective effect allowing maintaining the initial renal functional parameters, in contrast to the standard disease management.

  11. Free Radical Damage in Ischemia-Reperfusion Injury: An Obstacle in Acute Ischemic Stroke after Revascularization Therapy

    Directory of Open Access Journals (Sweden)

    Ming-Shuo Sun

    2018-01-01

    Full Text Available Acute ischemic stroke is a common cause of morbidity and mortality worldwide. Thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy are the main revascularization therapies for acute ischemic stroke. However, ischemia-reperfusion injury after revascularization therapy can result in worsening outcomes. Among all possible pathological mechanisms of ischemia-reperfusion injury, free radical damage (mainly oxidative/nitrosative stress injury has been found to play a key role in the process. Free radicals lead to protein dysfunction, DNA damage, and lipid peroxidation, resulting in cell death. Additionally, free radical damage has a strong connection with inducing hemorrhagic transformation and cerebral edema, which are the major complications of revascularization therapy, and mainly influencing neurological outcomes due to the disruption of the blood-brain barrier. In order to get a better clinical prognosis, more and more studies focus on the pharmaceutical and nonpharmaceutical neuroprotective therapies against free radical damage. This review discusses the pathological mechanisms of free radicals in ischemia-reperfusion injury and adjunctive neuroprotective therapies combined with revascularization therapy against free radical damage.

  12. Successful Thrombolysis and Spasmolysis of Acute Leg Ischemia after Accidental Intra-arterial Injection of Dissolved Flunitrazepam Tablets

    International Nuclear Information System (INIS)

    Radeleff, B.; Stampfl, U.; Sommer, C.-M.; Bellemann, N.; Hyhlik-Duerr, A.; Weber, M.-A.; Boeckler, D.; Kauczor, H.-U.

    2011-01-01

    A 37-year-old man with known intravenous drug abuse presented in the surgical ambulatory care unit with acute leg ischemia after accidental intra-arterial injection of dissolved flunitrazepam tablets into the right femoral artery. A combination of anticoagulation, vasodilatation, and local selective and superselective thrombolysis with urokinase was performed to salvage the leg. As a result of the severe ischemia-induced pain, the patient had to be monitored over the complete therapy period on the intensive care unit with permanent administration of intravenous fluid and analgetics. We describe the presenting symptoms and the interventional technique, and we discuss the recent literature regarding the management of accidental intra-arterial injection of dissolved flunitrazepam tablets.

  13. Planned second-look laparoscopy in the management of acute mesenteric ischemia

    Science.gov (United States)

    Yanar, Hakan; Taviloglu, Korhan; Ertekin, Cemalettin; Ozcinar, Beyza; Yanar, Fatih; Guloglu, Recep; Kurtoglu, Mehmet

    2007-01-01

    AIM: To investigate the role of second-look laparoscopy in patients with acute mesenteric ischemia (AMI). METHODS: Between January 2000 and November 2005, 71 patients were operated for the treatment of AMI. The indications for a second-look were low flow state, bowel resection and anastomosis or mesenteric thromboembolectomy performed during the first operation. Regardless of the clinical course of patients, the second-look laparoscopic examination was performed 72 h post-operatively at the bed side in the ICU or operating room. RESULTS: The average time of admission to the hospital after the initiation of symptoms was 3 d (range, 5 h-9 d). In 14 patients, laparotomy was performed. In 11 patients, small and/or large bowel necrosis was detected and initial resection and anastomosis were conducted. A low flow state was observed in two patients and superior mesenteric artery thromboembolectomy with small bowel resection was performed in one patient. In 13 patients, a second-look laparoscopic examination revealed normal bowel viability, but in one patient, intestinal necrosis was detected. In two of the patients, a third operation was necessary to correct anastomotic leakage. The overall complication rate was 42.8%, and in-hospital mortality rate was 57.1% (n = 6). CONCLUSION: Second-look laparoscopy is a minimally invasive, technically simple procedure that is performed for diagnostic as well as therapeutic purposes. The simplicity and ease of this method may encourage wider application to benefit more patients. However, the timing of a second-look procedure is unclear particularly in a patient with anastomosis. PMID:17659674

  14. Long-term primary patency prognostic factors after endovascular therapy for acute lower limb ischemia

    International Nuclear Information System (INIS)

    Zhang Di; Gu Jianping; Lou Wensheng; He Xu; Chen Liang; Chen Guoping; Su Haobo; Song Jinhua; Wang Tao

    2012-01-01

    Objective: To assess prognostic factors regarding long-term primary patency for patients who underwent intra-arterial thrombolysis and/or adjuvant endovascular techniques due to acute lower limb ischemia. Methods: Consecutive patients with ALI of the lower extremities treated via interventional methods between January 2005 and June 2010 were identified and reviewed (exclude patient suffered from aortic dissection involved artery of lower extremity or trauma). Analyze the potential variables with univariable analysis and only factors associated with long-term primary patency with a P value less than 0.1 in univariable analysis were introduced into the Cox regression mode. Total long-term primary patency and grouped primary patency were assessed using Kaplan-Meier estimation. Results: The analyzed dataset included 107 limbs treated in 101 patients presenting with ALI (class Ⅰ 15, class Ⅱ A 36, class Ⅱ B to Ⅲ 56, according to Rutherford classification). Eight nine limbs were enrolled in follow-up.The mean followup was 34 months (range: 1 to 53 months). Primary patency at 12, 24 and 36 months was 87%, 68% and 55%, respectively. Multivariable analyses identified patients presenting with diabetes mellitus (P=0.00), PAOD (P<0.02) and thrombolysis time (P<0.02) were associated with primary patency. Compare the patency rate of patients with different thrombolysis time, the results showed that the patency rate of the patients thrombolysis time less than 4 d was higher than those more than 4 c. Conclusions: Interventional therapy remains an effective treatment option for patients presenting with lower extremity ALI. Diabetes mellitus and PAOD negatively affect the rates of limb primary patency. Thrombolysis should be limited to <4 days. (authors)

  15. MRI of experimental focal cerebral ischemia in sheep; MR-Bildgebung eines experimentellen Schlaganfallmodells beim Schaf

    Energy Technology Data Exchange (ETDEWEB)

    Foerschler, A. [Universitaetsklinikum Leipzig (Germany). Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie, Abt. fuer Neuroradiologie; Boltze, J. [Universitaetsklinikum Leipzig (Germany). Inst. fuer Klinische Immunologie und Transfusionsmedizin; Fraunhofer-Inst. fuer Zelltherapie und Immunologie (Germany); Waldmin, D. [Leipzig Univ. (Germany). Veterinaer-Anatomisches Inst.; Gille, U. [Fraunhofer-Inst. fuer Zelltherapie und Immunologie (Germany); Leipzig Univ. (Germany). Veterinaer-Anatomisches Inst.; Zimmer, C. [Technische Univ. Muenchen (Germany). Klinikum rechts der Isar, Abt. fuer Neuroradiologie

    2007-05-15

    Purpose: With respect to the specific characteristic of rete mirabile epidurale rostrale in sheep, the aim of this study was to investigate the use of time of flight (TOF) magnetic resonance angiography (MRA) to observe vascular anatomy and to validate MCA occlusion in a new model of experimental focal cerebral ischemia by permanent middle cerebral artery (MCA) occlusion in sheep (designed to study stroke therapy using autologous stem cells from umbilical cord blood). Furthermore, we wanted to assess the extent and natural time course of ischemic focal brain injury in sheep using functional and morphological magnetic resonance imaging (MRI). Materials and Method: 13 Merino sheep were examined. In 4 of the animals all, in 5 sheep 1 or 2 MCA branches were occluded and in 1 one case touched (sham operation). 4 controls did not undergo a surgical procedure. 23 MRI sessions were performed in 10 sheep. These sessions included T1, T2, T2{sup *} sequences, diffusion-weighted imaging (DWI) and TOF MRA before and 2 - 46 days after the onset of stroke using a 1.5T clinical MR scanner. Corrosion casts of the cerebral arteries of 3 sheep were prepared and compared to MRA. Results: The MRA visualized the vessel anatomy or occlusion distal to the rete mirabile. Anatomical variants concerning the variant origin of the MCA and inconstant arteria choroidea rostralis and communicans rostralis were revealed. Sheep with occluded left MCA showed space occupying lesions with a drop in ADC values. Depending on the number of preserved MCA branches (0; 1; 2), highly significant (p < 0.001) differences in lesion size (21 {+-} 5.7; 13; 1.7 {+-} 1.3 ml) could be found. No indication of ischemia but minimal contusion damage was observed in the sham operated animal. (orig.)

  16. Protective Effect of Platelet Rich Plasma on Experimental Ischemia/Reperfusion Injury in Rat Ovary.

    Science.gov (United States)

    Bakacak, Murat; Bostanci, Mehmet Suhha; İnanc, Fatma; Yaylali, Asli; Serin, Salih; Attar, Rukset; Yildirim, Gazi; Yildirim, Ozge Kizilkale

    2016-01-01

    Ovarian torsion is a common cause of local ischemic damage, reduced follicular activity and infertility. Platelet-rich plasma (PRP) contains growth factors with demonstrated cytoprotective properties; so we evaluated PRP efficacy in a rat ischemia/reperfusion (I/R) model. Sixty adult female Sprague-Dawley albino rats were randomly assigned to 6 groups of 8 animals each: Sham, Ischemia, I/R, Sham + PRP, I + PRP and I/R + PRP; and the remaining 12 used to prepare PRP. Ischemia groups were subjected to bilateral adnexal torsion for 3 h, while I/R and I/R + PRP groups received subsequent detorsion for 3 h. Intraperitoneal PRP was administered 30 min prior to ischemia (Ischemia + PRP) or reperfusion (I/R + PRP). Total oxidant status (TOS), oxidative stress index (OSI) and total ovarian histopathological scores were higher in Ischemia and I/R groups than in the Sham group (p OSI and histopathological scores in I + PRP and I/R + PRP groups compared to the corresponding Ischemia and I/R groups (p OSI (r = 0.877, p < 0.001). Peritoneal vascular endothelial growth factor was significantly higher in PRP-treated groups than corresponding untreated groups (p < 0.05). PRP is effective for the prevention of ischemia and reperfusion damage in rat ovary. © 2015 S. Karger AG, Basel.

  17. β2-Adrenergic Receptor-Mediated HIF-1α Upregulation Mediates Blood Brain Barrier Damage in Acute Cerebral Ischemia

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    Yanyun Sun

    2017-08-01

    Full Text Available Disruption of the blood brain barrier (BBB within the thrombolytic time window is an antecedent event to intracerebral hemorrhage in ischemic stroke. Our recent studies showed that 2-h cerebral ischemia induced BBB damage in non-infarcted area and secreted matrix metalloproteinase-2 (MMP-2 accounted for this disruption. However, the factors that affect MMP-2 secretion and regulate BBB damage remains unknown. Since hypoxia-inducible factor-1 alpha (HIF-1α was discovered as a mater regulator in hypoxia, we sought to investigate the roles of HIF-1α in BBB damage as well as the factors regulating HIF-1α expression in the ischemic brain. in vivo rat middle cerebral artery occlusion (MCAO and in vitro oxygen glucose deprivation (OGD models were used to mimic ischemia. Pretreatment with HIF-1α inhibitor YC-1 significantly inhibited 2-h MCAO-induced BBB damage, which was accompanied by suppressed occludin degradation and vascular endothelial growth factor (VEGF mRNA upregulation. Interestingly, β2-adrenergic receptor (β2-AR antagonist ICI 118551 attenuated ischemia-induced BBB damage by regulating HIF-1α expression. Double immunostaining showed that HIF-1α was upregulated in ischemic neurons but not in astrocytes andendothelial cells. Of note, HIF-1α inhibition with inhibitor YC-1 or siRNA significantly prevented OGD-induced VEGF upregulation as well as the secretion of VEGF and MMP-2 in neurons. More importantly, blocking β2-AR with ICI 118551 suppressedHIF-1α upregulation in ischemic neurons and attenuated occludin degradation induced by the conditioned media of OGD-treatedneurons. Taken together, blockade of β2-AR-mediated HIF-1α upregulation mediates BBB damage during acute cerebral ischemia. These findings provide new mechanistic understanding of early BBB damage in ischemic stroke and may help reduce thrombolysis-related hemorrhagic complications.

  18. Cerebrospinal Fluid Metabolomics After Natural Product Treatment in an Experimental Model of Cerebral Ischemia.

    Science.gov (United States)

    Huan, Tao; Xian, Jia Wen; Leung, Wing Nang; Li, Liang; Chan, Chun Wai

    2016-11-01

    Cerebrospinal fluid (CSF) is an important biofluid for diagnosis of and research on neurological diseases. However, in-depth metabolomic profiling of CSF remains an analytical challenge due to the small volume of samples, particularly in small animal models. In this work, we report the application of a high-performance chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) workflow for CSF metabolomics in Gastrodia elata and Uncaria rhynchophylla water extract (GUW)-treated experimental cerebral ischemia model of rat. The GUW is a commonly used Traditional Chinese Medicine (TCM) for hypertension and brain disease. This study investigated the amine- and phenol-containing biomarkers in the CSF metabolome. After GUW treatment for 7 days, the neurological deficit score was significantly improved with infarct volume reduction, while the integrity of brain histological structure was preserved. Over 1957 metabolites were quantified in CSF by dansylation LC-MS. The analysis of this comprehensive list of metabolites suggests that metabolites associated with oxidative stress, inflammatory response, and excitotoxicity change during GUW-induced alleviation of ischemic injury. This work is significant in that (1) it shows CIL LC-MS can be used for in-depth profiling of the CSF metabolome in experimental ischemic stroke and (2) identifies several potential molecular targets (that might mediate the central nervous system) and associate with pharmacodynamic effects of some frequently used TCMs.

  19. Borax partially prevents neurologic disability and oxidative stress in experimental spinal cord ischemia/reperfusion injury.

    Science.gov (United States)

    Koc, Emine Rabia; Gökce, Emre Cemal; Sönmez, Mehmet Akif; Namuslu, Mehmet; Gökce, Aysun; Bodur, A Said

    2015-01-01

    The aim of this study is to investigate the potential effects of borax on ischemia/reperfusion injury of the rat spinal cord. Twenty-one Wistar albino rats were divided into 3 groups: sham (no ischemia/reperfusion), ischemia/reperfusion, and borax (ischemia/reperfusion + borax); each group was consist of 7 animals. Infrarenal aortic cross clamp was applied for 30 minutes to generate spinal cord ischemia. Animals were evaluated functionally with the Basso, Beattie, and Bresnahan scoring system and inclined-plane test. The spinal cord tissue samples were harvested to analyze tissue concentrations of nitric oxide, nitric oxide synthase activity, xanthine oxidase activity, total antioxidant capacity, and total oxidant status and to perform histopathological examination. At the 72nd hour after ischemia, the borax group had significantly higher Basso, Beattie, and Bresnahan and inclined-plane scores than those of ischemia/reperfusion group. Histopathological examination of spinal cord tissues in borax group showed that treatment with borax significantly reduced the degree of spinal cord edema, inflammation, and tissue injury disclosed by light microscopy. Xanthine oxidase activity and total oxidant status levels of the ischemia/reperfusion group were significantly higher than those of the sham and borax groups (P borax group were significantly higher than those of the ischemia/reperfusion group (P borax groups in terms of total antioxidant capacity levels (P > .05). The nitric oxide levels and nitric oxide synthase activity of all groups were similar (P > .05). Borax treatment seems to protect the spinal cord against injury in a rat ischemia/reperfusion model and improve neurological outcome. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia

    Directory of Open Access Journals (Sweden)

    Felicita Pedata

    2014-01-01

    Full Text Available The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes. Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by activation of resident immune cells, that is, microglia, and production or activation of inflammation mediators. Proinflammatory cytokines, which upregulate cell adhesion molecules, exert an important role in promoting recruitment of leukocytes that in turn promote expansion of the inflammatory response in ischemic tissue. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. A2A receptors present on central cells and on blood cells account for important effects depending on the time-related evolution of the pathological condition. Evidence suggests that A2A receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A2A receptor agonists provide protracted protection by controlling massive blood cell infiltration in the hours and days after ischemia. Focus on inflammatory responses provides for adenosine A2A receptor agonists a wide therapeutic time-window of hours and even days after stroke.

  1. Chymase mediates injury and mitochondrial damage in cardiomyocytes during acute ischemia/reperfusion in the dog.

    Science.gov (United States)

    Zheng, Junying; Wei, Chih-Chang; Hase, Naoki; Shi, Ke; Killingsworth, Cheryl R; Litovsky, Silvio H; Powell, Pamela C; Kobayashi, Tsunefumi; Ferrario, Carlos M; Rab, Andras; Aban, Inmaculada; Collawn, James F; Dell'Italia, Louis J

    2014-01-01

    Cardiac ischemia and reperfusion (I/R) injury occurs because the acute increase in oxidative/inflammatory stress during reperfusion culminates in the death of cardiomyocytes. Currently, there is no drug utilized clinically that attenuates I/R injury in patients. Previous studies have demonstrated degranulation of mast cell contents into the interstitium after I/R. Using a dog model of I/R, we tested the role of chymase, a mast cell protease, in cardiomyocyte injury using a specific oral chymase inhibitor (CI). 15 adult mongrel dogs had left anterior descending artery occlusion for 60 min and reperfusion for 100 minutes. 9 dogs received vehicle and 6 were pretreated with a specific CI. In vivo cardiac microdialysis demonstrated a 3-fold increase in interstitial fluid chymase activity in I/R region that was significantly decreased by CI. CI pretreatment significantly attenuated loss of laminin, focal adhesion complex disruption, and release of troponin I into the circulation. Microarray analysis identified an I/R induced 17-fold increase in nuclear receptor subfamily 4A1 (NR4A1) and significantly decreased by CI. NR4A1 normally resides in the nucleus but can induce cell death on migration to the cytoplasm. I/R caused significant increase in NR4A1 protein expression and cytoplasmic translocation, and mitochondrial degradation, which were decreased by CI. Immunohistochemistry also revealed a high concentration of chymase within cardiomyocytes after I/R. In vitro, chymase added to culture HL-1 cardiomyocytes entered the cytoplasm and nucleus in a dynamin-dependent fashion, and promoted cytoplasmic translocation of NR4A1 protein. shRNA knockdown of NR4A1 on pre-treatment of HL-1 cells with CI significantly decreased chymase-induced cell death and mitochondrial damage. These results suggest that the beneficial effects of an orally active CI during I/R are mediated in the cardiac interstitium as well as within the cardiomyocyte due to a heretofore-unrecognized chymase

  2. Chymase mediates injury and mitochondrial damage in cardiomyocytes during acute ischemia/reperfusion in the dog.

    Directory of Open Access Journals (Sweden)

    Junying Zheng

    Full Text Available Cardiac ischemia and reperfusion (I/R injury occurs because the acute increase in oxidative/inflammatory stress during reperfusion culminates in the death of cardiomyocytes. Currently, there is no drug utilized clinically that attenuates I/R injury in patients. Previous studies have demonstrated degranulation of mast cell contents into the interstitium after I/R. Using a dog model of I/R, we tested the role of chymase, a mast cell protease, in cardiomyocyte injury using a specific oral chymase inhibitor (CI. 15 adult mongrel dogs had left anterior descending artery occlusion for 60 min and reperfusion for 100 minutes. 9 dogs received vehicle and 6 were pretreated with a specific CI. In vivo cardiac microdialysis demonstrated a 3-fold increase in interstitial fluid chymase activity in I/R region that was significantly decreased by CI. CI pretreatment significantly attenuated loss of laminin, focal adhesion complex disruption, and release of troponin I into the circulation. Microarray analysis identified an I/R induced 17-fold increase in nuclear receptor subfamily 4A1 (NR4A1 and significantly decreased by CI. NR4A1 normally resides in the nucleus but can induce cell death on migration to the cytoplasm. I/R caused significant increase in NR4A1 protein expression and cytoplasmic translocation, and mitochondrial degradation, which were decreased by CI. Immunohistochemistry also revealed a high concentration of chymase within cardiomyocytes after I/R. In vitro, chymase added to culture HL-1 cardiomyocytes entered the cytoplasm and nucleus in a dynamin-dependent fashion, and promoted cytoplasmic translocation of NR4A1 protein. shRNA knockdown of NR4A1 on pre-treatment of HL-1 cells with CI significantly decreased chymase-induced cell death and mitochondrial damage. These results suggest that the beneficial effects of an orally active CI during I/R are mediated in the cardiac interstitium as well as within the cardiomyocyte due to a heretofore

  3. Extract of grapefruit-seed reduces acute pancreatitis induced by ischemia/reperfusion in rats: possible implication of tissue antioxidants.

    Science.gov (United States)

    Dembinski, A; Warzecha, Z; Konturek, S J; Ceranowicz, P; Dembinski, M; Pawlik, W W; Kusnierz-Cabala, B; Naskalski, J W

    2004-12-01

    Grapefruit seed extract (GSE) has been shown to exert antibacterial, antifungal and antioxidant activity possibly due to the presence of naringenin, the flavonoid with cytoprotective action on the gastric mucosa. No study so far has been undertaken to determine whether this GSE is also capable of preventing acute pancreatic damage induced by ischemia/reperfusion (I/R), which is known to result from reduction of anti-oxidative capability of pancreatic tissue, and whether its possible preventive effect involves an antioxidative action of this biocomponent. In this study carried out on rats with acute hemorrhagic pancreatitis induced by 30 min partial pancreatic ischemia followed by 6 h of reperfusion, the GSE or vehicle (vegetable glycerin) was applied intragastrically in gradually increasing amounts (50-500 microl) 30 min before I/R. Pretreatment with GSE decreased the extent of pancreatitis with maximal protective effect of GSE at the dose 250 microl. GSE reduced the pancreatitis-evoked increase in serum lipase and poly-C specific ribonuclease activity, and attenuated the marked fall in pancreatic blood flow and pancreatic DNA synthesis. GSE administered alone increased significantly pancreatic tissue content of lipid peroxidation products, malondialdehyde and 4-hydroxyalkens, and when administered before I/R, GSE reduced the pancreatitis-induced lipid peroxidation. We conclude that GSE exerts protective activity against I/R-induced pancreatitis probably due to the activation of antioxidative mechanisms in the pancreas and the improvement of pancreatic blood flow.

  4. Effects of standard ethanolic extract from Erythrina velutina in acute cerebral ischemia in mice.

    Science.gov (United States)

    Rodrigues, Francisca Taciana Sousa; de Sousa, Caren Nádia Soares; Ximenes, Naiara Coelho; Almeida, Anália Barbosa; Cabral, Lucas Moraes; Patrocínio, Cláudio Felipe Vasconcelos; Silva, Aline Holanda; Leal, Luzia Kalyne Almeida Moreira; Honório Júnior, José Eduardo Ribeiro; Macedo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2017-12-01

    The objective of this study was to verify a possible neuroprotective effect of the ethanolic extract of Erythrina velutina (EEEV). Male Swiss mice were submitted to transient cerebral ischemia by occlusion of both carotid arteries for 30 min and treated for 5 days with EEEV (200 or 400 mg/kg) or Memantine (MEM) 10 mg/kg, with initiation of treatment 2 or 24 h after Ischemia. On the 6th day after the induction of ischemia, the animals were submitted to evaluation of locomotor activity and memory and then sacrificed. The brains were dissected for the removal of the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) for determination of amino acid concentrations. In the step down and Y-maze tests, ischemia caused damage to the animals and treatment with EEEV or MEM reversed this effect. The animals submitted to ischemia also showed memory deficit in the object recognition test, an effect that was reverted by EEEV400 and MEM10. Amino acid dosage showed an increase in excitatory amino acid concentrations in the PFC of the ischemic animals and this effect was reversed by the treatment with EEEV400/24H. Regarding the inhibitory amino acids, ischemia caused an increase of taurine in the PFC while treatment with MEM10/24H or EEEV400/24H reversed this effect. In HC, an increase in excitatory amino acids was also observed in ischemiated animals having treatment with EEEV200/2H or EEEV400/24H reversed this effect. Similar effect was also observed in the same area in relation to the inhibitory amino acids with treatment with MEM10/24H or EEEV400/24H. In the ST, ischemia was also able to cause an increase in excitatory amino acids that was reversed more efficiently by the treatments with MEM10/24H and EEEV200. Also in this area, an increase of taurine and GABA was observed and only the treatment with EEEV200/2H showed a reversion of this effect. In view of these findings, EEEV presents a neuroprotective effect possibly due to its action on amino acid

  5. Global Ischemia ECG pattern for diagnosis of acute left main occlusion: prevalence and associated mortality in patients with suspected acute myocardial infarction

    DEFF Research Database (Denmark)

    Stengaard, Carsten; Sørensen, Jacob Thorsted; Andersen, M.P.

    2011-01-01

    .J. Terkelsen2, 1Aarhus University Hospital, Aarhus, Department of medicine and Cardiology A - Aarhus - Denmark, 2Aarhus University Hospital, Skejby, Department of Cardiology - Aarhus - Denmark, 3Aalborg University, Department of Health Science and Technology - Aalborg - Denmark, 4Tampere University Hospital...... ischemia ECG pattern (GIP) has been proposed for diagnosis of acute left main stem (LM) occlusion. The GIP is defined by ST-elevation of 1mm in lead aVR and ST-depression of 0.5mm in seven or more ECG leads. Previous studies focus on the sensitivity of GIP in patients with confirmed LM occlusion. We...

  6. Protein-energy malnutrition developing after global brain ischemia induces an atypical acute-phase response and hinders expression of GAP-43.

    Science.gov (United States)

    Smith, Shari E; Figley, Sarah A; Schreyer, David J; Paterson, Phyllis G

    2014-01-01

    Protein-energy malnutrition (PEM) is a common post-stroke problem. PEM can independently induce a systemic acute-phase response, and pre-existing malnutrition can exacerbate neuroinflammation induced by brain ischemia. In contrast, the effects of PEM developing in the post-ischemic period have not been studied. Since excessive inflammation can impede brain remodeling, we investigated the effects of post-ischemic malnutrition on neuroinflammation, the acute-phase reaction, and neuroplasticity-related proteins. Male, Sprague-Dawley rats were exposed to global forebrain ischemia using the 2-vessel occlusion model or sham surgery. The sham rats were assigned to control diet (18% protein) on day 3 after surgery, whereas the rats exposed to global ischemia were assigned to either control diet or a low protein (PEM, 2% protein) diet. Post-ischemic PEM decreased growth associated protein-43, synaptophysin and synaptosomal-associated protein-25 immunofluorescence within the hippocampal CA3 mossy fiber terminals on day 21, whereas the glial response in the hippocampal CA1 and CA3 subregions was unaltered by PEM. No systemic acute-phase reaction attributable to global ischemia was detected in control diet-fed rats, as reflected by serum concentrations of alpha-2-macroglobulin, alpha-1-acid glycoprotein, haptoglobin, and albumin. Acute exposure to the PEM regimen after global brain ischemia caused an atypical acute-phase response. PEM decreased the serum concentrations of albumin and haptoglobin on day 5, with the decreases sustained to day 21. Serum alpha-2-macroglobulin concentrations were significantly higher in malnourished rats on day 21. This provides the first direct evidence that PEM developing after brain ischemia exerts wide-ranging effects on mechanisms important to stroke recovery.

  7. Assessment of anastomotic reliability with pulse oximetry in graded intestinal ischemia: an experimental study in dogs.

    Science.gov (United States)

    Türkyilmaz, Z; Sönmez, K; Başaklar, A C; Demiroğullari, B; Numanoğlu, V; Ekingen, G; Dursun, A; Altin, M A; Kale, N

    1997-12-01

    Pulse oximetry has been proposed as an appropriate and feasible technique in the assessment of intestinal ischemia in recent years. In this study the authors aimed to assess the reliability of anastomoses in the dog small intestine in which there is graded irreversible ischemia as measured by pulse oxymeter. In a control group of four dogs, without any devascularization, three small bowel anastomoses were formed in each dog. The study group consisted of 12 dogs. In each animal three intestinal segments with different levels of ischemia were created by ligating the marginal vessels proximally and distally in sequence beginning from the midpoint of the segmental vascular arcade. Preanastomotic pulse oximeter readings between 80% and 90% were assigned to mild ischemia, 70% and 80% to moderate, and 60% and 70% to severe ischemia group. Pulse oximetry measurements were obtained from probes applied to the antimesenteric serosal surfaces at the midpoint of small intestinal segments. A total of 48 intestinal segments (12 nonischemic in the control group and 36 with three different levels of ischemia in the study group) were transected in the midpoint and anastomosed in double layers. Postanastomotic SaO2 values were also noted. The anastomoses were evaluated 48 hours later macroscopically if there was any leakage, and biopsy specimens were obtained for histopathologic ischemic gradings. All results were studied statistically. Histopathologic grades between each group were statistically different (P .05), worsening as the level of ischemia increased. Pre- and postanastomotic pulse oximetry measurements correlated very well with the histological gradings (r = -0.90, P anastomoses) in severe ischemia groups. In the moderate ischemia group with an average preanastomotic pulse reading of 76.75%, each of the leaking anastomoses had a postanastomotic pulse measurement of lower than 70%. The finding that the difference between histopathologic grades of control and mild ischemia

  8. Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex.

    Science.gov (United States)

    Kutsuna, Nobuo; Yamashita, Akiko; Eriguchi, Takashi; Oshima, Hideki; Suma, Takeshi; Sakatani, Kaoru; Yamamoto, Takamitsu; Yoshino, Atsuo; Katayama, Yoichi

    2014-01-01

    Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  9. Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia.

    Directory of Open Access Journals (Sweden)

    Wanchao Yang

    Full Text Available Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O2,13%O2,15%O2 and 18%O2 (targeted to PaO2 30-39 mmHg, 40-49 mmHg, 50-59 mmHg, and 60-69 mmHg, respectively or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO2 60-80 mmHg for 180 min. The mean artery pressure (MAP, blood gas, and cerebral blood flow (CBF were evaluated. The cortical vascular permeability and brain edema were examined. The ipsilateral cortex damage and the percentage of hippocampal apoptotic neurons were evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL assay as well as flow cytometry, respectively. Immunofluorescence and western blotting were performed to determine aquaporin-4 (AQP4 expression. In rats treated with severe hypoxia (PaO2 50 mmHg, hypercapnia protected against these pathophysiological changes. Moreover, hypercapnia treatment significantly reduced brain damage in the ischemic ipsilateral cortex and decreased the percentage of apoptotic neurons in the hippocampus after the CCA ligated rats were exposed to mild or moderate hypoxemia (PaO2 > 50 mmHg; especially under mild hypoxemia (PaO2 > 60 mmHg, hypercapnia significantly attenuated the expression of AQP4 protein with brain edema (p < 0.05. Hypercapnia exerts beneficial effects under mild to moderate hypoxemia and augments detrimental effects under severe hypoxemia on brain damage in a rat model of hypoxia-ischemia.

  10. Serial Holter ST-segment monitoring after first acute myocardial infarction. Prevalence, variability, and long-term prognostic importance of transient myocardial ischemia

    DEFF Research Database (Denmark)

    Mickley, H; Nielsen, J R; Berning, J

    1998-01-01

    Based on serial Holter monitoring performed 7 times within 3 years after a first acute myocardial infarction, we assessed the prevalence, variability and long-term clinical importance of transient myocardial ischemia (TMI) defined as episodes of ambulatory ST-segment depression. In all, 121...... consecutive male patients variability was found within and between patients...

  11. Evidence that estrogen receptors play a limited role in mediating enhanced recovery of bile flow in female rats in the acute phase of liver ischemia reperfusion injury

    NARCIS (Netherlands)

    de Vries, Heleen A. H.; Ponds, Fraukje A. M.; Nieuwenhuijs, Vincent B.; Morphett, Arthur; Padbury, Robert T. A.; Barritt, Greg J.

    2013-01-01

    Introduction. Female patients exhibit better survival and less hepatic damage from ischemia reperfusion (IR) injury following surgery. However, the effects of sex and estrogens on liver function in the acute phase of IR are not well understood. Objective. The aim was to investigate this question.

  12. Dynamics of cognitive disturbances in rats with acute cerebral ischemia on the background of introduction of 0.9 % solution NaCl

    Directory of Open Access Journals (Sweden)

    Андрій Ігорович Семененко

    2015-06-01

    Full Text Available For today there are no clear recommendations on infusion therapy at the disease and injuries of brain, and infusion preparations are commonly used empirically. Within the framework of the complex study of an influence of the different infusion remedies on brain at an experimental ischemia of brain, an aim of this work is to investigate how the 0,9 % solution of NaCl influences on the dynamics of cognitive functions and neurological status of the rats with an acute cerebral ischemia at the course medical introduction into an animal organism.Methods. Experiments were carried out on 60 white rats-males. An acute disturbance of cerebral blood circulation (ADCBC was modeled by means of the two-sided dressing of internal carotid arteries. The 0,9 % solution of NаСІ was injected intravenously in catheterized thigh vein 2,5 ml/kg 2 times/day (5 ml/kg for a day. The first introduction was carried out in 30 minutes after ADCBC and then every day in 12 hours during 7 days. The control groups consist of intact rats that received 0,9 % NаСІ and animals with a model ischemia without treatment.Neurological deficiency in animals was defined on the scale stroke-index McGrow C. P. The dynamics of position-finding activity was assessed in experiment “an open field”. An assessment of animal capacity to training and memorization of an aversive stimulus was studied in the test of conditioned response of passive avoidance. The results were processed using the program StatPlus 2009.Results. The study showed that bilateral carotid occlusion in rats without treatment is followed not only by the high animal lethality but also by the development of a hard neurological symptomatology and then by essential disturbance of mnestic functions in animals that survived during the recovery period of model insult (р<0,01.The study of lethality dynamics, neurological status, behavioral responses in rats with ADCBC on the model of bilateral carotid occlusion showed that the

  13. Tympanic membrane changes in experimental acute otitis media and myringotomy

    DEFF Research Database (Denmark)

    Alzbutiene, G.; Hermansson, A.; Caye-Thomasen, P.

    2008-01-01

    OBJECTIVE: The present experimental study explored pathomorphological changes and calcium depositions in the tympanic membrane during experimental acute otitis media caused by nontypeable Haemophilus influenzae in myringotomized and nonmyringotomized ears. MATERIAL AND METHODS: A rat model of exp...

  14. The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hua, Fang, E-mail: fhua2@emory.edu [Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, 1365B Clifton Road, Suite 5100, Atlanta, GA 30322 (United States); Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G. [Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, 1365B Clifton Road, Suite 5100, Atlanta, GA 30322 (United States)

    2009-12-18

    TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-{kappa}B). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-{kappa}B and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-{kappa}B activity and phosphorylation of the inhibitor of kappa B (I{kappa}B{alpha}) increased in ischemic brains, but IRF3, inhibitor of {kappa}B kinase complex-{epsilon} (IKK{epsilon}), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-{kappa}B activity or p-I{kappa}B{alpha} induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-{kappa}B signaling and brain injury after acute cerebral I/R.

  15. The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

    International Nuclear Information System (INIS)

    Hua, Fang; Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G.

    2009-01-01

    TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-κB and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-κB activity and phosphorylation of the inhibitor of kappa B (IκBα) increased in ischemic brains, but IRF3, inhibitor of κB kinase complex-ε (IKKε), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-κB activity or p-IκBα induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-κB signaling and brain injury after acute cerebral I/R.

  16. Acute Testicular Ischemia following Endovascular Abdominal Aortic Aneurysm Repair Identified in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Nathan Finnerty

    2014-01-01

    Full Text Available Endovascular aneurysm repair (EVAR is perhaps the most widely utilized surgical procedure for patients with large abdominal aortic aneurysms. This procedure is minimally invasive and reduces inpatient hospitalization requirements. The case involves a 72-year-old male who presented to the emergency department with right testicular ischemia two days following EVAR. Given the minimal inpatient hospitalization associated with this procedure, emergency physicians are likely to encounter associated complications. Ischemic and thromboembolic events following EVAR are extremely rare but require prompt vascular surgery intervention to minimize morbidity and mortality.

  17. Brain scan in cerebral ischemia. An experimental model in the rat

    International Nuclear Information System (INIS)

    Turner, J.H.

    1975-01-01

    A rapid embolic method for consistent induction of stroke in the rat is described. Brain scans were performed using a micro-pinhole collimator system, and the value of the model for studies in localization of radiopharmaceuticals in cerebral ischemia is demonstrated

  18. The past, the present and the future of experimental research on myocardial ischemia and protection

    Czech Academy of Sciences Publication Activity Database

    Ošťádal, Bohuslav

    2009-01-01

    Roč. 61, č. 1 (2009), s. 3-12 ISSN 1734-1140 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : myocardial ischemia * protection * cell death Subject RIV: FA - Cardiovascular Disease s incl. Cardiotharic Surgery Impact factor: 2.086, year: 2009

  19. Experimental acute thrombotic stroke in baboons

    International Nuclear Information System (INIS)

    Del Zoppo, G.J.; Copeland, B.R.; Harker, L.A.; Waltz, T.A.; Zyroff, J.; Hanson, S.R.; Battenberg, E.

    1986-01-01

    To study the effects of antithrombotic therapy in experimental stroke, we have characterized a baboon model of acute cerebrovascular thrombosis. In this model an inflatable silastic balloon cuff has been implanted by transorbital approach around the right middle cerebral artery (MCA), proximal to the take-off of the lenticulostriate arteries (LSA). Inflation of the balloon for 3 hours in six animals produced a stereotypic sustained stroke syndrome characterized by contralateral hemiparesis. An infarction volume of 3.2 +/- 1.5 cm3 in the ipsilateral corpus striatum was documented by computerized tomographic (CT) scanning at 10 days following stroke induction and 3.9 +/- 1.9 cm3 (n = 4) at 14 days by morphometric neuropathologic determinations of brain specimens fixed in situ by pressure-perfusion with 10% buffered formalin. Immediate pressure-perfusion fixation following deflation of the balloon was performed in 16 additional animals given Evans blue dye intravenously prior to the 3 hour MCA balloon occlusion. Light microscopy and transmission electron microscopy consistently confirmed the presence of thrombotic material occluding microcirculatory branches of the right LSA in the region of Evans blue stain, but not those of the contralateral corpus striatum. When autologous 111In-platelets were infused intravenously in four animals from the above group prior to the transient 3 hour occlusion of the right MCA, gamma scintillation camera imaging of each perfused-fixed whole brain demonstrated the presence of a single residual focus of 111In-platelet activity involving only the Evans blue-stained right corpus striatum. Focal right hemispheric activity was equivalent to 0.55 +/- 0.49 ml of whole blood, and the occlusion score derived from histologic examination of the microcirculation of the Evans blue-stained corpus striatum averaged 34.8 +/- 2.8

  20. Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Yucel, Ahmet Fikret; Pergel, Ahmet; Aydin, Ibrahim; Alacam, Hasan; Karabicak, Ilhan; Kesicioglu, Tugrul; Tumkaya, Levent; Kalkan, Yildiray; Ozer, Ender; Arslan, Zakir; Sehitoglu, Ibrahim; Sahin, Dursun Ali

    2015-01-01

    This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-α levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-α levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-α effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use.

  1. Risk Factors for Long-Term Mortality and Amputation after Open and Endovascular Treatment of Acute Limb Ischemia.

    Science.gov (United States)

    Genovese, Elizabeth A; Chaer, Rabih A; Taha, Ashraf G; Marone, Luke K; Avgerinos, Efthymios; Makaroun, Michel S; Baril, Donald T

    2016-01-01

    Acute limb ischemia (ALI) is a highly morbid and fatal vascular emergency with little known about contemporary, long-term patient outcomes. The goal was to determine predictors of long-term mortality and amputation after open and endovascular treatment of ALI. A retrospective review of ALI patients at a single institution from 2005 to 2011 was performed to determine the impact of revascularization technique on 5-year mortality and amputation. For each main outcome 2 multivariable models were developed; the first adjusted for preoperative clinical presentation and procedure type, the second also adjusted for postoperative adverse events (AEs). A total of 445 limbs in 411 patients were treated for ALI. Interventions included surgical thrombectomy (48%), emergent bypass (18%), and endovascular revascularization (34%). Mean age was 68 ± 15 years, 54% were male, and 23% had cancer. Most patients presented with Rutherford classification IIa (54%) or IIb (39%). The etiology of ALI included embolism (27%), in situ thrombosis (28%), thrombosed bypass grafts (32%), and thrombosed stents (13%). Patients treated with open procedures had significantly more advanced ischemia and higher rates of postoperative respiratory failure, whereas patients undergoing endovascular interventions had higher rates of technical failure. Rates of postprocedural bleeding and cardiac events were similar between both treatments. Excluding Rutherford class III patients (n = 12), overall 5-year mortality was 54% (stratified by treatment, 65% for thrombectomy, 63% for bypass, and 36% for endovascular, P < 0.001); 5-year amputation was 28% (stratified by treatment, 18% for thrombectomy, 27% for bypass, and 17% for endovascular, P = 0.042). Adjusting for comorbidities, patient presentation, AEs, and treatment method, the risk of mortality increased with age (hazard ratio [HR] = 1.04, P < 0.001), female gender (HR = 1.50, P = 0.031), cancer (HR = 2.19, P < 0.001), fasciotomy (HR = 1.69, P = 0.204) in

  2. Conventional alpha beta (αβ) T cells do not contribute to acute intestinal ischemia-reperfusion injury in mice.

    Science.gov (United States)

    Yu, Yi; Feng, Xiaoyan; Vieten, Gertrud; Dippel, Stephanie; Imvised, Tawan; Gueler, Faikah; Ure, Benno M; Kuebler, Jochen F; Klemann, Christian

    2017-01-01

    Ischemia-reperfusion injury (IRI) is associated with significant patient mortality and morbidity. The complex cascade of IRI is incompletely understood, but inflammation is known to be a key mediator. In addition to the predominant innate immune responses, previous research has also indicated that αβ T cells contribute to IRI in various organ models. The aim of this study was to clarify the role αβ T cells play in IRI to the gut. Adult wild-type (WT) and αβ T cell-deficient mice were subjected to acute intestinal IRI with 30min ischemia followed by 4h reperfusion. The gene expression of pro-inflammatory cytokines was measured by qPCR, and the influx of leukocyte subpopulations in the gut was assessed via flow cytometry and histology. Pro-inflammatory cytokines in the serum were measured, and transaminases were assessed as an indicator of distant organ IRI. Intestinal IRI led to an increased expression of pro-inflammatory cytokines in the gut tissue and an influx of leukocytes that predominantly consisted of neutrophils and macrophages. Furthermore, intestinal IRI increased serum IL-6, TNF-α, and ALT/AST levels. The αβ T cell-deficient mice did not exhibit a more significant increase in pro-inflammatory cytokines in the gut or serum following IR than the WT mice. There was also no difference between WT- and αβ T cell-deficient mice in terms of neutrophil infiltration or macrophage activation. Furthermore, the increase in transaminases was equal in both groups indicating that the level of distant organ injury was comparable. An increasing body of evidence demonstrates that αβ T cells play a key role in IRI. In the gut, however, αβ T cells are not pivotal in the first hours following acute IRI as deficiency does not impact cytokine production, neutrophil recruitment, macrophage activation, or distant organ injury. Thus, αβ T cells may be considered innocent bystanders during the acute phase of intestinal IRI.

  3. Conventional alpha beta (αβ T cells do not contribute to acute intestinal ischemia-reperfusion injury in mice.

    Directory of Open Access Journals (Sweden)

    Yi Yu

    Full Text Available Ischemia-reperfusion injury (IRI is associated with significant patient mortality and morbidity. The complex cascade of IRI is incompletely understood, but inflammation is known to be a key mediator. In addition to the predominant innate immune responses, previous research has also indicated that αβ T cells contribute to IRI in various organ models. The aim of this study was to clarify the role αβ T cells play in IRI to the gut.Adult wild-type (WT and αβ T cell-deficient mice were subjected to acute intestinal IRI with 30min ischemia followed by 4h reperfusion. The gene expression of pro-inflammatory cytokines was measured by qPCR, and the influx of leukocyte subpopulations in the gut was assessed via flow cytometry and histology. Pro-inflammatory cytokines in the serum were measured, and transaminases were assessed as an indicator of distant organ IRI.Intestinal IRI led to an increased expression of pro-inflammatory cytokines in the gut tissue and an influx of leukocytes that predominantly consisted of neutrophils and macrophages. Furthermore, intestinal IRI increased serum IL-6, TNF-α, and ALT/AST levels. The αβ T cell-deficient mice did not exhibit a more significant increase in pro-inflammatory cytokines in the gut or serum following IR than the WT mice. There was also no difference between WT- and αβ T cell-deficient mice in terms of neutrophil infiltration or macrophage activation. Furthermore, the increase in transaminases was equal in both groups indicating that the level of distant organ injury was comparable.An increasing body of evidence demonstrates that αβ T cells play a key role in IRI. In the gut, however, αβ T cells are not pivotal in the first hours following acute IRI as deficiency does not impact cytokine production, neutrophil recruitment, macrophage activation, or distant organ injury. Thus, αβ T cells may be considered innocent bystanders during the acute phase of intestinal IRI.

  4. Comparison of Low-Dose Catheter-Directed Thrombolysis with and without Pharmacomechanical Thrombectomy for Acute Lower Extremity Ischemia.

    Science.gov (United States)

    Gandhi, Sagar S; Ewing, Joseph A; Cooper, Emily; Chaves, Jose Mauro; Gray, Bruce H

    2018-01-01

    Catheter-directed thrombolysis (CDT) and/or pharmacomechanical thrombectomy (PMT) can dissolve/remove thrombus; PMT alone, however, may require the adjunctive use of CDT. The aim of this study was to compare the use of CDT with and without PMT for the treatment of acute lower extremity ischemia (ALI). We retrospectively reviewed all patients with ALI who underwent CDT with or without PMT between January 2008 and April 2014 (n = 99). Patients with incomplete medical charts were excluded (n = 16). Remaining patients were divided into 2 cohorts: group 1 included patients who underwent PMT + CDT (n = 54); group 2 included those who underwent CDT alone (n = 29). Lesions were further characterized by anatomic location: iliac disease (n = 14), femoropopliteal disease (n = 53), tibial disease (n = 2), and multilevel disease (n = 14). Data collection included patient and limb characteristics, duration of treatment, complications, clinical outcomes, adjunctive interventions, and follow-up. No significant differences were seen between treatment groups in terms of patient characteristics, occlusion length and location, Rutherford class, median duration of ischemia time (P = 0.22), or mean lysis time (P = 0.58). Treatment groups were also similar with regard to outcomes, including periprocedure complications, patency, reintervention, limb salvage, and amputation-free survival. There was no different between PMT + CDT and CDT alone in terms of periprocedural complications or outcomes. In the quest to resolve ALI, initial thrombus extraction with PMT may not reduce the need, duration, or efficacy of CDT. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Ischemia-reperfusion rat model of acute pancreatitis: protein carbonyl as a putative early biomarker of pancreatic injury.

    Science.gov (United States)

    Schanaider, Alberto; de Carvalho, Thales Penna; de Oliveira Coelho, Simone; Renteria, Juan Miguel; Eleuthério, Elis Cristina Araújo; Castelo-Branco, Morgana Teixeira Lima; Madi, Kalil; Baetas-da-Cruz, Wagner; de Souza, Heitor Siffert Pereira

    2015-08-01

    Acute pancreatitis (AP) is an inflammatory disorder that can affect adjacent and/or remote organs. Some evidence indicates that the production of reactive oxygen species is able to induce AP. Protein carbonyl (PC) derivatives, which can also be generated through oxidative cleavage mechanisms, have been implicated in several diseases, but there is little or no information on this biomarker in AP. We investigated the association between some inflammatory mediators and PC, with the severity of ischemia-reperfusion AP. Wistar rats (n = 56) were randomly assigned in the following groups : control; sham, 15- or 180-min clamping of splenic artery, with 24 or 72 h of follow-up. The relationships between serum level of PC and thiobarbituric acid reactive species (TBARS) to myeloperoxidase (MPO) activity in tissue homogenates and to cytokines in culture supernatants of pancreatic samples were analyzed. MPO activity was related to the histology scores and increased in all clamping groups. Tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin-6 were higher in the 180-min groups. Significant correlations were found between MPO activity and the concentrations of TNF-α and IL-1β. PC levels increased in the 15-min to 24-h group. TBARS levels were not altered substantially. MPO activity and TNF-α and IL-1β concentrations in pancreatic tissue are correlated with AP severity. Serum levels of PC appear to begin to rise early in the course of the ischemia-reperfusion AP and are no longer detected at later stages in the absence of severe pancreatitis. These data suggest that PC can be an efficient tool for the diagnosis of early stages of AP.

  6. Extraction of long-chain fatty acids in isolated rat heart during acute low-flow ischemia.

    Science.gov (United States)

    Richter, W S; Fischer, S; Ernst, N; Munz, D L

    2001-07-01

    Although beta-oxidation of fatty acids is suppressed rapidly during ischemia, the behavior of fatty acid extraction at different flow rates is incompletely understood. This study assessed the relationship between flow and extraction of (123)I-iodophenylpentadecanoic acid (IPPA) in the isolated heart model, especially at low flow. Isolated hearts from male Wistar rats (n = 15) were subjected to retrograde perfusion with constant flow (Krebs Henseleit solution containing 10 mmol/L glucose). A latex balloon in the left ventricle allowed isovolumetric contractions and ventricular pressure measurements. The extraction of (123)I-IPPA was assessed with the indicator dilution technique and (99m)Tc-albumin as the intravascular reference. The flow was either increased from the control flow (8 mL/min) until 300% or reduced until 10%. (123)I-IPPA extraction was measured three times before and 10 min after flow alteration. The tracer uptake was estimated from the product of net extraction and flow. The mean (123)I-IPPA extraction at the control flow (third measurement) was 51.6% +/- 2.8%. Between flow rates of approximately 25% and 300%, (123)I-IPPA extraction increased exponentially at decreasing flow rates. At flow rates < or =25% of the control flow, (123)I-IPPA extraction was exponentially higher than predicted. (123)I-IPPA uptake and flow changed largely in parallel. During low flow, the rate-pressure product showed the expected decline (perfusion-contraction matching). The extraction of (123)I-IPPA is preserved and slightly increased (relative to flow) during acute low-flow ischemia.

  7. Patient delay is the main cause of treatment delay in acute limb ischemia: an investigation of pre- and in-hospital time delay

    DEFF Research Database (Denmark)

    Londero, Louise Skovgaard; Nørgaard, Birgitte; Houlind, Kim Christian

    2014-01-01

    Abstract BACKGROUND: The prognosis of acute limb ischemia is severe, with amputation rates of up to 25% and in-hospital mortality of 9-15%. Delay in treatment increases the risk of major amputation and may be present at different stages, including patient delay, doctors´ delay and waiting time...... in the emergency department. It is important to identify existing problems in order to reduce time delay. The aim of this study was to collect data for patients with acute limb ischemia and to evaluate the time delay between the different events from onset of symptoms to specialist evaluation and further treatment...... (median (range)) was identified. From onset of symptoms to first contact with a doctor the time for all patients were 24 (0-1200) hours. Thirty patients needed immediate intervention. In the group of fourteen patients who had immediate operation, the median time from vascular evaluation...

  8. Endogenous EGF as a potential renotrophic factor in ischemia-induced acute renal failure.

    Science.gov (United States)

    Schaudies, R P; Nonclercq, D; Nelson, L; Toubeau, G; Zanen, J; Heuson-Stiennon, J A; Laurent, G

    1993-09-01

    The time course for the increases in soluble renal epidermal growth factor (EGF) after ischemia has been established. These elevated levels of EGF have been compared with the degree of tissue injury as well as the extent of cell proliferation in the recovering tissue. Levels of soluble immunoreactive EGF (irEGF) in control animals were 9.74 +/- 1.1 ng/g wet wt (n = 4-8 for all values) and rose to 83.9 +/- 30 ng/g within 12 h after injury. Soluble irEGF content peaked at 88.8 +/- 15 ng/g at 24 h postinjury and returned to control values by 72 h. We previously reported that trypsin digestion of crude renal membranes (CRM) generates rat EGF that is indistinguishable from that isolated from the submandibular gland. Initial levels of trypsin-releasable membrane-associated irEGF were 439 +/- 26 ng/g. These levels fell to 46.6 +/- 9.6 ng/g at 48 h after injury. The total renal EGF demonstrated an 80% decline 48 h after injury but returned to 50% of the initial values after 72 h representing significant new synthesis of EGF-containing proteins between 48 and 72 h postinjury. Immunohistochemical staining of kidney paraffin sections for EGF immunoreactivity demonstrated staining intensities that paralleled the amount of irEGF in the trypsin-digested CRM fraction, suggesting that the membrane-associated irEGF is the predominant form detected by this technique. Regenerative hyperplasia subsequent to tubular insult was monitored by immunostaining nuclei of S phase cells after pulse labeling with the thymidine analogue 5-bromo-2'-deoxyuridine. Cell proliferation was particularly prominent in the outer stripe of outer medulla of kidneys exposed to ischemia and reached a maximum (19-fold higher than the baseline value) 48 h after reperfusion. Renal cell turnover returned to control values by day 7. The observation that the peak in soluble EGF levels (24 h) precedes the peak in tubular regeneration (48 h) by 24 h is consistent with the hypothesis that EGF is one of the mitogenic

  9. The experimental study on bowel ischemia in closed loop obstruction by using multi-phase spiral CT

    International Nuclear Information System (INIS)

    Zhang Xiaoming; Yang Hanfeng; Huang Xiaohua; Tang Xianying; Jian Pu; Yang Zhengwei; Zhou Jiyong; Zhao Zongwen

    2005-01-01

    Objective: To evaluate the bowel ischemia in experimental closed loop obstruction by using multi-phase spiral CT. Methods: Twenty-four New Zealand rabbits of both sexes (mean age, 4 months, and mean body weight, 2.5-3.0 kg) were divided randomly into three groups with each group containing 8 rabbits. After clamping 10-15 cm segments of small bowel and their veins for 0.5 hours (Group A), 1-2 hours (Group B), and 3-5 hours (Group C), respectively, multi-phase spiral CT was performed at baseline, and at arterial, venous, and delayed phases after intravenous contrast administration. Then the rabbits were sacrificed to observe their surgical and histological changes. Two radiologists, blinded to the animal model classification and their histological results, individually reviewed the CT images to observe the CT appearances of the closed loop. Statistical significance criteria was determined by P 0.05) at baseline, however, they were significantly different (P<0.05) at all phases after enhancement. Among rabbits without necrotic closed loop, 11 of 13 had continuous enhancement at all phases, while only 1 of 11 rabbits with necrotic closed loop showed continuous enhancement (P<0.05). Conclusion: The ischemia of bowel wall in different phases after clamping small bowel and their veins can be evaluated by using enhanced multi-phase spiral CT. Continuous enhancement of bowel wall in multi-phase spiral CT can be seen prominently in the early bowel ischemia, but necrotic bowel shows no enhancement. (authors)

  10. [Characteristics of antiischemic and nootropic properties of ademol in a rat model of acute brain ischemia].

    Science.gov (United States)

    Khodakivs'kyĭ, O A

    2013-01-01

    In experiments with the rat model of acute disorder of encephalic circulation (bilateral carotid occlusion) it was found that introduction of derivate of adamantan 1-adamantiloxy-3-morfolino-2 propanol (under conventional name ademol) in the dose 2 mg/kg intraabdominal in treatment regimen (in an hour after reconstruction of insult and further 1 time every 24 hours during 21 days) was accompanied by a recovery of mnemotropic properties and is more effective than cytikolin, resulting in a decreased lethality and neurological deficiency in acute and recovery periods of insults. The data received proved the usefulness of development of ademol based cerebroprotective remedy.

  11. Acute torsion and ischemia of the appendix in a young child

    Directory of Open Access Journals (Sweden)

    Dhruvin H. Hirpara

    2018-04-01

    Full Text Available Torsion of the vermiform appendix is a rare diagnosis; its clinical and radiographic presentation can mimic that of acute appendicitis. We report the case of a two-year-old boy presenting with a one day history of lower abdominal pain and serial ultrasound examinations suspicious for atypical acute appendicitis. Operative findings revealed a necrotic and engorged appendix with a 720° clockwise torsion at its base. Final pathology was consistent with ischemic necrosis in the setting of lymphoid hyperplasia. A brief update on the current body of literature regarding pediatric torsion of the vermiform appendix is provided. Keywords: Appendicitis, Volvulus, Torsion

  12. Acute myocardial ischemia: magnetic resonance contrast enhancement with gadolinium-DTPA

    International Nuclear Information System (INIS)

    McNamara, M.T.; Higgins, C.B.; Ehman, R.L.; Revel, D.; Sievers, R.; Brasch, R.C.

    1984-01-01

    Gadolinium-DTPA (Gd-DTPA) was used to improve the diagnostic utility of magnetic resonance (MR) in detecting early ischemia, before the onset of infarction. Following one minute of left anterior descending coronary artery occlusion, 9 dogs were intraveneously injected with either 0.5 mM/kg of Gd-DTPA (6 dogs) or normal saline (3 dogs). There was no visible difference in intensity or alterations in magnetic relaxation times between normal and ischemic myocardium in the control (saline-injected) animals. The Gd-DTPA-injected dogs had a well-defined segment of high intensity representing the ischemic myocardium in the anterior wall of the left ventricle. Both T1 and T2 were significantly shortened in the normal myocardium of the Gd-DTPA animals, but relatively greater T2 relaxation rate enhancement resulted in reduced intensity of normal myocardium, thus increasing contrast with ischemic myocardium. It is concluded that Gd-DTPA has the potential to expand the sensitivity and diagnostic utility of MR in the study of occlusive coronary artery disease

  13. Surgical treatment of cerebral ischemia by means of diode laser: first experimental results and comparison with theoretical model

    Science.gov (United States)

    Signorelli, C. D.; Giaquinta, A.; Iofrida, G.; Donato, G.; Signorelli, Fr.; Bellecci, C.; Lo Feudo, T.; Gaudio, P.; Gelfusa, M.

    2007-07-01

    In the present paper feasibility and potential advantages of using diode laser for surgical treatment of cerebral ischemia and intracranial aneurysms will be evaluated. At this purpose non linear mathematical model was developed and experimentally validated to investigate the effects of the changes in tissue physical properties, in terms of operating time, tensile strength and tissue damage during medical laser application. The numerical simulations have been carried on by a finite-elements based software package (FEMLAB). In vitro results of human saphenous veins of inferior limbs (n=55) after 799 nm diode laser soldering, combined with an indocyanine green-enhanced, will be presented. The simulations results and their comparison with experimental measurements will be reported.

  14. Effects of Ascorbic Acid, Alpha-Tocopherol and Allopurinol on Ischemia-Reperfusion Injury in Rabbit Skeletal Muscle: An Experimental Study

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    Bilgehan Erkut

    2007-01-01

    Full Text Available Purpose Ischemia reperfusion injury to skeletal muscle, following an acute arterial occlusion is important cause of morbidity and mortality. The aim of the present study was to determine and evaluate the effects of ascorbic acide, alpha-tocopherol and allopurinol on ischemia reperfusion injury in rabbit skeletal muscle. Methods Forty-eight New Zealand white rabbits, all male, weighing between 2.5 to 3.0 (mean 2.8 kg, were used in the study. They were separated into four groups. Group I was the control group without any drugs. The other groups were treatment groups (groups II, III, and IV. Group II rabbits administrated 50 mg/kg ascorbic acide and 100 mg/kg alpha-tocopherol 3 days prior to ischemia, group III rabbits received 50 mg/kg allopurinol 2 days prior to ischemia, and group IV rabbits were administrated both 50 mg/kg ascorbic acide, 100 mg/kg alpha-tocopherol 3 days prior to ischemia and 50 mg/kg allopurinol 2 days prior to ischemia. Two hours ischemia and 2 hours reperfusion were underwent to the treatment groups. At the end of the reperfusion periods, muscle samples were taken from rectus femoris muscle for determination of superoxide dismutase, catalase and glutathione peroxidase activities as antioxidant enzymes, and malondialdehyde as an indicator of lipid peroxidation and xanthine oxidase levels as source hydroxyl radical. Besides, histopathological changes (edema, inflammation, ring formation and splitting formation were evaluated in the muscle specimens. Results In the treatment groups; superoxide dismutase (U/mgprotein, catalase (U/mgprotein, and glutathione peroxidase (U/mgprotein levels increased, malondialdehyde (nmol/mgprotein and xanthine oksidase (mU/mgprotein levels decreased compared to control I ( p < 0.05. Increase of superoxide dismutase, catalase, and glutathione peroxidase levels were the highest and decrease of malondialdehyde and xanthine oxidase levels were the highest in group IV compared to groups II and III

  15. Effects of Ascorbic Acid, Alpha-Tocopherol and Allopurinol on Ischemia-Reperfusion Injury in Rabbit Skeletal Muscle: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Bilgehan Erkut

    2007-01-01

    Full Text Available Purpose: Ischemia reperfusion injury to skeletal muscle, following an acute arterial occlusion is important cause of morbidity and mortality. The aim of the present study was to determine and evaluate the effects of ascorbic acide, alpha-tocopherol and allopurinol on ischemia reperfusion injury in rabbit skeletal muscle.Methods: Forty-eight New Zealand white rabbits, all male, weighing between 2.5 to 3.0 (mean 2.8 kg, were used in the study. They were separated into four groups. Group I was the control group without any drugs. The other groups were treatment groups (groups II, III, and IV. Group II rabbits administrated 50 mg/kg ascorbic acide and 100 mg/kg alpha-tocopherol 3 days prior to ischemia, group III rabbits received 50 mg/kg allopurinol 2 days prior to ischemia, and group IV rabbits were administrated both 50 mg/kg ascorbic acide, 100 mg/kg alpha-tocopherol 3 days prior to ischemia and 50 mg/kg allopurinol 2 days prior to ischemia. Two hours ischemia and 2 hours reperfusion were underwent to the treatment groups. At the end of the reperfusion periods, muscle samples were taken from rectus femoris muscle for determination of superoxide dismutase, catalase and glutathione peroxidase activities as antioxidant enzymes, and malondialdehyde as an indicator of lipid peroxidation and xanthine oxidase levels as source hydroxyl radical. Besides, histopathological changes (edema, inflammation, ring formation and splitting formation were evaluated in the muscle specimens. Results: In the treatment groups; superoxide dismutase (U/mgprotein, catalase (U/mgprotein, and glutathione peroxidise (U/mgprotein levels increased, malondialdehyde (nmol/mgprotein and xanthine oksidase (mU/mgprotein levels decreased compared to control I (p < 0.05. Increase of superoxide dismutase, catalase, and glutathione peroxidase levels were the highest and decrease of malondialdehyde and xanthine oxidase levels were the highest in group IV compared to groups II and III

  16. High Homocysteine and Blood Pressure Related to Poor Outcome of Acute Ischemia Stroke in Chinese Population

    Science.gov (United States)

    Liu, Changjiang; Zhao, Liang; Zhou, Mo; Sun, Wenjie; Xu, Tan; Tong, Weijun

    2014-01-01

    Objectives To assess the association between plasma homocysteine (Hcy), blood pressure (BP) and poor outcome at hospital discharge among acute ischemic stroke patients, and if high Hcy increases the risk of poor outcome based on high BP status in a northern Chinese population. Methods Between June 1, 2009 and May 31, 2013, a total of 3695 acute ischemic stroke patients were recruited from three hospitals in northern Chinese cities. Demographic characteristics, lifestyle risk factors, medical history, and other clinical characteristics were recorded for all subjects. Poor outcome was defined as a discharge modified Rankin Scale (mRS) score ≥3 or death. The association between homocysteine concentration, admission blood pressure, and risk of poor outcome following acute ischemic stroke was analyzed by using multivariate non-conditional logistic regression models. Results Compared with those in the lowest quartile of Hcy concentration in a multivariate-adjusted model, those in the highest quartile of Hcy concentration had increased risk of poor outcome after acute ischemic stroke, (OR = 1.33, P<0.05). The dose-response relationship between Hcy concentration and risk of poor outcome was statistically significant (p-value for trend  = 0.027). High BP was significantly associated with poor outcome following acute ischemic stroke (adjusted OR = 1.44, 95%CI, 1.19–1.74). Compared with non-high BP with nhHcy, in a multivariate-adjusted model, the ORs (95% CI) of non-high BP with hHcy, high BP with nhHcy, and high BP with hHcy to poor outcome were 1.14 (0.85–1.53), 1.37 (1.03–1.84) and 1.70 (1.29–2.34), respectively. Conclusion The present study suggested that high plasma Hcy and blood pressure were independent risk factors for prognosis of acute ischemic stroke, and hHcy may further increase the risk of poor outcome among patients with high blood pressure. Additionally, the results indicate that high Hcy with high BP may cause increased susceptibility

  17. Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

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    Shuai Hou

    2016-05-01

    Full Text Available We observed mitochondrial connexin43 (mtCx43 expression under cerebral ischemia-reperfusion (I/R injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO. Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD activity and malondialdehyde (MDA content. MtCx43, p-mtCx43, protein kinase C (PKC, and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX and diazoxide (DZX groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.

  18. Carbon monoxide-Releasing Molecule-2 (CORM-2 attenuates acute hepatic ischemia reperfusion injury in rats

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    Zhang Weihui

    2010-05-01

    Full Text Available Abstract Background Hepatic ischemia-reperfusion injury (I/Ri is a serious complication occurring during liver surgery that may lead to liver failure. Hepatic I/Ri induces formation of reactive oxygen species, hepatocyte apoptosis, and release of pro-inflammatory cytokines, which together causes liver damage and organ dysfunction. A potential strategy to alleviate hepatic I/Ri is to exploit the potent anti-inflammatory and cytoprotective effects of carbon monoxide (CO by application of so-called CO-releasing molecules (CORMs. Here, we assessed whether CO released from CORM-2 protects against hepatic I/Ri in a rat model. Methods Forty male Wistar rats were randomly assigned into four groups (n = 10. Sham group underwent a sham operation and received saline. I/R group underwent hepatic I/R procedure by partial clamping of portal structures to the left and median lobes with a microvascular clip for 60 minutes, yielding ~70% hepatic ischemia and subsequently received saline. CORM-2 group underwent the same procedure and received 8 mg/kg of CORM-2 at time of reperfusion. iCORM-2 group underwent the same procedure and received iCORM-2 (8 mg/kg, which does not release CO. Therapeutic effects of CORM-2 on hepatic I/Ri was assessed by measuring serum damage markers AST and ALT, liver histology score, TUNEL-scoring of apoptotic cells, NFkB-activity in nuclear liver extracts, serum levels of pro-inflammatory cytokines TNF-α and IL-6, and hepatic neutrophil infiltration. Results A single systemic infusion with CORM-2 protected the liver from I/Ri as evidenced by a reduction in serum AST/ALT levels and an improved liver histology score. Treatment with CORM-2 also up-regulated expression of the anti-apoptotic protein Bcl-2, down-regulated caspase-3 activation, and significantly reduced the levels of apoptosis after I/Ri. Furthermore, treatment with CORM-2 significantly inhibited the activity of the pro-inflammatory transcription factor NF-κB as measured in

  19. T1-mapping for assessment of ischemia-induced acute kidney injury and prediction of chronic kidney disease in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hueper, Katja; Gutberlet, Marcel; Wacker, Frank; Hartung, Dagmar [Hannover Medical School, Department of Radiology, Hannover (Germany); Hannover Medical School, REBIRTH Cluster of Excellence, Hannover (Germany); Peperhove, Matti; Tewes, Susanne; Barrmeyer, Amelie [Hannover Medical School, Department of Radiology, Hannover (Germany); Rong, Song [Hannover Medical School, Department of Nephrology, Hannover (Germany); Zunyi Medical College, Laboratory of Organ Transplantation, Zunyi (China); Gerstenberg, Jessica; Haller, Herman; Gueler, Faikah [Hannover Medical School, Department of Nephrology, Hannover (Germany); Mengel, Michael [University of Alberta, Department of Laboratory Medicine and Pathology, Edmonton (Canada); Meier, Martin [Hannover Medical School, REBIRTH Cluster of Excellence, Hannover (Germany); Hannover Medical School, Institute for Animal Science, Hannover (Germany); Chen, Rongjun [Hannover Medical School, Department of Nephrology, Hannover (Germany); Zhejiang University, The Kidney Disease Center of the First Affiliated Hospital, Hangzhou (China)

    2014-09-15

    To investigate whether T1-mapping allows assessment of acute kidney injury (AKI) and prediction of chronic kidney disease (CKD) in mice. AKI was induced in C57Bl/6N mice by clamping of the right renal pedicle for 35 min (moderate AKI, n = 26) or 45 min (severe AKI, n = 23). Sham animals served as controls (n = 9). Renal histology was assessed in the acute (day 1 + day 7; d1 + d7) and chronic phase (d28) after AKI. Furthermore, longitudinal MRI-examinations (prior to until d28 after surgery) were performed using a 7-Tesla magnet. T1-maps were calculated from a fat-saturated echoplanar inversion recovery sequence, and mean and relative T1-relaxation times were determined. Renal histology showed severe tubular injury at d1 + d7 in both AKI groups, whereas, at d28, only animals with prolonged 45-min ischemia showed persistent signs of AKI. Following both AKI severities T1-values significantly increased and peaked at d7. T1-times in the contralateral kidney without AKI remained stable. At d7 relative T1-values in the outer stripe of the outer medulla were significantly higher after severe than after moderate AKI (138 ± 2 % vs. 121 ± 3 %, p = 0.001). T1-elevation persisted until d28 only after severe AKI. Already at d7 T1 in the outer stripe of the outer medulla correlated with kidney volume loss indicating CKD (r = 0.83). T1-mapping non-invasively detects AKI severity in mice and predicts further outcome. (orig.)

  20. T1-mapping for assessment of ischemia-induced acute kidney injury and prediction of chronic kidney disease in mice

    International Nuclear Information System (INIS)

    Hueper, Katja; Gutberlet, Marcel; Wacker, Frank; Hartung, Dagmar; Peperhove, Matti; Tewes, Susanne; Barrmeyer, Amelie; Rong, Song; Gerstenberg, Jessica; Haller, Herman; Gueler, Faikah; Mengel, Michael; Meier, Martin; Chen, Rongjun

    2014-01-01

    To investigate whether T1-mapping allows assessment of acute kidney injury (AKI) and prediction of chronic kidney disease (CKD) in mice. AKI was induced in C57Bl/6N mice by clamping of the right renal pedicle for 35 min (moderate AKI, n = 26) or 45 min (severe AKI, n = 23). Sham animals served as controls (n = 9). Renal histology was assessed in the acute (day 1 + day 7; d1 + d7) and chronic phase (d28) after AKI. Furthermore, longitudinal MRI-examinations (prior to until d28 after surgery) were performed using a 7-Tesla magnet. T1-maps were calculated from a fat-saturated echoplanar inversion recovery sequence, and mean and relative T1-relaxation times were determined. Renal histology showed severe tubular injury at d1 + d7 in both AKI groups, whereas, at d28, only animals with prolonged 45-min ischemia showed persistent signs of AKI. Following both AKI severities T1-values significantly increased and peaked at d7. T1-times in the contralateral kidney without AKI remained stable. At d7 relative T1-values in the outer stripe of the outer medulla were significantly higher after severe than after moderate AKI (138 ± 2 % vs. 121 ± 3 %, p = 0.001). T1-elevation persisted until d28 only after severe AKI. Already at d7 T1 in the outer stripe of the outer medulla correlated with kidney volume loss indicating CKD (r = 0.83). T1-mapping non-invasively detects AKI severity in mice and predicts further outcome. (orig.)

  1. Changes in metabolic profiles during acute kidney injury and recovery following ischemia/reperfusion.

    Science.gov (United States)

    Wei, Qingqing; Xiao, Xiao; Fogle, Paul; Dong, Zheng

    2014-01-01

    Changes of metabolism have been implicated in renal ischemia/reperfusion injury (IRI). However, a global analysis of the metabolic changes in renal IRI is lacking and the association of the changes with ischemic kidney injury and subsequent recovery are unclear. In this study, mice were subjected to 25 minutes of bilateral renal IRI followed by 2 hours to 7 days of reperfusion. Kidney injury and subsequent recovery was verified by serum creatinine and blood urea nitrogen measurements. The metabolome of plasma, kidney cortex, and medulla were profiled by the newly developed global metabolomics analysis. Renal IRI induced overall changes of the metabolome in plasma and kidney tissues. The changes started in renal cortex, followed by medulla and plasma. In addition, we identified specific metabolites that may contribute to early renal injury response, perturbed energy metabolism, impaired purine metabolism, impacted osmotic regulation and the induction of inflammation. Some metabolites, such as 3-indoxyl sulfate, were induced at the earliest time point of renal IRI, suggesting the potential of being used as diagnostic biomarkers. There was a notable switch of energy source from glucose to lipids, implicating the importance of appropriate nutrition supply during treatment. In addition, we detected the depressed polyols for osmotic regulation which may contribute to the loss of kidney function. Several pathways involved in inflammation regulation were also induced. Finally, there was a late induction of prostaglandins, suggesting their possible involvement in kidney recovery. In conclusion, this study demonstrates significant changes of metabolome kidney tissues and plasma in renal IRI. The changes in specific metabolites are associated with and may contribute to early injury, shift of energy source, inflammation, and late phase kidney recovery.

  2. Acute Ischemia Induced by High-Density Culture Increases Cytokine Expression and Diminishes the Function and Viability of Highly Purified Human Islets of Langerhans.

    Science.gov (United States)

    Smith, Kate E; Kelly, Amy C; Min, Catherine G; Weber, Craig S; McCarthy, Fiona M; Steyn, Leah V; Badarinarayana, Vasudeo; Stanton, J Brett; Kitzmann, Jennifer P; Strop, Peter; Gruessner, Angelika C; Lynch, Ronald M; Limesand, Sean W; Papas, Klearchos K

    2017-11-01

    Encapsulation devices have the potential to enable cell-based insulin replacement therapies (such as human islet or stem cell-derived β cell transplantation) without immunosuppression. However, reasonably sized encapsulation devices promote ischemia due to high β cell densities creating prohibitively large diffusional distances for nutrients. It is hypothesized that even acute ischemic exposure will compromise the therapeutic potential of cell-based insulin replacement. In this study, the acute effects of high-density ischemia were investigated in human islets to develop a detailed profile of early ischemia induced changes and targets for intervention. Human islets were exposed in a pairwise model simulating high-density encapsulation to normoxic or ischemic culture for 12 hours, after which viability and function were measured. RNA sequencing was conducted to assess transcriptome-wide changes in gene expression. Islet viability after acute ischemic exposure was reduced compared to normoxic culture conditions (P < 0.01). Insulin secretion was also diminished, with ischemic β cells losing their insulin secretory response to stimulatory glucose levels (P < 0.01). RNA sequencing revealed 657 differentially expressed genes following ischemia, with many that are associated with increased inflammatory and hypoxia-response signaling and decreased nutrient transport and metabolism. In order for cell-based insulin replacement to be applied as a treatment for type 1 diabetes, oxygen and nutrient delivery to β cells will need to be maintained. We demonstrate that even brief ischemic exposure such as would be experienced in encapsulation devices damages islet viability and β cell function and leads to increased inflammatory signaling.

  3. Acute mesenteric ischemia and duodenal ulcer perforation: a unique double pathology

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    Haruna Lois

    2012-10-01

    Full Text Available Abstract Background Acute mesenteric ischaemia and duodenal perforation are surgical emergencies with serious consequences. Patients presenting with acute mesenteric ischaemia alone face a high mortality rate as high as 60% whereas those presenting with peptic ulcer perforation the mortality rates range from 6-14%. There are very few reported cases of patients presenting with this dual pathology. Case presentation We report a unique case of a 53 year old Italian lady who presented with acute mesenteric ischaemia and duodenal perforation. This is the first report of massive bowel ischaemia and duodenal perforation with no apparent underlying common pathophysiology leading to this presentation. Conclusion Early management in the intensive care unit and appropriate surgical intervention maximised the patient’s chances of survival despite the poor prognosis associated with her dual pathology. The rare pathology of the patient described can be explained by two possible hypotheses: peptic ulcer disease causing duodenal ulceration, which precipitated ischaemic infarction of the small bowel. The second hypothesis is the patient developed a stress related ulcer following ischaemic bowel infarction secondary to arterial thrombosis.

  4. Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

    DEFF Research Database (Denmark)

    Inácio, Ana R; Liu, Yawei; Clausen, Bettina H

    2015-01-01

    of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation......BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death...... strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. RESULTS: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number...

  5. Independent cellular effects of cold ischemia and reperfusion: experimental molecular study.

    Science.gov (United States)

    Lledó-García, E; Humanes-Sánchez, B; Mojena-Sánchez, M; Rodrígez, J C J; Hernández-Fernández, C; Tejedor-Jorge, A; Fernández, A L

    2013-04-01

    There is less information available on cell cultures on the exclusive effects of either duration of cold ischemia (CI) or rewarming-reperfusion in the kidney subjected to initial warm ischemia (WI). Therefore, the goals of our work were: (1) to evaluate the consequences on tubular cellular viability of different durations of CI on a kidney after an initial period of WI, and (2) to analyze the additional effect on tubular cell viability of rewarming of the same kidney. Sixteen mini-pig were used. All the animals were performed a right nephrectomy after 45-minute occlusion of the vascular pedicle. The kidneys were then divided into 2 groups (phase 1): cold storage in university of wisconsin (UW) solution for 3 hours (group A, n = 8) at 4°C, or cold storage in UW for 12 hours (group B, n = 8) at 4°C. Four organs of group A and four organs of group B were autotrasplanted (AT) and reperfused for 1 hour (phase 2). Nephrectomy was finally done. Biopsies were taken from all groups to perform cultures of proximal tubule epithelium cells. The biopsies were subjected to studies of cellular morphological viability (contrast phase microscopy [CPM]) and quantitative (confluence cell [CC]) parameters. Phase of pure CI effects (phase 1): Both CC rate and CPM parameters were significantly lower in group B compared with group A, where cell activity reached almost normal results. Phase of CI + AT (phase 2): At produced additional harmful effects in cell cultures compared with those obtained in phase 1, more evident in group B cells. The presence of cold storage followed by rewarming-reperfusion induces independent and cumulative detrimental effects in viability of renal proximal tubule cells. CI periods ≤ 3 hours may ameliorate the injuries secondary to reperfusion in comparison with longer CI periods. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Clinical manifestation as acute coronary syndrome without electrocardiographically ischemia: a clue for aortic dissection

    Directory of Open Access Journals (Sweden)

    Hung Yi Chen

    2015-06-01

    Full Text Available Aortic dissection is a critical condition requiring immediate assessment and management. Clinical presentation is commonly associated with severe chest pain and high blood pressure. However, misdiagnosis is frequent because of various features. We presented a case of 51-year-old woman who complained of dyspnea for 3 d after she experienced back pain for one week. She was presented with severe respiration distress with impending respiration failure on arrival to our hospital. Her chest X-ray showed cardiomegaly with acute pulmonary edema. The laboratory data revealed elevated cardiac enzyme and electrocardiography demonstrated sinus tachycardia. She was hospitalized under the initial diagnosis of acute coronary syndrome. The patient remained hemodynamically stable, and experienced one episode of chest discomfort. After electrocardiography, she was found with bigeminy ventricular premature beats without ST-T change. Follow-up cardiac enzyme demonstrated progressive declined. Cardiac catheterization was performed on the third day of admission, and coronary angiography revealed large intimal flap on aortic root with bilateral coronary artery involvement. Surgical management was arranged after immediate chest computed tomography study.

  7. Evaluation of the Effects of Atorvastatin and Ischemic Postconditioning Preventing on the Ischemia and Reperfusion Injury: Experimental Study in Rats

    Directory of Open Access Journals (Sweden)

    Henrique Budib Dorsa Pontes

    Full Text Available Abstract Introduction: Reperfusion injury leads to systemic morphological and functional pathological alterations. Some techniques are already estabilished to attenuate the damage induced by reperfusion. Ischemic preconditioning is one of the standard procedures. In the last 20 years, several experimental trials demonstrated that the ischemic postconditioning presents similar effectiveness. Recently experimental trials demonstrated that statins could be used as pharmacological preconditioning. Methods: 41 Wistar rats (Rattus norvegicus albinus were distributed in 5 groups: Ischemia and Reperfusion (A, Ischemic Postconditioning (B, Statin (C, Ischemic Postconditioning + Statins (D and SHAM (E. After euthanasia, lungs, liver, kidneys and ileum were resected and submitted to histopathological analysis. Results: The average of lung parenchymal injury was A=3.6, B=1.6, C=1.2, D=1.2, E=1 (P=0.0029. The average of liver parenchymal injury was A=3, B=1.5, C=1.2, D=1.2, E = 0 (P<0.0001. The average of renal parenchymal injury was A=4, B=2.44, C=1.22, D=1.11, E=1 (P<0.0001. The average of intestinal parenchymal injury was A=2, B=0.66, C=0, D=0, E=0 (P=0.0006. The results were submitted to statistics applying Kruskal-Wallis test, estabilishing level of significance P<0.05. Conclusion: Groups submitted to ischemic postconditioning, to pre-treatment with statins and both methods associated demonstrated less remote reperfusion injuries, compared to the group submitted to ischemia and reperfusion without protection.

  8. Local fibrinolytic therapy for patients with cerebral embolism and reversibility of cerebral ischemia in ultra-acute stage

    International Nuclear Information System (INIS)

    Koizumi, Takayuki

    1993-01-01

    The present study was undertaken to determine candidates for fibrinolytic therapy in cerebral embolism. Forty-three patients were examined by single photon emission computed tomography (SPECT) using 99m c-d, hexamethyl-propylene-amine oxime (HM-PAO) or N-isopropyl p[ 123 I]-iodoamphetamine ( 123 I-IMP) just before and after intra-arterial local fibrinolytic therapy. Regional cerebellar ratio (R/Ce) and asymmetry index (AI) were calculated just before the treatment (n=9). Quantitative analysis was performed after the treatment (n=all). SPECT images taken within 24 hours after the treatment fell into three patters: normal perfusion, hypoperfusion, and hyperperfusion. Patients showing normal perfusion pattern after complete recanalization developed no or smaller infarction on CT scans. However, patients showing either hypoperfusion or hyperperfusion developed large infarction. Regions with R/Ce ratio of 0.3 or smaller and/or AI of 1.5 or greater were irreversible, which was associated with cerebral infarction regardless of the duration of ischemia. On the other hand, regions with R/Ce of 0.5 or greater or AI of 1.2 or smaller were reversible with no association of infarction. Intra-arterial local fibrinolytic therapy seems to be helpful for patients with slight reduction of regional cerebral blood flow (i.e., R/Ce>0.5, AI 1.5). These findings indicate that SPECT is capable of determining reversibility of ischemic region, thereby contributing to better management of patients with acute cerebral embolism. (N.K.)

  9. The Use of the “Preclosure” Technique for Antegrade Aspiration Thrombectomy with Large Catheters in Acute Limb Ischemia

    International Nuclear Information System (INIS)

    Funke, C.; Pfiffner, R.; Husmann, M.; Pfammatter, T.

    2013-01-01

    This study was designed to assess retrospectively short- and mid-term outcomes of the use of a suture-mediated closure device to close the antegrade access in patients undergoing percutaneous aspiration thrombectomy with large catheters for acute leg ischemia. Between November 2005 and February 2010, a suture-mediated active closure system (ProGlide ® 6F, Abbott) was placed before arterial sheath (mean 9 F, range 6–12 F) introduction in 101 patients (74 men, 73 %, mean age 70.1 ± 12.6 years standard deviation). Data regarding mortality, complications, and factors contributing to vascular complications at the access site was collected for 6 month after the intervention to detect device-related problems. As a coincidence, 77 patients had follow-up visits for a duplex ultrasound. There were a total of 19 vascular complications (19 %) at the puncture site, all of which were of hemorrhagic nature and none of which consisted of vessel occlusion. Two major outcome complications (2 %) occurred. A retroperitoneal hematoma and a serious inguinal bleeding required additive treatment and did not result in permanent sequelae. Nine cases involved death of which eight were not attributable to the closure and one remained unclear. Successful closure was achieved in 95 patients (94 %); additional manual compression was sufficient in the majority of the remaining patients. Numerous factors contributing to vascular complications were encountered. With acceptable short- and mid-term outcomes, the “preclose” technique can be a reliable option for the closure of a large antegrade femoral access even for patients at a high risk of vascular complications, such as those undergoing aspiration thrombectomy.

  10. The Use of the 'Preclosure' Technique for Antegrade Aspiration Thrombectomy with Large Catheters in Acute Limb Ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Funke, C., E-mail: claas_funke@hotmail.com; Pfiffner, R. [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology (Switzerland); Husmann, M. [University Hospital Zurich, Clinic of Angiology (Switzerland); Pfammatter, T. [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology (Switzerland)

    2013-04-15

    This study was designed to assess retrospectively short- and mid-term outcomes of the use of a suture-mediated closure device to close the antegrade access in patients undergoing percutaneous aspiration thrombectomy with large catheters for acute leg ischemia. Between November 2005 and February 2010, a suture-mediated active closure system (ProGlide{sup Registered-Sign} 6F, Abbott) was placed before arterial sheath (mean 9 F, range 6-12 F) introduction in 101 patients (74 men, 73 %, mean age 70.1 {+-} 12.6 years standard deviation). Data regarding mortality, complications, and factors contributing to vascular complications at the access site was collected for 6 month after the intervention to detect device-related problems. As a coincidence, 77 patients had follow-up visits for a duplex ultrasound. There were a total of 19 vascular complications (19 %) at the puncture site, all of which were of hemorrhagic nature and none of which consisted of vessel occlusion. Two major outcome complications (2 %) occurred. A retroperitoneal hematoma and a serious inguinal bleeding required additive treatment and did not result in permanent sequelae. Nine cases involved death of which eight were not attributable to the closure and one remained unclear. Successful closure was achieved in 95 patients (94 %); additional manual compression was sufficient in the majority of the remaining patients. Numerous factors contributing to vascular complications were encountered. With acceptable short- and mid-term outcomes, the 'preclose' technique can be a reliable option for the closure of a large antegrade femoral access even for patients at a high risk of vascular complications, such as those undergoing aspiration thrombectomy.

  11. A single intracoronary injection of midkine reduces ischemia/reperfusion injury in swine hearts: a novel therapeutic approach for acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Hisaaki eIshiguro

    2011-06-01

    Full Text Available Several growth factors are effective for salvaging myocardium and limiting infarct size in experimental studies with small animals. Their benefit in large animals and feasibility in clinical practice remains to be elucidated. We investigate the cardioprotective effect of midkine (MK in swine subjected to ischemia/reperfusion (I/R. I/R was created in swine by left anterior descending coronary artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter. MK protein was injected as a bolus through the catheter at the initiation of reperfusion (midkine injected group; MKT. Saline was injected in controls (CONT. Survival rate 24h after I/R was significantly higher in MKT than in CONT, whereas infarct size/area at risk was almost 5 times smaller. Echocardiography in MKT revealed a significantly higher percent wall thickening of the interventricular septum, a higher % fractional shortening and a lower E/e’ compared with CONT. LV catheterization in MKT showed a lower LVEDP, and a higher dP/dtmax compared with CONT. TUNEL-positive myocytes and CD45-positive cell infiltration in the peri-infarct area were significantly less in MKT than in CONT. Here, we showed that a single intracoronary injection of MK protein in swine hearts at the onset of reperfusion dramatically reduces infarct size and mortality and ameliorates systolic/diastolic LV function. This beneficial effect is associated with a reduction of apoptotic and inflammatory reactions. MK application during percutaneous coronary intervention may become a promising adjunctive therapy in acute coronary syndromes.

  12. Manipulations of core temperatures in ischemia-reperfusion lung injury in rabbits.

    Science.gov (United States)

    Chang, Hung; Huang, Kun-Lun; Li, Min-Hui; Hsu, Ching-Wang; Tsai, Shih-Hung; Chu, Shi-Jye

    2008-01-01

    The present study was designed to determine the effect of various core temperatures on acute lung injury induced by ischemia-reperfusion (I/R) in our isolated rabbit lung model. Typical acute lung injury was successfully induced by 30 min of ischemia followed by 90 min of reperfusion observation. The I/R elicited a significant increase in pulmonary arterial pressure, microvascular permeability (measured by using the capillary filtration coefficient, Kfc), Delta Kfc ratio, lung weight gain and the protein concentration of the bronchoalveolar lavage fluid. Mild hypothermia significantly attenuated acute lung injury induced by I/R, all parameters having decreased significantly (p<0.05); conversely, mild hyperthermia did not further exacerbate acute lung injury. These experimental data suggest that mild hypothermia significantly ameliorated acute lung injury induced by ischemia-reperfusion in rabbits.

  13. Algorithm for the automatic computation of the modified Anderson-Wilkins acuteness score of ischemia from the pre-hospital ECG in ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Fakhri, Yama; Sejersten-Ripa, Maria; Schoos, Mikkel Malby

    2017-01-01

    BACKGROUND: The acuteness score (based on the modified Anderson-Wilkins score) estimates the acuteness of ischemia based on ST-segment, Q-wave and T-wave measurements obtained from the electrocardiogram (ECG) in patients with ST Elevation Myocardial Infarction (STEMI). The score (range 1 (least...... the acuteness score. METHODS: We scored 50 pre-hospital ECGs from STEMI patients, manually and by the automated algorithm. We assessed the reliability test between the manual and automated algorithm by interclass correlation coefficient (ICC) and Bland-Altman plot. RESULTS: The ICC was 0.84 (95% CI 0.......72-0.91), PECGs, all within the upper (1.46) and lower (-1.12) limits...

  14. Experimental models of hepatotoxicity related to acute liver failure

    Energy Technology Data Exchange (ETDEWEB)

    Maes, Michaël [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Vinken, Mathieu, E-mail: mvinken@vub.ac.be [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Jaeschke, Hartmut [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City (United States)

    2016-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. - Highlights: • The murine APAP model is very close to what is observed in patients. • The Gal/ET model is useful to study TNFα-mediated apoptotic signaling mechanisms. • Fas receptor activation is an effective model of apoptosis and secondary necrosis. • The ConA model is a relevant model of auto-immune hepatitis and viral hepatitis. • Multiple time point evaluation needed in experimental models of acute liver injury.

  15. Radial forearm free flap morbidity: A rare case of a normal preoperative arteriogram and acute intraoperative hand ischemia

    OpenAIRE

    Bruner, Terrence W; Hanasono, Matthew M; Skoracki, Roman J

    2011-01-01

    The radial forearm free flap is ideal for reconstructive microsurgery due to its thin, pliable fasciocutaneous tissue, reliable anatomy and ease and simplicity of flap elevation. However, one of the major complications is hand ischemia due to sacrifice of the radial artery, although it is a rare occurrence. A case involving a 73-year-old man who developed intraoperative hand ischemia after elevation of a radial forearm free flap is presented.

  16. Musculus gastrocnemius tetanus kinetics in alcohol-intoxicated rats with experimentally-induced hindlimb vascular ischemia under conditions of low-frequence muscle fatigue

    Directory of Open Access Journals (Sweden)

    O. A. Melnychuk

    2014-04-01

    Full Text Available Alcohol intoxication and ischemic injury of skeletal muscles often accompany each other. It is shown that patients hospitalized with chronic alcoholism develop muscle fatigue. Skeletal muscle dysfunction in alcohol-dependent patients is caused by ethanol-associated myofibrillar atrophy and metabolic disbalance, while compression-ischemic lesions result from unconsciousness of the patient, in case of taking the critical alcohol dose. Therefore, the aim of this study is to discover typical m. gastrocnemius (cap. med. tetanic kinetics changes in alcohol intoxicated rats with experimentally induced vascular ischemia of hindlimb muscles under conditions of low-frequency progressive muscle fatigue. Experiments were carried out on 10 young male Wistar rats (149.5 ± 5.8 g kept under standard vivarium conditions and diet. The investigation was conducted in two phases: chronic (30 days and acute (3 hours experiment. All surgical procedures were carried out aseptically under general anesthesia. Ishemic m. gastrocnemius (cap. med. tetanic kinetic changes and force productivity in alcohol intoxicated rats were investigated in the isometric mode, with direct electrical stimulation. The fatigue of m. gastrocnemius (cap. med. was evaluated by three characteristic criteria: the first sag effect, the secondary force rise, the second sag effect. There have been 10 similar experiments: 5 series in each study group with 10 tetanic runs in each series. The highest amplitude of the native m. gastrocnemius (cap. med. tetanus relative to isoline was taken as 100% force response. The same pattern of m. gastrocnemius (cap. med. low-frequency fatigue development was found in both rat groups under study. It is evidenced by the absence of substantial m. gastrocnemius (cap. med. tetanus kinetics differences in alcohol intoxicated rats, compared with non-alcohol intoxicated rats during fatigue test. However, the appreciable m. gastrocnemius (cap. med. tetanic force reduction

  17. Is Chronic Curcumin Supplementation Neuroprotective Against Ischemia for Antioxidant Activity, Neurological Deficit, or Neuronal Apoptosis in an Experimental Stroke Model?

    Science.gov (United States)

    Altinay, Serdar; Cabalar, Murat; Isler, Cihan; Yildirim, Funda; Celik, Duygu S; Zengi, Oguzhan; Tas, Abdurrahim; Gulcubuk, Ahmet

    2017-01-01

    To investigate the neuroprotective effect of chronic curcumin supplementation on the rat forebrain prior to ischemia and reperfusion. Forebrain ischemia was induced by bilateral common carotid artery occlusion for 1/2 hour, followed by reperfusion for 72 hours. Older rats were divided into five groups: Group I received 300 mg/kg oral curcumin for 21 days before ischemia and 300 mg/kg intraperitoneal curcumin after ischemia; Group II received 300 mg/kg intraperitoneal curcumin after ischemia; Group III received 300 mg/kg oral curcumin for 21 days before ischemia; Group IV had only ischemia; Group V was the sham-operated group. The forebrain was rapidly dissected for biochemical parameter assessment and histopathological examination. In forebrain tissue, enzyme activities of superoxide dismutase, glutathione peroxidase, and catalase were significantly higher in Group I than Groups II or III (p curcumin-treated groups compared with the ischemic group. We also found a marked reduction in apoptotic index after 72 hours in the groups receiving curcumin. Significantly more TUNEL-positive cells were observed in the ischemic group compared to those treated with curcumin. We demonstrated the neuroprotective effect of chronic curcumin supplement on biochemical parameters, neurological scores and apoptosis following ischemia and reperfusion injury in rats.

  18. Poly[ADP-ribose] polymerase-1 expression is related to cold ischemia, acute tubular necrosis, and delayed renal function in kidney transplantation.

    Directory of Open Access Journals (Sweden)

    Francisco O'Valle

    Full Text Available UNLABELLED: Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD transplantation. Ischemia-reperfusion (IR injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1 activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN. MATERIALS AND METHODS: Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls and in murine Parp-1 knockout model of IR injury. RESULTS: PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603, time to effective diuresis (r = 0.770, serum creatinine levels at biopsy (r = 0.649, and degree of ATN (r = 0.810 (p = 0.001, Pearson test. In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function.

  19. Experimental models of brain ischemia: a review of techniques, magnetic resonance imaging and investigational cell-based therapies

    Directory of Open Access Journals (Sweden)

    Alessandra eCanazza

    2014-02-01

    Full Text Available Stroke continues to be a significant cause of death and disability worldwide. Although major advances have been made in the past decades in prevention, treatment and rehabilitation, enormous challenges remain in the way of translating new therapeutic approaches from bench to bedside. Thrombolysis, while routinely used for ischemic stroke, is only a viable option within a narrow time window. Recently, progress in stem cell biology has opened up avenues to therapeutic strategies aimed at supporting and replacing neural cells in infarcted areas. Realistic experimental animal models are crucial to understand the mechanisms of neuronal survival following ischemic brain injury and to develop therapeutic interventions. Current studies on experimental stroke therapies evaluate the efficiency of neuroprotective agents and cell-based approaches using primarily rodent models of permanent or transient focal cerebral ischemia. In parallel, advancements in imaging techniques permit better mapping of the spatial-temporal evolution of the lesioned cortex and its functional responses. This review provides a condensed conceptual review of the state of the art of this field, from models and magnetic resonance imaging techniques through to stem cell therapies.

  20. Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis

    International Nuclear Information System (INIS)

    Miller, M.J.; Adams, J.; Gu, X.A.; Zhang, X.J.; Clark, D.A.

    1990-01-01

    We examined the local hemodynamic response of intestinal loops during acute necrotizing enterocolitis (NEC) in anesthetized rabbits. NEC was induced in ileal loops by transmural injection of a solution containing casein (10 mg/ml) and calcium gluconate (50 mg/ml) acidified to pH 4.0 with propionic or acetic acid. Control loops received casein only (pH 5.0). Mucosal damage was quantified by the blood-to-lumen movement of [51Cr]EDTA, fluid shifts into the lumen, and histology. Mean arterial pressure and loop blood flow were steady over the 3-hr period, loop fluid volume decreased, and there was no evidence of necrosis or epithelial damage. In loops receiving acidified casein and calcium gluconate, there was an immediate dramatic increase in loop blood flow that returned to baseline by 50 min. In addition, loop fluid volume was dramatically increased, necrosis was noted in the form of blunting and loss of villi, and sevenfold increase in [51Cr]EDTA permeability was evident. Administration of CV 1808 (30 mg/kg/hr), a selective adenosine2 agonist, which maintained and elevated loop blood flow throughout the 3 hr protocol, failed to alter the changes in loop fluid volume or prevent necrosis. Histamine levels in loop fluid levels were significantly elevated 20-30 min after NEC induction when compared to saline controls, indicating an early activation of mucosal defenses with this luminal insult. Thus, this model of NEC is characterized by a transient, acute hyperemia, increased intestinal permeability, and histamine release. As mucosal damage was independent of ischemia and could not be prevented by vasodilatory therapy, this model supports the clinical findings that NEC is correlated with luminal factors related to feeding and independent of cardiovascular stress

  1. Successful medical management of acute mesenteric ischemia due to superior mesenteric and portal vein thrombosis in a 27-year-old man with protein S deficiency: a case report.

    Science.gov (United States)

    Osti, N P; Sah, D N; Bhandari, R S

    2017-11-09

    Acute mesenteric ischemia poses a diagnostic challenge due to nonspecific clinical clues and lack of awareness owing to its rarity. Ischemia due to mesenteric venous thrombosis has a good prognosis compared to arterial cause and can be managed conservatively with early diagnosis. The portomesenteric venous system is an unusual site of thrombosis in patients with protein S deficiency, and its thrombosis is an uncommon cause of acute mesenteric ischemia. We present a case of a 27-year-old Mongolian man who presented with acute abdominal pain increasing in severity, and refractory to repeated attempts at treatment with a misdiagnosis of acute peptic ulcer disease. Contrast-enhanced computed tomography of his abdomen detected complete occlusion of the superior mesenteric vein, an extension of acute thrombus into the portal vein, and ischemic mid-jejunal loops. Early diagnosis and immediate anticoagulation with continuous intravenous infusion of unfractionated heparin prevented subsequent consequences. On further workup, our patient was diagnosed with isolated protein S deficiency. We started lifelong thromboprophylaxis with warfarin to prevent recurrence and our patient was asymptomatic on the latest follow-up 5 months after discharge. Despite accurate detection of acute mesenteric ischemia by contrast-enhanced computed tomography, high index of suspicion is indispensable for its early diagnosis. Early diagnosis and immediate anticoagulation will prevent subsequent complications and need for surgical intervention. Young patients without known risk factors presenting with venous thrombosis in atypical sites should be investigated for prothrombotic diseases.

  2. Trends in the incidence, treatment, and outcomes of acute lower extremity ischemia in the United States Medicare population.

    Science.gov (United States)

    Baril, Donald T; Ghosh, Kaushik; Rosen, Allison B

    2014-09-01

    Acute lower extremity ischemia (ALI) is a common vascular surgery emergency associated with high rates of morbidity and mortality. The purpose of this study was to assess contemporary trends in the incidence of ALI, the methods of treatment, and the associated mortality and amputation rates in the U.S. Medicare population. This was an observational study using Medicare claims data between 1998 and 2009. Outcomes examined included trends in the incidence of ALI; trends in interventions for ALI; and trends in amputation, mortality, and amputation-free survival rates. Between 1998 and 2009, the incidence of hospitalization for ALI decreased from 45.7 per 100,000 to 26.0 per 100,000 (P for trend < .001). The percentage of patients undergoing surgical intervention decreased from 57.1% to 51.6% (P for trend < .001), whereas the percentage of patients undergoing endovascular interventions increased from 15.0% to 33.1% (P for trend < .001). In-hospital mortality rates decreased from 12.0% to 9.0% (P for trend < .001), whereas 1-year mortality rates remained stable at 41.0% and 42.5% (P for trend not significant). In-hospital amputation rates remained stable at 8.1% and 6.4% (P for trend not significant), whereas 1-year amputation rates decreased from 14.8% to 11.0% (P for trend < .001). In-hospital amputation-free survival after hospitalization for ALI increased from 81.2% to 85.4% (P for trend < .001); however, 1-year amputation-free survival remained unchanged. Between 1998 and 2009, the incidence of ALI among the U.S. Medicare population declined significantly, and the percentage of patients treated with endovascular techniques markedly increased. During this time, 1-year amputation rates declined. Furthermore, although in-hospital mortality rates declined after presentation with ALI, 1-year mortality rates remained unchanged. Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  3. Effects of Remote Ischemic Conditioning Methods on Ischemia-Reperfusion Injury in Muscle Flaps: An Experimental Study in Rats

    Directory of Open Access Journals (Sweden)

    Durdane Keskin

    2017-09-01

    Full Text Available Background The aim of this study was to investigate the effects of remote ischemic conditioning on ischemia-reperfusion injury in rat muscle flaps histopathologically and biochemically. Methods Thirty albino rats were divided into 5 groups. No procedure was performed in the rats in group 1, and only blood samples were taken. A gracilis muscle flap was elevated in all the other groups. Microclamps were applied to the vascular pedicle for 4 hours in order to achieve tissue ischemia. In group 2, no additional procedure was performed. In groups 3, 4, and 5, the right hind limb was used and 3 cycles of ischemia-reperfusion for 5 minutes each (total, 30 minutes was applied with a latex tourniquet (remote ischemic conditioning. In group 3, this procedure was performed before flap elevation (remote ischemic preconditoning. In group 4, the procedure was performed 4 hours after flap ischemia (remote ischemic postconditioning. In group 5, the procedure was performed after the flap was elevated, during the muscle flap ischemia episode (remote ischemic perconditioning. Results The histopathological damage score in all remote conditioning ischemia groups was lower than in the ischemic-reperfusion group. The lowest histopathological damage score was observed in group 5 (remote ischemic perconditioning. Conclusions The nitric oxide levels were higher in the blood samples obtained from the remote ischemic perconditioning group. This study showed the effectiveness of remote ischemic conditioning procedures and compared their usefulness for preventing ischemia-reperfusion injury in muscle flaps.

  4. Effects of Remote Ischemic Conditioning Methods on Ischemia-Reperfusion Injury in Muscle Flaps: An Experimental Study in Rats.

    Science.gov (United States)

    Keskin, Durdane; Unlu, Ramazan Erkin; Orhan, Erkan; Erkilinç, Gamze; Bogdaycioglu, Nihal; Yilmaz, Fatma Meric

    2017-09-01

    The aim of this study was to investigate the effects of remote ischemic conditioning on ischemia-reperfusion injury in rat muscle flaps histopathologically and biochemically. Thirty albino rats were divided into 5 groups. No procedure was performed in the rats in group 1, and only blood samples were taken. A gracilis muscle flap was elevated in all the other groups. Microclamps were applied to the vascular pedicle for 4 hours in order to achieve tissue ischemia. In group 2, no additional procedure was performed. In groups 3, 4, and 5, the right hind limb was used and 3 cycles of ischemia-reperfusion for 5 minutes each (total, 30 minutes) was applied with a latex tourniquet (remote ischemic conditioning). In group 3, this procedure was performed before flap elevation (remote ischemic preconditoning). In group 4, the procedure was performed 4 hours after flap ischemia (remote ischemic postconditioning). In group 5, the procedure was performed after the flap was elevated, during the muscle flap ischemia episode (remote ischemic perconditioning). The histopathological damage score in all remote conditioning ischemia groups was lower than in the ischemic-reperfusion group. The lowest histopathological damage score was observed in group 5 (remote ischemic perconditioning). The nitric oxide levels were higher in the blood samples obtained from the remote ischemic perconditioning group. This study showed the effectiveness of remote ischemic conditioning procedures and compared their usefulness for preventing ischemia-reperfusion injury in muscle flaps.

  5. Effects of Erdosteine on Experimental Acute Pancreatitis Model.

    Science.gov (United States)

    Karapolat, Banu; Karapolat, Sami; Gurleyik, Emin; Yasar, Mehmet

    2017-10-01

    To create acute pancreatitis condition experimentally in rats using cerulein, and to reveal histopathological effects in pancreatic tissue with erdosteine. An experimental study. Department of General Surgery, Duzce University, Turkey, from June to October 2014. Thirty male Wistar albino rats were divided into three groups. No procedures were applied to Group 1. The rats in Group 2 and Group 3 were injected cerulein, to establish an experimental pancreatitis model and the blood amylase and lipase values were examined. The rats in Group 3 were given 10 mg/kg erdosteine. This treatment was continued for another 2 days and the rats were sacrificed. The pancreatic tissues were examined histopathologically for edema, inflammation, acinar necrosis, fat necrosis, and vacuolization. The lipase and amylase values and the histopathological examination of pancreatic tissues evidenced that the experimental acute pancreatitis model was established and edema, inflammation, acinar necrosis, fat necrosis, and vacuolization were observed in the pancreatic tissues. The statistical results suggest that erdosteine can decrease the edema, inflammation, acinar necrosis, fat necrosis and vacuolization scores in the tissues. The severity of acute pancreatitis, induced by cerulein in rats, is reduced with the use of erdosteine.

  6. [Brain protection against cerebral ischemia].

    Science.gov (United States)

    Kitagawa, Kazuo

    2013-01-01

    Previous clinical trials failed to show the benefit of several potentially protective drugs in acute ischemic stroke. However, there would be three main approaches for brain protection against stroke. The first is to develop a novel thrombolytic agent which is more efficient and safer than alteplase. Tenecteplase and desmoteplase are in progress as a new thrombolytic drug. The second strategy is to augment collateral circulation through leptomeningeal anastomosis. Administration of G-CSF could enhance arteriogenesis, but it takes several days to develop functional collateral. For this purpose, partial aortic balloon clumping or stimulation of pterygopalatine ganglion may be promising. The third one is to protect neurovascular unit against reperfusion injury. Brain hypothermia is the most effective strategy in experimental ischemia, and the clinical trial for hypothermia combined with thrombolysis therapy is in progress. Activation of endogenous protective response, as presented by ischemic tolerance, has focused on remote ischemic conditioning. Although the precise mechanisms of remote preconditioning remain unclear, intermittent limb ischemia is a safe approach. Remote ischemic conditioning is now investigated in acute patients with thrombolysis therapy.

  7. Acute Mesenteric Ischemia

    Science.gov (United States)

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  8. An experimental model of hemolysis-induced acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Saruc M.

    2003-01-01

    Full Text Available The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH in 20% (v/v ethanol on the first experimental day (day 0. One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha and platelet-activating factor (PAF contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70% of 50 rats, moderate hemolysis in seven (14%, and no hemolysis in eight (16%. Thirty-three of 35 (94.2% rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8% had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.

  9. Peripheral Stent Thrombosis Leading to Acute Limb Ischemia and Major Amputation: Incidence and Risk Factors in the Aortoiliac and Femoropopliteal Arteries

    International Nuclear Information System (INIS)

    Katsanos, Konstantinos; Al-Lamki, Said A. M.; Parthipun, Aneeta; Spiliopoulos, Stavros; Patel, Sanjay Dhanji; Paraskevopoulos, Ioannis; Zayed, Hany; Diamantopoulos, Athanasios

    2017-01-01

    PurposeTo report the real-world incidence and risk factors of stent thrombosis in the aortoiliac and femoropopliteal arteries in case of bare nitinol stent (BNS) or covered nitinol stent (CNS) placement from a single-centre retrospective audit.Materials and MethodsMedical records of consecutive patients treated with peripheral stent placement for claudication or critical limb ischemia were audited for definite stent thrombosis defined as imaging confirmed stent thrombosis that presented as acute limb-threatening ischemia. Cases were stratified between aortoiliac and femoropopliteal anatomy. Cox regression analysis was employed to adjust for baseline clinical and procedural confounders and identify predictors of stent thrombosis and major limb loss.Results256 patients (n = 277 limbs) were analysed over a 5-year period (2009–2014) including 117 aortoiliac stents (34 CNS; 12.8 ± 5.0 cm and 83 BNS; 7.8 ± 4.0 cm) and 160 femoropopliteal ones (60 CNS; 21.1 ± 11.0 cm and 100 BNS; 17.5 ± 11.9 cm). Median follow-up was 1 year. Overall stent thrombosis rate was 6.1% (17/277) after a median of 43 days (range 2–192 days) and affected almost exclusively the femoropopliteal segment (12/60 in the CNS cohort vs. 4/100 in the BNS; p = 0.001). Annualized stent thrombosis rates (per 100 person-years) were 12.5% in case of CNS and 1.4% in case of BNS (HR 6.3, 95% CI 2.4–17.9; p = 0.0002). Corresponding major amputations rates were 8.7 and 2.5%, respectively (HR 4.5, 95% CI 2.7–27.9; p = 0.0006). On multivariable analysis, critical leg ischemia and CNS placement were the only predictors of stent thrombosis. Diabetes, critical leg ischemia, femoropopliteal anatomy, long stents and CNS were independent predictors of major amputations.ConclusionsPlacement of long femoropopliteal covered nitinol stents is associated with an increased incidence of acute stent thrombosis and ensuing major amputation. Risks are significantly lower in the aortoiliac vessels

  10. Peripheral Stent Thrombosis Leading to Acute Limb Ischemia and Major Amputation: Incidence and Risk Factors in the Aortoiliac and Femoropopliteal Arteries

    Energy Technology Data Exchange (ETDEWEB)

    Katsanos, Konstantinos, E-mail: katsanos@med.upatras.gr [King’s Health Partners, Department of Interventional Radiology, Imaging Sciences Division, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Al-Lamki, Said A. M. [The Royal Hospital, Department of Radiology (Oman); Parthipun, Aneeta [King’s Health Partners, Department of Interventional Radiology, Imaging Sciences Division, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Spiliopoulos, Stavros [ATTIKO Athens University Hospital, 2nd Department of Radiology, Interventional Radiology Unit (Greece); Patel, Sanjay Dhanji [King’s Health Partners, Academic Department of Surgery, Cardiovascular Division, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Paraskevopoulos, Ioannis [King’s Health Partners, Department of Interventional Radiology, Imaging Sciences Division, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Zayed, Hany [King’s Health Partners, Academic Department of Surgery, Cardiovascular Division, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom); Diamantopoulos, Athanasios [King’s Health Partners, Department of Interventional Radiology, Imaging Sciences Division, Guy’s and St. Thomas’ Hospitals, NHS Foundation Trust (United Kingdom)

    2017-03-15

    PurposeTo report the real-world incidence and risk factors of stent thrombosis in the aortoiliac and femoropopliteal arteries in case of bare nitinol stent (BNS) or covered nitinol stent (CNS) placement from a single-centre retrospective audit.Materials and MethodsMedical records of consecutive patients treated with peripheral stent placement for claudication or critical limb ischemia were audited for definite stent thrombosis defined as imaging confirmed stent thrombosis that presented as acute limb-threatening ischemia. Cases were stratified between aortoiliac and femoropopliteal anatomy. Cox regression analysis was employed to adjust for baseline clinical and procedural confounders and identify predictors of stent thrombosis and major limb loss.Results256 patients (n = 277 limbs) were analysed over a 5-year period (2009–2014) including 117 aortoiliac stents (34 CNS; 12.8 ± 5.0 cm and 83 BNS; 7.8 ± 4.0 cm) and 160 femoropopliteal ones (60 CNS; 21.1 ± 11.0 cm and 100 BNS; 17.5 ± 11.9 cm). Median follow-up was 1 year. Overall stent thrombosis rate was 6.1% (17/277) after a median of 43 days (range 2–192 days) and affected almost exclusively the femoropopliteal segment (12/60 in the CNS cohort vs. 4/100 in the BNS; p = 0.001). Annualized stent thrombosis rates (per 100 person-years) were 12.5% in case of CNS and 1.4% in case of BNS (HR 6.3, 95% CI 2.4–17.9; p = 0.0002). Corresponding major amputations rates were 8.7 and 2.5%, respectively (HR 4.5, 95% CI 2.7–27.9; p = 0.0006). On multivariable analysis, critical leg ischemia and CNS placement were the only predictors of stent thrombosis. Diabetes, critical leg ischemia, femoropopliteal anatomy, long stents and CNS were independent predictors of major amputations.ConclusionsPlacement of long femoropopliteal covered nitinol stents is associated with an increased incidence of acute stent thrombosis and ensuing major amputation. Risks are significantly lower in the aortoiliac vessels

  11. Neurocardiac protection with milrinone for restoring acute cerebral hypoperfusion and delayed ischemic injury after experimental subarachnoid hemorrhage.

    Science.gov (United States)

    Mutoh, Tomoko; Mutoh, Tatsushi; Sasaki, Kazumasu; Nakamura, Kazuhiro; Tatewaki, Yasuko; Ishikawa, Tatsuya; Taki, Yasuyuki

    2017-02-15

    Acute cerebral hypoperfusion following subarachnoid hemorrhage (SAH) is highly related to the pathogenesis of delayed cerebral ischemia (DCI), but the therapeutic option is poorly available. This study aimed to clarify the effect of milrinone (MIL) on cerebral blood flow (CBF) and related outcomes after experimental SAH. Twenty-seven male C57BL/6 mice were assigned to either sham surgery (SAH-sham; n=6), SAH induced by endovascular perforation (control; n=10), or SAH followed by cardiac support with intravenous MIL (n=11) performed 1.5-h after SAH induction. CBF, neurobehavioral function, occurrence of DCI were assessed by MR-continuous arterial spin labeling, daily neurological score testing, and diffusion- and T2-weighted MR images on days 1 and 3, respectively. Initial global CBF depression was notable in mice of control and MIL groups as compared to the SAH-sham group (Pprotective agent against EBI. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Creatine kinase activity in dogs with experimentally induced acute inflammation

    Directory of Open Access Journals (Sweden)

    Dimitrinka Zapryanova

    2013-01-01

    Full Text Available The main purpose of this study was to investigate the effect of acute inflammation on total creatine kinase (CK activity in dogs. In these animals, CK is an enzyme found predominantly in skeletal muscle and significantly elevated serum activity is largely associated with muscle damage. Plasma increases in dogs are associated with cell membrane leakage and will therefore be seen in any condition associated with muscular inflammation. The study was induced in 15 mongrel male dogs (n=9 in experimental group and n=6 in control group at the age of two years and body weight 12-15 kg. The inflammation was reproduced by inoculation of 2 ml turpentine oil subcutaneously in lumbar region. The plasma activity of creatine kinase was evaluated at 0, 6, 24, 48, 72 hours after inoculation and on days 7, 14 and 21 by a kit from Hospitex Diagnostics. In the experimental group, the plasma concentrations of the CK-activity were increased at the 48th hour (97.48±6.92 U/L and remained significantly higher (p<0.05 at the 72 hour (97.43±2.93 U/L compared to the control group (77.08±5.27 U/L. The results of this study suggest that the evaluation of creatine kinase in dogs with experimentally induced acute inflammation has a limited diagnostic value. It was observed that the creatine kinase activity is slightly affected by the experimentally induced acute inflammation in dogs.

  13. [MRI semiotics features of experimental acute intracerebral hematomas].

    Science.gov (United States)

    Burenchev, D V; Skvortsova, V I; Tvorogova, T V; Guseva, O I; Gubskiĭ, L V; Kupriianov, D A; Pirogov, Iu A

    2009-01-01

    The aim of this study was to assess the possibility of revealing intracerebral hematomas (ICH), using MRI, within the first hours after onset and to determine their MRI semiotics features. Thirty animals with experimental ICH were studied. A method of two-stage introduction of autologous blood was used to develop ICH as human spontaneous intracranial hematomas. Within 3-5h after blood introduction to the rat brain. The control MRI was performed in the 3rd and 7th days after blood injections. ICH were definitely identified in the first MRI scans. The MRI semiotics features of acute ICH and their transformations were assessed. The high sensitivity of MRI to ICH as well as the uniform manifestations in all animals were shown. In conclusion, the method has high specificity for acute ICH detection.

  14. Myocardial uptake of iodinated free fatty acids and 201Tl in experimental ischemia

    International Nuclear Information System (INIS)

    Westera, G.; Wall, E.E. van der; Visser, F.C.; Scholtalbers, A.S.; Eenige, M.J. van; Roos, J.P.

    1984-01-01

    In an experimental study, we evaluated the uptake of ( 131 I)-17-iodo heptadecanoic acid ( 131 I-HDA), ( 125 I)-15-4 (4-iodophenyl) pentadecanoic acid ( 125 I-PPA) and thallium-201 ( 201 Tl) in the dog heart. Twenty dogs were studied and divided into 3 groups: in group A, 10 dogs (4 normal, 6 with coronary artery occlusion) were studied with 131 I-HDA and 201 Tl; in group B, 5 dogs (with occlusion) received 125 I-PPA and 201 Tl; and in group C, 5 dogs (with occlusion) were studied with 125 I-PPA and 131 I-HDA. Two min after administration of the compounds the hearts were excised and stored in formaldehyde. After sectioning of the left ventricle, total uptake was counted and expressed in percentage of injected dose. Uptake in the normal myocardium (group A) was 4.2+-0.6% for 131 I-HDA and 4.6+-0.7% for 201 Tl; in the occluded dog hearts (group A) we measured values of 2.6+-0.4% for 131 I-HDA (p 201 Tl (p 131 I-HDA, 125 I-PPA and 201 Tl in groups B and C was not significantly different: group B, 125 I-PPA 2.8+-0.8% and 201 Tl 2.5+-0.5%; group C, 125 I-PPA 1.9+-0.7% and 131 I-HDA 1.6+-0.6%. Moreover, regional distribution of both iodinated fatty acids was quite comparable with the distribution of 201 Tl. We conclude that 131 I-HDA and 125 I-PPA show similar uptake as 201 Tl and are distributed according to coronary artery perfusion, which underscores their value as myocardial imaging agents. (orig.) [de

  15. Drug induced acute kidney injury: an experimental animal study

    International Nuclear Information System (INIS)

    Khan, M.W.A.; Khan, B.T.; Qazi, R.A.; Ashraf, M.; Waqar, M.

    2017-01-01

    Objective: To assess the extent of drug induced nephrotoxicity in laboratory animals for determining the role and extent of iatrogenic kidney damage in patients exposed to nephrotoxic drugs in various clinical setups. Study Design: Randomized control trail. Place and Duration of study: Pharmacology department and animal house of Army Medical College from Jan 2011 to Aug 2011. Material and Methods: Thirty six mixed breed rabbits were used in this study. Animals were randomly divided into six groups consisting of six rabbits in each. Groups were named A, B, C, D, E and F. Group A was control group. Group B was given 0.9% normal saline. Group C rabbits were given acute nephrotoxic single dose of amphotericin B deoxycholate. Group D received 0.9% normal saline 10ml/kg followed by amphotericin B infusion. Group E was injected acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Group F received saline loading along with acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Results: Biochemical and histopathological analysis showed significant kidney injury in rabbits exposed to acute nephrotoxic doses of amphotericin B and cyclosporine. Toxicity was additive when the two drugs were administered simultaneously. Group of rabbits with saline loading had significantly lesser kidney damage. Conclusion: Iatrogenic acute kidney damage is a major cause of morbidity in experimental animals exposed to such nephrotoxic drugs like amphotericin B and cyclosporine, used either alone or in combination. Clinical studies are recommended to assess the extent of iatrogenic renal damage in patients and its economic burden. Efficient and cost effective protective measure may be adopted in clinical setups against such adverse effects. (author)

  16. Different dose-dependent effects of hydrogen sulfide on ischemia-reperfusion induced acute kidney injury in rats

    Directory of Open Access Journals (Sweden)

    Fateme Azizi

    2017-12-01

    Conclusion: Our study demonstrates that different doses of Sodium hydrosulfide (NaHS can play diverse role in renal ischemia reperfusion injury. However, NaHS in the low-doses could protect the kidney from the RIR injury, in a higher dose NaHS exaggerated the renal function by increases plasma creatinine and BUN. Therefore, determining of the therapeutic doses of NaHS may be important in the protection of kidney from the RIR injury.

  17. Protective effects of phosphodiesterase-4-specific inhibitor rolipram on acute ischemia-reperfusion injury in rat kidney.

    Science.gov (United States)

    Mammadov, Emin; Aridogan, Ibrahim Atilla; Izol, Volkan; Acikalin, Arbil; Abat, Deniz; Tuli, Abdullah; Bayazit, Yildirim

    2012-12-01

    To investigate the effect of Rolipram, a phosphodiesterase-4-inhibitor, on renal ischemia-reperfusion injury (IRI) in rats. Thirty rats were divided into 5 different groups of 6 rats. Nothing was done to the control group. In the second group, the renal pedicle was clamped for 30 minutes. In the third group, 1 mg/kg of Rolipram was given by intraperitoneal injection 30 minutes before clamping. The fourth group received the same injection when the clamp was placed, as did the fifth group 30 minutes after the clamp was opened. Clamping time was set at 30 minutes. Twenty-four hours later, nephrectomy was performed in all the groups. Half of each kidney was examined histopathologically. Levels of biochemical agents, such as malondialdehyde, superoxide dismutase, and catalase, were measured in the other half. The malondialdehyde (MDA) levels significantly decreased and reached control levels in the group in which Rolipram was administered 30 minutes after reperfusion (P = .07). The catalase and superoxide dismutase activities obtained from renal homogentisates of the ischemia groups were evaluated; there were striking increases in tissue levels of these 2 enzymes in the groups in which Rolipram was administered during ischemia and 30 minutes after ischemia (P < .001). Histopathologically, there was no significant difference in inflammation between the Rolipram-administrated groups compared with group 1 (control) and group 2 (IRI). Tubular necrosis and apoptosis was significantly lower in group 5 than the other groups, except group 1 (P < .001). We suggest that in surgical procedures that can lead to renal IRI, the administration of Rolipram can decrease oxidative renal tissue damage and the severe deterioration of renal function. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Mesenteric Ischemia

    Directory of Open Access Journals (Sweden)

    Shannon Toohey

    2016-07-01

    Full Text Available Audience: This simulation session is appropriate for emergency medicine residents at any level or medical students. Introduction: Mesenteric ischemia is a rare, but serious cause of abdominal pain. Practitioners must recognize the diagnosis quickly. The clinical course rapidly advances from bowel ischemia to infarction, sepsis, and frequently death. Mesenteric ischemia accounts for approximately 1% of all ED cases of abdominal pain in the elderly, but the mortality is as high as 93%. Objectives: At the end of this simulation session, the learner will: 1 Recognize signs and symptoms of mesenteric ischemia; 2 order appropriately imaging and labs in the workup of an elderly patient with abdominal pain; 3 manage a patient with mesenteric ischemia, a rare, but serious cause of abdominal pain in the elderly; 4 discuss anchoring bias, specifically related to patients referred to the ED with an established diagnosis by outside specialists. Methods: This educational session is a high-fidelity simulation.

  19. DIGE proteome analysis reveals suitability of ischemic cardiac in vitro model for studying cellular response to acute ischemia and regeneration.

    Directory of Open Access Journals (Sweden)

    Sina Haas

    Full Text Available Proteomic analysis of myocardial tissue from patient population is suited to yield insights into cellular and molecular mechanisms taking place in cardiovascular diseases. However, it has been limited by small sized biopsies and complicated by high variances between patients. Therefore, there is a high demand for suitable model systems with the capability to simulate ischemic and cardiotoxic effects in vitro, under defined conditions. In this context, we established an in vitro ischemia/reperfusion cardiac disease model based on the contractile HL-1 cell line. To identify pathways involved in the cellular alterations induced by ischemia and thereby defining disease-specific biomarkers and potential target structures for new drug candidates we used fluorescence 2D-difference gel electrophoresis. By comparing spot density changes in ischemic and reperfusion samples we detected several protein spots that were differentially abundant. Using MALDI-TOF/TOF-MS and ESI-MS the proteins were identified and subsequently grouped by functionality. Most prominent were changes in apoptosis signalling, cell structure and energy-metabolism. Alterations were confirmed by analysis of human biopsies from patients with ischemic cardiomyopathy.With the establishment of our in vitro disease model for ischemia injury target identification via proteomic research becomes independent from rare human material and will create new possibilities in cardiac research.

  20. Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.

    Science.gov (United States)

    Liu, Xiaobai; Wang, Zhenhua; Wang, Ping; Yu, Bo; Liu, Yunhui; Xue, Yixue

    2013-07-21

    It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs' protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia. Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated. GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia. These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.

  1. Transient myocardial ischemia after a first acute myocardial infarction and its relation to clinical characteristics, predischarge exercise testing and cardiac events at one-year follow-up

    DEFF Research Database (Denmark)

    Mickley, H; Pless, P; Nielsen, J R

    1993-01-01

    recording 11 +/- 5 days after AMI 23 patients (19%) had 123 ischemic episodes (group 1), whereas 100 patients demonstrated no ischemia (group 2). Exercise-induced ST-segment depression was more prevalent in group 1 (83%) than in group 2 (47%) (p ... as judged from a shorter exercise duration before significant ST-segment depression (5.5 +/- 2.4 vs 7.7 +/- 4.1 minutes; p depression on exercise testing (4.1 +/- 2.6 vs 2.6 +/- 1.6 mm; p exercise test results revealed an impaired hemodynamic......The relation between early out-of-hospital ambulatory ST-segment monitoring, clinical characteristics, predischarge maximal exercise testing and cardiac events was determined in 123 consecutive men (age 55 +/- 8 years) with a first acute myocardial infarction (AMI). During 36 hours of ambulatory...

  2. Evaluation of acute ischemia in pre-procedure ECG predicts myocardial salvage after primary PCI in STEMI patients with symptoms >12hours

    DEFF Research Database (Denmark)

    Fakhri, Yama; Busk, Martin; Schoos, Mikkel Malby

    2016-01-01

    -presenters). The Anderson-Wilkin's score (AW-score) estimates the acuteness of myocardial ischemia from the electrocardiogram (ECG) in STEMI patients. We hypothesized that the AW-score is superior to symptom duration in identifying substantial salvage potential in late-presenters. METHODS: The AW-score (range 1......-4) was obtained from the pre-pPCI ECG in 55 late-presenters and symptoms 12-72 hours. Myocardial perfusion imaging was performed to assess area at risk before pPCI and after 30days to assess myocardial salvage index (MSI). We correlated both the AW-score and pain-to-balloon with MSI and determined the salvage...

  3. Renoprotective effect of paricalcitol via a modulation of the TLR4-NF-κB pathway in ischemia/reperfusion-induced acute kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae-Won, E-mail: maestro97@hanmail.net; Kim, Sun Chul, E-mail: linefe99@hanmail.net; Ko, Yoon Sook, E-mail: rainboweyes@hanmail.net; Lee, Hee Young, E-mail: cell1023@hanmail.net; Cho, Eunjung, E-mail: icdej@naver.com; Kim, Myung-Gyu, E-mail: gyu219@hanmail.net; Jo, Sang-Kyung, E-mail: sang-kyung@korea.ac.kr; Cho, Won Yong, E-mail: wonyong@korea.ac.kr; Kim, Hyoung Kyu, E-mail: hyoung@korea.ac.kr

    2014-02-07

    Highlights: • Paricalcitol. • Attenuation of renal inflammation. • Modulation of TLR4-NF-κB signaling. - Abstract: Background: The pathophysiology of ischemic acute kidney injury (AKI) is thought to include a complex interplay between vascular endothelial cell dysfunction, inflammation, and tubular cell damage. Several lines of evidence suggest a potential anti-inflammatory effect of vitamin D in various kidney injury models. In this study, we investigated the effect of paricalcitol, a synthetic vitamin D analog, on renal inflammation in a mouse model of ischemia/reperfusion (I/R) induced acute kidney injury (AKI). Methods: Paricalcitol was administered via intraperitoneal (IP) injection at 24 h before ischemia, and then I/R was performed through bilateral clamping of the renal pedicles. Twenty-four hours after I/R, mice were sacrificed for the evaluation of injury and inflammation. Additionally, an in vitro experiment using HK-2 cells was also performed to examine the direct effect of paricalcitol on tubular cells. Results: Pre-treatment with paricalcitol attenuated functional deterioration and histological damage in I/R induced AKI, and significantly decreased tissue neutrophil and macrophage infiltration and the levels of chemokines, the pro-inflammatory cytokine interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). It also decreased IR-induced upregulation of Toll-like receptor 4 (TLR4), and nuclear translocation of p65 subunit of NF-κB. Results from the in vitro study showed pre-treatment with paricalcitol suppressed the TNF-α-induced depletion of cytosolic IκB in HK-2 cells. Conclusion: These results demonstrate that pre-treatment with paricalcitol has a renoprotective effect in ischemic AKI, possibly by suppressing TLR4-NF-κB mediated inflammation.

  4. RC-3095, a Selective Gastrin-Releasing Peptide Receptor Antagonist, Does Not Protect the Lungs in an Experimental Model of Lung Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Vera L. Oliveira-Freitas

    2015-01-01

    Full Text Available RC-3095, a selective GRPR antagonist, has been shown to have anti-inflammatory properties in different models of inflammation. However, its protective effect on lungs submitted to lung ischemia-reperfusion injury has not been addressed before. Then, we administrated RC-3095 intravenously before and after lung reperfusion using an animal model of lung ischemia-reperfusion injury (LIRI by clamping the pulmonary hilum. Twenty Wistar rats were subjected to an experimental model in four groups: SHAM, ischemia-reperfusion (IR, RC-Pre, and RC-Post. The final mean arterial pressure significantly decreased in IR and RC-Pre compared to their values before reperfusion (P<0.001. The RC-Post group showed significant decrease of partial pressure of arterial oxygen at the end of the observation when compared to baseline (P=0.005. Caspase-9 activity was significantly higher in the RC-Post as compared to the other groups (P<0.013. No significant differences were observed in eNOS activity among the groups. The groups RC-Pre and RC-Post did not show any significant decrease in IL-1β (P=0.159 and TNF-α (P=0.260, as compared to IR. The histological score showed no significant differences among the groups. In conclusion, RC-3095 does not demonstrate a protective effect in our LIRI model. Additionally, its use after reperfusion seems to potentiate cell damage, stimulating apoptosis.

  5. Establishment of selected acute pulmonary thromboembolism model in experimental sheep

    International Nuclear Information System (INIS)

    Fan Jihai; Gu Xiulian; Chao Shengwu; Zhang Peng; Fan Ruilin; Wang Li'na; Wang Lulu; Wang Ling; Li Bo; Chen Taotao

    2010-01-01

    Objective: To establish a selected acute pulmonary thromboembolism model in experimental sheep suitable for animal experiment. Methods: By using Seldinger's technique the catheter sheath was placed in both the femoral vein and femoral artery in ten sheep. Under C-arm DSA guidance the catheter was inserted through the catheter sheath into the pulmonary artery. Via the catheter appropriate amount of sheep autologous blood clots was injected into the selected pulmonary arteries. The selected acute pulmonary thromboembolism model was thus established. Pulmonary angiography was performed to check the results. The pulmonary arterial pressure, femoral artery pressure,heart rates and partial pressure of oxygen in arterial blood (PaO 2 ) were determined both before and after the treatment. The above parameters obtained after the procedure were compared with the recorded parameters measured before the procedure, and the sheep model quality was evaluated. Results: The baseline of pulmonary arterial pressure was (27.30 ± 9.58) mmHg,femoral artery pressure was (126.4 ± 13.72) mmHg, heart rate was (103 ± 15) bpm and PaO 2 was (87.7 ± 12.04) mmHg. Sixty minutes after the injection of (30 ± 5) ml thrombotic agglomerates, the pulmonary arterial pressures rose to (52 ± 49) mmHg, femoral artery pressures dropped to (100 ± 21) mmHg. The heart rates went up to (150 ± 26) bpm. The PaO 2 fell to (25.3 ± 11.2) mmHg. After the procedure the above parameters were significantly different from that measured before the procedure in all ten animals (P < 0.01). The pulmonary arteriography clearly demonstrated that the selected pulmonary arteries were successfully embolized. Conclusion: The anatomy of sheep's femoral veins,vena cava system, pulmonary artery and right heart system are suitable for the establishment of the catheter passage, for this reason, selected acute pulmonary thromboembolism model can be easily created in experimental sheep. The technique is feasible and the model

  6. RENAL ISCHEMIA-REPERFUSION INJURY CONTRIBUTES TO RENAL DAMAGE IN EXPERIMENTAL ANTI-MYELOPEROXIDASE-ASSOCIATED PROLIFERATIVE GLOMERULONEPHRITIS

    NARCIS (Netherlands)

    BROUWER, E.; Klok, P.A; HUITEMA, M.G.; Weening, J.J.; Kallenberg, Cees

    The occurrence of focal fibrinoid necrosis of capillary loops in the very early stages of ANCA-associated necrotizing crescentic glomerulonephritis (NCGN) and the increased prevalence of this disease at older age suggest that renal ischemia may play an additional role in its pathophysiology. In the

  7. Alcohol and acute pancreatitis. An experimental study in the rat.

    Science.gov (United States)

    Jalovaara, P; Apaja, M

    1978-01-01

    The effect of chronic alcohol pretreatment and various pancreatobiliary secretions on the severity of experimental pancreatitis was studied in the rat. 95 rats were pretreated with ethanol (20% w/v, 1.1 ml/100 g body weight) five times weekly for 10 to 12 weeks by gastric intubation. 88 rats served as controls. Pancreatic lesions were produced by retograde injection of different pancreatobiliary secretions into the pancreatic ducts. The secretions were collected from both normal and chronically alcohol-fed rats, and each was used for induction of experimental pancreatitis in the control and alcohol pretreated rats. Bile obtained from normal rats was no more toxic to the pancreas than 0.9% saline solution, while bile obtained from the chronically alcohol-fed rats caused significantly more serious lesions to the pancreas than did normal rat bile. Bile-pancreatic juice (mixture of secretions at papilla of Vater) of normal and chronically alcohol-fed rats was as toxic as the bile of the alcohol-fed rats. Alcohol pretreatment had no significant effect on the severity of pancreatitis when control and alcohol-fed groups separately or the whole material according to pretreatment was examined. These results suggest that the metabolic effects of ethanol on the pancreas as such do not sensitize the pancreas to acute pancreatitis. An exogenous mechanism is required. The reflux of toxic alcoholic bile into the pancreas might act as an induction factor in acute alcohol pancreatitis.

  8. [Experimental study of acute brain swelling under acute intracranial hypertension (author's transl)].

    Science.gov (United States)

    Shigemori, M; Watanabe, M; Kuramoto, S

    1976-12-01

    There are many problems about the cause, pathophysiology and treatment of acute brain swelling under intracranial hypertension frequently encountered in the neurosurgical clinics. Generally, rapid increase of the cerebral vasoparesis caused by unknown etiology is thought to be the main cause of acute brain swelling under intracranial hypertension. Moreover, disturbance of the cerebral venous circulatory system is discussed recently by many authors. But, research from the point of systemic respiration and hemodynamics is necessary for resolving these problems. This experiment was designed to study the effects of respiration and hemodynamics on the cerebral vasoparesis. Using 22 adult dogs, acute intracranial hypertension was produced by epidural balloon inflation sustained at the level of 300 - 400 mmH2O. Simultaneously with measurement of intracranial pressure at the epidural space, superior sagittal sinus pressure, respirogram, systemic blood pressure (femoral artery), central venous pressure, common carotid blood flow, EKG and bipolar lead EEG were monitored continuously. The experimental group was divided by the respiratory loading into 5 groups as follows: control (6 cases), 10% CO2 hypercapnia (4 cases), 10% O2 hypoxia (4 cases), stenosis of airway (5 cases), 100% O2-controled respiration (3 cases). 1) Cerebral vasoparesis under acute intracranial hypertension took place earlier and showed more rapid progression in groups of stenosis of airway, hypercapnia and hypoxia than control group of spontaneous respiration in room air. No occurrence of cerebral vasoparesis was found out in a group of 100% O2 controlled respiration. It is proved that increased airway resistance or asphyxia, hypercapnia and hypoxia have strictly reference to the occurrence and progression of cerebral vasoparesis and for the prevention of cerebral vasoparesis, correct 100% O2 cont rolled respiration is effective. 2) From the hemodynamic change, the progression of rapid increase of cerebral

  9. Normal distribution and medullary-to-cortical shift of Nestin-expressing cells in acute renal ischemia.

    Science.gov (United States)

    Patschan, D; Michurina, T; Shi, H K; Dolff, S; Brodsky, S V; Vasilieva, T; Cohen-Gould, L; Winaver, J; Chander, P N; Enikolopov, G; Goligorsky, M S

    2007-04-01

    Nestin, a marker of multi-lineage stem and progenitor cells, is a member of intermediate filament family, which is expressed in neuroepithelial stem cells, several embryonic cell types, including mesonephric mesenchyme, endothelial cells of developing blood vessels, and in the adult kidney. We used Nestin-green fluorescent protein (GFP) transgenic mice to characterize its expression in normal and post-ischemic kidneys. Nestin-GFP-expressing cells were detected in large clusters within the papilla, along the vasa rectae, and, less prominently, in the glomeruli and juxta-glomerular arterioles. In mice subjected to 30 min bilateral renal ischemia, glomerular, endothelial, and perivascular cells showed increased Nestin expression. In the post-ischemic period, there was an increase in fluorescence intensity with no significant changes in the total number of Nestin-GFP-expressing cells. Time-lapse fluorescence microscopy performed before and after ischemia ruled out the possibility of engraftment by the circulating Nestin-expressing cells, at least within the first 3 h post-ischemia. Incubation of non-perfused kidney sections resulted in a medullary-to-cortical migration of Nestin-GFP-positive cells with the rate of expansion of their front averaging 40 microm/30 min during the first 3 h and was detectable already after 30 min of incubation. Explant matrigel cultures of the kidney and aorta exhibited sprouting angiogenesis with cells co-expressing Nestin and endothelial marker, Tie-2. In conclusion, several lines of circumstantial evidence identify a sub-population of Nestin-expressing cells with the mural cells, which are recruited in the post-ischemic period to migrate from the medulla toward the renal cortex. These migrating Nestin-positive cells may be involved in the process of post-ischemic tissue regeneration.

  10. Circadian variation of transient myocardial ischemia in the early out-of-hospital period after first acute myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H; Pless, P; Nielsen, J R

    1991-01-01

    with a peak activity occurring in the evening hours (p less than 0.01). Thus, 43% of ischemic episodes and 42% of ischemic time occurred between 6 P.M. and 12 midnight. The characteristics of morning and evening episodes were similar, except for the heart rate at maximal ST-segment depression, which...... was significantly higher during morning episodes (p less than 0.02). Patients with transient myocardial ischemia had a diurnal distribution similar to the circadian variation displayed during ischemic activity. Thus, 16 of the 21 patients had ischemic episodes from 6 P.M. to 12 midnight versus 10 patients from 6 A...

  11. Anti-inflammatory and antioxidant effects of infliximab on acute lung injury in a rat model of intestinal ischemia/reperfusion.

    Science.gov (United States)

    Guzel, Ahmet; Kanter, Mehmet; Guzel, Aygul; Pergel, Ahmet; Erboga, Mustafa

    2012-06-01

    The purpose of this study was to investigate the role of infliximab on acute lung injury induced by intestinal ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab; each group contain 10 animals. Sham group animals underwent laparotomy without I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation were followed by 1 h of reperfusion. In the infliximab group, 3 days before I/R, infliximab (3 mg/kg) was administered by intravenously. All animals were sacrificed at the end of reperfusion and lung tissues samples were obtained for biochemical and histopathological investigation in all groups. To date, no more biochemical and histopathological changes on intestinal I/R injury in rats by infliximab treatment have been reported. Infliximab treatment significantly decreased the elevated tissue malondialdehyde levels and increased of reduced superoxide dismutase, and glutathione peroxidase enzyme activities in lung tissues samples. Intestinal I/R caused severe histopathological injury including edema, hemorrhage, increased thickness of the alveolar wall and a great number of inflammatory cells that infiltrated the interstitium and alveoli. Infliximab treatment significantly attenuated the severity of intestinal I/R injury. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase and arise in the expression of surfactant protein D in lung tissue of acute lung injury induced by intestinal I/R with infliximab therapy. It was concluded that infliximab treatment might be beneficial in acute lung injury, therefore, shows potential for clinical use. Because of its anti-inflammatory and antioxidant effects, infliximab pretreatment may have protective effects in acute lung injury induced by intestinal I/R.

  12. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

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    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  13. Radionuclide uptake during the evolution of experimental acute osteomyelitis

    International Nuclear Information System (INIS)

    Norris, S.H.; Watt, I.

    1981-01-01

    The findings of technetium 99m MDP and gallium 67 citrate scintigraphy are described in the first four days following experimental acute osteomyelitis of the tibia of rabbits. On the day of inoculation, defects in activity are observed in both the perfusion and bone phases of technetium scintigraphy. Similar defects are achieved by saline injection. On subsequent days technetium scintigraphy reveals an increased activity in the perfusion stage but a persisting defect of activity in the bone phase. Gallium activity is increased throughout the period of the study in inoculated animals but not in those injected with saline. It is concluded that 99 Tcsup(m) MDP, in its perfusion phase, and 67 Ga citrate are highly sensitive indicators of bone inflammation and that early osteomyelitis is characterized by increased activity with these agents together with a technetium bone scan defect. (author)

  14. Effect of complete hilar versus only renal artery clamping on renal histomorphology following ischemia/reperfusion injury in an experimental model.

    Science.gov (United States)

    Umul, M; Cal, A C; Turna, B; Oktem, G; Aydın, H H

    2016-01-01

    To evaluate the effect of temporary complete hilar versus only renal artery clamping with different duration of warm ischemia on renal functions, and possibly identify a "safe" clamping type and duration of renal ischemia. Fifty male rabbits have been incorporated to study. Rabbits were subjected to ischemia/reperfusion injury by temporary vascular clamping. Reagents were randomized to 3 experimental groups (only renal artery clamping, complete hilar clamping, sham surgery) and sub-groups were determined according to different clamping times (30 and 60 minutes). Median laparotomy and left renal hilus dissection were performed to sham group. Only artery or complete hilar clamping was performed for 30 or 60 minutes by microvascular bulldog clamps to other reagents. Rabbits were sacrificed 10 days after primary surgery and left nephrectomy performed. Nephrectomy materials were evaluated for the level of nitric-oxide synthase (NOS) immunoreactivity, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity and an electron microscopic examination was performed. NOS immunoreactivity was correlated with the temporary clamping time. We also observed that complete hilar vascular clamping entails an increase on NOS immunoreactivity. MDA levels were similar for all experimental surgery groups (p = 0.42). The SOD activity was decreased among all subgroups compared with sham surgery. But the significant decrease occurred in 30 minutes only artery and 30 minutes complete hilar clamping groups in proportion to sham surgery (p = 0.026 and p = 0.019, respectively). This current study suggested that only renal artery clamping under 30 minutes is more appropriate during renal surgical procedures requiring temporary vascular clamping.

  15. Protective effects of tempol in an experimental ovarian ischemia-reperfusion injury model in female Wistar albino rats.

    Science.gov (United States)

    Pınar, Neslihan; Soylu Karapınar, Oya; Özcan, Oğuzhan; Atik Doğan, Esin; Bayraktar, Suphi

    2017-07-01

    The aim of this study was to investigate the antioxidant effects of tempol on ovarian ischemia-reperfusion (I/R) injury in rats. Forty female Wistar albino rats were randomly divided into 5 groups: Group I, sham; Group II, ischemia (I); Group III, I/R; Group IV, I/R + tempol 30 mg/kg i.p; Group V, I/R + tempol 50 mg/kg i.p. Oxidative stress index (OSI) was significantly higher in the ischemia group and the I/R group than in the sham group. Catalase levels were significantly lower in the I/R group than in the I/R + tempol 30 mg/kg i.p. and the I/R + tempol 50 mg/kg i.p. groups. Glutathione peroxidase levels were lower in the I/R group than in the I/R + tempol 30 mg/kg i.p. and the I/R + tempol 50 mg/kg i.p. groups. MDA levels were significantly lower in the I/R + tempol 30 mg/kg i.p. group and the I/R + tempol 50 mg/kg i.p. group than in the I/R group. The levels of the histopathological parameters were significantly decreased in the I/R + tempol 50 mg/kg i.p. group compared with the I/R group. Tempol can be used for reducing ovarian I/R injury.

  16. Gene expression in cerebral ischemia: a new approach for neuroprotection.

    Science.gov (United States)

    Millán, Mónica; Arenillas, Juan

    2006-01-01

    Cerebral ischemia is one of the strongest stimuli for gene induction in the brain. Hundreds of genes have been found to be induced by brain ischemia. Many genes are involved in neurodestructive functions such as excitotoxicity, inflammatory response and neuronal apoptosis. However, cerebral ischemia is also a powerful reformatting and reprogramming stimulus for the brain through neuroprotective gene expression. Several genes may participate in both cellular responses. Thus, isolation of candidate genes for neuroprotection strategies and interpretation of expression changes have been proven difficult. Nevertheless, many studies are being carried out to improve the knowledge of the gene activation and protein expression following ischemic stroke, as well as in the development of new therapies that modify biochemical, molecular and genetic changes underlying cerebral ischemia. Owing to the complexity of the process involving numerous critical genes expressed differentially in time, space and concentration, ongoing therapeutic efforts should be based on multiple interventions at different levels. By modification of the acute gene expression induced by ischemia or the apoptotic gene program, gene therapy is a promising treatment but is still in a very experimental phase. Some hurdles will have to be overcome before these therapies can be introduced into human clinical stroke trials. Copyright 2006 S. Karger AG, Basel.

  17. Effects of valproic acid and dexamethasone administration on early bio-markers and gene expression profile in acute kidney ischemia-reperfusion injury in the rat.

    Directory of Open Access Journals (Sweden)

    Ryan W Speir

    Full Text Available Renal ischemia-reperfusion (IR causes acute kidney injury (AKI with high mortality and morbidity. The objective of this investigation was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Under general anesthesia, left renal ischemia was induced in Wister rats by occluding renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n = 8/group received Valproic Acid (150 mg/kg; VPA, Dexamethasone (3 mg/kg; Dex or Vehicle (saline intraperitoneally. Animals were sacrificed at 3, 24 or 120 h post-IR. Plasma creatinine (mg/dL at 24 h was reduced (P<0.05 in VPA (2.7±1.8 and Dex (2.3±1.2 compared to Vehicle (3.8±0.5 group. At 3 h, urine albumin (mg/mL was higher in Vehicle (1.47±0.10, VPA (0.84±0.62 and Dex (1.04±0.73 compared to naïve (uninjured/untreated control (0.14±0.26 group. At 24 h post-IR urine lipocalin-2 (μg/mL was higher (P<0.05 in VPA, Dex and Vehicle groups (9.61-11.36 compared to naïve group (0.67±0.29; also, kidney injury molecule-1 (KIM-1; ng/mL was higher (P<0.05 in VPA, Dex and Vehicle groups (13.7-18.7 compared to naïve group (1.7±1.9. Histopathology demonstrated reduced (P<0.05 ischemic injury in the renal cortex in VPA (Grade 1.6±1.5 compared to Vehicle (Grade 2.9±1.1. Inflammatory cytokines IL1β and IL6 were downregulated and anti-apoptotic molecule BCL2 was upregulated in VPA group. Furthermore, kidney DNA microarray demonstrated reduced injury, stress, and apoptosis related gene expression in the VPA administered rats. VPA appears to ameliorate kidney IR injury via reduced inflammatory cytokine, apoptosis/stress related gene expression, and improved regeneration. KIM-1, lipocalin-2 and albumin appear to be promising early urine biomarkers for the diagnosis of AKI.

  18. Local lysis with Alteplase for the treatment of acute embolic leg ischemia following the use of the Duett trademark closure device: preliminary results

    International Nuclear Information System (INIS)

    Schuermann, K.; Buecker, A.; Wingen, M.; Tacke, J.; Wein, B.; Guenther, R.W.; Janssens, U.

    2004-01-01

    Purpose: To analyze retrospectively the result of the alteplase lysis therapy of embolic complications following the use of the Duett closure device. Methods and Materials: For 3.5 years, the Duett closure device was used in 1,398 angiographies to close the femoral puncture site. The Duett device consists of a balloon and a liquid procoagulant containing collagen and thrombin, which is injected into the puncture tract under endovascular balloon protection of the arterial puncture site. In 9 patients (0.64%), the procoagulant was incidentally injected into the femoral artery causing acute leg ischemia. Eight patients received local lysis therapy with alteplase via a contralateral femoral access. One patient underwent surgery. On average, 21 mg alteplase (4-35 mg) were administered within 14 h (4-21 h). The course of the lysis was followed angiographyically and clinically. All patients were inteerviewed by telephone 23 months (4-35 months) later.Results: In 3 patients, lysis was complete. In 5 patients, only little thrombotic material remained. In all patients, symptoms of ischemia resolved completely within the first hours after initiation of lysis. In 5 cases, bleeding occurred at the puncture site closed with the Duett device during lysis, including development of a false aneurysm in 2 cases. Complications led to premature termination (n=2) or interruption of the lysis (n=3). All complications were treated conservatively. Clinically, long-term sequelae were paresthesia and hypoesthesia in the lower leg and foot in 2 patients treated with lysis, and in the patient who underwent surgery. (orig.) [de

  19. Molecular MRI of Cardiomyocyte Apoptosis with Simultaneous Delayed Enhancement MRI Distinguishes Apoptotic and Necrotic Myocytes In Vivo: Potential for Midmyocardial Salvage in Acute Ischemia

    Science.gov (United States)

    Sosnovik, David E.; Garanger, Elisabeth; Aikawa, Elena; Nahrendorf, Matthias; Figuiredo, Jose-Luiz; Dai, Guangping; Reynolds, Fred; Rosenzweig, Anthony; Weissleder, Ralph; Josephson, Lee

    2009-01-01

    Background A novel dual contrast molecular MRI technique to image both cardiomyocyte (CM) apoptosis and necrosis in-vivo within 4-6 hours of ischemia is presented. The technique utilizes the annexin-based nanoparticle AnxCLIO-Cy5.5 (apoptosis) and simultaneous delayed enhancement (DE) imaging with a novel gadolinium chelate, Gd-DTPA-NBD (necrosis). Methods and Results Mice with transient coronary ligation were injected intravenously at the onset of reperfusion with AnxCLIO-Cy5.5 (n=7) or the control probe Inact_CLIO-Cy5.5 (n=6). T2* weighted MR images (9.4 Tesla) were acquired within 4-6 hours of reperfusion. The contrast-to-noise ratio (CNR) between injured and uninjured myocardium was measured. The mice were then injected with Gd-DTPA-NBD and DE imaging was performed within 10-30 minutes. Uptake of AnxCLIO-Cy5.5 was most prominent in the midmyocardium and was significantly greater than that of Inact_CLIO-Cy5.5 (CNR 8.82 +/− 1.5 versus 3.78 +/− 1.1, p DTPA-NBD. Wall thickening was significantly reduced in segments with DE and/or transmural accumulation of AnxCLIO-Cy5.5 (p DTPA-NBD confirmed the presence of large numbers of apoptotic but potentially viable CMs (AnxCLIO-Cy5.5 positive, Gd-DTPA-NBD negative) in the midmyocardium. Conclusions A novel technique to image CM apoptosis and necrosis in-vivo within 4-6 hours of injury is presented, and reveals large areas of apoptotic but viable myocardium in the midmyocardium. Strategies to salvage the numerous apoptotic but potentially viable CMs in the midmyocardium in acute ischemia should be investigated. PMID:19920044

  20. The porcine acute phase protein response to acute clinical and subclinical experimental infection with Streptococcus suis

    DEFF Research Database (Denmark)

    Sørensen, Nanna Skall; Tegtmeier, C.; Andresen, Lars Ole

    2006-01-01

    The pig acute phase protein (APP) response to experimental Streptococcus suis (S. suis) infection was mapped by the measurement of the positive APPs C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp) and major acute phase protein (pig-MAP) and the negative APPs albumin...... and apolipoprotein (Apo) A-I. The aim was to elucidate the differences in the acute phase behaviour of the individual APPs during a typical bacterial septicaemic, infection. Pigs were inoculated subcutaneously with live S. suis serotype 2 and blood was sampled before and on various days post inoculation (p...... the experiment with maximum levels around 10 times the day 0-levels, and pig-MAP was elevated on days 1-12 p.i. with peak levels of around seven times the day 0-levels. Apo A-I was decreased from days 1 to 8 and showed minimum levels of about 40% of day 0-levels around 1-2 days p.i. No clear pattern of changes...

  1. Perfusion measurements of the brain: using dynamic CT for the quantitative assessment of cerebral ischemia in acute stroke

    International Nuclear Information System (INIS)

    Klotz, Ernst; Koenig, Matthias

    1999-01-01

    Objective: Perfusion CT has been successfully used as a functional imaging technique for the differential diagnosis of patients with hyperacute stroke. We investigated to what extent this technique can also be used for the quantitative assessment of cerebral ischemia. Methods and material: We studied linearity, spatial resolution and noise behaviour of cerebral blood flow (CBF) determination with computer simulations and phantom measurements. Statistical ROI based analysis of CBF images of a subset of 38 patients from a controlled clinical stroke study with currently more than 75 patients was done to check the power of relative cerebral blood flow (rCBF) values to predict definite infarction and ischemic penumbra. Classification was performed using follow-up CT and MR data. Results: Absolute CBF values were systematically underestimated, the degree depended on the cardiac output of the patients. Phantom measurements and simulations indicated very good linearity allowing reliable calculation of rCBF values. Infarct and penumbra areas in 19 patients receiving standard heparin therapy had mean rCBF values of 0.19 and 0.62, respectively. The corresponding values for 19 patients receiving local intraarterial fibrinolysis were 0.18 and 0.57. The difference between infarct and penumbra values was highly significant (P<0.0001) in both groups. No penumbra area was found with an rCBF value of less than 0.20. While in the heparin group only 25% of all areas with an rCBF between 0.20 and 0.35 survived, in the fibrinolytic group 61% of these areas could be saved (P<0.05). Conclusion: Perfusion CT is a fast and practical technique for routine clinical application. It provides substantial and important additional information for the selection of the optimal treatment strategy for patients with hyperacute stroke. Relative values of cerebral blood flow discriminate very well between areas of reversible and irreversible ischemia; an rCBF value of 0.20 appears to be a definite lower

  2. Effect of hyperthermia on experimental acute pancreatitis Efeito da hipertermia na pancreatite aguda experimental

    Directory of Open Access Journals (Sweden)

    José Luiz Jesus de Almeida

    2006-12-01

    Full Text Available BACKGROUD: Recent studies indicate that hyperthermia can change inflammatory mechanisms and protect experimental animals from deleterious effects of secretagogue-induced acute pancreatitis AIM: To evaluate the effects of hyperthermia post-treatment on cerulein-induced acute pancreatitis in rats METHODS: Twenty animals were divided in two groups: group I (n = 10, rats with cerulein-induced acute pancreatitis undergone hyperthermia, and group II (n = 10, animals with cerulein-induced acute pancreatitis that were kept normothermic. In all groups, amylase serum levels, histologic damage, vascular permeability and pancreatic water content were assessed. Acute pancreatitis was induced by administration of two cerulein injections (20 mcg/kg. A single dose of Evans' blue dye was administered along with the second dose of cerulein. All animals also received a subcutaneous injection of saline solution. After this process, animals undergone hyperthermia were heated in a cage with two 100 W lamps. Body temperature was increased to 39.5ºC and maintained at that level for 45 minutes. Normothermia rats were kept at room temperature in a second cage RESULTS: Control animals had typical edema, serum amylase activity and morphologic changes of this acute pancreatitis model. Hyperthermia post-treatment ameliorated the pancreatic edema, whereas the histologic damage and the serum amylase level remained unchanged CONCLUSIONS: The findings suggest a beneficial effect of the thermal stress on inflammatory edema in experimental acute pancreatitis.RACIONAL: Estudos recentes indicam que a hipertermia pode modificar mecanismos inflamatórios e proteger animais experimentais dos efeitos deletérios da pancreatite aguda induzida por secretagogos OBJETIVO: Avaliar a eficácia da hipertermia como tratamento da pancreatite aguda induzida por ceruleína em ratos MÉTODOS: Vinte animais foram divididos em dois grupos: grupo I (n = 10, ratos com pancreatite aguda induzida por

  3. Magnetic resonance spectroscopy and imaging in cerebral ischemia

    International Nuclear Information System (INIS)

    Rijen, P.C. van.

    1991-01-01

    In-vivo proton and phosphorus magnetic resonance spectroscopy was used to detect changes in cerebral metabolism during ischemia and other types of metabolic stress. Magnetic resonance imaging was performed in an animal model to observe morphological alterations during focal cerebral ischemia. Spectroscopy was performed in animal models with global ischemia, in volunteers during hyperventilation and pharmaco-logically altered cerebral perfusion, and in patients with acute and prolonged focal cerebral ischemia. (author). 396 refs.; 44 figs.; 14 tabs

  4. Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury

    Science.gov (United States)

    Suchal, Kapil; Malik, Salma; Gamad, Nanda; Malhotra, Rajiv Kumar; Goyal, Sameer N.; Chaudhary, Uma; Bhatia, Jagriti; Ojha, Shreesh; Arya, Dharamvir Singh

    2016-01-01

    Kaempferol (KMP), a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR) model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p.) was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB), inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3), TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2). In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway. PMID:27087891

  5. Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Kapil Suchal

    2016-01-01

    Full Text Available Kaempferol (KMP, a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p. was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB, inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3, TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2. In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway.

  6. The Protective Effects of Alpha-Lipoic Acid and Coenzyme Q10 Combination on Ovarian Ischemia-Reperfusion Injury: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Ahmet Ali Tuncer

    2016-01-01

    Full Text Available Objective. This study aims to evaluate whether alpha-lipoic acid and/or coenzyme Q10 can protect the prepubertal ovarian tissue from ischemia-reperfusion injury in an experimental rat model of ovarian torsion. Materials and Methods. Forty-two female preadolescent Wistar-Albino rats were divided into 6 equal groups randomly. The sham group had laparotomy without torsion; the other groups had torsion/detorsion procedure. After undergoing torsion, group 2 received saline, group 3 received olive oil, group 4 received alpha-lipoic acid, group 5 received coenzyme Q10, and group 6 received both alpha-lipoic acid and coenzyme Q10 orally. The oxidant-antioxidant statuses of these groups were compared using biochemical measurement of oxidized/reduced glutathione, glutathione peroxidase and malondialdehyde, pathological evaluation of damage and apoptosis within the ovarian tissue, and immunohistochemical assessment of nitric oxide synthase. Results. The left ovaries of the alpha-lipoic acid + coenzyme Q10 group had significantly lower apoptosis scores and significantly higher nitric oxide synthase content than the left ovaries of the control groups. The alpha-lipoic acid + coenzyme Q10 group had significantly higher glutathione peroxidase levels and serum malondialdehyde concentrations than the sham group. Conclusions. The combination of alpha-lipoic acid and coenzyme Q10 has beneficial effects on oxidative stress induced by ischemia-reperfusion injury related to ovarian torsion.

  7. Changing circadian variation of transient myocardial ischemia during the first year after a first acute myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H; Pless, P; Nielsen, J R

    1992-01-01

    In a consecutive series of 123 men (aged 55 +/- 8 years) with a recent first acute myocardial infarction (AMI), 24-hour ambulatory ST-segment monitoring was performed early after discharge (day 11 +/- 5), 6 months (day 185 +/- 6) and 1 year (day 368 +/- 8) after AMI. No difference in the prevalen...

  8. Impact of lesion location on procedural and acute angiographic outcomes in patients with critical limb ischemia treated for peripheral artery disease with orbital atherectomy: A CONFIRM registries subanalysis.

    Science.gov (United States)

    Lee, Michael S; Mustapha, Jihad; Beasley, Robert; Chopra, Paramjit; Das, Tony; Adams, George L

    2016-02-15

    This analysis compares the procedural and acute angiographic outcomes in patients with critical limb ischemia (CLI) treated with orbital atherectomy in above-the-knee (ATK)/popliteal (POP) lesions versus below-the-knee (BTK) lesions. Lesion location affects the procedural outcomes and the opportunity for limb salvage in patients with CLI suffering from peripheral artery disease (PAD). The CONFIRM registry series was analyzed and includes 1109 real-world patients (1544 lesions) suffering from CLI treated with orbital atherectomy. The rates of dissection, perforation, slow flow, vessel closure, spasm, embolism, and thrombus formation were compared between CLI patients with ATK/POP lesions and BTK lesions. Patients with ATK/POP lesions had a higher final residual stenosis (10 vs. 9%; P = 0.004) and use of more adjunctive therapies (e.g. balloons and stents; 1.3 vs. 1.1%; P atherectomy was successful in CLI patients regardless of lesion location. BTK lesions were associated with increased rates of perforation, slow flow and spasm which may be explained by more challenging procedural characteristics in these patients such as smaller vessel size and tortuosity. The higher incidence of emboli in ATK/POP lesions is most likely attributed to the higher prevalence of severe calcium observed in this cohort. © 2015 Wiley Periodicals, Inc.

  9. Subanalysis of the CONFIRM Registries: Acute Procedural Outcomes in Claudicant and Critical Limb Ischemia Patients With Varying Levels of Calcification Treated for Peripheral Arterial Disease With Orbital Atherectomy.

    Science.gov (United States)

    Adams, George L; Das, Tony; Lee, Michael S; Beasley, Robert; Mustapha, Jihad

    2015-11-01

    Patients with peripheral arterial disease (PAD) can be classified into groups based upon the severity of the disease using the Rutherford classification system. This analysis compares the procedural outcomes of PAD patients treated with orbital atherectomy stratified by Rutherford class (1-3 = intermittent claudication; 4-6 = critical limb ischemia [CLI]), and acute angiographic outcomes of these patients stratified by degree of lesion calcification. The CONFIRM registry series was analyzed and included 1697 patients with intermittent claudication (Rutherford class 1-3) and 1320 patients with CLI (Rutherford class 4-6) treated with orbital atherectomy. The composite rate of dissection, perforation, slow-flow, vessel closure, spasm, embolism, and thrombus formation was compared between claudicants and CLI patients with varying degrees of lesion calcification. Patients with CLI were older and had a higher prevalence of diabetes, coronary artery disease, and renal disease (Patherectomy resulted in similar low procedural complication rates in the CLI group compared with the claudicant group. These results suggest that orbital atherectomy is safe and effective for treating calcified lesions in high-risk patients with varying severity of PAD symptoms.

  10. UHPLC-LTQ-Orbitrap MS combined with spike-in method for plasma metabonomics analysis of acute myocardial ischemia rats and pretreatment effect of Danqi Tongmai tablet.

    Science.gov (United States)

    Yan, Bingpeng; Deng, Yanping; Hou, Jinjun; Bi, Qirui; Yang, Min; Jiang, Baohong; Liu, Xuan; Wu, Wanying; Guo, Dean

    2015-02-01

    Undoubtedly, metabonomics can reveal the comprehensive efficacies of traditional Chinese medicine (TCM) formulae and its complex mechanism at the molecular biological level. In this study, an attempt was made to address the pretreatment effect of a TCM formula. In this case, as a critical point, we should first know how to really reflect the various endogenous metabolites in a disease status before a TCM formula is employed in a therapeutic procedure. Here, we explored an approach that combined high resolution LTQ-Orbitrap mass spectrometry with a spike-in method to characterize endogenous metabolites in acute myocardial ischemia (AMI) rats. As a result, 19 potential biomarkers in rat plasma were identified and 10 related disturbed pathways were perturbed in the early stages of AMI development. Subsequently, the metabonomics method was applied to investigate the pretreatment effect of the TCM formula named the Danqi Tongmai tablet (DQTM). The results revealed that the DQTM pretreatment could reduce the AMI injury and partially regulate the perturbed TCA cycle and amino and nucleotide metabolism, which were presumable related to energy metabolism and myocardial cells apoptosis/necrosis. In conclusion, UHPLC-LTQ-Orbitrap MS combined with a spike-in method were successfully applied to the metabonomics analysis of DQTM, which demonstrated that not only a comprehensive metabolic profile in the early stages of AMI development was achieved, but also that the underlying holistic efficacies were assessed and it was helpful to understand the possible mechanism of pretreatment with DQTM.

  11. Recurrent ischemia across the spectrum of acute coronary syndromes: prevalence and prognostic significance of (re-)infarction and ST-segment changes in a large contemporary registry.

    Science.gov (United States)

    Yan, Andrew T; Steg, Philippe Gabriel; Fitzgerald, Gordon; Feldman, Laurent J; Eagle, Kim A; Gore, Joel M; Anderson, Frederick A; López-Sendón, Jose; Gurfinkel, Enrique P; Brieger, David; Goodman, Shaun G

    2010-11-05

    There are limited recent data on the prevalence and potentially different adverse impact of the various types of recurrent ischemia (RI) in unselected patients with acute coronary syndromes(ACS). We examined the clinical features and treatment associated with, and the differential prognostic impact of, the various types of RI in unselected patients across the broad spectrum of ACS in the contemporary era. The Global Registry of Acute Coronary Events (GRACE) was a prospective, multinational registry of patients hospitalized for ACS. Data were collected on standardized case report forms. Of the 29,400 ACS patients enrolled in May 2000-March 2007, 21% developed RI; 2.4%, 4.9%, and 16% had myocardial (re-)infarction [(re-)MI], RI with ST-segment changes, and RI without ST-segment changes (not mutually exclusive), respectively. Rates of in-hospital mortality and complications, and 6-month mortality were significantly higher among patients with RI compared to those without; the rates were highest for patients who developed (re-)MI, followed by those with RI and ST-segment changes. After adjusting for other validated prognosticators in the GRACE risk score, all three types of RI retained an independent association with both higher in-hospital and post-discharge 6-month mortality. Early revascularization was associated with lower in-hospital mortality only in the group with (re-)MI (P for interaction=0.003). Despite the current use of intensive medical therapies, RI remains a common and serious consequence across the spectrum of ACS. Different types of RI confer a variable adverse prognostic impact. Re-MI is associated with the worst outcome, which appears to be mitigated by early revascularization. Our findings underscore the persistent need to improve the treatment of ACS. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  12. Ischemia-modified albumin levels in the prediction of acute critical neurological findings in carbon monoxide poisoning

    Directory of Open Access Journals (Sweden)

    Murat Daş

    2016-04-01

    Full Text Available The aim of the study was to determine whether serum ischemia-modified albumin (IMA levels in patients with carbon monoxide (CO poisoning were higher compared with a control group of healthy volunteers. In addition, the study sought to determine if there was a correlation between serum IMA levels and carboxyhemoglobin (COHB levels and other critical neurological findings (CNFs. In this prospective study, the IMA levels of 100 patients with CO poisoning and 50 control individuals were compared. In addition, the IMA and COHB levels were analyzed according to absence or presence CNFs in patients with CO poisoning. The levels of IMA (mg/dL on admittance, and during the 1st hour and 3rd hour, in patients with CO poisoning (49.90 ± 35.43, 30.21 ± 14.81, and 21.87 ± 6.03 were significantly higher, compared with the control individuals (17.30 ± 2.88. The levels of IMA in the 6th hour were not higher compared with control individuals. The levels of IMA on admittance, and during the 1st hour, 3rd hour, and 6th hour, and COHB (% levels in patients who had CNFs were higher compared with IMA levels and COHB levels in patients who had no CNFs (p < 0.001. However, when the multivariate model was created, it was observed that IMA level on admittance was a poor indicator for prediction of CNFs (odds ratio = 1.05; 95% confidence interval, 1.01–1.08. We therefore concluded that serum IMA levels could be helpful in the diagnosis of CO poisoning. However, we believe that IMA levels cannot be used to predict which patients will develop CNFs due to CO poisoning.

  13. [Effects of the of renal warm ischemia time on the recovery of filtration function in the experiment].

    Science.gov (United States)

    Guseinov, R G; Popov, S V; Gorshkov, A N; Sivak, K V; Martov, A G

    2017-12-01

    To investigate experimentally ultrastructural and biochemical signs of acute injury to the renal parenchyma after warm renal ischemia of various duration and subsequent reperfusion. The experiments were performed on 44 healthy conventional female rabbits of the "Chinchilla" breed weighted 2.6-2.7 kg, which were divided into four groups. In the first, control, group included pseudo-operated animals. In the remaining three groups, an experimental model of warm ischemia of renal tissue was created, followed by a 60-minute reperfusion. The renal warm ischemia time was 30, 60 and 90 minutes in the 2nd, 3rd and 4th groups, respectively. Electron microscopy was used to study ultrastructural disturbances of the renal parenchyma. Biochemical signs of acute kidney damage were detected by measuring the following blood serum and/or urine analytes: NGAL, cystatin C, KIM-1, L-FABP, interleukin-18. The glomerular filtration was evaluated by creatinine clearance, which was determined on days 1, 5, 7, 14, 21 and 35 of follow-up. A 30-minute renal warm ischemia followed by a 60-minute reperfusion induced swelling and edema of the brush membrane, vacuolation of the cytoplasm of the endothelial cells of the proximal tubules, and microvilli restructuring. The observed disorders were reversible, and the epithelial cells retained their viability. After 60 minutes of ischemia and 60 minutes of reperfusion, the observed changes in the ultrastructure of the epithelial cells were much more pronounced, some of the epithelial cells were in a state of apoptosis. 90 min of ischemia and 60 min of reperfusion resulted in electron-microscopic signs of the mass cellular death of the tubular epithelium. Concentration in serum and/or biochemical urine markers of acute renal damage increased sharply after ischemic-reperfusion injury. Restoration of indicators was observed only in cases when the renal warm ischemia time did not exceed 60 minutes. The decrease in creatinine clearance occurred in the

  14. Dictionary-driven Ischemia Detection from Cardiac Phase-Resolved Myocardial BOLD MRI at Rest

    Science.gov (United States)

    Bevilacqua, Marco; Dharmakumar, Rohan; Tsaftaris, Sotirios A.

    2016-01-01

    Cardiac Phase-resolved Blood-Oxygen-Level Dependent (CP–BOLD) MRI provides a unique opportunity to image an ongoing ischemia at rest. However, it requires post-processing to evaluate the extent of ischemia. To address this, here we propose an unsupervised ischemia detection (UID) method which relies on the inherent spatio-temporal correlation between oxygenation and wall motion to formalize a joint learning and detection problem based on dictionary decomposition. Considering input data of a single subject, it treats ischemia as an anomaly and iteratively learns dictionaries to represent only normal observations (corresponding to myocardial territories remote to ischemia). Anomaly detection is based on a modified version of One-class Support Vector Machines (OCSVM) to regulate directly the margins by incorporating the dictionary-based representation errors. A measure of ischemic extent (IE) is estimated, reflecting the relative portion of the myocardium affected by ischemia. For visualization purposes an ischemia likelihood map is created by estimating posterior probabilities from the OCSVM outputs, thus obtaining how likely the classification is correct. UID is evaluated on synthetic data and in a 2D CP–BOLD data set from a canine experimental model emulating acute coronary syndromes. Comparing early ischemic territories identified with UID against infarct territories (after several hours of ischemia), we find that IE, as measured by UID, is highly correlated (Pearson’s r = 0.84) w.r.t. infarct size. When advances in automated registration and segmentation of CP–BOLD images and full coverage 3D acquisitions become available, we hope that this method can enable pixel-level assessment of ischemia with this truly non-invasive imaging technique. PMID:26292338

  15. Chinese Medicine Injection Qingkailing for Treatment of Acute Ischemia Stroke: A Systematic Review of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Fafeng Cheng

    2012-01-01

    Full Text Available Qingkailing (QKL injection was a famous traditional Chinese patent medicine, which was extensively used to treat the acute stages of cerebrovascular disease. The aim of this study was to assess the quantity, quality and overall strength of the evidence on QKL in the treatment of acute ischemic stroke. Methods. An extensive search was performed within MEDLINE, Cochrane, CNKI, Vip and Wan-Fang up to November 2011. Randomized controlled trails (RCTs on QKL for treatment of acute stroke were collected, irrespective of languages. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards, and RevMan5 was used for data analysis. Results. 7 RCTs (545 patients were included and the methodological quality was evaluated as generally low. The pooled results showed that QKL combined with conventional treatment was more effective in effect rate, and the score of MESSS and TNF-α level compared with conventional treatment alone, but there was no significant difference in mortality of two groups. Only one trial reported routine life status. There were four trials reported adverse events, and no obvious adverse event occurred in three trials while one reported adverse events described as eruption and dizziness.

  16. [Experimental study on potential for cardiac assist by latissimus dorsi myograft--an importance of muscle ischemia].

    Science.gov (United States)

    Morita, K; Koyanagi, K; Sakamoto, Y; Wakabayashi, K; Tanaka, K; Horikoshi, S; Matsui, M; Arai, T

    1991-03-01

    We have studied contractile property and fatigue rates of skeletal muscle ventricle (SMV) constructed using the latissimus dorsi muscles of 11 dogs. The role of early interruption of collateral blood supply in the prevention of muscle ischemia and SMV fatigue was evaluated. Systolic function of SMV was measured in a hydraulic test system; afterload was set at 70 mmHg and preload 15 or 25 mmHg. Control SMV (GI: N = 7), which was fashioned immediately after interruption of collateral blood supply, generated an initial SMV pressure of 222 +/- 50 mmHg and stroke volume of 15 +/- 7 ml/beat with muscle stimulation at a burst-frequency of 50 Hz, but could sustain flow for only 3.5 +/- 0.8 minutes. SMV subjected to a vascular delay (Group II: N = 4) demonstrated improvement of fatigue rates; duration of flow 32.4 +/- 14.0 and sufficient contractile property (initial SMV pressure 182 +/- 17 mmHg, stroke volume 1- +/- 2 ml/beat). Thermography surface temperature mapping revealed remarkable improvement of blood distribution in GII muscles. Flow rates of thoracodorsal artery were significantly greater in GII muscles compared to those in GI muscles (15.0 +/- 3.7 ml/min/LD 100 g, 10.1 +/- 3.1 ml/min/LD 100 g, p less than 0.05, respectively). Despite significant improvement of functional durability in GII muscles, the ratio of oxygen consumption to lactate output was not different between 2 groups. These results suggest that early interruption of collateral blood supply can minimize muscle ischemia, resulting in diminishing fatigue of latissimus dorsi muscles without changes in skeletal muscle metabolism.

  17. Rapid morphological changes and loss of collagen following experimental acute colonic obstruction

    DEFF Research Database (Denmark)

    Krarup, Peter-Martin; Rehn, Martin; Sand-Dejmek, Janna

    2013-01-01

    Anastomosis of an acutely obstructed colon is associated with an increased risk of dehiscence. In experimental models, acute obstruction decreases collagen in the colonic wall, but the time course and propagation along the colon of the biochemical changes are unknown. Furthermore, there is a pauc......Anastomosis of an acutely obstructed colon is associated with an increased risk of dehiscence. In experimental models, acute obstruction decreases collagen in the colonic wall, but the time course and propagation along the colon of the biochemical changes are unknown. Furthermore...

  18. Global Ischemia ECG pattern for diagnosis of acute left main occlusion: prevalence and associated mortality in patients with suspected acute myocardial infarction

    DEFF Research Database (Denmark)

    Stengaard, Carsten; Sørensen, Jacob Thorsted; Andersen, M.P.

    2011-01-01

    , Department of Cardiology, Heart Center - Tampere - Finland, 5Duke University Medical Center, Department of Medicine, Division of Cardiology - Durham - United States of America, Topic(s): Infarction acute phase STEMI Citation: European Heart Journal ( 2011 ) 32 ( Abstract Supplement ), 1054 Purpose: A global...... occlusion of 4.3%. Mortality in patients with GIP was significantly higher compared to patients without GIP (preports...

  19. Leukocytic Response and Peripheral Venous Blood Lymphocyte Apoptosis as a Marker of Tissue Ischemia in Acute Massive Blood Loss

    Directory of Open Access Journals (Sweden)

    N. V. Borovkova

    2013-01-01

    Full Text Available Objective: to estimate the level of peripheral venous blood lymphocyte apoptosis and intraoperative hypoxia in victims with acute massive blood loss. Subjects and methods. Twenty-two patients with open and close chest and abdominal traumas complicated by acute massive blood loss were examined. All the patients were emergently operated on to stop bleeding. Tissue metabolism was evaluated from gases, acid-base parameters, and plasma lactate, glucose, potassium, and sodium levels. Apoptosis of mononuclear cells was studied and dead leukocytes were counted using flow cytometry. Results. Preoperatively, the victims were found to have venous hypoxemia, hyperlactatemia, hyperglycemia, moderate leukocytosis, and higher dead leukocyte counts. There were also raised counts of lymphocytes coming into the process of apoptosis. A significant relationship was found between monocyte counts and hypoxia values. At the end of surgery, oxygen balance values became stable and exerted an effect on the count of leukocytes, the relative level of granulocytes, the relative and absolute counts of dead and damaged leukocytes, and the concentration of lymphocytes in the victims’ venous blood during the early stages of apoptosis, as evidenced by nonlinear regression models. Conclusion. The indicators of immunocompetent cell apoptosis and the count of venous blood dead leukocytes along with lactate levels and venous hypoxemia parameters reflect the degree of tissue hypoxia and may be used as specific markers.

  20. Myocardial oxygenation and transmural lactate metabolism during experimental acute coronary stenosis in pigs.

    Science.gov (United States)

    Gonschior, P; Gonschior, G M; Conzen, P F; Hobbhahn, J; Goetz, A E; Peter, K; Brendel, W

    1992-01-01

    Measurement of surface tissue pO2 (ptO2) with surface electrodes is increasingly applied in experimental medicine. Its use on the beating heart may seem to be problematic because transmural gradients of tissue pO2 would reduce the validity of pO2 determinations in the epicardial layers. This study attempted to determine whether ptO2 may be a valid and sensitive indicator of transmural myocardial oxygenation. In order to measure ptO2, two eight-channel Clark-type electrodes were placed on a beating porcine left ventricle (n = 13). Measurements were made at different degrees of acute stenosis of the left anterior descending artery (LAD). A 24-F cannula was inserted into the great cardiac vein, draining the poststenotic myocardium to obtain coronary venous blood samples. Transmural metabolic changes were detected simultaneously by coronary venous blood gas parameters and lactate levels. Epicardial tissue pO2 was 49 +/- 2 mm Hg (mean +/- SEM) before stenosis and decreased to a mean value of 25 +/- 2 mm Hg during stenosis. Different degrees of LAD stenosis (ptO2 range: 12-35 mm Hg) were substantial enough to alter arterio-coronary venous lactate difference (avd lactate) from +0.31 +/- 0.07 mmol/l (control) to -0.62 +/- 0.15 mmol/l (stenosis). A significant linear correlation between changes of ptO2 (delta ptO2) and changes of avd lactate (delta avd lactate) resulted (y = 0.59 + 0.62x; r = 0.86; p less than or equal to 0.001). However, linear regression analysis between delta ptO2 correlated with the corresponding data from coronary venous pO2 (delta pO2cv) oxygen content (delta O2contcv), and oxygen saturation (delta O2satcv) showed no significant correlations. We conclude that measurement of ptO2 is a sensitive and valuable indicator of transmural oxygenation in ischemic myocardium, whereas pO2cv, O2contcv and O2satcv do not seem to be valid predictors of ischemia in myocardial oxygenation.

  1. Failure of experimental acute intra-gastric gas and fluid ...

    African Journals Online (AJOL)

    USER

    2010-07-26

    Jul 26, 2010 ... of acute gastric dilatation-volvulus in dog and man have been widely studied ... blood count (CBC), serum biochemistry analysis, urinalysis and fecal examination for .... to the multiple nature of the risk factors involved in the.

  2. Plastic Change along the Intact Crossed Pathway in Acute Phase of Cerebral Ischemia Revealed by Optical Intrinsic Signal Imaging

    Directory of Open Access Journals (Sweden)

    Xiaoli Guo

    2016-01-01

    Full Text Available The intact crossed pathway via which the contralesional hemisphere responds to the ipsilesional somatosensory input has shown to be affected by unilateral stroke. The aim of this study was to investigate the plasticity of the intact crossed pathway in response to different intensities of stimulation in a rodent photothrombotic stroke model. Using optical intrinsic signal imaging, an overall increase of the contralesional cortical response was observed in the acute phase (≤48 hours after stroke. In particular, the contralesional hyperactivation is more prominent under weak stimulations, while a strong stimulation would even elicit a depressed response. The results suggest a distinct stimulation-response pattern along the intact crossed pathway after stroke. We speculate that the contralesional hyperactivation under weak stimulations was due to the reorganization for compensatory response to the weak ipsilateral somatosensory input.

  3. Point-of-Care Ultrasound in Necrotizing Acute Pancreatitis Complicated by Perforated Ileum Due to Nonocclusive Mesenteric Ischemia

    Directory of Open Access Journals (Sweden)

    Sonia López-Cuenca

    2016-09-01

    Full Text Available Necrotizing acute pancreatitis is the most severe form of pancreatitis, and it is a potentially life-threatening condition. Its diagnosis and severity are based on radiological signs. Although computed tomography is the most used imaging tool, ultrasound can be a quick and useful technique in emergency and intensive care scenarios. The use of abdominal ultrasound is generally limited to ruling out cholecystitis. Bowel gas can limit the accuracy of pancreatic imaging. When the pancreas is visualized, ultrasound can reveal pancreatic enlargement, echotextural changes, and peripancreatic fluid. We present a patient with necrotizing pancreatitis who developed peritonitis due to ileal perforation, where the use of ultrasound as a bedside imaging technique was very useful.

  4. Exercise preconditioning improves behavioral functions following transient cerebral ischemia induced by 4-vessel occlusion (4-VO) in rats.

    Science.gov (United States)

    Tahamtan, Mahshid; Allahtavakoli, Mohammad; Abbasnejad, Mehdi; Roohbakhsh, Ali; Taghipour, Zahra; Taghavi, Mohsen; Khodadadi, Hassan; Shamsizadeh, Ali

    2013-12-01

    There is evidence that exercise decreases ischemia/reperfusion injury in rats. Since behavioral deficits are the main outcome in patients after stroke, our study was designed to investigate whether exercise preconditioning improves the acute behavioral functions and also brain inflammatory injury following cerebral ischemia. Male rats weighing 250-300 g were randomly allocated into five experimental groups. Exercise was performed on a treadmill 30min/day for 3 weeks. Ischemia was induced by 4-vessel occlusion method. Recognition memory was assessed by novel object recognition task (NORT) and step-through passive avoidance task. Sensorimotor function and motor movements were evaluated by adhesive removal test and ledged beam-walking test, respectively. Brain inflammatory injury was evaluated by histological assessment. In NORT, the discrimination ratio was decreased after ischemia (P test, a significant reduction in response latency was observed in the ischemic group. Exercise preconditioning significantly decreased the response latency in the ischemic rats (P test, latency to touch and remove the sticky labels from forepaw was increased following induction of ischemia (all P beam-walking test, the slip ratio was increased following ischemia (P < 0.05).  In the ischemia group, marked neuronal injury in hippocampus was observed. These neuropathological changes were attenuated by exercise preconditioning (P < 0.001). Our results showed that exercise preconditioning improves behavioral functions and maintains more viable cells in the dorsal hippocampus of the ischemic brain.

  5. Probiotics enhance pancreatic glutathione biosynthesis and reduce oxidative stress in experimental acute pancreatitis

    NARCIS (Netherlands)

    Lutgendorff, Femke; Trulsson, Lena M.; van Minnen, L. Paul; Rijkers, Ger T.; Timmerman, Harro M.; Franzen, Lennart E.; Gooszen, Hein G.; Akkermans, Louis M. A.; Soderholm, Johan D.; Sandstrom, Per A.

    2008-01-01

    Factors determining severity of acute pancreatitis (AP) are poorly understood. Oxidative stress causes acinar cell injury and contributes to the severity, whereas prophylactic probiotics ameliorate experimental pancreatitis. Our objective was to study how probiotics affect oxidative stress,

  6. Cellular infiltrates and injury evaluation in a rat model of warm pulmonary ischemia-reperfusion

    NARCIS (Netherlands)

    Van Putte, BP; Kesecioglu, J; Hendriks, JMH; Persy, VP; van Marck, E; Van Schil, PEY; De Broe, ME

    Introduction Beside lung transplantation, cardiopulmonary bypass, isolated lung perfusion and sleeve resection result in serious pulmonary ischemia - reperfusion injury, clinically known as acute respiratory distress syndrome. Very little is known about cells infiltrating the lung during ischemia -

  7. Noninvasive Multimodal Imaging to Predict Recovery of Locomotion after Extended Limb Ischemia.

    Directory of Open Access Journals (Sweden)

    Jason S Radowsky

    Full Text Available Acute limb ischemia is a common cause of morbidity and mortality following trauma both in civilian centers and in combat related injuries. Rapid determination of tissue viability and surgical restoration of blood flow are desirable, but not always possible. We sought to characterize the response to increasing periods of hind limb ischemia in a porcine model such that we could define a period of critical ischemia (the point after which irreversible neuromuscular injury occurs, evaluate non-invasive methods for characterizing that ischemia, and establish a model by which we could predict whether or not the animal's locomotion would return to baselines levels post-operatively. Ischemia was induced by either application of a pneumatic tourniquet or vessel occlusion (performed by clamping the proximal iliac artery and vein at the level of the inguinal ligament. The limb was monitored for the duration of the procedure with both 3-charge coupled device (3CCD and infrared (IR imaging for tissue oxygenation and perfusion, respectively. The experimental arms of this model are effective at inducing histologically evident muscle injury with some evidence of expected secondary organ damage, particularly in animals with longer ischemia times. Noninvasive imaging data shows excellent correlation with post-operative functional outcomes, validating its use as a non-invasive means of viability assessment, and directly monitors post-occlusive reactive hyperemia. A classification model, based on partial-least squares discriminant analysis (PLSDA of imaging variables only, successfully classified animals as "returned to normal locomotion" or "did not return to normal locomotion" with 87.5% sensitivity and 66.7% specificity after cross-validation. PLSDA models generated from non-imaging data were not as accurate (AUC of 0.53 compared the PLSDA model generated from only imaging data (AUC of 0.76. With some modification, this limb ischemia model could also serve as a

  8. Remote Ischemic Postconditioning (RIPC) of the Upper Arm Results in Protection from Cardiac Ischemia-Reperfusion Injury Following Primary Percutaneous Coronary Intervention (PCI) for Acute ST-Segment Elevation Myocardial Infarction (STEMI).

    Science.gov (United States)

    Cao, Bangming; Wang, Haipeng; Zhang, Chi; Xia, Ming; Yang, Xiangjun

    2018-02-19

    BACKGROUND The aim of this study was to evaluate the role of remote ischemic postconditioning (RIPC) of the upper arm on protection from cardiac ischemia-reperfusion injury following primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). MATERIAL AND METHODS Eighty patients with STEMI were randomized into two groups: primary PCI (N=44) and primary PCI+RIPC (N=36). RIPC consisted of four cycles of 5 minutes of occlusion and five minutes of reperfusion by cuff inflation and deflation of the upper arm, commencing within one minute of the first PCI balloon dilatation. Peripheral venous blood samples were collected before PCI and at 0.5, 8, 24, 48, and 72 hours after PCI. Levels of creatine kinase-MB (CK-MB), serum creatinine (Cr), nitric oxide (NO), and stromal cell-derived factor-1α (SDF-1α) were measured. The rates of acute kidney injury (AKI) and the estimated glomerular filtration rate (eGFR) were calculated. RESULTS Patients in the primary PCI+RIPC group, compared with the primary PCI group, had significantly lower peak CK-MB concentrations (PPCI in patients with acute STEMI might provide cardiac and renal protection from ischemia-reperfusion injury via the actions of SDF-1α, and NO.

  9. Neuromodulation therapy does not influence blood flow distribution or left-ventricular dynamics during acute myocardial ischemia.

    Science.gov (United States)

    Kingma, J G; Linderoth, B; Ardell, J L; Armour, J A; DeJongste, M J; Foreman, R D

    2001-08-13

    Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with angina pectoris refractory to conventional therapeutic strategies. The purpose of this study was to determine whether spinal cord stimulation (SCS) in dogs affects regional myocardial blood flow and left-ventricular (LV) function before and during transient obstruction of the left anterior descending coronary artery (LAD). In anesthetized dogs, regional myocardial blood flow distribution was determined using radiolabeled microspheres and left-ventricular function was measured by impedance-derived pressure-volume loops. SCS was accomplished by stimulating the dorsal T1-T2 segments of the spinal cord using epidural bipolar electrodes at 90% of motor threshold (MT) (50 Hz, 0.2-ms duration). Effects of 5-min SCS were assessed under basal conditions and during 4-min occlusion of the LAD. SCS alone evoked no change in regional myocardial blood flow or cardiovascular indices. Transient LAD occlusion significantly diminished blood flow within ischemic, but not in non-ischemic myocardial tissue. Left ventricular pressure-volume loops were shifted rightward during LAD occlusion. Cardiac indices were altered similarly during LAD occlusion and concurrent SCS. SCS does not influence the distribution of blood flow within the non-ischemic or ischemic myocardium. Nor does it modify LV pressure-volume dynamics in the anesthetized experimental preparation.

  10. Fibroblast growth factor-1 improves cardiac functional recovery and enhances cell survival after ischemia and reperfusion: a fibroblast growth factor receptor, protein kinase C, and tyrosine kinase-dependent mechanism

    NARCIS (Netherlands)

    Palmen, Meindert; Daemen, Mat J. A. P.; de Windt, Leon J.; Willems, Jodil; Dassen, Willem R. M.; Heeneman, Sylvia; Zimmermann, Rene; van Bilsen, Marc; Doevendans, Pieter A.

    2004-01-01

    We sought to investigate the role of fibroblast growth factor (FGF)-1 during acute myocardial ischemia and reperfusion. The FGFs display cardioprotective effects during ischemia and reperfusion. We investigated FGF-1-induced cardioprotection during ischemia and reperfusion and the intracellular

  11. Multiple therapeutic effects of progranulin on experimental acute ischaemic stroke.

    Science.gov (United States)

    Kanazawa, Masato; Kawamura, Kunio; Takahashi, Tetsuya; Miura, Minami; Tanaka, Yoshinori; Koyama, Misaki; Toriyabe, Masafumi; Igarashi, Hironaka; Nakada, Tsutomu; Nishihara, Masugi; Nishizawa, Masatoyo; Shimohata, Takayoshi

    2015-07-01

    In the central nervous system, progranulin, a glycoprotein growth factor, plays a crucial role in maintaining physiological functions, and progranulin gene mutations cause TAR DNA-binding protein-43-positive frontotemporal lobar degeneration. Although several studies have reported that progranulin plays a protective role against ischaemic brain injury, little is known about temporal changes in the expression level, cellular localization, and glycosylation status of progranulin after acute focal cerebral ischaemia. In addition, the precise mechanisms by which progranulin exerts protective effects on ischaemic brain injury remains unknown. Furthermore, the therapeutic potential of progranulin against acute focal cerebral ischaemia, including combination treatment with tissue plasminogen activator, remains to be elucidated. In the present study, we aimed to determine temporal changes in the expression and localization of progranulin after ischaemia as well as the therapeutic effects of progranulin on ischaemic brain injury using in vitro and in vivo models. First, we demonstrated a dynamic change in progranulin expression in ischaemic Sprague-Dawley rats, including increased levels of progranulin expression in microglia within the ischaemic core, and increased levels of progranulin expression in viable neurons as well as induction of progranulin expression in endothelial cells within the ischaemic penumbra. We also demonstrated that the fully glycosylated mature secretory isoform of progranulin (∼88 kDa) decreased, whereas the glycosylated immature isoform of progranulin (58-68 kDa) markedly increased at 24 h and 72 h after reperfusion. In vitro experiments using primary cells from C57BL/6 mice revealed that the glycosylated immature isoform was secreted only from the microglia. Second, we demonstrated that progranulin could protect against acute focal cerebral ischaemia by a variety of mechanisms including attenuation of blood-brain barrier disruption

  12. Physiological responses to acute experimental hypoxia in the air ...

    Indian Academy of Sciences (India)

    When C. batrachus was exposed for different periods at experimental hypoxia level (0.98±0.1 mg/L, DO), hemoglobin and hematocrit concentrations were increased, along with decrease in mean cellular hemoglobin concentration, which reflected a physiological adaptation to enhance oxygen transport capacity. Significant ...

  13. Physiological responses to acute experimental hypoxia in the air ...

    Indian Academy of Sciences (India)

    2013-03-05

    Mar 5, 2013 ... for different periods at experimental hypoxia level (0.98±0.1 mg/L, DO), hemoglobin and hematocrit .... 2.1 Fish maintenance and acclimatization to normoxic .... method that uses glucose oxidase and peroxidase reaction to.

  14. Some pathogenetic aspects of experimental pneumococcal meningitis in acute period

    Directory of Open Access Journals (Sweden)

    V. V. Pilipenko

    2011-01-01

    Full Text Available Morphological displays of cerebral microcirculation derangements in a brain cortex with their semiquantitative estimation have been studied in experimental mice model of the first 24-72 hours period of pneumococcal meningitis.Also displays oxidative stress and activity antioxidative protectional system by means of definition of markers of these processes – malondialdehide, reduced glutathione and glucose-6-phosphate-dehydrogenase activity have been investigated. The received results testify to morphological signs of the expressed derangements of cerebral microcirculation in a brain cortex already by first 24 hour of an experimental meningitis. The maximum expressiveness oxidative stress and activity antioxidative protectional system of reduced glutathione with the max activity of glucose-6-phosphatedehydrogenase in a mice brain cortex was noted at first 48hour durations of experimental disease. Signs of irreversible changes of mice cortex neurons are not revealed at 24–72-hour duration of experimental pneumococcal meningitis.

  15. Experimental study of possible therapy of the acute radiation syndrome

    International Nuclear Information System (INIS)

    Willborn, M.

    1981-01-01

    These experimental studies showed that the survival time of rats, irradiated in a whole-body irradiation with 3000 rad 60 Co-gamma, can be positively influenced by the administration of an antibiotic and also by glucocorticoids. Contrary to our expectations, the combined application of the glucocorticoid and the antibiotic did not increase the survival time of the animals with gastrointestinal syndromes compared with the exclusive administration of the antibiotic. The mineral corticoid aldosterone resulted to be ineffective. (orig.) [de

  16. Brain Aquaporin-4 in Experimental Acute Liver Failure

    Science.gov (United States)

    Rama Rao, Kakulavarapu V.; Jayakumar, Arumugam R.; Tong, Xiaoying; Curtis, Kevin M.; Norenberg, Michael D.

    2016-01-01

    Intracranial hypertension due to brain edema and associated astrocyte swelling is a potentially lethal complication of acute liver failure (ALF). Mechanisms of edema formation are not well understood but elevated levels of blood and brain ammonia and its byproduct glutamine have been implicated in this process. We examined mRNA and protein expression of the water channel protein aquaporin-4 (AQP4) in cerebral cortex in a rat model of ALF induced by the hepatotoxin thioacetamide. Rats with ALF showed increased AQP4 protein in the plasma membrane (PM). Total tissue levels of AQP4 protein and mRNA levels were not altered indicating that increased AQP4 is not transcriptionally mediated but is likely due to a conformational change in the protein, i.e. a more stable anchoring of AQP4 to the PM and/or interference with its degradation. By immunohistochemistry there was an increase in AQP4 immunoreactivity in the PM of perivascular astrocytes in ALF. Rats with ALF showed increased levels of α-syntrophin, a protein involved in the anchoring of AQP4 to perivascular astrocytic end-feet. Increased AQP4 and α-syntrophin levels were inhibited by L-histidine, an inhibitor of glutamine transport into mitochondria, suggesting a role for glutamine in the increase of PM levels of AQP4. These results indicate that increased AQP4 PM levels in perivascular astrocytic end-feet are likely critical to the development of brain edema in ALF. PMID:20720509

  17. Experimental Study of Phlebitis Ointment Administration in Acute Superficial Thrombophlebitis

    Directory of Open Access Journals (Sweden)

    Guangzong Li

    2018-01-01

    Full Text Available Acute superficial thrombophlebitis is a venous system disease. Animal models with mannitol induced phlebitis were treated with an orally administered “phlebitis ointment.” 24 rabbits were randomly divided into 4 groups. The therapy group was treated with “phlebitis ointment” and a control group received “Mai Luo Shu Tong granules.” Levels of blood TNF-α, IL-6, CRP, and IL-1β were measured. The tissue expression levels of NF-КBp65 and PKC genes were evaluated. The therapy group showed a better improvement of the clinical status and similar vascular morphology than the control group. A blank group showed no vascular changes through pathological investigation. In contrast, significant vascular changes were seen in the model group. The control group showed slight vascular modifications. Small thrombi could be found in the lumen despite the intact tunica intima. Both control and therapy group showed less inflammatory cells infiltration than the model group and upregulation of NF-КBp65 and PKC genes. The phlebitis ointment reduced the levels of necrosis factor-α, interleukin-6, C-reactive protein, and interleukin-1ß. The expressions of NF-КBp65 and PKC genes, which are the primary mechanisms underlying the development of thrombophlebitis, were improved significantly in tissues of both therapy group and control group.

  18. Experimental study on acute toxicity of Qingnao tablet to mice

    Science.gov (United States)

    Xie, Guoqi; Wang, Huamin; Ma, Zhenzhen; Hao, Shaojun; Li, Jun; Wang, Hongyu; Wen, Zhonghua; Zhang, Zhengchen

    2018-04-01

    To investigate the effect of Qingnao tablets on acute toxicity in mice. Forty mice, half male and half female, were randomly divided into normal saline group and Qingnao tablet group. After fasting for 12 hours, the mice were given 0. 4 ml / 10 g in maximum volume. In 1st, the rats were perfused 3 times (every 8 hours). The rats in the saline group were perfused with the same volume of saline in the same way. The mice were observed continuously within 3 hours and then every hour. The mice were given a normal diet for 14 consecutive days, and the changes of autonomous activity, reaction, diet, stool, secretion, eye and nose were observed daily. The mice fasted on the 13th day and weighed on the 14th day. And then put the mice to death, The changes of the liver, heart, spleen, lung, kidney, stomach, intestines, and brain were observed by the naked eye. There was no obvious abnormality in normal saline group. The autonomous activity of mice in the administration group decreased after initial administration, and gradually returned to normal after 2 hours of administration. On the day of administration, the stool of the mice became dark brown, and the feces returned to normal after 1.1 days of normal urination. No other mice had abnormal secretion, reaction, eye nose, diet, etc. On the 14th day, there were no visible heart, liver, spleen, lung, kidney, gastrointestinal tract in normal saline group and Qingnao tablet group. Abnormal changes in brain and other organs (edema, color, etc.). In the normal saline group and Qingnao tablet group, the initial weight of the mice was: 21.70 ± 0.97N 21.71 ± 1.13, and the weight of the mice on the 7th day was 29.70 ± 2.4c28.65 ± 3.11. On the 14th day, the body weight was 32.38 ± 3.40, 33.77 ± 3.82. Qingnao tablet has no obvious toxicity to the main organs of mice, so it can be considered safe in clinical use.

  19. STING Signaling Promotes Inflammation in Experimental Acute Pancreatitis.

    Science.gov (United States)

    Zhao, Qinglan; Wei, Yi; Pandol, Stephen J; Li, Lingyin; Habtezion, Aida

    2018-05-01

    Acute pancreatitis (AP) is characterized by severe inflammation and acinar cell death. Transmembrane protein 173 (TMEM173 or STING) is a DNA sensor adaptor protein on immune cells that recognizes cytosolic nucleic acids and transmits signals that activate production of interferons and the innate immune response. We investigated whether leukocyte STING signaling mediates inflammation in mice with AP. We induced AP in C57BL/6J mice (control) and C57BL/6J-Tmem173gt/J mice (STING-knockout mice) by injection of cerulein or placement on choline-deficient DL-ethionine supplemented diet. In some mice, STING signaling was induced by administration of a pharmacologic agonist. AP was also induced in C57BL/6J mice with bone marrow transplants from control or STING-knockout mice and in mice with disruption of the cyclic GMP-AMP synthase (Cgas) gene. Pancreata were collected, analyzed by histology, and acini were isolated and analyzed by flow cytometry, quantitative polymerase chain reaction, immunoblots, and enzyme-linked immunosorbent assay. Bone-marrow-derived macrophages were collected from mice and tested for their ability to detect DNA from dying acinar cells in the presence and absence of deoxyribonuclease (DNaseI). STING signaling was activated in pancreata from mice with AP but not mice without AP. STING-knockout mice developed less severe AP (less edema, inflammation, and markers of pancreatic injury) than control mice, whereas mice given a STING agonist developed more severe AP than controls. In immune cells collected from pancreata, STING was expressed predominantly in macrophages. Levels of cGAS were increased in mice with vs without AP, and cGAS-knockout mice had decreased edema, inflammation, and other markers of pancreatic injury upon induction of AP than control mice. Wild-type mice given bone marrow transplants from STING-knockout mice had less pancreatic injury and lower serum levels of lipase and pancreatic trypsin activity following induction of AP than

  20. Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia.

    Science.gov (United States)

    Pace, Marta; Adamantidis, Antoine; Facchin, Laura; Bassetti, Claudio

    2017-01-01

    Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD) before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH) and orexin/hypocretin (OX) systems. This study aims to 1) assess the relationship between sleep and recovery; 2) test the association between MCH and OX systems with the pathological mechanisms of stroke. Sprague-Dawley rats were assigned to four experimental groups: (i) SD_IS: SD performed before ischemia; (ii) IS: ischemia; (iii) SD_Sham: SD performed before sham surgery; (iv) Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR. A reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group. Our data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke.

  1. Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia.

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    Marta Pace

    Full Text Available Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH and orexin/hypocretin (OX systems. This study aims to 1 assess the relationship between sleep and recovery; 2 test the association between MCH and OX systems with the pathological mechanisms of stroke.Sprague-Dawley rats were assigned to four experimental groups: (i SD_IS: SD performed before ischemia; (ii IS: ischemia; (iii SD_Sham: SD performed before sham surgery; (iv Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR.A reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group.Our data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke.

  2. Evaluation of the gender difference in the protective effects of ischemic postconditioning on ischemia-reperfusion-induced acute kidney injury in rats

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    Atefeh Mahmoudi

    2013-11-01

    Full Text Available Background: Several studies indicate that gender differences exist in tolerance of the kidney to ischemia reperfusion (IR injury. Recently, postconditioning (POC, induction of brief repetitive periods of IR, has been introduced to reduce the extent of the damage to the kidney. This method was shown to attenuate renal IR injury by modifying oxidative stress and reducing lipid peroxidation. Considering the gender effect on the results of several treatment methods, in this study, we investigated the impact of gender on the protective effect of POC on the rat kidney.Methods: In this study, after right nephrectomy, 48 male and female rats were randomly divided into 6 groups of 8 rats: In IR group, with the use of bulldog clamp, 45 minutes of left renal artery ischemia was induced followed by 24 hours of reperfusion. In the sham group, all of the above surgical procedures were applied except that IR was not induced. In the POC group, after the induction of 45 minutes ischemia, 4 cycles of 10 seconds of intermittent ischemia and reperfusion were applied before restoring of blood to the kidney. 24 hours later, serum and renal tissue samples were collected for renal functional monitoring and oxidative stress evaluation.Results: Postconditioning attenuated renal dysfunction considering the significant decrease in plasma creatinine and BUN compared with IR group only in male rats (P<0.05. Also, POC attenuated oxidative stress in male rats’ kidney tissues as demonstrated by a significantly reduced malondialdehyde (MDA level and increased superoxide dismutase (SOD activity (P<0.05. In female rats, there were no changes in functional markers and oxidative stress status in POC group compared to IR group. Conclusion: Considering gender difference, POC had protective effect against IR injury by attenuating functional and oxidative stress markers in male rat kidneys. This protective effect was not seen in female rats.

  3. Protective effect of salvianolic acid B against intestinal ischemia ...

    African Journals Online (AJOL)

    transplantation, strangulated hernias due to gastric barrier ... using pentabarbital sodium at the dose of 50 ..... prevents iodinated contrast media-induced acute renal injury in rats via ... mesenchymal stem cells reduce rat intestinal ischemia-.

  4. [Pathophysiology of hormonal, immune, metabolic changes in acute and chronic pancreatitis. Experimental and clinical studies].

    Science.gov (United States)

    Trubitsyna, I E; Chikunova, B Z; Tkachenko, E V; Tsaregorodtseva, T M; Vinokurova, L V; Varvanina, G G

    2008-01-01

    There is literature review of the acute and chronic pancreatitis experimental models. Patogenetic necrosis mechanisms with fibrosis progress in pancreas were revealed. The stimulation of the proteolytic enzymes synthesis and secretion, that was examined in experiments were compared with clinical examinations. The patients with chronic pancreatitis were investigated in the Central Research Institute of Gastroenterology.

  5. ACTION OF VITAMIN E ON EXPERIMENTAL SEVERE ACUTE LIVER FAILURE.

    Science.gov (United States)

    Miguel, Fabiano Moraes; Schemitt, Elizângela Gonçalves; Colares, Josieli Raskopf; Hartmann, Renata Minuzzo; Morgan-Martins, Maria Isabel; Marroni, Norma Possa

    2017-01-01

    Severe Acute Liver Failure (ALF) is a life-threatening clinical syndrome characterized by hepatocyte necrosis, loss of hepatic architecture, and impairment of liver functions. One of the main causes of ALF is hepatotoxicity from chemical agents, which damage hepatocytes and result in increase of reactive oxygen species. The vitamin E isoform is the one with the strongest biological antioxidant activity. To evaluate the antioxidant effect of vitamin E in this ALF model. We used 56 rats (mean weight of 300 g) divided into eight groups, four groups assessed at 24 hours and 4 assessed at 48 hours after induction: control group (CO); Vitamin E (Vit. E); Thioacetamide (TAA) and Thioacetamide + Vitamina E (TAA+Vit.E). Rats were submitted to injections of thioacetamide (400 mg/kg i.p.) at baseline and 8 hours later. Vitamin E (100 mg/kg ip) was administered 30 minutes after the second dose of thioacetamide. The 48-hour group rats received two additional doses of vitamin E (24h and 36h). At 24h or 48 hours after the administration of the first dose of TAA, rats were weighed and anesthetized and their blood sampled for evaluation of liver integrity through enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Liver tissue was sampled for assessment of lipid peroxidation (LPO) by the technique TBARS, antioxidant enzymes SOD, CAT, GPx and GST activity, levels of the NO 2 /NO 3 and histology by H&E in two times. The results were expressed as mean ± standard deviation and statistically analyzed by ANOVA followed by Student-Newman-Keuls, with P E, we observed a reduction in liver enzymes AST (U/L) (101.32±19.45 in 24 hours and 97.85±29.65 in 48 hours) related to the TAA group (469.56± 0.69 in 24 hours and 598.23±55.45 in 48 hours) and ALT (U/L) (76.59±8.56 in 24 hours and 68.47±6.49 in 48 hours) compared to the TAA group (312.21±10.23 in 24 hours and 359.15±17.58 in 48 hours). There was a reduction of LPO (nmol/mg Prot) in the TAA+Vit.E group (0

  6. Open lung approach vs acute respiratory distress syndrome network ventilation in experimental acute lung injury.

    Science.gov (United States)

    Spieth, P M; Güldner, A; Carvalho, A R; Kasper, M; Pelosi, P; Uhlig, S; Koch, T; Gama de Abreu, M

    2011-09-01

    Setting and strategies of mechanical ventilation with positive end-expiratory pressure (PEEP) in acute lung injury (ALI) remains controversial. This study compares the effects between lung-protective mechanical ventilation according to the Acute Respiratory Distress Syndrome Network recommendations (ARDSnet) and the open lung approach (OLA) on pulmonary function and inflammatory response. Eighteen juvenile pigs were anaesthetized, mechanically ventilated, and instrumented. ALI was induced by surfactant washout. Animals were randomly assigned to mechanical ventilation according to the ARDSnet protocol or the OLA (n=9 per group). Gas exchange, haemodynamics, pulmonary blood flow (PBF) distribution, and respiratory mechanics were measured at intervals and the lungs were removed after 6 h of mechanical ventilation for further analysis. PEEP and mean airway pressure were higher in the OLA than in the ARDSnet group [15 cmH(2)O, range 14-18 cmH(2)O, compared with 12 cmH(2)O; 20.5 (sd 2.3) compared with 18 (1.4) cmH(2)O by the end of the experiment, respectively], and OLA was associated with improved oxygenation compared with the ARDSnet group after 6 h. OLA showed more alveolar overdistension, especially in gravitationally non-dependent regions, while the ARDSnet group was associated with more intra-alveolar haemorrhage. Inflammatory mediators and markers of lung parenchymal stress did not differ significantly between groups. The PBF shifted from ventral to dorsal during OLA compared with ARDSnet protocol [-0.02 (-0.09 to -0.01) compared with -0.08 (-0.12 to -0.06), dorsal-ventral gradients after 6 h, respectively]. According to the OLA, mechanical ventilation improved oxygenation and redistributed pulmonary perfusion when compared with the ARDSnet protocol, without differences in lung inflammatory response.

  7. MicroRNA-381 Favors Repair of Nerve Injury Through Regulation of the SDF-1/CXCR4 Signaling Pathway via LRRC4 in Acute Cerebral Ischemia after Cerebral Lymphatic Blockage

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    Jian-Min Piao

    2018-04-01

    Full Text Available Background/Aims: Acute cerebral ischemia is a manifestation of cerebral vascular insufficiency and has a high mortality. However, the therapy for acute cerebral ischemia is still limited. This study aimed to investigate the effect of microRNA-381 (miR-381 on the repair of nerve injury in rats with acute cerebral ischemia after cerebral lymphatic blockage (CLB by targeting leucine-rich repeat C4 protein (LRRC4 through the Stromal cell-derived factor-1/CXC chemokine receptor-4 signaling pathway. Methods: Rat models of CLB and middle cerebral artery occlusion (MCAO were established, and 56 Wistar rats were divided into sham, MCAO, CLB + MCAO, CLB + MCAO + miR-381 inhibitor, CLB + MCAO + miR-381 mimic, CLB + MCAO + AMD3100 and CLB + MCAO + miR-381 mimic + AMD3100 groups. Modified neurological severity score (mNSS was used to determine nerve injury, TTC staining to measure infarction volume, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL staining and flow cytometry to evaluate cell apoptosis, immunofluorescence to measure BrdU-positive cell number, enzyme-linked immunosorbent assay (ELISA to determine contents of tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, interleukin-6 (IL-6, interleukin-10 (IL-10, nerve growth factor (NGF and neurite outgrowth inhibitor -A (Nogo-A, Reverse transcription quantitative polymerase chain reaction (RT-qPCR and Western blotting to evaluate expression of miR-381, LRRC4, SDF-1, CXCR4, pERK, Slit2 and vascular endothelial growth factor (VEGF. Results: LRRC4 was a target gene of miR-381. Compared with the results in the CLB + MCAO group, mNSS, infarction volume, apoptosis rate and TNF-α, IL-1β, IL-6 and Nogo-A contents as well as LRRC4 expression in the CLB + MCAO + miR-381 inhibitor and CLB + MCAO + AMD3100 groups were increased (those in the CLB + MCAO + AMD3100 group > those in the CLB + MCAO + miR-381 mimic + AMD3100 group, while BrdU-positive cell number, contents of NGF and

  8. Renal ischemia reperfusion causes brain hippocampus oxidative ...

    African Journals Online (AJOL)

    Background: The acute kidney injury (AKI) may do damage to remote organs. Objective of the study is to investigate effect of seaweed extract (SE) on brain oxidative damage in kidney ischemia/reperfusion rats. Material and Methods: Animals were randomly divided into five groups. SE pre-fed to rats. Results: Kidney I/R ...

  9. Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

    Science.gov (United States)

    Cakiroglu, Figen; Enders-Comberg, Sora Maria; Pagel, Horst; Rohwedel, Jürgen; Lehnert, Hendrik; Kramer, Jan

    2016-03-01

    Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham-operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non-significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133- and CD34-positive EPC both in the peripheral blood and renal vessels. © 2015 International Federation for Cell Biology.

  10. Experimental Investigation of the Time Course Effects of Acute Exercise on False Episodic Memory

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    Ali Siddiqui

    2018-06-01

    Full Text Available Previous experimental work suggests that acute exercise may positively influence the accurate recall of past episodic events. However, few studies have examined whether acute exercise also reduces the number of false episodic memories. We evaluated this paradigm in conjunction with an examination of the temporal effects of acute exercise, which have previously been shown to play an important role in subserving episodic memory function. Twenty young adults participated in three experimental visits, including a non-exercise control visit, a visit involving an acute bout (20 min of moderate-intensity exercise occurring prior to the memory task, and a visit involving an acute bout of exercise occurring during the encoding of the memory task. All visits were counterbalanced and occurred at least 24 h apart. The Deese–Roediger–McDermott (DRM Paradigm, involving a separate word list trial for each visit, was employed to assess accurate and false episodic memory recall. For each visit, a short-term (immediate recall and a long-term (25-min delay memory recall was assessed. For both time points, the visit that involved exercise prior to encoding resulted in better short-term and long-term memory function (F(2 = 11.56, p < 0.001, η2p = 0.38. For both time points, the control visit resulted in a greater number of false memories. These findings suggest that acute moderate-intensity exercise may help to increase the accurate recall of past episodic memories and may help to reduce the rate of false memories.

  11. Pathogenesis of acute radiation effects in the urinary bladder. Experimental results

    International Nuclear Information System (INIS)

    Doerr, W.; Eckhardt, M.; Ehme, A.; Koi, S.

    1998-01-01

    Purpose: The present review summarizes experimental studies of the pathogenesis of acute radiation-induced changes in urinary bladder function. Material and methods: Transurethral cystometry was used for longitudinal assessment of bladder function in mice. With this technique, radiation-induced changes in storage capacity can be quantified. In histological studies, changes in urothelial cell density and in urothelial protein expression during the acute radiation response were determined. Acetylsalicylic acid (ASA) was used for the treatment of acute functional changes. Results: The histological studies did not reveal any systematic fluctuations in urothelial cell density during the time of the acute radiation response. However, characteristic changes in the expression of proteins associated with urothelial cell function, differentiation and cell contact were observed, which correlated with the functional impairment. By local or systemical application of ASA, a significant restoration of bladder function compared to placebo treatment could be achieved. Conclusion: Acute functional radiation effects in the urinary bladder are not based on urothelial denudation. However, changes in protein expression indicate an impairment of the urothelial barrier function. The results of ASA treatment demonstrate that prostaglandins are involved in the response. Alterations in urothelial or endothelial prostaglandin metabolism may be primarily radiation-induced or secondary because of the impaired urothelial barrier. (orig.) [de

  12. Therapeutic potential of the novel hybrid molecule JM-20 against focal cortical ischemia in rats

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    Yanier Núñez Figueredo

    2016-08-01

    Full Text Available Context: Despite the great mortality and morbidity of stroke, treatment options remain limited. We previously showed that JM-20, a novel synthetic molecule, possessed a strong neuroprotective effect in rats subjected to transient middle cerebral artery occlusion. However, to verify the robustness of the pre-clinical neuroprotective effects of JM-20 to get good prognosis in the translation to the clinic, it is necessary to use other experimental models of brain ischemia. Aims: To evaluate the neuroprotective effects of JM-20 following the onset of permanent focal cerebral ischemia induced in rats by thermocoagulation of blood into pial blood vessels of cerebral cortices. Methods: Ischemic lesion was induced by thermocoagulation of blood into pial blood vessels of primary motor and somatosensory cortices. Behavioral performance was evaluated by the cylinder testing for a period of 2, 3 and 7 days after surgery, and was followed by histopathological study in brain cortex stained with hematoxylin- eosin. Results: Ischemic injury resulted in impaired function of the forelimb evidenced by high asymmetry punctuation, and caused histopathological alterations indicative of tissue damage at cerebral cortex. JM-20 treatment (4 and 8 mg/kg significantly decreased asymmetry scores and histological alterations with a marked preservation of cortical neurons. Conclusions: The effects of permanent brain ischemia were strongly attenuated by JM-20 administration, which expands and improves the current preclinical data of JM-20 as neuroprotector against cerebral ischemia, and strongly support the examination of its translation to the clinic to treat acute ischemic stroke.

  13. Thymoquinone protects end organs from abdominal aorta ischemia/reperfusion injury in a rat model

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    Mehmet Salih Aydin

    2015-02-01

    Full Text Available Introduction: Previous studies have demonstrated that thymoquinone has protective effects against ischemia reperfusion injury to various organs like lungs, kidneys and liver in different experimental models. Objective: We aimed to determine whether thymoquinone has favorable effects on lung, renal, heart tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Methods: Thirty rats were divided into three groups as sham (n=10, control (n=10 and thymoquinone (TQ treatment group (n=10. Control and TQ-treatment groups underwent abdominal aorta ischemia for 45 minutes followed by a 120-min period of reperfusion. In the TQ-treatment group, thymoquinone was given 5 minutes. before reperfusion at a dose of 20 mg/kg via an intraperitoneal route. Total antioxidant capacity, total oxidative status (TOS, and oxidative stress index (OSI in blood serum were measured and lung, kidney, and heart tissue histopathology were evaluated with light microscopy. Results: Total oxidative status and oxidative stress index activity in blood samples were statistically higher in the control group compared to the sham and TQ-treatment groups (P<0.001 for TOS and OSI. Control group injury scores were statistically higher compared to sham and TQ-treatment groups (P<0.001 for all comparisons. Conclusion: Thymoquinone administered intraperitoneally was effective in reducing oxidative stress and histopathologic injury in an acute abdominal aorta ischemia-reperfusion rat model.

  14. Point application with Angong Niuhuang sticker protects hippocampal and cortical neurons in rats with cerebral ischemia

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    Dong-shu Zhang

    2015-01-01

    Full Text Available Angong Niuhuang pill, a Chinese materia medica preparation, can improve neurological functions after acute ischemic stroke. Because of its inconvenient application and toxic components (Cinnabaris and Realgar, we used transdermal enhancers to deliver Angong Niuhuang pill by modern technology, which expanded the safe dose range and clinical indications. In this study, Angong Niuhuang stickers administered at different point application doses (1.35, 2.7, and 5.4 g/kg were administered to the Dazhui (DU14, Qihai (RN6 and Mingmen (DU4 of rats with chronic cerebral ischemia, for 4 weeks. The Morris water maze was used to determine the learning and memory ability of rats. Hematoxylin-eosin staining and Nissl staining were used to observe neuronal damage of the cortex and hippocampal CA1 region in rats with chronic cerebral ischemia. The middle- and high-dose point application of Angong Niuhuang stickers attenuated neuronal damage in the cortex and hippocampal CA1 region, and improved the memory of rats with chronic cerebral ischemia with an efficacy similar to interventions by electroacupuncture at Dazhui (DU14, Qihai (RN6 and Mingmen (DU4. Our experimental findings indicate that point application with Angong Niuhuang stickers can improve cognitive function after chronic cerebral ischemia in rats and is neuroprotective with an equivalent efficacy to acupuncture.

  15. Hepatic perfusion changes in an experimental model of acute pancreatitis: Evaluation by perfusion CT

    Energy Technology Data Exchange (ETDEWEB)

    Tutcu, Semra [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey); Serter, Selim, E-mail: serterselim@gmail.co [Department of Radiology, Celal Bayar University, School of Medicine, Manisa (Turkey); Kaya, Yavuz; Kara, Eray [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey); Nese, Nalan [Department of Pathology, Celal Bayar University, School of Medicine, Manisa (Turkey); Pekindil, Goekhan [Department of Radiology, Celal Bayar University, School of Medicine, Manisa (Turkey); Coskun, Teoman [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey)

    2010-08-15

    Purpose: It is known that acute pancreatitis may cause secondary changes in several organs. Liver is one of these involved organs. In different experimental studies hepatic damages were shown histopathologically in acute pancreatitis but there are a few studies about perfusion disorders that accompany these histopathologic changes. Perfusion CT (pCT) provides the ability to detect regional and global alterations in organ blood flow. The purpose of the study was to describe hepatic perfusion changes in experimental acute pancreatitis model with pCT. Materials and methods: Forty Sprague-Dawley rats of both genders with average weights of 250 g were used. Rats were randomized into two groups. Twenty rats were in control group and 20 in acute pancreatitis group. pCT was performed. Perfusion maps were formed by processing the obtained images with perfusion CT software. Blood flow (BF) and blood volume (BV) values were obtained from these maps. All pancreatic and liver tissues were taken off with laparotomy and histopathologic investigation was performed. Student's t test was used for statistical analyses. Results: In pCT we found statistically significant increase in blood volume in both lobes of liver and in blood flow in right lobe of the liver (p < 0.01). Although blood flow in left lobe of the liver increased, it did not reach statistical significance. Conclusion: The quantitative analysis of liver parenchyma with pCT showed that acute pancreatitis causes a significant perfusion changes in the hepatic tissue. Systemic mediators seem to be effective as well as local inflammatory changes in perfusion changes.

  16. Hepatic perfusion changes in an experimental model of acute pancreatitis: Evaluation by perfusion CT

    International Nuclear Information System (INIS)

    Tutcu, Semra; Serter, Selim; Kaya, Yavuz; Kara, Eray; Nese, Nalan; Pekindil, Goekhan; Coskun, Teoman

    2010-01-01

    Purpose: It is known that acute pancreatitis may cause secondary changes in several organs. Liver is one of these involved organs. In different experimental studies hepatic damages were shown histopathologically in acute pancreatitis but there are a few studies about perfusion disorders that accompany these histopathologic changes. Perfusion CT (pCT) provides the ability to detect regional and global alterations in organ blood flow. The purpose of the study was to describe hepatic perfusion changes in experimental acute pancreatitis model with pCT. Materials and methods: Forty Sprague-Dawley rats of both genders with average weights of 250 g were used. Rats were randomized into two groups. Twenty rats were in control group and 20 in acute pancreatitis group. pCT was performed. Perfusion maps were formed by processing the obtained images with perfusion CT software. Blood flow (BF) and blood volume (BV) values were obtained from these maps. All pancreatic and liver tissues were taken off with laparotomy and histopathologic investigation was performed. Student's t test was used for statistical analyses. Results: In pCT we found statistically significant increase in blood volume in both lobes of liver and in blood flow in right lobe of the liver (p < 0.01). Although blood flow in left lobe of the liver increased, it did not reach statistical significance. Conclusion: The quantitative analysis of liver parenchyma with pCT showed that acute pancreatitis causes a significant perfusion changes in the hepatic tissue. Systemic mediators seem to be effective as well as local inflammatory changes in perfusion changes.

  17. A New Therapeutic Modality for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin Induces Cardioprotection from Ischemia-Reperfusion Injury via Activation of PI3K/Akt Pathway and Anti-Inflammation in a Rat Model.

    Directory of Open Access Journals (Sweden)

    Kazuhiro Nagaoka

    Full Text Available There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction (AMI, for which the effectiveness of interventional reperfusion therapy is hampered by myocardial ischemia-reperfusion (IR injury. Pretreatment with statins before ischemia is shown to reduce MI size in animals. However, no benefit was found in animals and patients with AMI when administered at the time of reperfusion, suggesting insufficient drug targeting into the IR myocardium. Here we tested the hypothesis that nanoparticle-mediated targeting of pitavastatin protects the heart from IR injury.In a rat IR model, poly(lactic acid/glycolic acid (PLGA nanoparticle incorporating FITC accumulated in the IR myocardium through enhanced vascular permeability, and in CD11b-positive leukocytes in the IR myocardium and peripheral blood after intravenous treatment. Intravenous treatment with PLGA nanoparticle containing pitavastatin (Pitavastatin-NP, 1 mg/kg at reperfusion reduced MI size after 24 hours and ameliorated left ventricular dysfunction 4-week after reperfusion; by contrast, pitavastatin alone (as high as 10 mg/kg showed no therapeutic effects. The therapeutic effects of Pitavastatin-NP were blunted by a PI3K inhibitor wortmannin, but not by a mitochondrial permeability transition pore inhibitor cyclosporine A. Pitavastatin-NP induced phosphorylation of Akt and GSK3β, and inhibited inflammation and cardiomyocyte apoptosis in the IR myocardium.Nanoparticle-mediated targeting of pitavastatin induced cardioprotection from IR injury by activation of PI3K/Akt pathway and inhibition of inflammation and cardiomyocyte death in this model. This strategy can be developed as an innovative cardioprotective modality that may advance currently unsatisfactory reperfusion therapy for AMI.

  18. Experimental evidence of obesity as a risk factor for severe acute pancreatitis.

    Science.gov (United States)

    Frossard, Jean-Louis; Lescuyer, Pierre; Pastor, Catherine M

    2009-11-14

    The incidence of acute pancreatitis, an inflammation of the pancreas, is increasing worldwide. Pancreatic injury is mild in 80%-90% of patients who recover without complications. The remaining patients may develop a severe disease with local complications such as acinar cell necrosis, abscess and remote organ injury including lung injury. The early prediction of the severity of the disease is an important goal for physicians in management of patients with acute pancreatitis in order to optimize the therapy and to prevent organ dysfunction and local complications. For that purpose, multiple clinical scale scores have been applied to patients with acute pancreatitis. Recently, a new problem has emerged: the increased severity of the disease in obese patients. However, the mechanisms by which obesity increases the severity of acute pancreatitis are unclear. Several hypotheses have been suggested: (1) obese patients have an increased inflammation within the pancreas; (2) obese patients have an increased accumulation of fat within and around the pancreas where necrosis is often located; (3) increase in both peri- and intra-pancreatic fat and inflammatory cells explain the high incidence of pancreatic inflammation and necrosis in obese patients; (4) hepatic dysfunction associated with obesity might enhance the systemic inflammatory response by altering the detoxification of inflammatory mediators; and (5) ventilation/perfusion mismatch leading to hypoxia associated with a low pancreatic flow might reduce the pancreatic oxygenation and further enhance pancreatic injury. Recent experimental investigations also show an increased mortality and morbidity in obese rodents with acute pancreatitis and the implication of the adipokines leptin and adiponectin. Such models are important to investigate whether the inflammatory response of the disease is enhanced by obesity. It is exciting to speculate that manipulation of the adipokine milieu has the potential to influence the

  19. Role of the Use of Omental Flap in Prognosis of Cases with Induced Acute Pancreatitis in Experimental Dogs

    OpenAIRE

    Mohamed Hassan; Nader Shaaban; Ashraf M Abu-Seida; Mostafa Khodeir; Reem Jan; Hisham Elsharkawy; Engie Hefnawy

    2016-01-01

    Aim Acute pancreatitis frequently involves peripancreatic tissues and remote organ systems resulting in severe complications and high risk of mortality. Therefore, the present study was carried out to assess the effect of omental flap as a new treatment of acute pancreatitis. Methods Ten mongrel dogs with experimentally induced acute pancreatitis were randomly divided into two equal groups; treated and control groups. The pancreas was wrapped with omental flap in the treated group and the pan...

  20. Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Ekeløf, Sarah V; Halladin, Natalie L; Jensen, Svend E

    2016-01-01

    Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia-reperfusion injury. Melatonin......, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized...... to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma...

  1. Correlation of myocardial p-(123)I-iodophenylpentadecanoic acid retention with (18)F-FDG accumulation during experimental low-flow ischemia.

    Science.gov (United States)

    Shi, Cindy Q; Young, Lawrence H; Daher, Edouard; DiBella, Edward V R; Liu, Yi-Hwa; Heller, Eliot N; Zoghbi, Sami; Wackers, Frans J Th; Soufer, Robert; Sinusas, Albert J

    2002-03-01

    Myocardial ischemia is associated with reduced free fatty acid (FFA) beta-oxidation and increased glucose utilization. This study evaluated the potential of dynamic SPECT imaging of a FFA analog, p-(123)I-iodophenylpentadecanoic acid (IPPA), for detection of ischemia and compares retention of IPPA with (18)F-FDG accumulation. In a canine model of regional low-flow ischemia (n = 9), serial IPPA SPECT images (2 min per image) were acquired over 52--90 min. In a subset of dogs (n = 6), (18)F-FDG was injected after completing SPECT imaging and allowed to accumulate for 40 min before killing the animals. Flow was assessed with radiolabeled microspheres. Myocardial metabolism was evaluated independently by selective coronary arterial and venous sampling. Serial IPPA SPECT images showed an initial defect in the ischemic region (0.70% plus minus 0.03% ischemic-to-nonischemic ratio), which normalized within 48 min because of the slower IPPA clearance from the ischemic region (t(1/2) = 54.2 plus minus 3.3 min) relative to the nonischemic region (t(1/2) = 36.7 plus minus 5.6 min) (P < 0.05). Delayed myocardial IPPA and (18)F-FDG activities were correlated (r = 0.70; n = 576 segments), and both were maximally increased in segments with a moderate flow reduction (IPPA, 151% of nonischemic; (18)F-FDG, 450% of nonischemic; P < 0.05). Serial SPECT imaging showed delayed myocardial clearance of IPPA in ischemic regions with moderate flow reduction, which lead to increased late myocardial retention of IPPA. Retention of IPPA correlated with (18)F-FDG accumulation, supporting the potential of IPPA as a noninvasive marker of ischemic myocardium.

  2. CSF transthyretin neuroprotection in a mouse model of brain ischemia

    DEFF Research Database (Denmark)

    Santos, Sofia Duque; Lambertsen, Kate Lykke; Clausen, Bettina Hjelm

    2010-01-01

    Brain injury caused by ischemia is a major cause of human mortality and physical/cognitive disability worldwide. Experimentally, brain ischemia can be induced surgically by permanent middle cerebral artery occlusion. Using this model, we studied the influence of transthyretin in ischemic stroke. ...

  3. MR imaging with Gd-DTPA enhancement in experimental acute injury of the spinal cord

    International Nuclear Information System (INIS)

    Hackney, D.B.; Asato, R.; Joseph, P.M.; McGrath, J.T.; Grossman, R.I.; Shetty, A.

    1986-01-01

    The authors performed MR imaging with Gd-DTPA enhancement in adult male Sprague-Dawley rats, with experimentally induced acute spinal cored injuries. After epidural compression of the spinal cored the pathologic changes of acute cord contusion were allowed to develop for 30 minutes to 4 hours. MR imaging was then performed at 1.4 T. Both short spin-echo (TR = 400 msec, TE = 15-20 msec) and long spin-echo (TR = 2,000 msec, TE = 100 msec) images were obtained. After the initial imaging, Gd-DTPA (0.1 mmol/kg) and Evans blue dye were administered intravenously and imaging was repeated. Enhancement of normal central gray matter was consistently observed. However, neither pathologic enhancement on MR images nor extravasation of Evans blue dye on histologic inspection were identified

  4. Acute phase response in two consecutive experimentally induced E. coli intramammary infections in dairy cows

    Directory of Open Access Journals (Sweden)

    Saatsi Johanna

    2008-06-01

    Full Text Available Abstract Background Acute phase proteins haptoglobin (Hp, serum amyloid A (SAA and lipopolysaccharide binding protein (LBP have suggested to be suitable inflammatory markers for bovine mastitis. The aim of the study was to investigate acute phase markers along with clinical parameters in two consecutive intramammary challenges with Escherichia coli and to evaluate the possible carry-over effect when same animals are used in an experimental model. Methods Mastitis was induced with a dose of 1500 cfu of E. coli in one quarter of six cows and inoculation repeated in another quarter after an interval of 14 days. Concentrations of acute phase proteins haptoglobin (Hp, serum amyloid A (SAA and lipopolysaccharide binding protein (LBP were determined in serum and milk. Results In both challenges all cows became infected and developed clinical mastitis within 12 hours of inoculation. Clinical disease and acute phase response was generally milder in the second challenge. Concentrations of SAA in milk started to increase 12 hours after inoculation and peaked at 60 hours after the first challenge and at 44 hours after the second challenge. Concentrations of SAA in serum increased more slowly and peaked at the same times as in milk; concentrations in serum were about one third of those in milk. Hp started to increase in milk similarly and peaked at 36–44 hours. In serum, the concentration of Hp peaked at 60–68 hours and was twice as high as in milk. LBP concentrations in milk and serum started to increase after 12 hours and peaked at 36 hours, being higher in milk. The concentrations of acute phase proteins in serum and milk in the E. coli infection model were much higher than those recorded in experiments using Gram-positive pathogens, indicating the severe inflammation induced by E. coli. Conclusion Acute phase proteins would be useful parameters as mastitis indicators and to assess the severity of mastitis. If repeated experimental intramammary

  5. The relationship between the apparent diffusion coefficient measured by magnetic resonance imaging, anoxic depolarization, and glutamate efflux during experimental cerebral ischemia.

    Science.gov (United States)

    Harris, N G; Zilkha, E; Houseman, J; Symms, M R; Obrenovitch, T P; Williams, S R

    2000-01-01

    A reduction in the apparent diffusion coefficient (ADC) of water measured by magnetic resonance imaging (MRI) has been shown to occur early after cerebrovascular occlusion. This change may be a useful indicator of brain tissue adversely affected by inadequate blood supply. The objective of this study was to test the hypothesis that loss of membrane ion homeostasis and depolarization can occur simultaneously with the drop in ADC. Also investigated was whether elevation of extracellular glutamate ([GLU]e) would occur before ADC changes. High-speed MRI of the trace of the diffusion tensor (15-second time resolution) was combined with simultaneous recording of the extracellular direct current (DC) potential and on-line [GLU]e from the striatum of the anesthetized rat. After a control period, data were acquired during remote middle cerebral artery occlusion for 60 minutes, followed by 30 minutes of reperfusion, and cardiac arrest-induced global ischemia. After either focal or global ischemia, the ADC was reduced by 10 to 25% before anoxic depolarization occurred. After either insult, the time for half the maximum change in ADC was significantly shorter than the corresponding DC potential parameter (P potential and did not peak until much later after either ischemic insult. This study demonstrates that ADC changes can occur before membrane depolarization and that high [GLU]e has no involvement in the early rapid ADC decrease.

  6. G-CSF in acute myocardial infarction - experimental and clinical findings.

    Science.gov (United States)

    Ince, Hüseyin; Petzsch, Michael; Rehders, Tim C; Dunkelmann, Simone; Nienaber, Christoph A

    2006-09-01

    Early data from clinical studies suggest that intracoronary injection of autologous progenitor cells may beneficially affect postinfarction remodeling and perfusion. Beyond intracoronary infusion of autologous bone marrow mononuclear CD34+ cells (MNCCD34+), mobilization of stem cells by G-CSF has recently attracted attention because of various advantages such as the noninvasive nature of MNCCD34+ mobilization by subcutaneous injections. It is the aim of the present work to give an overview about the current experimental and clinical findings of G-CSF treatment in acute myocardial infarction.

  7. Detection of experimentally produced acute pulmonary arterial occlusion by methyl iodide-131 inhalation imaging

    International Nuclear Information System (INIS)

    Grossman, Z.D.; McAfee, J.G.; Subramanian, G.

    1981-01-01

    Methyl iodide-131 (CH 3 I-131) is described as an agent for detection of acute experimentally produced pulmonary arterial occlusion in dogs. When gaseous CH 3 I-131 is inhaled, radioactivity passes instantaneously from the alveoli to the lung capillary bed. Where pulmonary blood flow exists, activity is washed out into the systemic circulation, but in areas of blood stasis, a transient pulmonary hot spot remains. CH 3 I-131 is easily produced and inexpensive, but administration is awkward and strict radiation safety precautions are mandatory

  8. Acute phase proteins in bovine milk in an experimental model of Staphylococcus aureus subclinical mastitis

    DEFF Research Database (Denmark)

    Eckersall, P D; Young, F J; Nolan, A M

    2006-01-01

    and serum amyloid A increase in serum during mastitis. The concentrations of these proteins were determined in an experimental model using a field strain of Staphylococcus aureus to induce subclinical mastitis in dairy cows. The expression of mRNA coding for these proteins was assessed and the presence of M......The objectives were to establish the origin of 2 acute phase proteins in milk during subclinical bovine mastitis and to characterize the relationship between those proteins in milk and blood. Haptoglobin (Hp) and mammary-associated serum amyloid A (M-SAA3) appear in milk during mastitis, whereas Hp...

  9. Superior mesenteric arterial branch occlusion causing partial jejunal ischemia: a case report

    Directory of Open Access Journals (Sweden)

    Van De Winkel Nele

    2012-02-01

    Full Text Available Abstract Introduction Ischemic bowel disease comprises both mesenteric ischemia and colonic ischemia. Mesenteric ischemia can be divided into acute and chronic ischemia. These are two separate entities, each with their specific clinical presentation and diagnostic and therapeutic modalities. However, diagnosis may be difficult due to the vague symptomatology and subtle signs. Case presentation We report the case of a 68-year-old Caucasian woman who presented with abdominal discomfort, anorexia, melena and fever. A physical examination revealed left lower quadrant tenderness and an irregular pulse. Computed tomography of her abdomen as well as computed tomography enterography, enteroscopy, angiography and small bowel enteroclysis demonstrated an ischemic jejunal segment caused by occlusion of a branch of the superior mesenteric artery. The ischemic segment was resected and an end-to-end anastomosis was performed. The diagnosis of segmental small bowel ischemia was confirmed by histopathological study. Conclusion Mesenteric ischemia is a pathology well-known by surgeons, gastroenterologists and radiologists. Acute and chronic mesenteric ischemia are two separate entities with their own specific clinical presentation, radiological signs and therapeutic modalities. We present the case of a patient with symptoms and signs of chronic mesenteric ischemia despite an acute etiology. To the best of our knowledge, this is the first report presenting a case of acute mesenteric ischemia with segmental superior mesenteric artery occlusion.

  10. Placebo-controlled trial of nebulization with adrenaline in acute bronchiolitis: a quasi-experimental study

    International Nuclear Information System (INIS)

    Afzal, M.F.; Iqbal, S.M.; Sultan, M.A.

    2012-01-01

    Background: Bronchiolitis is an acute inflammatory obstruction. of small In children that occurs In first two years of life and is by fever, rhinitis, cough, tachypnoea, expiratory wheeze and increased respiratory effort To study efficacy of nebulized adrenaline compared with placebo in acute bronchiolitis. Quasi-experimental study carried out at Department of aediatrics, King Edward Medical University/ Mayo Hospital, Lahore from October 2006 through March 2007. After consent from parents, sixty children of age between 2 months to 2 years with the first episode consistent with clinical case definition of bronchiolitis were included by using convenient sampling. clinical scoring system was used to grade the severity of disease as well as to monitor the efficacy of intervention. Those having score = 8 were randomly allocated to the two study groups. The information was recorded at 0 minute and effect of each method of treatment was followed for 90 minutes. Results: Our study population was 60 children. The mean age was 11:1:6 Months. Male to female ratio was 1.2: 1. Mean weight of the Children was 9:1:3 kg. Improvement in clinical score, oxygen saturation, and length of hospital at 0 and 90 minutes was noted in both groups but when compared with placebo, there was no Statistically significant difference. Conclusion: There is no difference in the efficacy of nebulization with adrenaline compared with placebo in the management of acute bronchiolitis. (author)

  11. Effects of Schizolobium parahyba extract on experimental Bothrops venom-induced acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Monique Silva Martines

    Full Text Available BACKGROUND: Venom-induced acute kidney injury (AKI is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV-induced AKI. METHODOLOGY: Groups of 8 to 10 rats received infusions of 0.9% saline (control, C, SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance, renal blood flow (RBF, Doppler, blood pressure (BP, intra-arterial transducer, renal vascular resistance (RVR, urinary osmolality (UO, freezing point, urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA], lactate dehydrogenase (LDH, kinetic method, hematocrit (Hct, microhematocrit, fibrinogen (Fi, Klauss modified and blinded renal histology (acute tubular necrosis score. PRINCIPAL FINDINGS: BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. CONCLUSION: SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR.

  12. The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats

    Science.gov (United States)

    Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

    2015-01-01

    Objective The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Methods Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. Results The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (pkefir group were significantly higher than ischemia group (pkefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (pkefir group compared with ischemia group (pkefir group were significantly higher than ischemia group at 24 h (pkefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future. PMID:26113960

  13. The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats.

    Science.gov (United States)

    Guven, Mustafa; Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

    2015-05-01

    The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (pkefir group were significantly higher than ischemia group (pkefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (pkefir group compared with ischemia group (pkefir group were significantly higher than ischemia group at 24 h (pkefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

  14. Myocardial ischemia and angina pectoris

    International Nuclear Information System (INIS)

    Selwyn, A.P.; Fox, K.M.; Jonathan, A.; Lavender, P.; Watson, I.

    1981-01-01

    Ambulatory monitoring of ST segment changes was performed in 60 patients presenting with angina, positive ECG stress tests and coronary artery disease, 85% of ischemic ECG events were asymptomatic, 37% occurred with no increase in heart rate and 15% of episodes either lasted 20 minutes or more or fluctuated in severity. A controlled pilot study in ten patients showed depression. Radionuclide studies in 50 patients with angina and coronary artery disease have shown that stress (i.e., atrial pacing) produced different patterns of disturbed regional myocardial perfusion related to the patient's exercise capacity and eventually leading to a decrease in regional myocardial perfusion during the ischemic episode. ST segment depression appeared only after the decrease in regional myocardial perfusion. These findings combined with past research suggest that patients with angina and coronary artery disease can suffer frequent asymptomatic disturbances of the regional myocardial perfusion. The frequency of these episodes and the time course for the recovery of the metabolic consequences mean that segments of ventricular myocardium may be constantly abnormal. The relative importance of changes in coronary tone and malfunction of platelets in the diseased coronary tree needs to be examined in clinical research. Pilot studies of antiplatelet agents have shown a significant beneficial effect on episodes of ischemia occurring at night and those occurring without any increase in heart rate. The techniques and observations in these patients with coronary artery disease all suggest that acute transient regional myocardial ischemia is caused by a variety of mechnisms. Further research using objective methods is required to discover the causes of ischemia and to rationalize treatment. (orig./MG) [de

  15. Blockade of Rennin-Angiotensin system blunts the fibrotic response in experimental acute pyelonephritis

    Directory of Open Access Journals (Sweden)

    Singal A

    2005-01-01

    Full Text Available Aim: To study the impact of Renin-Angiotensin system blockade in experimental acute pyelonephritis, induced by a novel surgical approach via dorsal lumbotomy incision. Materials and Methods : 45 Adult female WISTAR rats aged 8-12 weeks, underwent direct inoculation of 0.1 ml of E.coli suspension into the parenchyma of the surgically exposed kidney. 3 groups of rats were studied: Group A - treated with antibiotics only; Group B- Captopril and antibiotics and Group C- Losartan and antibiotics. Changes of acute inflammation, parenchymal destruction and scarring were compared between the groups on histopathological sections. Kruskal-Wallis test was used for statistical analysis. Results : Changes consistent with acute pyelonephritis were seen in all the kidneys. Mean% scar area in Group A, Group B and Group C was 37.08±1.79, 24.40±1.88 and 24.68±1.32% respectively at end of six weeks. Mean tubular density in Group A, B and C was 17.26±1.92, 47.18±3.00 and 47.00±5.08-tubules/lac mm2 respectively. The differences between the control and the treated animals were significant, though the results did not differ between the losartan and captopril treated rats. Conclusions : Dorsal lumbotomy approach to the kidney provides a good exposure of the kidney. Induction of acute pyelonephritis by direct inoculation of bacteria into renal cortex produced a consistent scar at 6 weeks. Blockade of renin angiotensin system by either captopril or losartan decreased the renal scar area by almost 1/3 at 6 weeks.

  16. Neuroprotective effects of ebselen following forebrain ischemia: involvement of glutamate and nitric oxide.

    Science.gov (United States)

    Koizumi, Hiroyasu; Fujisawa, Hirosuke; Suehiro, Eiichi; Shirao, Satoshi; Suzuki, Michiyasu

    2011-01-01

    Ebselen is a mimic of glutathione peroxidase that reacts with peroxynitrite and inhibits nitric oxide (NO) synthase. Ebselen has beneficial effects on the neurological outcome of patients with stroke. In this study, the mechanisms by which ebselen can elicit neuroprotective effects against ischemic brain injury were investigated in male Wistar rats. Experimental forebrain ischemia was induced by bilateral common carotid artery occlusion with hemorrhagic hypotension. Ebselen was administered to animals in the treatment group 2 hours prior to the induction of forebrain ischemia, and placebo was administered in the control group. Cerebral blood flow (CBF) was measured by the hydrogen clearance method. Cortical extracellular levels of excitatory amino acids (EAAs) and NO were evaluated using in vivo microdialysis. Neuronal damage in the CA1 subfield of the hippocampus was assessed in brains harvested after a 24-hour period of survival. CBF did not recover to normal physiological levels after ischemic insults in either the control or treatment groups. The differences in the sequential changes in extracellular EAA and NO levels between groups were not statistically significant. There was a significantly larger mean density of intact, undamaged neurons in the CA1 subfield in the treatment group than in the control group. The neuroprotective effects of ebselen were reflected in the histological findings, without significant inhibition of glutamate release or NO synthesis during the acute phase of experimentally induced cerebral ischemia.

  17. Avaliação do pós-condicionamento isquêmico no tratamento da isquemia mesentérica: estudo experimental em ratos Evaluation of ischemic postconditioning effect on mesenteric ischemia treatment: experimental study in rats

    Directory of Open Access Journals (Sweden)

    Carlos Henrique Marques dos Santos

    2009-06-01

    Full Text Available OBJETIVO: Avaliar o efeito do pré e pós-condicionamento isquêmico sobre a lesão tecidual na mucosa intestinal de ratos submetidos ao processo de isquemia e reperfusão mesentérica. MÉTODOS: Foram estudados 30 ratos Wistar, distribuídos em três grupos: grupo A, em que se realizou isquemia (30 minutos e reperfusão (60 minutos mesentérica; grupo B, isquemia e reperfusão mesentérica precedidos pelo pré-condicionamento isquêmico por três ciclos de isquemia e reperfusão com duração de dois minutos cada; grupo C, isquemia e reperfusão mesentérica e, precedendo o início da reperfusão, foi realizado o pós-condicionamento isquêmico por três ciclos de reperfusão e isquemia com duração de dois minutos cada. Ao final, ressecou-se um segmento do intestino delgado para análise histológica. Avaliaram-se os resultados pela classificação de Chiu et al. e procedeu-se ao tratamento estatístico. RESULTADOS: As médias dos graus de lesão tecidual segundo a classificação de Chiu et al. foram: no grupo A, 3,5; grupo B, 1,2; grupo C, 1. A diferença entre o resultado do grupo A com os resultados dos grupos B e C foi considerada estatisticamente significativa (P OBJECTIVE: To assess the preconditioning and postconditioning effect on intestinal mucosal lesions in rats undergone mesenteric ischemia and reperfusion procedure. METHODS: Thirty Wistar rats were studied and divided into three groups: Group A, 10 rats undergone mesenteric ischemia (30 minutes and reperfusion (60 minutes; Group B, 10 rats undergone mesenteric ischemia and reperfusion preceded by ischemic preconditioning for three cycles of ischemia and reperfusion for two minutes each; Group C, 10 rats undergone mesenteric ischemia and reperfusion and, preceding the beginning of reperfusion, ischemic postconditioning was performed for three cycles of reperfusion and ischemia for two minutes each. Then, a segment of small intestine was resected for histological analysis. We

  18. A fresh look into the pathophysiology of ischemia-induced complications in patients with chronic kidney disease undergoing hemodialysis

    Directory of Open Access Journals (Sweden)

    Honore PM

    2015-03-01

    Full Text Available Patrick M Honore,1 Rita Jacobs,1 Elisabeth De Waele,1 Viola Van Gorp,1 Jouke De Regt,1 Olivier Joannes-Boyau,2 Willem Boer,3 Herbert D Spapen1 1Intensive Care Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; 2Intensive Care Unit, Haut Leveque University Hospital of Bordeaux, University of Bordeaux 2, Pessac, France; 3Intensive Care Department, Ziekenhuis Oost Limburg, Genk, Belgium Abstract: Recent case reports of acute esophageal necrosis in patients with chronic kidney disease (CKD undergoing hemodialysis encouraged us to look beyond hypoperfusion/ischemia as a sole explanation for this dramatic complication. At least three intriguing pathways, ie, accumulation of protein-bound toxins, endotoxin translocation, and altered mucosal defense mechanisms, have been proposed to explain the inherent susceptibility of CKD patients to developing ischemia-related and cardiovascular events. Interestingly, all the proposed pathways can be potentially antagonized or attenuated. At present, however, it is not known whether one pathway predominates or if any interaction exists between these pathways. More solid experimental and clinical data are warranted to acquire a better insight into the complex pathogenesis of CKD-associated ischemia. Keywords: chronic kidney disease, ischemia, pathophysiology, cardiovascular events

  19. Transcutaneous electrical nerve stimulation: nonparallel antinociceptive effects on chronic clinical pain and acute experimental pain.

    Science.gov (United States)

    Cheing, G L; Hui-Chan, C W

    1999-03-01

    To investigate to what extent a single 60-minute session of transcutaneous electrical nerve stimulation (TENS) would modify chronic clinical pain, acute experimental pain, and the flexion reflex evoked in chronic low back pain patients. Thirty young subjects with chronic low back pain were randomly allocated to two groups, receiving either TENS or placebo stimulation to the lumbosacral region for 60 minutes. The flexion reflex was elicited by an electrical stimulation applied to the subject's right sole and recorded electromyographically from the biceps femoris and the tibialis anterior muscles. Subjective sensation of low back pain and the electrically induced pain were measured by two separate visual analog scales, termed VAS(LBP) and VAS(FR), respectively. Data obtained before, during, and 60 minutes after TENS and placebo stimulations were analyzed using repeated measures ANOVA. The VAS(LBP) score was significantly reduced to 63.1% of the prestimulation value after TENS (pTENS protocol had different degrees of antinociceptive influence on chronic and acute pain in chronic low back pain patients.

  20. Preinfarct Health Status and the Use of Early Invasive Versus Ischemia-Guided Management in Non-ST-Elevation Acute Coronary Syndrome.

    Science.gov (United States)

    Qintar, Mohammed; Smolderen, Kim G; Chan, Paul S; Gosch, Kensey L; Jones, Philip G; Buchanan, Donna M; Girotra, Saket; Spertus, John A

    2017-10-01

    Early invasive management improves outcomes in non-ST-elevation myocardial infarction (NSTEMI). The association between preinfarct health status and the selecting patients for early invasive management is unknown. The Prospective Registry Evaluating outcomes after Myocardial Infarctions: Events and Recovery and Translational Research Investigating Underlying disparities in acute Myocardial infarction Patients' Health status are consecutive US multicenter registries, in which the associations between preinfarct angina frequency and quality of life (both assessed by the Seattle Angina Questionnaire on admission) and the Global Registry of Acute Coronary Events (GRACE) risk score and referral to early invasive management (coronary angiography within 48 hours) were evaluated using Poisson regression, after adjusting for site, demographics, and clinical and psychosocial variables. Of 3,768 patients with NSTEMI, 2,182 (57.9%) patients were referred for early invasive treatment. Patients with excellent, good, or very good baseline angina-specific quality of life, respectively, were more likely to receive early angiography, even after adjustment, as compared with patients reporting poor baseline quality of life because of angina (62.1.0%, 60.9%, 59.6%, vs 51.2%; adjusted relative risk [RR] = 1.09, 95% confidence interval [CI] 1.04 to 1.16; RR = 1.13, 95% CI 1.01 to 1.27; RR 1.14, 95% CI 0.99 to 1.31, respectively). Finally, patients with a GRACE score in the highest risk decile (199.5 to management. Further work is needed to understand the role of preinfarct health status and in-hospital treatment strategy. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Influência do antibiótico nas lesões de isquemia e reperfusão intestinal: estudo experimental em ratos The influence of antibiotics on intestinal ischemia and reperfusion: experimental study in rats

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    Maria de Lourdes Pessole Biondo-Simões

    2000-01-01

    Full Text Available Muito se tem questionado sobre os efeitos da isquemia intestinal seguida de reperfusão (I/R, chamando a atenção para o papel dos leucócitos na patobiologia da I/R. A fisiopatogenia das lesões está intimamente ligada à geração de radicais de oxigênio durante o período em que se processa a reperfusão. A ruptura da barreira intestinal permitindo a translocação bacteriana agravaria ainda mais estas lesões. Este estudo tem por objetivo avaliar as lesões intestinais na vigência de isquemia e na reperfusão com e sem antibioticoterapia. Submeteram-se 42 ratos Wistar à anestesia e laparotomia mediana. Obteve-se isquemia intestinal por clampeamento das artérias mesentéricas cranial e caudal por 30 minutos. Após reperfundiu-se por igual tempo. Metade destes animais receberam 50 mg/kg de eritromicina por via oral nas 24 horas que antecederam o procedimento. Cada um destes grupos foi subdividido em outros 3, constituíndo os subgrupos de controle, isquemia e isquemia/reperfusão. Ao final, ressecaram-se segmentos do intestins delgado para processamento histológico. Avaliaram-se os resultados pela escala de CHIU e col. e submeteram-se os resultados à tratamento estatístico. Observou-se que a mucosa intestinal apresentava-se com padrão normal nos grupos de controle, tanto com antibioticoprofilaxia como sem. Os intestinos submetidos à isquemia com ou se antibioticoprofilaxia mostraram, lesões com descolamento e perda de vilosidades até infartamento transmucoso. Os intestinos reperfundidos apresentavam lesões semelhantes. Verificou-se que os intestinos reperfundidos que receberam antibioticoprofilaxia apresentavam lesões mais graves do que os que sofreram isquemia sem antibioticoprofilaxia (p=0,0303. Concluiu-se que o uso de antibióticos pré-isquemia não diminui a gravidade das lesões histopatológicas da mucosa intestinal, não protegendo das lesões após a reperfusão.The role of the white blood cells in the ischemia and

  2. Acute pulmonary injury induced by experimental muscle trauma Lesão pulmonar aguda induzida por trauma muscular experimental

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    Márcia Andréa da Silva Carvalho Sombra

    2011-01-01

    Full Text Available PURPOSE: To develop an easily reproducible model of acute lung injury due to experimental muscle trauma in healthy rats. METHODS: Eighteen adult Wistar rats were randomized in 3 groups (n=6: G-1- control, G-2 - saline+trauma and G-3 - dexamethasone+trauma. Groups G-1 and G-2 were treated with saline 2,0ml i.p; G-3 rats were treated with dexamethasone (DE (2 mg/kg body weight i.p.. Saline and DE were applied 2h before trauma and 12h later. Trauma was induced in G-2 and G-3 anesthetized (tribromoethanol 97% 100 ml/kg i.p. rats by sharp section of anterior thigh muscles just above the knee, preserving major vessels and nerves. Tissue samples (lung were collected for myeloperoxidase (MPO assay and histopathological evaluation. RESULTS: Twenty-four hours after muscle injury there was a significant increase in lung neutrophil infiltration, myeloperoxidase activity and edema, all reversed by dexamethasone in G-3. CONCLUSION: Trauma by severance of thigh muscles in healthy rats is a simple and efficient model to induce distant lung lesions.OBJETIVO: Desenvolver um modelo facilmente reprodutível de lesão pulmonar aguda decorrente de trauma muscular experimental em ratos sadios. MÉTODOS: Dezoito ratos Wistar adultos foram randomizados em 3 grupos (n=6: G-1-controle, G-2 - trauma+salina e G-3 - trauma+dexametasona. Grupos G-1 e G-2 foram tratados com salina 2,0 ml ip, G-3 ratos foram tratados com dexametasona (DE (2 mg/kg peso corporal ip. Salina e DE foram aplicadas 2h antes e 12h depois do trauma. Trauma foi induzido em ratos G-2 e G-3 anestesiados (tribromoetanol 97% de 100 ml/kg, i.p. por secção da musculatura anterior da coxa logo acima da articulação do joelho, preservando os grandes vasos e nervos. Amostras de tecido (pulmão foram coletadas para avaliação da mieloperoxidase (MPO, e exames histopatológicos. RESULTADOS: Vinte e quatro horas após a indução da lesão muscular houve um aumento significativo na infiltração de neutr

  3. Higher levels of spontaneous breathing reduce lung injury in experimental moderate acute respiratory distress syndrome.

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    Carvalho, Nadja C; Güldner, Andreas; Beda, Alessandro; Rentzsch, Ines; Uhlig, Christopher; Dittrich, Susanne; Spieth, Peter M; Wiedemann, Bärbel; Kasper, Michael; Koch, Thea; Richter, Torsten; Rocco, Patricia R; Pelosi, Paolo; de Abreu, Marcelo Gama

    2014-11-01

    To assess the effects of different levels of spontaneous breathing during biphasic positive airway pressure/airway pressure release ventilation on lung function and injury in an experimental model of moderate acute respiratory distress syndrome. Multiple-arm randomized experimental study. University hospital research facility. Thirty-six juvenile pigs. Pigs were anesthetized, intubated, and mechanically ventilated. Moderate acute respiratory distress syndrome was induced by repetitive saline lung lavage. Biphasic positive airway pressure/airway pressure release ventilation was conducted using the airway pressure release ventilation mode with an inspiratory/expiratory ratio of 1:1. Animals were randomly assigned to one of four levels of spontaneous breath in total minute ventilation (n = 9 per group, 6 hr each): 1) biphasic positive airway pressure/airway pressure release ventilation, 0%; 2) biphasic positive airway pressure/airway pressure release ventilation, > 0-30%; 3) biphasic positive airway pressure/airway pressure release ventilation, > 30-60%, and 4) biphasic positive airway pressure/airway pressure release ventilation, > 60%. The inspiratory effort measured by the esophageal pressure time product increased proportionally to the amount of spontaneous breath and was accompanied by improvements in oxygenation and respiratory system elastance. Compared with biphasic positive airway pressure/airway pressure release ventilation of 0%, biphasic positive airway pressure/airway pressure release ventilation more than 60% resulted in lowest venous admixture, as well as peak and mean airway and transpulmonary pressures, redistributed ventilation to dependent lung regions, reduced the cumulative diffuse alveolar damage score across lungs (median [interquartile range], 11 [3-40] vs 18 [2-69]; p ventilation more than 0-30% and more than 30-60% showed a less consistent pattern of improvement in lung function, inflammation, and damage compared with biphasic positive airway

  4. Unilateral Partial Nephrectomy with Warm Ischemia Results in Acute Hypoxia Inducible Factor 1-Alpha (HIF-1α and Toll-Like Receptor 4 (TLR4 Overexpression in a Porcine Model.

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    Zhiyong Zhang

    Full Text Available Ischemia/reperfusion (I/R during partial nephrectomy (PN contributes to acute kidney injury (AKI, which is inaccurately assessed using existent clinical markers of renal function. We evaluated I/R-related changes in expression in hypoxia inducible factor 1α (HIF-1α and toll-like receptor 4 (TLR4, within kidney tissue and peripheral blood leukocytes (PBL in a porcine model of PN.Three adult pigs each underwent unilateral renal hilar cross clamping for 180 min followed by a 15 min reperfusion. The contralateral kidney served as control. Biopsies of clamped kidneys were obtained at baseline (time 0, every 60 min during the hypoxic phase, and post-reperfusion. Control kidneys were biopsied once at 180 min. Peripheral blood was sampled at time 0, every 30 min during the hypoxic phase, and post-reperfusion. HIF-1α and TLR4 expression in kidney tissue and PBL were analyzed by Western blotting. I/R-related histological changes were assessed.Expression of HIF-1α in clamped kidneys and PBL was below detection level at baseline, rising to detectable levels after 60 min of hypoxia, and continuing to rise throughout the hypoxic and reperfusion phases. Expression of TLR-4 in clamped kidneys followed a similar trend with initial detection after 30-60 min of hypoxia. Control kidneys exhibited no change in HIF-1α or TLR-4 expression. I/R-related histologic changes were minimal, primarily mild tubular dilatation.In a porcine model of PN, HIF-1α and TLR4 exhibited robust, I/R-related increases in expression in kidney tissue and PBL. Further studies investigating these molecules as potential markers of AKI are warranted.

  5. Nitro-Oxidative Stress after Neuronal Ischemia Induces Protein Nitrotyrosination and Cell Death

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    Marta Tajes

    2013-01-01

    Full Text Available Ischemic stroke is an acute vascular event that obstructs blood supply to the brain, producing irreversible damage that affects neurons but also glial and brain vessel cells. Immediately after the stroke, the ischemic tissue produces nitric oxide (NO to recover blood perfusion but also produces superoxide anion. These compounds interact, producing peroxynitrite, which irreversibly nitrates protein tyrosines. The present study measured NO production in a human neuroblastoma (SH-SY5Y, a murine glial (BV2, a human endothelial cell line (HUVEC, and in primary cultures of human cerebral myocytes (HC-VSMCs after experimental ischemia in vitro. Neuronal, endothelial, and inducible NO synthase (NOS expression was also studied up to 24 h after ischemia, showing a different time course depending on the NOS type and the cells studied. Finally, we carried out cell viability experiments on SH-SY5Y cells with H2O2, a prooxidant agent, and with a NO donor to mimic ischemic conditions. We found that both compounds were highly toxic when they interacted, producing peroxynitrite. We obtained similar results when all cells were challenged with peroxynitrite. Our data suggest that peroxynitrite induces cell death and is a very harmful agent in brain ischemia.

  6. Facilitated beam-walking recovery during acute phase by kynurenic acid treatment in a rat model of photochemically induced thrombosis causing focal cerebral ischemia.

    Science.gov (United States)

    Abo, Masahiro; Yamauchi, Hideki; Suzuki, Masahiko; Sakuma, Mio; Urashima, Mitsuyoshi

    We previously demonstrated the presence of activated areas in the non-injured contralateral sensorimotor cortex in addition to the ipsilateral sensorimotor cortex of the area surrounding a brain infarction, using a rat model of focal photochemically induced thrombosis (PIT) and functional magnetic resonance imaging. Using this model, we next applied gene expression profiling to screen key molecules upregulated in the activated area. RNA was extracted from the ipsilateral and contralateral sensorimotor cortex to the focal brain infarction and from the sham controlled cortex, and hybridized to gene-expression profiling arrays containing 1,322 neurology-related genes. Results showed that glycine receptors were upregulated in both the ipsilateral and contralateral cortex to the focal ischemic lesion. To prove the preclinical significance of upregulated glycine receptors, kynurenic acid, an endogenous antagonist to glycine receptors on neuronal cells, was administered intrathecally. As a result, the kynurenic acid significantly improved behavioral recovery within 10 days from paralysis induced by the focal PIT (p beam walking. These results suggest that intrathecal administration of a glycine receptor antagonist may facilitate behavioral recovery during the acute phase after brain infarction. Copyright (c) 2006 S. Karger AG, Basel.

  7. Reduced microvascular volume and hemispherically deficient vasoreactivity to hypercapnia in acute ischemia: MRI study using permanent middle cerebral artery occlusion rat model.

    Science.gov (United States)

    Suh, J Y; Shim, Woo H; Cho, Gyunggoo; Fan, Xiang; Kwon, Seon J; Kim, Jeong K; Dai, George; Wang, Xiaoying; Kim, Young R

    2015-06-01

    Vasoreactivity to hypercapnia has been used for assessing cerebrovascular tone and control altered by ischemic stroke. Despite the high prognostic potential, traits of hypercapnia-induced hemodynamic changes have not been fully characterized in relation with baseline vascular states and brain tissue damage. To monitor cerebrovascular responses, T2- and T2*-weighted magnetic resonance imaging (MRI) images were acquired alternatively using spin- and gradient-echo echo plannar imaging (GESE EPI) sequence with 5% CO2 gas inhalation in normal (n=5) and acute stroke rats (n=10). Dynamic relative changes in cerebrovascular volume (CBV), microvascular volume (MVV), and vascular size index (VSI) were assessed from regions of interest (ROIs) delineated by the percent decrease of apparent diffusion coefficient (ADC). The baseline CBV was not affected by middle cerebral artery occlusion (MCAO) whereas the baseline MVV in ischemic areas was significantly lower than that in the rest of the brain and correlated with ADC. Vasoreactivity to hypercapnic challenge was considerably attenuated in the entire ipsilesional hemisphere including normal ADC regions, in which unsolicited, spreading depression-associated increases of CBV and MVV were observed. The lesion-dependent inhomogeneity in baseline MVV indicates the effective perfusion reserve for accurately delineating the true ischemic damage while the cascade of neuronal depolarization is probably responsible for the hemispherically lateralized changes in overall neurovascular physiology.

  8. Respiratory and Systemic Effects of LASSBio596 Plus Surfactant in Experimental Acute Respiratory Distress Syndrome

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    Johnatas Dutra Silva

    2016-02-01

    Full Text Available Background/Aims: Exogenous surfactant has been proposed as adjunctive therapy for acute respiratory distress syndrome (ARDS, but it is inactivated by different factors present in the alveolar space. We hypothesized that co-administration of LASSBio596, a molecule with significant anti-inflammatory properties, and exogenous surfactant could reduce lung inflammation, thus enabling the surfactant to reduce edema and improve lung function, in experimental ARDS. Methods: ARDS was induced by cecal ligation and puncture surgery in BALB/c mice. A sham-operated group was used as control (CTRL. After surgery (6 hours, CTRL and ARDS animals were assigned to receive: (1 sterile saline solution; (2 LASSBio596; (3 exogenous surfactant or (4 LASSBio596 plus exogenous surfactant (n = 22/group. Results: Regardless of exogenous surfactant administration, LASSBio596 improved survival rate and reduced collagen fiber content, total number of cells and neutrophils in PLF and blood, cell apoptosis, protein content in BALF, and urea and creatinine levels. LASSBio596 plus surfactant yielded all of the aforementioned beneficial effects, as well as increased BALF lipid content and reduced surface tension. Conclusion: LASSBio596 exhibited major anti-inflammatory and anti-fibrogenic effects in experimental sepsis-induced ARDS. Its association with surfactant may provide further advantages, potentially by reducing surface tension.

  9. The Effects of Experimentally Manipulated Social Status on Acute Eating Behavior: A Randomized, Crossover Pilot Study

    Science.gov (United States)

    Cardel, MI; Johnson, SL; Beck, J; Dhurandhar, E; Keita, AD; Tomczik, AC; Pavela, G; Huo, T; Janicke, DM; Muller, K; Piff, PK; Peters, JC; Hill, JO; Allison, DB

    2016-01-01

    Both subjective and objectively measured social status has been associated with multiple health outcomes, including weight status, but the mechanism for this relationship remains unclear. Experimental studies may help identify the causal mechanisms underlying low social standing as a pathway for obesity. Our objective was to investigate the effects of experimentally manipulated social status on ad libitum acute dietary intakes and stress-related outcomes as potential mechanisms relating social status and weight. This was a pilot feasibility, randomized, crossover study in Hispanic young adults (n=9; age 19–25; 67% female; BMI ≥18.5 and ≤30 kg/m2). At visit 1, participants consumed a standardized breakfast and were randomized to a high social status position (HIGH) or low social status position (LOW) in a rigged game of Monopoly™. The rules for the game differed substantially in terms of degree of ‘privilege’ depending on randomization to HIGH or LOW. Following Monopoly™, participants were given an ad libitum buffet meal and energy intakes (kcal) were estimated by pre- and post-weighing foods consumed. Stress-related markers were measured at baseline, after the game of Monopoly™, and after lunch. Visit 2 used the same standardized protocol; however, participants were exposed to the opposite social status condition. When compared to HIGH, participants in LOW consumed 130 more calories (p=0.07) and a significantly higher proportion of their daily calorie needs in the ad libitum buffet meal (39% in LOW versus 31% in HIGH; p=0.04). In LOW, participants reported decreased feelings of pride and powerfulness following Monopoly™ (p=0.05) and after their lunch meal (p=0.08). Relative to HIGH, participants in LOW demonstrated higher heart rates following Monopoly™ (p=0.06), but this relationship was not significant once lunch was consumed (p=0.31). Our pilot data suggest a possible causal relationship between experimentally manipulated low social status

  10. The effects of experimentally manipulated social status on acute eating behavior: A randomized, crossover pilot study.

    Science.gov (United States)

    Cardel, M I; Johnson, S L; Beck, J; Dhurandhar, E; Keita, A D; Tomczik, A C; Pavela, G; Huo, T; Janicke, D M; Muller, K; Piff, P K; Peters, J C; Hill, J O; Allison, D B

    2016-08-01

    Both subjective and objectively measured social status has been associated with multiple health outcomes, including weight status, but the mechanism for this relationship remains unclear. Experimental studies may help identify the causal mechanisms underlying low social standing as a pathway for obesity. Our objective was to investigate the effects of experimentally manipulated social status on ad libitum acute dietary intakes and stress-related outcomes as potential mechanisms relating social status and weight. This was a pilot feasibility, randomized, crossover study in Hispanic young adults (n=9; age 19-25; 67% female; BMI ≥18.5 and ≤30kg/m(2)). At visit 1, participants consumed a standardized breakfast and were randomized to a high social status position (HIGH) or low social status position (LOW) in a rigged game of Monopoly™. The rules for the game differed substantially in terms of degree of 'privilege' depending on randomization to HIGH or LOW. Following Monopoly™, participants were given an ad libitum buffet meal and energy intakes (kcal) were estimated by pre- and post-weighing foods consumed. Stress-related markers were measured at baseline, after the game of Monopoly™, and after lunch. Visit 2 used the same standardized protocol; however, participants were exposed to the opposite social status condition. When compared to HIGH, participants in LOW consumed 130 more calories (p=0.07) and a significantly higher proportion of their daily calorie needs in the ad libitum buffet meal (39% in LOW versus 31% in HIGH; p=0.04). In LOW, participants reported decreased feelings of pride and powerfulness following Monopoly™ (p=0.05) and after their lunch meal (p=0.08). Relative to HIGH, participants in LOW demonstrated higher heart rates following Monopoly™ (p=0.06), but this relationship was not significant once lunch was consumed (p=0.31). Our pilot data suggest a possible causal relationship between experimentally manipulated low social status and

  11. Rapid reversal of human intestinal ischemia-reperfusion induced damage by shedding of injured enterocytes and reepithelialisation.

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    Joep P M Derikx

    Full Text Available BACKGROUND: Intestinal ischemia-reperfusion (IR is a phenomenon related to physiological conditions (e.g. exercise, stress and to pathophysiological events (e.g. acute mesenteric ischemia, aortic surgery. Although intestinal IR has been studied extensively in animals, results remain inconclusive and data on human intestinal IR are scarce. Therefore, an experimental harmless model for human intestinal IR was developed, enabling us to clarify the sequelae of human intestinal IR for the first time. METHODS AND FINDINGS: In 30 patients undergoing pancreatico-duodenectomy we took advantage of the fact that in this procedure a variable length of jejunum is removed. Isolated jejunum (5 cm was subjected to 30 minutes ischemia followed by reperfusion. Intestinal Fatty Acid Binding Protein (I-FABP arteriovenous concentration differences across the bowel segment were measured before and after ischemia to assess epithelial cell damage. Tissue sections were collected after ischemia and at 25, 60 and 120 minutes reperfusion and stained with H&E, and for I-FABP and the apoptosis marker M30. Bonferroni's test was used to compare I-FABP differences. Mean (SEM arteriovenous concentration gradients of I-FABP across the jejunum revealed rapidly developing epithelial cell damage. I-FABP release significantly increased from 290 (46 pg/ml before ischemia towards 3,997 (554 pg/ml immediately after ischemia (p<0.001 and declined gradually to 1,143 (237 pg/ml within 1 hour reperfusion (p<0.001. Directly after ischemia the intestinal epithelial lining was microscopically normal, while subepithelial spaces appeared at the villus tip. However, after 25 minutes reperfusion, enterocyte M30 immunostaining was observed at the villus tip accompanied by shedding of mature enterocytes into the lumen and loss of I-FABP staining. Interestingly, within 60 minutes reperfusion the epithelial barrier resealed, while debris of apoptotic, shedded epithelial cells was observed in the lumen

  12. Low free triiodothyronine levels predict symptomatic intracranial hemorrhage and worse short-term outcome of thrombolysis in patients with acute ischemia stroke.

    Science.gov (United States)

    Qiu, Mingjing; Fang, Min; Liu, Xueyuan

    2017-11-01

    The aim of the study was to determine whether thyroid hormones level on admission in patients with ischemic stroke, treated with intravenous recombinant tissue type plasminogen activator (rtPA), was associated with symptomatic intracranial hemorrhage (sICH) and worse outcomes at 3 months.Patients with acute ischemic stroke (AIS) receiving intravenous rtPA thrombolytic treatment on our stroke unit between January 2015 and June 2016 were included in this study. Serum-free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (tT3), total thyroxine (tT4), and thyroid-stimulating hormone (TSH) were detected on admission. The endpoints were sICH, and poor functional outcomes at 3 and 6 months.In all, 159 patients (106 males; mean age 65.36 ± 10.02 years) were included. FT3 was independently associated with sICH (odds ratio [OR] 0.204, 95% confidence interval [CI] 0.065-0.642) and poor outcomes at 3 months (OR 0.396, 95% CI 0.180-1.764). The cut-off values of fT3 for sICH was 3.54 pg/mL (sensitivity 83%; specificity 83%; area under the curve 0.88). FT3 values ≤3.54 pg/mL increased risk for sICH by 3.16-fold (95% CI 0.75-1.0) compared with fT3 values >3.54 pg/mL.Low fT3 levels at admission were independently associated with sICH and worse outcomes at 3 months in AIS patients receiving rtPA thrombolytic therapy.

  13. Metabolic Adaptation to Muscle Ischemia

    Science.gov (United States)

    Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

    2000-01-01

    Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

  14. Neonatal maternal separation increases susceptibility to experimental colitis and acute stress exposure in male mice

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    Isabella M. Fuentes

    2016-12-01

    Full Text Available Experiencing early life stress can result in maladjusted stress response via dysregulation of the hypothalamic-pituitary-adrenal axis and serves as a risk factor for developing chronic pelvic pain disorders. We investigated whether neonatal maternal separation (NMS would increase susceptibility to experimental colitis or exposure to acute or chronic stress. Male mice underwent NMS from postnatal day 1–21 and as adults were assessed for open field behavior, hindpaw sensitivity, and visceromotor response (VMR to colorectal distension (CRD. VMR was also measured before and after treatment with intracolonic trinitrobenzene sulfonic acid (TNBS or exposure to acute or chronic water avoidance stress (WAS. Myeloperoxidase (MPO activity, proinflammatory gene and corticotropin-releasing factor (CRF receptor expression were measured in distal colon. Baseline VMR was not affected by NMS, but undergoing CRD increased anxiety-like behaviors and mechanical hindpaw sensitivity of NMS mice. Treatment with TNBS dose-dependently decreased body weight and survival only in NMS mice. Following TNBS treatment, IL-6 and artemin mRNA levels were decreased in the distal colon of NMS mice, despite increased MPO activity. A single WAS exposure increased VMR during CRD in NMS mice and increased IL-6 mRNA and CRF2 protein levels in the distal colon of naïve mice, whereas CRF2 protein levels were heightened in NMS colon both at baseline and post-WAS exposure. Taken together, these results suggest that NMS in mice disrupts inflammatory- and stress-induced gene expression in the colon, potentially contributing towards an exaggerated response to specific stressors later in life.

  15. Impact of global Fxr deficiency on experimental acute pancreatitis and genetic variation in the FXR locus in human acute pancreatitis

    NARCIS (Netherlands)

    Nijmeijer, Rian M.; Schaap, Frank G.; Smits, Alexander J. J.; Kremer, Andreas E.; Akkermans, Louis M. A.; Kroese, Alfons B. A.; Rijkers, Ger T.; Schipper, Marguerite E. I.; Verheem, André; Wijmenga, Cisca; Gooszen, Hein G.; van Erpecum, Karel J.

    2014-01-01

    Infectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is expressed in the ileum, liver and other organs including the

  16. Migraine and ischemia

    NARCIS (Netherlands)

    van der Wammes-van der Heijden, E.A.

    2009-01-01

    An association between migraine and ischemic events, especially ischemic stroke, has been debated for many years. Whether migraine is a risk factor for ischemic events or ischemia triggers migraine, or both, is still unclear. This thesis explores different relationships between migraine and

  17. The effects of acute inflammation on cognitive functioning and emotional processing in humans: A systematic review of experimental studies.

    Science.gov (United States)

    Bollen, Jessica; Trick, Leanne; Llewellyn, David; Dickens, Chris

    2017-03-01

    The cognitive neuropsychological model of depression proposes that negative biases in the processing of emotionally salient information have a central role in the development and maintenance of depression. We have conducted a systematic review to determine whether acute experimental inflammation is associated with changes to cognitive and emotional processing that are thought to cause and maintain depression. We identified experimental studies in which healthy individuals were administered an acute inflammatory challenge (bacterial endotoxin/vaccination) and standardised tests of cognitive function were performed. Fourteen references were identified, reporting findings from 12 independent studies on 345 participants. Methodological quality was rated strong or moderate for 11 studies. Acute experimental inflammation was triggered using a variety of agents (including endotoxin from E. coli, S. typhi, S. abortus Equi and Hepatitis B vaccine) and cognition was assessed over hours to months, using cognitive tests of i) attention/executive functioning, ii) memory and iii) social/emotional processing. Studies found mixed evidence that acute experimental inflammation caused changes to attention/executive functioning (2 of 6 studies showed improvements in attention executive function compared to control), changes in memory (3 of 5 studies; improved reaction time: reduced memory for object proximity: poorer immediate and delayed memory) and changes to social/emotional processing (4 of 5 studies; reduced perception of emotions, increased avoidance of punishment/loss experiences, and increased social disconnectedness). Acute experimental inflammation causes negative biases in social and emotional processing that could explain observed associations between inflammation and depression. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion.

    Science.gov (United States)

    Rogers, Natasha M; Zhang, Zheng J; Wang, Jiao-Jing; Thomson, Angus W; Isenberg, Jeffrey S

    2016-08-01

    Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  19. Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions.

    Science.gov (United States)

    Dutta, Sara; Mincholé, Ana; Quinn, T Alexander; Rodriguez, Blanca

    2017-10-01

    Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models (ten Tusscher and Panfilov, 2006; Grandi et al., 2010; Carro et al., 2011; O'Hara et al., 2011) to simulate key electrophysiological consequences of acute myocardial ischemia in single cell and tissue simulations. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia. However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental acute respiratory distress syndrome.

    Science.gov (United States)

    Weiss, Yoram G; Maloyan, Alina; Tazelaar, John; Raj, Nichelle; Deutschman, Clifford S

    2002-09-01

    The acute respiratory distress syndrome (ARDS) provokes three pathologic processes: unchecked inflammation, interstitial/alveolar protein accumulation, and destruction of pulmonary epithelial cells. The highly conserved heat shock protein HSP-70 can limit all three responses but is not appropriately expressed in the lungs after cecal ligation and double puncture (2CLP), a clinically relevant model of ARDS. We hypothesize that restoring expression of HSP-70 using adenovirus-mediated gene therapy will limit pulmonary pathology following 2CLP. We administered a vector containing the porcine HSP-70 cDNA driven by a CMV promoter (AdHSP) into the lungs of rats subjected to 2CLP or sham operation. Administration of AdHSP after either sham operation or 2CLP increased HSP-70 protein expression in lung tissue, as determined by immunohistochemistry and Western blot hybridization. Administration of AdHSP significantly attenuated interstitial and alveolar edema and protein exudation and dramatically decreased neutrophil accumulation, relative to a control adenovirus. CLP-associated mortality at 48 hours was reduced by half. Modulation of HSP-70 production reduces pathologic changes and may improve outcome in experimental ARDS.

  1. Paraquat poisoning: an experimental model of dose-dependent acute lung injury due to surfactant dysfunction

    Directory of Open Access Journals (Sweden)

    M.F.R. Silva

    1998-03-01

    Full Text Available Since the most characteristic feature of paraquat poisoning is lung damage, a prospective controlled study was performed on excised rat lungs in order to estimate the intensity of lesion after different doses. Twenty-five male, 2-3-month-old non-SPF Wistar rats, divided into 5 groups, received paraquat dichloride in a single intraperitoneal injection (0, 1, 5, 25, or 50 mg/kg body weight 24 h before the experiment. Static pressure-volume (PV curves were performed in air- and saline-filled lungs; an estimator of surface tension and tissue works was computed by integrating the area of both curves and reported as work/ml of volume displacement. Paraquat induced a dose-dependent increase of inspiratory surface tension work that reached a significant two-fold order of magnitude for 25 and 50 mg/kg body weight (P<0.05, ANOVA, sparing lung tissue. This kind of lesion was probably due to functional abnormalities of the surfactant system, as was shown by the increase in the hysteresis of the paraquat groups at the highest doses. Hence, paraquat poisoning provides a suitable model of acute lung injury with alveolar instability that can be easily used in experimental protocols of mechanical ventilation

  2. Cocaine-associated lower limb ischemia.

    LENUS (Irish Health Repository)

    Collins, Chris G

    2011-07-25

    Cocaine-associated thrombosis has been reported in the literature with reports of vascular injuries to cardiac, pulmonary, intestinal, placental, and musculoskeletal vessels; however, injury of the pedal vessels is rare. We report on a 31-year-old man who presented 2 months following a cocaine binge with limb-threatening ischemia without an otherwise identifiable embolic source. Angiography confirmed extensive occlusive disease of the tibioperoneal vessels. The patient improved following therapy with heparin and a prostacyclin analogue. Cocaine-induced thrombosis should be considered in patients presenting with acute arterial insufficiency in the lower limb without any other identifiable cause.

  3. Reducing pressure ulcers in patients with prolonged acute mechanical ventilation: a quasi-experimental study.

    Science.gov (United States)

    Loudet, Cecilia Inés; Marchena, María Cecilia; Maradeo, María Roxana; Fernández, Silvia Laura; Romero, María Victoria; Valenzuela, Graciela Esther; Herrera, Isabel Eustaquia; Ramírez, Martha Teresa; Palomino, Silvia Rojas; Teberobsky, Mariana Virginia; Tumino, Leandro Ismael; González, Ana Laura; Reina, Rosa; Estenssoro, Elisa

    2017-01-01

    To determine the effectiveness of a quality management program in reducing the incidence and severity of pressure ulcers in critical care patients. This was a quasi-experimental, before-and-after study that was conducted in a medical-surgical intensive care unit. Consecutive patients who had received mechanical ventilation for ≥ 96 hours were included. A "Process Improvement" team designed a multifaceted interventional process that consisted of an educational session, a pressure ulcer checklist, a smartphone application for lesion monitoring and decision-making, and a "family prevention bundle". Fifty-five patients were included in Pre-I group, and 69 were included in the Post-I group, and the incidence of pressure ulcers in these groups was 41 (75%) and 37 (54%), respectively. The median time for pressure ulcers to develop was 4.5 [4 - 5] days in the Pre-I group and 9 [6 - 20] days in the Post-I group after admission for each period. The incidence of advanced-grade pressure ulcers was 27 (49%) in the Pre-I group and 7 (10%) in the Post-I group, and finally, the presence of pressure ulcers at discharge was 38 (69%) and 18 (26%), respectively (p pressure ulcers. The duration of mechanical ventilation and the presence of organ failure were positively associated with the development of pressure ulcers, while the multifaceted intervention program acted as a protective factor. A quality program based on both a smartphone application and family participation can reduce the incidence and severity of pressure ulcers in patients on prolonged acute mechanical ventilation.

  4. Subclinical chronic kidney disease modifies the diagnosis of experimental acute kidney injury.

    Science.gov (United States)

    Succar, Lena; Pianta, Timothy J; Davidson, Trent; Pickering, John W; Endre, Zoltán H

    2017-09-01

    Extensive structural damage within the kidney must be present before serum creatinine increases. However, a subclinical phase of chronic kidney disease (CKD) usually goes undetected. Here we tested whether experimental subclinical CKD would modify functional and damage biomarker profiles of acute kidney injury (AKI). Subclinical CKD was induced in rats by adenine or aristolochic acid models but without increasing serum creatinine. After prolonged recovery (three to six weeks), AKI was induced with a subnephrotoxic dose of cisplatin. Urinary levels of kidney injury molecule-1 (KIM-1), cytochrome C, monocyte chemotactic protein-1 (MCP-1), clusterin, and interleukin-18 increased during CKD induction, without an increase in serum creatinine. After AKI in adenine-induced CKD, serum creatinine increased more rapidly, while increased urinary KIM-1, clusterin, and MCP-1 were delayed and reduced. Increased serum creatinine and biomarker excretion were associated with diffuse tubulointerstitial injury in the outer stripe of outer medulla coupled with over 50% cortical damage. Following AKI in aristolochic acid-induced CKD, increased serum creatinine, urinary KIM-1, clusterin, MCP-1, cytochrome C, and interleukin-18 concentrations and excretion were greater at day 21 than day 42 and inversely correlated with cortical injury. Subclinical CKD modified functional and damage biomarker profiles in diametrically opposite ways. Functional biomarker profiles were more sensitive, while damage biomarker diagnostic thresholds and increases were diminished and delayed. Damage biomarker concentrations and excretion were inversely linked to the extent of prior cortical damage. Thus, thresholds for AKI biomarkers may need to be lower or sampling delayed in the known presence of CKD. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  5. The antiulcer effect of Cibotium barometz leaves in rats with experimentally induced acute gastric ulcer

    Directory of Open Access Journals (Sweden)

    AL-Wajeeh NS

    2017-03-01

    Full Text Available Nahla Saeed Al-Wajeeh,1 Maryam Hajrezaie,1 Nawal Al-Henhena,1 Sareh Kamran,1 Elham Bagheri,1 Maryam Zahedifard,1 Kamelia Saremi,1 Suzita Mohd Noor,1 Hapipah Mohd Ali,2 Mahmood Ameen Abdulla11Department of Biomedical Science, Faculty of Medicine, 2Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, MalaysiaAbstract: Cibotium barometz is a pharmaceutical plant customarily used in traditional medicine in Malaysia for the treatment of different diseases, such as gastric ulcer. The gastroprotective effect of C. barometz leaves against ethanol-induced gastric hemorrhagic abrasions in Sprague Dawley rats has been evaluated in terms of medicinal properties. Seven groups of rats (normal control and ulcerated control groups, omeprazole 20 mg/kg, 62.5, 125, 250, and 500 mg/kg of C. barometz correspondingly were used in antiulcer experiment and pretreated with 10% Tween 20. After 1 hour, the normal group was orally administered 10% Tween 20, whereas absolute alcohol was fed orally to ulcerated control, omeprazole, and experimental groups. Gastric’s homogenate were assessed for endogenous enzymes activities. Stomachs were examined macroscopically and histologically. Grossly, the data demonstrated a significant decrease in the ulcer area of rats pretreated with plant extract in a dose-dependent manner with respect to the ulcerated group. Homogenates of the gastric tissue exhibited significantly increased endogenous enzymes activities in rats pretreated with C. barometz extract associated with the ulcerated control group. Histology of rats pretreated with C. barometz extract group using hematoxylin and eosin staining exhibited a moderate-to-mild disruption of the surface epithelium with reduction in submucosal edema and leucocyte infiltration in a dose-dependent manner. In addition, it showed heat shock protein70 protein up-expression and BCL2-associated X protein downexpression. These outcomes might be attributed to the

  6. Experimentally induced acute uric acid nephropathy in rabbits: Findings of high resolution gray scale and doppler ultrasonographies

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ik; Chung, Soo Young; Lee, Kyung Won; Kim, Hong Dae; Ko, Eun Young; Won, Mi Sook; Noh, Jung Woo [Hallym University College of Medicine, Seoul (Korea, Republic of); Park, Moon Hyang [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2001-12-15

    To evaluate changes of the high-resolution (HR) gray scale and doppler ultrasonographic (US) characteristics of experimentally induced acute uric acid (UA) nephropathy in rabbits. Acute UA nephropathy was induced in ten rabbits using supersaturated lithium carbonate solution. The rabbits were divided in two groups. Group I consisted of five rabbits, and they were injected with a single dose of 150 ml of saturated UA over one hour. During tis period, serial US studies of the kidneys of these rabbits were performed every ten minutes. Group II consisted of the remaining five rabbits, and three injections of 50 ml of saturated UA solution were given on the first, fifth and eight day and follow-up was done upto twenty fifth day. Sequential HR and Doppler US, renal biopsy and blood sampling were performed on day 1, 5, 8, 21, and 25 in the group II rabbits. In group I, HR and Doppler US examination revealed the normal resistive index without significant abnormality. On the other hand, US studies of group II showed poor renal corticomedullary differentiation, decreased renal blood flow and elevated resistive index. There was statistically significant correlation among US findings, histologic characteristics and chemical index (BUN, creatinine) of renal function. In addition, sequentially increased size and volume of the kidney were noted in both groups. HR gray scale and doppler US characteristics of experimentally induced acute UA nephropathy in rabbits were similar to those of acute renal failure caused by other well-known causes.

  7. Experimentally induced acute uric acid nephropathy in rabbits: Findings of high resolution gray scale and doppler ultrasonographies

    International Nuclear Information System (INIS)

    Yang, Ik; Chung, Soo Young; Lee, Kyung Won; Kim, Hong Dae; Ko, Eun Young; Won, Mi Sook; Noh, Jung Woo; Park, Moon Hyang

    2001-01-01

    To evaluate changes of the high-resolution (HR) gray scale and doppler ultrasonographic (US) characteristics of experimentally induced acute uric acid (UA) nephropathy in rabbits. Acute UA nephropathy was induced in ten rabbits using supersaturated lithium carbonate solution. The rabbits were divided in two groups. Group I consisted of five rabbits, and they were injected with a single dose of 150 ml of saturated UA over one hour. During tis period, serial US studies of the kidneys of these rabbits were performed every ten minutes. Group II consisted of the remaining five rabbits, and three injections of 50 ml of saturated UA solution were given on the first, fifth and eight day and follow-up was done upto twenty fifth day. Sequential HR and Doppler US, renal biopsy and blood sampling were performed on day 1, 5, 8, 21, and 25 in the group II rabbits. In group I, HR and Doppler US examination revealed the normal resistive index without significant abnormality. On the other hand, US studies of group II showed poor renal corticomedullary differentiation, decreased renal blood flow and elevated resistive index. There was statistically significant correlation among US findings, histologic characteristics and chemical index (BUN, creatinine) of renal function. In addition, sequentially increased size and volume of the kidney were noted in both groups. HR gray scale and doppler US characteristics of experimentally induced acute UA nephropathy in rabbits were similar to those of acute renal failure caused by other well-known causes.

  8. Ischemia and reperfusion in skin flaps: effects of mannitol and vitamin C in reducing necrosis area in a rat experimental model Isquemia e reperfusão de retalhos cutâneos: efeitos do manitol e vitamina C na redução de áreas de necrose em modelo experimental no rato

    Directory of Open Access Journals (Sweden)

    Winston Bonetti Yoshida

    2005-10-01

    Full Text Available PURPOSE: The aim of the present study was to develop an experimental model of ischemia-reperfusion injury in rat skin flap and to verify the effect of mannitol and vitamin C on reducing necrosis area. METHODS: A 6-x 3-cm groin skin flap was raised and submitted to 8 hours of ischemia by clamping the vascular pedicle and to 7 days of reperfusion. The animals were divided in four groups: S1 and S2 (10 animals each and C and T (14 animals each. In groups S1 and S2 skin flaps were not submitted to ischemia and animals received lactated Ringer's solution (S1 and antioxidant solution (S2 . In groups C and T, flaps were subjected to 8 hours of warm ischemia and animals received Lactated Ringer's solution (Group C and antioxidant solution immediately before reperfusion, (Group T. Flap survival was evaluated on the seventh day using a paper template technique and computer-assistant imaging analysis of necrotic and normal areas. RESULTS: Statistical analysis showed no area differences between groups C and T. CONCLUSION: The experimental model provided consistent necrotic area in control groups and drugs used were not effective in improving skin flap survival.OBJETIVO: Neste trabalho foi padronizado modelo experimental de isquemia e reperfusão em retalho cutâneo em ratos no qual estudou-se possibilidade de uma solução antioxidante, composta por Ringer lactato, vitamina C e manitol de reduzir a área de necrose. MÉTODOS: O modelo consistiu de levantamento de retalho cutâneo axial de 6,0 x 3,0cm, submetido à isquemia de 8 horas e reperfusão de 7 dias. Os animais foram divididos em quatro grupos: grupos S1, S2 (10 animais cada, C e T (14 animais cada. Nos grupos S1 e S2 todos os procedimentos dos demais grupos foram efetuados, exceto a isquemia e reperfusão: S1 recebeu apenas Ringer lactato e S2 a solução antioxidante. Os grupos C e T foram submetidos à isquemia. O grupo C recebeu somente Ringer lactato e o grupo T a solução antioxidante. No 7

  9. Nifedipine for angina and acute myocardial ischemia

    NARCIS (Netherlands)

    P.G. Hugenholtz (Paul); J.W. de Jong (Jan Willem); P.D. Verdouw (Pieter); P.W.J.C. Serruys (Patrick)

    1983-01-01

    textabstractThis paper reviews the mechanisms believed to be responsible for myocardial ischaemia and the mode of action of calcium antagonist drugs. The clinical management of patients with myocardial ischaemia is discussed in the context of current knowledge about patho-physiology and drug action.

  10. Effect of carbon dioxide pneumoperitoneum on the severity of acute pancreatitis: an experimental study in rats.

    Science.gov (United States)

    Yol, S; Bostanci, E B; Ozogul, Y; Zengin, N I; Ozel, U; Bilgihan, A; Akoglu, M

    2004-12-01

    In the management of mild acute biliary pancreatitis, it is generally recommended to perform laparoscopic cholecystectomy after the subsidence of the attack during the same hospital admission. The effect of laparoscopy on abdominal organs has been widely investigated but not in acute pancreatitis. This study used an animal model of mild acute pancreatitis to examine the effects of CO(2) pneumoperitoneum on acute pancreatitis in rats. Mild acute pancreatitis was induced in 30 male Sprague-Dawley rats by surgical ligation of the biliopancreatic duct. After 2 days, animals were assigned to three groups: sham operation (animals were anesthetized for 30 min without undergoing laparotomy), CO(2) pneumoperitoneum (applied for 30 min at a pressure of 12 mmHg), and laparotomy (performed for 30 min, and then the abdomen was closed). Two hours after the surgical procedures, animals were killed and levels of lactate dehydrogenase, aspartate aminotransferase, glucose, urea, hematocrit, and leukocyte count among Ranson's criteria and levels of amylase, lipase, and total bilirubin were measured to determine the severity of acute pancreatitis. Histopathologic examination of the pancreas was done, and malondialdehyde and glutathione levels of the pancreas and lung were determined. The only significant differences between the groups were in lactate dehydrogenase and aspartate aminotransferase levels, which were significantly higher in the pneumoperitoneum group compared to the sham operation group. CO(2) pneumoperitoneum for 30 min at a pressure of 12 mmHg did not affect the severity of acute pancreatitis induced by ligation of the biliopancreatic duct in rats.

  11. Noninvasive Ventilatory Correction as an Adjunct to an Experimental Systemic Reperfusion Therapy in Acute Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Kristian Barlinn

    2010-01-01

    Full Text Available Background. Obstructive sleep apnea (OSA is a common condition in patients with acute ischemic stroke and associated with early clinical deterioration and poor functional outcome. However, noninvasive ventilatory correction is hardly considered as a complementary treatment option during the treatment phase of acute ischemic stroke. Summary of Case. A 55-year-old woman with an acute middle cerebral artery (MCA occlusion received intravenous tissue plasminogen activator (tPA and enrolled into a thrombolytic research study. During tPA infusion, she became drowsy, developed apnea episodes, desaturated and neurologically deteriorated without recanalization, re-occlusion or intracerebral hemorrhage. Urgent noninvasive ventilatory correction with biphasic positive airway pressure (BiPAP reversed neurological fluctuation. Her MCA completely recanalized 24 hours later. Conclusions. Noninvasive ventilatory correction should be considered more aggressively as a complementary treatment option in selected acute stroke patients. Early initiation of BiPAP can stabilize cerebral hemodynamics and may unmask the true potential of other therapies.

  12. Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations

    DEFF Research Database (Denmark)

    Frith, Christopher Donald; Goslings, J C; Gaarder, C

    2010-01-01

    Acute traumatic coagulopathy (ATC) is an impairment of hemostasis that occurs early after injury and is associated with a 4-fold higher mortality, increased transfusion requirements and organ failure....

  13. Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Mortensen, Shila; Boye, Mette

    2009-01-01

    The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other...... parts of innate host defence reactions remain somewhat elusive. In order to gain new insight into this early host defence response in the context of bacterial infection we studied gene expression changes in peripheral lymphoid tissues as compared to hepatic expression changes, 14-18 h after lung...... with measurements of interleukin-6 and selected acute phase proteins in serum. C-reactive protein and serum amyloid A were clearly induced 14-18 h after infection. Extrahepatic expression of acute phase proteins was found to be dramatically altered as a result of the lung infection with an extrahepatic acute phase...

  14. Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate receptor during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit

    NARCIS (Netherlands)

    R.J. de Knegt (Robert); J. Kornhuber (Johannes); S.W. Schalm (Solko); K. Rusche (K.); P.F. Riederer (Peter); J. Tan (J.)

    1993-01-01

    textabstractBinding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate (NMDA) receptor population on brain homogenates in rabbits was studied during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. Homogenates were

  15. Experimental Effects of Acute Exercise on Prospective Memory and False Memory.

    Science.gov (United States)

    Green, David; Loprinzi, Paul D

    2018-01-01

    Research demonstrates that acute exercise can enhance retrospective episodic memory performance. However, limited research has examined the effects of acute exercise on prospective memory, and no studies have examined the effects of exercise on false memory performance. This study examined the potential effects of acute exercise on prospective memory and false memory performance. A between-group randomized controlled trial was employed, with participants (college students; M age  = 20 years) randomized into an exercise group (15-minute acute bout of treadmill walking; N = 25) or a control group (15 minutes of sitting; N = 26). Prospective memory was assessed from two laboratory and two naturalistic assessments outside the lab. False memory was assessed using a word-list trial. There were no statistically significant differences in prospective memory based on group allocation (F Group×Time  = 1.17; P = 0.32; η 2  = 0.06). However, the control group recalled more false words and had a higher rate of false memory recognition (F Group×Time  = 3.15; P = 0.01; η 2  = 0.26). These findings indicate that acute moderate-intensity aerobic exercise is not associated with prospective memory performance but provides some suggestive evidence that acute exercise may reduce the rate of false memories.

  16. Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway.

    Science.gov (United States)

    Yue, Rongzheng; Zuo, Chuan; Zeng, Jing; Su, Baihai; Tao, Ye; Huang, Songmin; Zeng, Rui

    2017-11-01

    To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors. After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.

  17. Experimental Effects of Acute Exercise on Iconic Memory, Short-Term Episodic, and Long-Term Episodic Memory

    Directory of Open Access Journals (Sweden)

    Danielle Yanes

    2018-06-01

    Full Text Available The present experiment evaluated the effects of acute exercise on iconic memory and short- and long-term episodic memory. A two-arm, parallel-group randomized experiment was employed (n = 20 per group; Mage = 21 year. The experimental group engaged in an acute bout of moderate-intensity treadmill exercise for 15 min, while the control group engaged in a seated, time-matched computer task. Afterwards, the participants engaged in a paragraph-level episodic memory task (20 min delay and 24 h delay recall as well as an iconic memory task, which involved 10 trials (at various speeds from 100 ms to 800 ms of recalling letters from a 3 × 3 array matrix. For iconic memory, there was a significant main effect for time (F = 42.9, p < 0.001, η2p = 0.53 and a trend towards a group × time interaction (F = 2.90, p = 0.09, η2p = 0.07, but no main effect for group (F = 0.82, p = 0.37, η2p = 0.02. The experimental group had higher episodic memory scores at both the baseline (19.22 vs. 17.20 and follow-up (18.15 vs. 15.77, but these results were not statistically significant. These findings provide some suggestive evidence hinting towards an iconic memory and episodic benefit from acute exercise engagement.

  18. Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations

    NARCIS (Netherlands)

    Frith, D.; Goslings, J. C.; Gaarder, C.; Maegele, M.; Cohen, M. J.; Allard, S.; Johansson, P. I.; Stanworth, S.; Thiemermann, C.; Brohi, K.

    2010-01-01

    Background: Acute traumatic coagulopathy (ATC) is an impairment of hemostasis that occurs early after injury and is associated with a 4-fold higher mortality, increased transfusion requirements and organ failure. Objectives: The purpose of the present study was to develop a clinically relevant

  19. Hypothermic total liquid ventilation after experimental aspiration-associated acute respiratory distress syndrome.

    Science.gov (United States)

    Rambaud, Jérôme; Lidouren, Fanny; Sage, Michaël; Kohlhauer, Matthias; Nadeau, Mathieu; Fortin-Pellerin, Étienne; Micheau, Philippe; Zilberstein, Luca; Mongardon, Nicolas; Ricard, Jean-Damien; Terada, Megumi; Bruneval, Patrick; Berdeaux, Alain; Ghaleh, Bijan; Walti, Hervé; Tissier, Renaud

    2018-05-02

    Ultrafast cooling by total liquid ventilation (TLV) provides potent cardio- and neuroprotection after experimental cardiac arrest. However, this was evaluated in animals with no initial lung injury, whereas out-of-hospital cardiac arrest is frequently associated with early-onset pneumonia, which may lead to acute respiratory distress syndrome (ARDS). Here, our objective was to determine whether hypothermic TLV could be safe or even beneficial in an aspiration-associated ARDS animal model. ARDS was induced in anesthetized rabbits through a two-hits model including the intra-tracheal administration of a pH = 1 solution mimicking gastric content and subsequent gaseous non-protective ventilation during 90 min (tidal volume [Vt] = 10 ml/kg with positive end-expiration pressure [PEEP] = 0 cmH 2 O). After this initial period, animals either received lung protective gas ventilation (LPV; Vt = 8 ml/kg and PEEP = 5 cmH 2 O) under normothermic conditions, or hypothermic TLV (TLV; Vt = 8 ml/kg and end-expiratory volume = 15 ml/kg). Both strategies were applied for 120 min with a continuous monitoring of respiratory and cardiovascular parameters. Animals were then euthanized for pulmonary histological analyses. Eight rabbits were included in each group. Before randomization, all animals elicited ARDS with arterial oxygen partial pressure over inhaled oxygen fraction ratios (PaO 2 /FiO 2 ) below 100 mmHg, as well as decreased lung compliance. After randomization, body temperature rapidly decreased in TLV versus LPV group (32.6 ± 0.6 vs. 38.2 ± 0.4 °C after 15 min). Static lung compliance and gas exchanges were not significantly different in the TLV versus LPV group (PaO 2 /FiO 2  = 62 ± 4 vs. 52 ± 8 mmHg at the end of the procedure, respectively). Mean arterial pressure and arterial bicarbonates levels were significantly higher in TLV versus LPV. Histological analysis also showed significantly lower inflammation in

  20. Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

    Science.gov (United States)

    Montazeri, Mahbobeh; Ebrahimzadeh, Mohammad Ali; Ahmadpour, Ehsan; Sharif, Mehdi; Sarvi, Shahabeddin

    2016-01-01

    Current therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 × 103 tachyzoites of the virulent T. gondii strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 × 106 tachyzoites of the virulent strain RH of T. gondii in rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasma activity was observed using propranolol (P toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasma activity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent murine toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine. PMID:27645234

  1. Statins in acute neurologic disease:which one, which dose, when to start, and when not to stop

    Institute of Scientific and Technical Information of China (English)

    Bong-Su Kang; Gene Sung; May Kim-Tenser; Nerses Sanossian

    2016-01-01

    Statins could have physiologic properties that may beneift patients that have been diagnosed with various acute neurological diseases. This review aims tosummarize the literature pertaining to stain use in acute neurological disease such as subarachnoid hemorrhage, intracerebral hemorrhage (ICH), cerebral ischemia (CI), traumatic brain injury, status epilepticus and meningitis. The authors reviewed published abstracts and manuscripts pertaining to experimental and clinical trials relevant to statins in acute neurological disease. Although acute statin therapy in the setting of subarachnoid hemorrhage might reduce delayed cerebral ischemia and mortality, it should not be considered standard care at this time. Acute statins therapy has not demonstrated anybeneift yet folowing an ICH or CI. Acute statin withdrawal may worsen outcome in acute CI. Observational and case-control studies suggest that pretreatment with statin at time of onset may be associated with better outcomes. Even though preclinical studies have shown statins to have beneifcial effects, there has been no clinical evidence. In conclusion, current published studies have not shown that acute statin therapy has any beneifcal effects in acute neurologic diseases and therefore further large randomized clinical trials are needed.

  2. Experimental Effects of Acute Exercise on Iconic Memory, Short-Term Episodic, and Long-Term Episodic Memory.

    Science.gov (United States)

    Yanes, Danielle; Loprinzi, Paul D

    2018-06-11

    The present experiment evaluated the effects of acute exercise on iconic memory and short- and long-term episodic memory. A two-arm, parallel-group randomized experiment was employed ( n = 20 per group; M age = 21 year). The experimental group engaged in an acute bout of moderate-intensity treadmill exercise for 15 min, while the control group engaged in a seated, time-matched computer task. Afterwards, the participants engaged in a paragraph-level episodic memory task (20 min delay and 24 h delay recall) as well as an iconic memory task, which involved 10 trials (at various speeds from 100 ms to 800 ms) of recalling letters from a 3 × 3 array matrix. For iconic memory, there was a significant main effect for time (F = 42.9, p memory scores at both the baseline (19.22 vs. 17.20) and follow-up (18.15 vs. 15.77), but these results were not statistically significant. These findings provide some suggestive evidence hinting towards an iconic memory and episodic benefit from acute exercise engagement.

  3. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

    Science.gov (United States)

    Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

    2011-11-01

    Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

  4. Neurotherapeutic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats

    Directory of Open Access Journals (Sweden)

    Shevtsov MA

    2014-05-01

    Full Text Available Maxim A Shevtsov,1,2 Boris P Nikolaev,3 Ludmila Y Yakovleva,3 Anatolii V Dobrodumov,4 Anastasiy S Dayneko,5 Alexey A Shmonin,5,6 Timur D Vlasov,5 Elena V Melnikova,5 Alexander D Vilisov,4,5 Irina V Guzhova,1 Alexander M Ischenko,3 Anastasiya L Mikhrina,7 Oleg V Galibin,5 Igor V Yakovenko,2 Boris A Margulis1 1Institute of Cytology of the Russian Academy of Sciences (RAS, St Petersburg, Russia; 2AL Polenov Russian Research Scientific Institute of Neurosurgery, St Petersburg, Russia; 3Research Institute of Highly Pure Biopreparations, St Petersburg, Russia; 4Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS, St Petersburg, Russia; 5First St Petersburg IP Pavlov State Medical University, St Petersburg, Russia; 6Federal Almazov Medical Research Centre, St Petersburg, Russia; 7IM Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (RAS, St Petersburg, Russia Abstract: Recombinant 70 kDa heat shock protein (Hsp70 is an antiapoptotic protein that has a cell protective activity in stress stimuli and thus could be a useful therapeutic agent in the management of patients with acute ischemic stroke. The neuroprotective and neurotherapeutic activity of recombinant Hsp70 was explored in a model of experimental stroke in rats. Ischemia was produced by the occlusion of the middle cerebral artery for 45 minutes. To assess its neuroprotective capacity, Hsp70, at various concentrations, was intravenously injected 20 minutes prior to ischemia. Forty-eight hours after ischemia, rats were sacrificed and brain tissue sections were stained with 2% triphenyl tetrazolium chloride. Preliminary treatment with Hsp70 significantly reduced the ischemic zone (optimal response at 2.5 mg/kg. To assess Hsp70’s neurotherapeutic activity, we intravenously administered Hsp70 via the tail vein 2 hours after reperfusion (2 hours and 45 minutes after ischemia. Rats were then kept alive for 72 hours. The

  5. Effects of urtica dioica extract on experimental acute pancreatitis model in rats.

    Science.gov (United States)

    Yilmaz, Baris; Basar, Omer; Aktas, Bora; Altinbas, Akif; Ekiz, Fuat; Büyükcam, Fatih; Albayrak, Aynur; Ginis, Zeynep; Oztürk, Gülfer; Coban, Sahin; Ucar, Engin; Kaya, Oskay; Yüksel, Osman; Caner, Sedat; Delibasi, Tuncay

    2014-01-01

    Acute pancreatitis is the acute inflammation of pancreas and peripancreatic tissues, and distant organs are also affected. The aim of this study was to investigate the effect of Urtica dioica extract (UDE) treatment on cerulein induced acute pancreatitis in rats. Twenty-one Wistar Albino rats were divided into three groups: Control, Pancreatitis, and UDE treatment group. In the control group no procedures were performed. In the pancreatitis and treatment groups, pancreatitis was induced with intraperitoneal injection of cerulein, followed by intraperitoneal injection of 1 ml saline (pancreatitis group) and 1 ml 5.2% UDE (treatment group). Pancreatic tissues were examined histopathologically. Pro-inflammatory cytokines (tumor necrosis factor-α), amylase and markers of apoptosis (M30, M65) were also measured in blood samples. Immunohistochemical staining was performed with Caspase-3 antibody. Histopathological findings in the UDE treatment group were less severe than in the pancreatitis group (5.7 vs 11.7, p = 0.010). TNF-α levels were not statistically different between treated and control groups (63.3 vs. 57.2, p = 0.141). UDE treatment was associated with less apoptosis [determined by M30, caspase-3 index (%)], (1.769 vs. 0.288, p = 0.056; 3% vs. 2.2%, p = 0.224; respectively). UDE treatment of pancreatitis merits further study.

  6. [Morphological changes of the intestine in experimental acute intestinal infection in the treatment of colloidal silver].

    Science.gov (United States)

    Polov'ian, E S; Chemich, N D; Moskalenko, R A; Romaniuk, A N

    2012-06-01

    At the present stage of infectionist practice in the treatment of acute intestinal infections caused by opportunistic microorganisms, colloidal silver is used with a particle size of 25 nm as an alternative to conventional causal therapy. In 32 rats, distributed in 4 groups of 8 animals each (intact; healthy, got colloidal silver; with a modeled acute intestinal infection in the basic treatment and with the addition of colloidal silver), histological examination was performed of small and large intestine of rats. Oral administration of colloidal silver at a dose of 0.02 mg/day to intact rats did not lead to changes in morphometric parameters compared to the norm, and during early convalescence in rats with acute intestinal infections were observed destructive and compensatory changes in the intestine, which depended on the treatment regimen. With the introduction of colloidal silver decreased activity of the inflammatory process and the severity of morphological changes in tissues of small and large intestine, indicating that the positive effect of study drug compared with baseline therapy.

  7. Roles of Oxidative Stress, Apoptosis, PGC-1α and Mitochondrial Biogenesis in Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Ding-I Yang

    2011-10-01

    Full Text Available The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ co-activator 1α (PGC1-α. PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis.

  8. Myocardial ischemia in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Lima Filho, Moyses de Oliveira; Figueiredo, Geraldo L.; Simoes, Marcus V.; Pyntia, Antonio O.; Marin Neto, Jose Antonio

    2000-01-01

    Myocardial ischemia in hypertrophic cardiomyopathy is multifactorial and explains the occurrence of angina, in about 50% of patients. The pathophysiology of myocardial ischemia may be explained by the increase of the ventricular mass and relative paucity of the coronary microcirculation; the elevated ventricular filling pressures and myocardial stiffness causing a compression of the coronary microvessels; the impaired coronary vasodilator flow reserve caused by anatomic and functional abnormalities; and the systolic compression of epicardial vessel (myocardial bridges). Myocardial ischemia must be investigated by perfusion scintigraphic methods since its presence influences the prognosis and has relevant clinical implications for management of patients. Patients with hypertrophic cardiomyopathy and documented myocardial ischemia usually need to undergo invasive coronary angiography to exclude the presence of concomitant atherosclerotic coronary disease. (author)

  9. Does Regional Lung Strain Correlate With Regional Inflammation in Acute Respiratory Distress Syndrome During Nonprotective Ventilation? An Experimental Porcine Study.

    Science.gov (United States)

    Retamal, Jaime; Hurtado, Daniel; Villarroel, Nicolás; Bruhn, Alejandro; Bugedo, Guillermo; Amato, Marcelo Britto Passos; Costa, Eduardo Leite Vieira; Hedenstierna, Göran; Larsson, Anders; Borges, João Batista

    2018-06-01

    It is known that ventilator-induced lung injury causes increased pulmonary inflammation. It has been suggested that one of the underlying mechanisms may be strain. The aim of this study was to investigate whether lung regional strain correlates with regional inflammation in a porcine model of acute respiratory distress syndrome. Retrospective analysis of CT images and positron emission tomography images using [F]fluoro-2-deoxy-D-glucose. University animal research laboratory. Seven piglets subjected to experimental acute respiratory distress syndrome and five ventilated controls. Acute respiratory distress syndrome was induced by repeated lung lavages, followed by 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressures (mean, 4 cm H2O) and high inspiratory pressures (mean plateau pressure, 45 cm H2O). All animals were subsequently studied with CT scans acquired at end-expiration and end-inspiration, to obtain maps of volumetric strain (inspiratory volume - expiratory volume)/expiratory volume, and dynamic positron emission tomography imaging. Strain maps and positron emission tomography images were divided into 10 isogravitational horizontal regions-of-interest, from which spatial correlation was calculated for each animal. The acute respiratory distress syndrome model resulted in a decrease in respiratory system compliance (20.3 ± 3.4 to 14.0 ± 4.9 mL/cm H2O; p < 0.05) and oxygenation (PaO2/FIO2, 489 ± 80 to 92 ± 59; p < 0.05), whereas the control animals did not exhibit changes. In the acute respiratory distress syndrome group, strain maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions, which was similar to the distribution of [F]fluoro-2-deoxy-D-glucose uptake observed in the positron emission tomography images, resulting in a positive spatial correlation between both variables (median R = 0.71 [0.02-0.84]; p < 0.05 in five of seven animals

  10. Neuroprotective effects of female sex steroids in cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Drača Sanja

    2013-03-01

    Full Text Available The central and peripheral nervous system are important targets of sex steroids. Sex steroids affect the brain development and differentiation, and influence neuronal functions. Recent evidence emphasizes a striking sex-linked difference in brain damage after experimental stroke, as well as the efficacy of hormones in treating cerebral stroke injury. Several different models of cerebral ischemia have been utilized for hormone neuroprotection studies, including transient or permanent middle cerebral artery occlusion, transient global ischemia, and transient forebrain ischemia. Extensive experimental studies have shown that female sex steroids such as progesterone and 176-estradiol exert neuroprotective effects in the experimental models of stroke, although deleterious effects have also been reported. Also, a significance of numerous factors, including gender and age of experimental animals, localization of brain lesion, duration of ischemia and precise dose of steroids has been pointed out. There are multiple potential mechanisms that might be invoked to explain the beneficial effects of female sex steroids in brain injury, involving neuroprotection, anti-inflammatory properties, effects on vasculature and altered transcriptional regulation. A several clinical trials on the effects of sex hormones to traumatic brain injury have been performed, suggesting that hormone therapy may represent a new therapeutic tool to combat certain diseases, such as traumatic brain injury. Further basic science studies and randomized clinical trials are necessary to reveal a potential application of these molecules as a new therapeutic strategy.

  11. Temporary interventional pneumonectomy used as an emergency treatment for acute massive pulmonary embolism: the initial experimental results

    International Nuclear Information System (INIS)

    Fan Yong; Liu Yang; Wu Qi; Li Ping; Tian Jing; Bao Guijun; He Nengshu

    2009-01-01

    Objective: To evaluate regional airway obstruction with balloon catheter in stabilizing the vital signs in experimental animals suffered from acute massive pulmonary embolism. Methods: Pulmonary embolism of right lung artery by using auto-blood clots or detachable latex balloons was established in 27 healthy sheep. When the blood oxygen saturation decreased by 25% compared to that before the procedure, the placement of balloon catheter in corresponding right main bronchus was carried out in 18 sheep (study group). Five sheep were used as control group. The blood oxygen saturation in the remaining four sheep did not reach the intervention level. The pulmonary arterial pressure, the peripheral arterial pressure, the central venous pressure, the heart rate, the blood oxygen saturation, the arterial partial pressure of oxygen as well as of carbon dioxide were invasively determined. Results: The experimental model of acute massive pulmonary embolism was successfully established in 23 sheep. After the establishment of pulmonary embolism, increased heart rate, tachypnea, a decrease of ≥ 25% in blood oxygen saturation within 30 minutes and a rise in pulmonary arterial pressure were detected. After the placement of balloon catheter in study group, a reduction of the pulmonary arterial pressure and an elevation of the blood oxygen saturation as well as the arterial partial pressure of oxygen rose were observed.The difference between study group and control group was statistically significant (P<0.05). Conclusion: The result of this animal experiment indicates that obstruction of airway with balloon can be served as a first aid for acute massive pulmonary embolism, which can stabilizes the animal's vital signs and, therefore, can help gain precious time for the follow-up thrombolysis treatment. (authors)

  12. Proinflammatory and anti-inflammatory cytokines present in the acute phase of experimental colitis treated with Saccharomyces boulardii.

    Science.gov (United States)

    Grijó, Nathália Nahas; Borra, Ricardo Carneiro; Sdepanian, Vera Lucia

    2010-09-01

    To study the proinflammatory and anti-inflammatory cytokines present in the acute phase of trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis treated with Saccharomyces boulardii. Thirty male Wistar rats were divided into three groups: (1) treated group--received Saccharomyces boulardii for 14 days; (2) non-treated group--received sodium chloride solution for 14 days; (3) control group. Colitis was induced on the seventh day of the study in the treated and the non-treated groups using TNBS (10 mg) dissolved in 50% ethanol. Quantification of cytokines, including interleukin (IL)-1beta (IL-1beta), IL-6, transforming growth factor-beta (TGF-beta), IL-10 and tumor necrosis factor-alpha (TNF-alpha), in the serum and colonic tissue collected on day 14 were carried out using an enzyme-linked immunosorbent assay (ELISA). The mean concentrations of TGF-beta in both the serum and the colonic tissue of the treated group were statistically higher than that of the control group. The mean concentration of TGF-beta in the colonic tissue of the non-treated group was also statistically higher than the control group. The group treated with Saccharomyces boulardii showed increased amounts of TGF-beta, an anti-inflammatory cytokine, during the acute phase of colitis. There were no differences in the amount of TNF-alpha, IL-1beta, IL-6, and IL-10 between the treated and the non-treated or the control groups during the acute phase of experimental colitis induced by TNBS.

  13. Autophagy and Liver Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Raffaele Cursio

    2015-01-01

    Full Text Available Liver ischemia-reperfusion (I-R injury occurs during liver resection, liver transplantation, and hemorrhagic shock. The main mode of liver cell death after warm and/or cold liver I-R is necrosis, but other modes of cell death, as apoptosis and autophagy, are also involved. Autophagy is an intracellular self-digesting pathway responsible for removal of long-lived proteins, damaged organelles, and malformed proteins during biosynthesis by lysosomes. Autophagy is found in normal and diseased liver. Although depending on the type of ischemia, warm and/or cold, the dynamic process of liver I-R results mainly in adenosine triphosphate depletion and in production of reactive oxygen species (ROS, leads to both, a local ischemic insult and an acute inflammatory-mediated reperfusion injury, and results finally in cell death. This process can induce liver dysfunction and can increase patient morbidity and mortality after liver surgery and hemorrhagic shock. Whether autophagy protects from or promotes liver injury following warm and/or cold I-R remains to be elucidated. The present review aims to summarize the current knowledge in liver I-R injury focusing on both the beneficial and the detrimental effects of liver autophagy following warm and/or cold liver I-R.

  14. Evaluation of the therapeutic effect of potassium permanganate at early stages of an experimental acute infection of Flavobacterium columnare in channel catfish (Ictalurus punctatus)

    Science.gov (United States)

    The efficacy of potassium permanganate (KMnO4) against early stages of an experimental acute infection of Flavobacterium columnare in channel catfish (Ictalurus punctatus) was evaluated. Fish were experimentally challenged, by waterborne exposure for 2 h to F. columnare after cutaneous abrasion, an...

  15. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    Directory of Open Access Journals (Sweden)

    Mónica Millán

    2008-01-01

    Full Text Available Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA.

  16. Treatment for infections complications of experimental acute radiation sickness with sulacillin, a combined antibiotic

    International Nuclear Information System (INIS)

    Chertkov, K.S.; Revskaya, E.A.

    1999-01-01

    The therapeutic efficiency of sulacillin (combination of ampicillin antibiotic with beta-lactamase sulbactam inhibitor) used for prevention and treatment of infections complications of the acute radiation disease (ARD) is considered. It is shown that sulacillin antiinfections effect essentially exceeds the activity of ampicillin by treatment of irradiated mice infected with a beta-lactamase-producing strain of Kl pneumoniae. Inclusion of the sulacillin as a principal antibiotic into the ARD therapeutic scheme provides for the 66.6 % survival of dogs at LD 90/45 [ru

  17. Role of unphosphorylated transcription factor STAT3 in late cerebral ischemia after subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Samraj, Ajoy K; Müller, Anne H; Grell, Anne-Sofie

    2014-01-01

    Molecular mechanisms behind increased cerebral vasospasm and local inflammation in late cerebral ischemia after subarachnoid hemorrhage (SAH) are poorly elucidated. Using system biology tools and experimental SAH models, we have identified signal transducer and activator of transcription 3 (STAT3...

  18. Movement does not promote recovery of motor output following acute experimental muscle pain

    DEFF Research Database (Denmark)

    Schabrun, Siobhan M.; Palsson, Thorvaldur Skuli; Thapa, Tribikram

    2018-01-01

    Objective.:  To examine the effect of motor activity on the magnitude and duration of altered corticomotor output following experimental muscle pain. Design. : Experimental, pre-post test. Setting. : University laboratory. Subjects. : Twenty healthy individuals. Methods.:  Participants were rando....... Understanding corticomotor depression in the postpain period and what factors promote recovery has relevance for clinical pain syndromes where ongoing motor dysfunction, in the absence of pain, may predispose to symptom persistence or recurrence....

  19. Experimental alveolitis in rats: microbiological, acute phase response and histometric characterization of delayed alveolar healing.

    Science.gov (United States)

    Rodrigues, Moacyr Tadeu Vicente; Cardoso, Camila Lopes; Carvalho, Paulo Sérgio Perri de; Cestari, Tânia Mary; Feres, Magda; Garlet, Gustavo Pompermaier; Ferreira, Osny

    2011-01-01

    The pathogenesis of alveolitis is not well known and therefore experimental situations that mimic some features of this disease should be developed. In this study, the evolution of the experimentally induced infection in rat sockets is characterized, which leads to clinical signs of suppurative alveolitis with remarkable wound healing disturbs. Non-infected (Group I) and experimentally infected sockets in Rattus novergicus (Group II) were histometrically evaluated regarding the kinetics of alveolar healing. In addition, the characterization of the present bacteria in inoculation material and the serum levels of C-reactive protein (CRP) were performed. The detected species were Capnocytophaga ochracea, Fusobacterium nucleatum ss nucleatum, Prevotella melaninogenica, Streptococcus anginosus, Treponema socranskii and Streptococcus sanguis. All experimentally infected rats developed suppurative alveolitis, showing higher levels of CRP in comparison to those non-infected ones. Furthermore, infected rats presented a significant delayed wound healing as measured by the histometric analysis (higher persistent polymorphonuclear infiltrate and lower density of newly formed bone). These findings indicate that rat sockets with experimentally induced infection produced higher levels of serum CRP, showing the potential of disseminated infection and a disturb in the alveolar repair process in an interesting experimental model for alveolitis studies.

  20. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    Directory of Open Access Journals (Sweden)

    Peter Moritz Becher

    2017-01-01

    Full Text Available Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

  1. Ischemia-infarction

    International Nuclear Information System (INIS)

    Bradley, W.G.

    1990-01-01

    Stroke is a non-specific term indicting an acute neurologic event. While arteriosclerosis is by far the leading cause of stroke, acute neurologic events can also result from hemorrhage secondary to rupture of an aneurysm or bleeding from an AVM. Less common causes of stroke include bleeding into metastatic or primary tumors or, even less commonly, subdural hematomas. Since arteriosclerotic strokes usually involve a known vascular distribution, they are generally distinguishable from strokes due to other causes by either CT or MRI. The use of CT or MRI is indicated in the acute setting since subsequent treatment, such as anticoagulation or surgical decompression, may depend on the findings of hemorrhage and mass effect from the imaging study. Unfortunately, when an arteriosclerotic etiology of stroke has been determined, the degree of abnormality on MRI or CT may not correlate well with the degree of clinical impairment

  2. Evaluation of outcome in Mesenteric Ischemia

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    Samad Shams Vahdati

    2017-04-01

    Full Text Available Background: Acute mesenteric ischemia (AMI is an infrequent but a complicated life threatening condition. It is the leading causes of mortality with the rate of 60-100%. The purpose of our study is to investigate demographic outcomes of the patients referred to the emergency department of Imam Reza hospital with the diagnosis of AMI. Methods and materials: All patients with the diagnosis of AMI from March 2014 to March 2016 who were referred to emergency department of Imam Reza hospital, were studied. Demographic characteristics (age, sex, the period from symptom onset till laparotomy, risk factors and the last outcomes of patients were noted in the check lists for each patient. P value less than 0.05 was determined as significant. Results: from 111 patients, 76 cases (68.8% were male, 35 cases (31.5% were female. Chief complaint of all patients was stomachache. Period of arriving to the emergency room in 5 cases (4.5% was 1-6 hours, in 3 cases (2.7% was 6-12 hours, and in 103 cases (92.8% has taken more than 12 hours. In 55 cases (49.5%, there was a significant relationship between clinical signs and physical examination findings, whereas in 56 cases (50.5% there was no relation. In our study 42 cases (37.8% were treated, whereas the morbidity and mortality rate were respectively 7 (6.3% and 62 (55.9%. According to the results of our study the most important finding was pain which was disproportionate to physical examination findings (P value< 0.052. Conclusion: Acute mesenteric ischemia is a severe and progressive disease so early diagnosis and appropriate treatment are very important. One of the main reasons of higher mortality rate in AMI is difficulty in early diagnosis, before necrosis occurrence. Major factor that determines the survival rate is the accurate diagnosis before necrosis and peritonitis happens.

  3. Oral zinc supplementation for children with acute diarrhoea: a quasi-experimental study.

    Science.gov (United States)

    Dalfa, Rola Abu; El Aish, Khaled I Abu; El Raai, Mohamed; El Gazaly, Nermeen; Shatat, Ahmed

    2018-02-21

    Diarrhoea causes 15% of under-5 mortality in developing countries. Zinc (Zn) stores in the body are known to be depleted during acute diarrhoea. The aim of this study was to evaluate the efficacy of Zn given with standard treatment to children with acute or moderate diarrhoea. In this quasi-unmasked, parallel-group study, we enrolled children with diarrhoea at El-Dorra Paediatric Hospital, Gaza Strip, occupied Palestinian territory. Inclusion criteria were children with more than three unformed stools in the preceding 24 h, duration of diarrhoea up to 72 h, and ability to accept oral fluids or feeds. Recruited children were assigned equally to either oral rehydration salts (control group) or oral rehydration salts plus Zn sulphate (Zn group; 10 mg for children younger than 6 months; 20 mg for children aged 6 months and older). All treatments were taken orally for 14 days. Primary outcomes were duration and frequency of diarrhoea. Secondary outcomes included changes in bodyweight, drugs side-effects, and episodes of any or severe dehydration. Data were analysed with SPSS. Outcome measures were compared with the Mann-Whitney U-test, student's t test, odds ratio, or χ 2 test. The study was approved by the ministry of health and the Helsinki Committee in the Gaza Strip. Parents of the children provided verbally informed consent before participation. We enrolled 140 children (aged 1-120 months). Duration of diarrhoea in the Zn group was shorter than in the control group (2·34 days in the Zn group vs 7·20 days in the control group; pZinc supplementation added to standard treatment with oral rehydration salts was effective and resulted in good treatment of diarrhoea. None. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Evaluation of neuronal apoptosis precursors in an experimental model of acute normovolemic hemodilution.

    Directory of Open Access Journals (Sweden)

    Fabrício O Frazilio

    Full Text Available The effects of acute anemia on neuronal cells and the safe limits of hematocrit are not well established. The objective of this study was to evaluate neuronal pro- and anti-apoptotic Bax and Bcl-x proteins, caspase-3 and -9 activity, and DNA fragmentation after acute normovolemic hemodilution (ANH.Twenty-four pigs were anesthetized and randomized into 4 groups: Sham, ANH to 15% hematocrit (ANH15%, ANH to 10% hematocrit (ANH10% and hypoxia (Hx. ANH was achieved by simultaneous blood withdrawal and hydroxyethyl starch infusion. Hx consisted of ventilation with a 6% inspired oxygen fraction for 60 minutes. Bax and Bcl-x proteins as well as DNA fragmentation were evaluated in cortical nuclear and mitochondrial fractions. Caspase-3 and -9 activity was evaluated in the cortical mitochondrial and hippocampal cytosolic fractions. The data were compared using analysis of variance followed by Tukey's test (P<0.05.No changes were observed in Bax protein expression after hemodilution in the ANH15% and ANH10% groups compared to the Sham group. Bax expression in the Hx group was increased in the nuclear and mitochondrial fractions compared to all other groups. No significant difference was observed in Bcl-x expression. Caspase-3 and -9 activity in the cytosolic and mitochondrial fractions was different in the Hx group compared to all other groups. No statistical significance in DNA fragmentation was found among the Sham, ANH15% or ANH10% groups.ANH to 10 and 15% hematocrit did not induce alterations in apoptosis precursors, suggesting that cerebral oxygenation was preserved during these anemic states.

  5. Histological evaluation of acute covering of an experimental neural tube defect with biomatrices in fetal sheep.

    NARCIS (Netherlands)

    Eggink, A.J.; Roelofs, L.A.J.; Lammens, M.M.Y.; Feitz, W.F.J.; Wijnen, R.M.H.; Mullaart, R.A.; Moerkerk, H.T.B. van; Kuppevelt, A.H.M.S.M. van; Crevels, A.J.; Hanssen, A.; Lotgering, F.K.; Berg, P.P. van den

    2006-01-01

    OBJECTIVE: The aim of the study was to determine the histological effect on the neural tissue of in utero covering of an experimental neural tube defect in fetal lambs, with the use of two different biomatrices. MATERIALS AND METHODS: In 23 fetal sheep, surgery was performed at 79 days' gestation.

  6. The effect of aloe vera on ischemia--Reperfusion injury of sciatic nerve in rats.

    Science.gov (United States)

    Guven, Mustafa; Gölge, Umut Hatay; Aslan, Esra; Sehitoglu, Muserref Hilal; Aras, Adem Bozkurt; Akman, Tarik; Cosar, Murat

    2016-04-01

    Aloe vera is compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of aloe vera treatment in rats with experimental sciatic nerve ischemia/reperfusion injury. Twenty-eight male Wistar Albino rats were divided equally into 4 groups. Groups; Control group (no surgical procedure or medication), sciatic nerve ischemia/reperfusion group, sciatic nerve ischemia/reperfusion+aloe vera group and sciatic nerve ischemia/reperfusion+methylprednisolone group. Ischemia was performed by clamping the infrarenal abdominal aorta. 24 hours after ischemia, all animals were sacrificed. Sciatic nerve tissues were also examined histopathologically and biochemically. Ischemic fiber degeneration significantly decreased in the pre-treated with aloe vera and treated with methylprednisolone groups, especially in the pre-treated with aloe vera group, compared to the sciatic nerve ischemia/reperfusion group (paloe vera group was not statistically different compared to the MP group (p>0.05). Aloe vera is effective neuroprotective against sciatic nerve ischemia/reperfusion injury via antioxidant and anti-inflammatory properties. Also aloe vera was found to be as effective as MP. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. 111In-platelet and 125I-fibrinogen deposition in the lungs in experimental acute pancreatitis

    International Nuclear Information System (INIS)

    Goulbourne, I.A.; Watson, H.; Davies, G.C.

    1987-01-01

    An experimental model of acute pancreatitis in rats has been used to study intrapulmonary 125 I-fibrinogen and 111 In-platelet deposition. Pancreatitis caused a significant increase in wet lung weight compared to normal, and this could be abolished by heparin or aspirin pretreatment. 125 I-fibrinogen was deposited in the lungs of animals to a significantly greater degree than in controls (P less than 0.01). 125 I-fibrinogen deposition was reduced to control levels by pretreatment with aspirin or heparin (P less than 0.05). The uptake of radiolabeled platelets was greater in pancreatitis than in controls (P less than 0.001). Pancreatitis appears to be responsible for platelet entrapment in the lungs. Platelet uptake was reduced by heparin treatment but unaffected by aspirin therapy

  8. Experimental acute rumen acidosis in sheep: consequences on clinical, rumen, and gastrointestinal permeability conditions and blood chemistry.

    Science.gov (United States)

    Minuti, A; Ahmed, S; Trevisi, E; Piccioli-Cappelli, F; Bertoni, G; Jahan, N; Bani, P

    2014-09-01

    Acute acidosis was induced in sheep, and gastrointestinal permeability was assessed by using lactulose as a permeability marker. Metabolism was evaluated by monitoring blood metabolites. Four rams (72.5 ± 4.6 kg BW) were used in a 2 × 2 changeover design experiment. The experimental period lasted 96 h from -24 to 72 h. After 24 h of fasting (from -24 to 0 h) for both controls and acidosis-induced rams (ACID), 0.5 kg of wheat flour was orally dosed at 0 and 12 h of the experimental period to ACID, while the basal diet (grass hay, ad libitum) was restored to control. At 24 h, a lactulose solution (30 g of lactulose in 200 mL of water) was orally administered. Blood samples were collected at -24, 0, 24, 48, and 72 h of the experimental periods for the analysis of metabolic profiles and during the 10 h after lactulose dosage to monitor lactulose changes in blood. In addition, rumen and fecal samples were collected at 24 h of the experimental period. The acidotic challenge markedly reduced (P < 0.01) rumen pH and VFA but increased rumen d- and l-lactic acid (P < 0.01). Concurrently, a decrease of fecal pH and VFA occurred in ACID (P < 0.01), together with an abrupt increase (P < 0.01) of lactate and fecal alkaline phosphatase. Blood lactulose was significantly increased in ACID peaking 2 h after lactulose dosage. Blood glucose, β-hydroxybutyrate, Ca, K, Mg, and alkaline phosphatase showed a significant reduction (P < 0.05) at 24 h, whereas urea and NEFA declined (P < 0.05) from 48 to 72 h. A strong inflammatory acute phase response with oxidative stress in ACID group was observed from 24 to 72 h; higher values of haptoglobin (P < 0.01) were measured from 24 to 72 h and of ceruloplasmin from 48 (P < 0.05) to 72 h (P < 0.01). Among the negative acute phase reactants, plasma albumin, cholesterol, paraoxonase, and Zn concentration also decreased (P < 0.05) in ACID at different time points between 24 and 72 h after acidotic challenge start. A rise (P < 0.05) of reactive

  9. Elucidating the impact of low doses of nano-formulated benznidazole in acute experimental Chagas disease.

    Directory of Open Access Journals (Sweden)

    Marcela S Rial

    2017-12-01

    Full Text Available Chagas disease is a neglected parasitic infection caused by the protozoan Trypanosoma cruzi (T. cruzi that affects more than 6 million people, mainly in Latin America. Benznidazole is still the drug of choice in many countries to treat it in spite of its dosage regimen and adverse side effects such as such as allergic dermatitis, peripheral neuropathy and anorexia. Thus, novel, safer, and more efficacious treatments for such neglected infection are urgently required.In this study, the efficacy of orally administered low doses of benznidazole (BNZ nanoparticles was evaluated during the acute phase in mice infected with T. cruzi Nicaragua (TcN that were immunosuppressed during the chronic stage of the disease. Moreover, the production of T. cruzi-specific antibodies, cardiac tissue inflammation and reactive oxygen species generation by Vero cells treated with both BNZ nanoparticles (BNZ-nps and raw BNZ (R-BNZ were also evaluated.T. cruzi infected mice treated with 10, 25 or 50 mg/kg/day of BNZ-nps survived until euthanasia (92 days post infection (dpi, while only 15% of infected untreated mice survived until the end of the experiment. PCR analysis of blood samples taken after induction of immunosuppression showed that a dosage of 25 mg/kg/day rendered 40% of the mice PCR-negative. The histological analysis of heart tissue showed a significant decrease in inflammation after treatments with 25 and 50 mg/kg/day, while a similar inflammatory damage was observed in both infected mice treated with R-BNZ (50 mg/kg/day and untreated mice. In addition, only BNZ-nps treated mice led to lower levels of T. cruzi-specific antibodies to 50-100%. Finally, mammalian Vero cells treated with BNZ-nps or R-BNZ lead to a significant increase in ROS production.Based on these findings, this research highlights the in-vitro/in-vivo efficacy of nanoformulated BNZ against T. cruzi acute infections in immunosuppressed and non-immunosuppressed mice and provides further

  10. Ischemic tolerance of rat hearts in acute and chronic phases of experimental diabetes

    Czech Academy of Sciences Publication Activity Database

    Ravingerová, T.; Neckář, Jan; Kolář, František

    2003-01-01

    Roč. 249, 1-2 (2003), s. 167-174 ISSN 0300-8177 R&D Projects: GA ČR GA305/01/0279; GA MŠk LN00A069 Grant - others:VEGA(SK) SR2/2063/22; SAV(SK) APVT 51-013802 Institutional research plan: CEZ:AV0Z5011922 Keywords : experimental diabetes * arrhythmias * infarction Subject RIV: ED - Physiology Impact factor: 1.763, year: 2003

  11. Experimental effects of acute exercise and music listening on cognitive creativity.

    Science.gov (United States)

    Frith, Emily; Loprinzi, Paul D

    2018-07-01

    The purpose of this study was to extend previous experimental work suggesting that both exercise and music-based interventions may influence creativity processes, by investigating the independent influences of exercise or music stimuli on verbal creative performances in the laboratory environment. 32 students at the University of Mississippi participated in this within-subject intervention, which included three laboratory visits per participant. Individuals participated in three 15-min, randomized experimental conditions: Treadmill walking, self-selected music, or a seated control period, and subsequently completed four creativity assessments during each visit (three tests of divergent thinking, and one test of convergent thinking), with the order of divergent thinking tasks counterbalanced. Creativity task performance was independently scored across four dependent parameters, which included fluency (i.e., total number of ideas), flexibility (i.e., total number of categories), originality (i.e., responses thought of by music on verbal creativity performance. The present study further highlights the critical need for improvement in the assessment and evaluation of laboratory-assessed cognitive creativity. Methodological strategies must be examined and refined for the meaningful and credible measurement and interpretation of experimental creativity. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Infusion of Bone Marrow Mesenchymal Stem Cells Attenuates Experimental Severe Acute Pancreatitis in Rats

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    Hang Zhao

    2016-01-01

    Full Text Available Background & Aims. Severe acute pancreatitis (SAP remains a high-mortality disease. Bone marrow (BM mesenchymal stem cells (MSCs have been demonstrated to have plasticity of transdifferentiation and to have immunomodulatory functions. In the present study, we assessed the roles of MSCs in SAP and the therapeutic effects of MSC on SAP after transplantation. Methods. A pancreatitis rat model was induced by the injection of taurocholic acid (TCA into the pancreatic duct. After isolation and characterization of MSC from BM, MSC transplantation was conducted 24 hrs after SAP induction by tail vein injection. The survival rate was observed and MSCs were traced after transplantation. The expression of TNF-α and IL-1β mRNA in the transplantation group was also analyzed. Results. The survival rate of the transplantation group was significantly higher compared to the control group (p<0.05. Infused MSCs were detected in the pancreas and BM 3 days after transplantation. The expression of TNF-α and IL-1β mRNA in the transplantation group was significantly lower than in the control group in both the pancreas and the lungs (p<0.05. Conclusions. MSC transplantation could improve the prognosis of SAP rats. Engrafted MSCs have the capacity of homing, migration, and planting during the treatment of SAP.

  13. Animal models of cerebral ischemia

    Science.gov (United States)

    Khodanovich, M. Yu.; Kisel, A. A.

    2015-11-01

    Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

  14. Ischemia-modified albumin levels in cerebrovascular accidents.

    Science.gov (United States)

    Gunduz, Abdulkadir; Turedi, Suleyman; Mentese, Ahmet; Altunayoglu, Vildan; Turan, Ibrahim; Karahan, Suleyman Caner; Topbas, Murat; Aydin, Murat; Eraydin, Ismet; Akcan, Buket

    2008-10-01

    Previous studies have demonstrated that ischemia-modified albumin (IMA) is a useful marker for the diagnosis of ischemic events. It was also recently demonstrated that IMA levels increase in the acute phase of cerebrovascular diseases. Yet the data regarding IMA levels in various types of cerebrovascular events are insufficient. The aim of this study was to evaluate IMA levels in various types of cerebrovascular events such as ischemic stroke, subarachnoid hemorrhage (SAH), and intracranial hemorrhage. This case-controlled study consisted of 106 consecutive patients, 43 with brain infarction (BI), 11 with brain hemorrhage (ICH), 52 with SAH, and a 43-member control group. We investigated whether there was a statistical correlation between these 3 groups and the control group. The relations among the 3 groups were also examined. Comparisons among groups were done with analysis of variance. Mean serum IMA levels were 0.280 +/- 0.045 absorbance units (ABSU) for BI patients, 0.259 +/- 0.053 ABSU for ICH patients, 0.243 +/- 0.061 ABSU for SAH patients, and 0.172 +/- 0.045 ABSU for the control group.There was a statistically significant difference between the mean IMA levels of BI, ICH, and SAH patients and the mean control patient IMA levels (P b .0001). Ischemia-modified albumin levels are high in cerebrovascular diseases. Ischemia-modified albumin measurement can also be used to distinguish SAH from BI during the acute phase of cerebrovascular event in the emergency department.

  15. Functional and structural correlates of magnetic resonance patterns in a new in vitro model of cerebral ischemia by transient occlusion of the medial cerebral artery.

    Science.gov (United States)

    Breschi, Gian Luca; Librizzi, Laura; Pastori, Chiara; Zucca, Ileana; Mastropietro, Alfonso; Cattalini, Alessandro; de Curtis, Marco

    2010-08-01

    Magnetic resonance imaging (MRI) during the acute phase of a stroke contributes to recognize ischemic regions and is potentially useful to predict clinical outcome. Yet, the functional significance of early MRI alterations during brain ischemia is not clearly understood. We achieved an experimental study to interpret MRI signals in a novel model of focal ischemia in the in vitro isolated guinea pig brain. By combining neurophysiological and morphological analysis with MR-imaging, we evaluated the suitability of MR to identify ischemic and peri-ischemic regions. Extracellular recordings demonstrated depolarizations in the ischemic core, but not in adjacent areas, where evoked activity was preserved and brief peri-infarct depolarizations occurred. Diffusion-weighted MRI and immunostaining performed after neurophysiological characterization showed changes restricted to the core region. Diffusion-weighted MR alterations did not include the penumbra region characterized by peri-infarct depolarizations. Therefore, by comparing neurophysiological, imaging and anatomical data, we can conclude that DW-MRI underestimates the extension of the tissue damage involved in brain ischemia.

  16. As bases experimentais da lesão por isquemia e reperfusão do fígado: revisão The experimental basis of hepatic ischemia-reperfusion injury: review

    Directory of Open Access Journals (Sweden)

    Luiz Eduardo C. Miranda

    2004-01-01

    Full Text Available O transplante hepático tornou-se o procedimento de escolha para o tratamento da doença hepática terminal. Não obstante o sucesso da cirurgia, a disfunção pós-operatória do fígado enxertado ainda representa importante causa de morbidade e mortalidade. O restabelecimento do fluxo sangüíneo ao fígado recém transplantado impõe a ele nova agressão, agravando a lesão causada pelo período de isquemia. Este fenômeno pouco compreendido é conhecido como lesão por isquemia e reperfusão e envolve disfunção endotelial, seqüestro de leucócitos e agregação de plaquetas, lesão por radicais livre de oxigênio, e distúrbios da microcirculação hepática. Essa revisão discute os vários aspectos fisiopatológicos que estão envolvidos na lesão por isquemia e reperfusão do fígado.Hepatic transplantation has become the main treatment for patients with terminal hepatic disease. Whatever the success of such surgery, the hepatic dysfunction associated with liver transplantation is an important cause of morbidity and mortality. Paradoxically, on restoring the blood supply, the liver is subjected to a further insult, aggravating the injury already caused by ischemia. This complex phenomenon is termed ischemia-reperfusion injury and involves endothelial cell dysfunction, leukocyte entrapment, platelet aggregation, oxidant stress and hepatic microcirculatory perfusion failure. This review discusses the physiopathlogicals mechanisms of liver ischemia-reperfusion injury.

  17. An Unusual Case of Colon Perforation Complicating Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Anthony A. Aghenta

    2009-08-01

    Full Text Available Colonic complications of severe acute pancreatitis occur rarely. Although there have been several theories on how pancreatic pseudocysts rupture into the colon, the exact pathogenesis remains unknown. We report an unusual case of pseudocysts complicating severe acute pancreatitis presenting with colonic perforation in a 71-year-old man with a history of chronic mesenteric ischemia. Pressure effects from a giant pseudocyst and intravascular volume depletion with acute insult on chronic mesenteric ischemia are highlighted as possible etiologic factors.

  18. Acute recanalization of carotid stenosis is not proper: an experimental ischaemic stroke study.

    Science.gov (United States)

    Kong, Qingtao; Hafeez, Adam; Yu, Wang; Ren, Changhong; Geng, Xiaokun; Xiao, Yao; Liu, Shimeng; Zhang, Ying; Mao, Ruili; Zhou, Jiying; Ding, Yuchuan; Ji, Xunming

    2015-05-01

    In a rat common carotid artery (CCA) stenosis model, the author determined the function of blood-brain barrier (BBB) at different time points and established an optimal time for CCA recanalization in rats with CCA stenosis combined with cerebral infarction. Common carotid artery severe stenosis combined with cerebral infarction was divided into two groups: CCA stenosis group (n = 48) and CCA stenosis recanalization group (n = 48). Common carotid artery stenosis recanalization was opened at time points of 1, 2, 3, 5, 7 and 14  days. Twenty-four hours after recanalization, neurological behaviour, motor function, brain water content and immunohistochemistry of laminin and fibronectin were used to assess brain injury. The peak systolic velocity (PSV) determined by colour Doppler flow imaging (CDFI) was used to assess blood flow of the CCA. In contrast to CCA stenosis without recanalization, in which severe neurological deficits and foot fault were observed at 1, 2 and 3  days, significantly less neurological deficits at 14 days and less foot fault placing at 5, 7 and 14  days were observed after recanalization (P vs acute phase), the levels of basal laminar proteins were significantly (P < 0.05) enhanced by vascular recanalization in both the ischaemic core and penumbra. Peak systolic velocity of CCA after recanalization reached the control level without stenosis. Our study suggests that the optimal time to open the CCA stenosis complicating cerebral infarction is at or after 7  days of CCA stenosis.

  19. Aquaporin-4 deletion in mice reduces encephalopathy and brain edema in experimental acute liver failure.

    Science.gov (United States)

    Rama Rao, Kakulavarapu V; Verkman, A S; Curtis, Kevin M; Norenberg, Michael D

    2014-03-01

    Brain edema and associated astrocyte swelling leading to increased intracranial pressure are hallmarks of acute liver failure (ALF). Elevated blood and brain levels of ammonia have been implicated in the development of brain edema in ALF. Cultured astrocytes treated with ammonia have been shown to undergo cell swelling and such swelling was associated with an increase in the plasma membrane expression of aquaporin-4 (AQP4) protein. Further, silencing the AQP4 gene in cultured astrocytes was shown to prevent the ammonia-induced cell swelling. Here, we examined the evolution of brain edema in AQP4-null mice and their wild type counterparts (WT-mice) in different models of ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Induction of ALF with TAA or APAP significantly increased brain water content in WT mice (by 1.6% ± 0.3 and 2.3 ± 0.4%, respectively). AQP4 protein was significantly increased in brain plasma membranes of WT mice with ALF induced by either TAA or APAP. In contrast to WT-mice, brain water content did not increase in AQP4-null mice. Additionally, AQP4-null mice treated with either TAA or APAP showed a remarkably lesser degree of neurological deficits as compared to WT mice; the latter displayed an inability to maintain proper gait, and demonstrated a markedly reduced exploratory behavior, with the mice remaining in one corner of the cage with its head tilted downwards. These results support a central role of AQP4 in the brain edema associated with ALF. Published by Elsevier Inc.

  20. Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination.

    Science.gov (United States)

    Schultz, Verena; van der Meer, Franziska; Wrzos, Claudia; Scheidt, Uta; Bahn, Erik; Stadelmann, Christine; Brück, Wolfgang; Junker, Andreas

    2017-08-01

    Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP- and SMI32- positive damaged axons and the density of SMI31-positive and silver impregnated preserved axons. Early de- and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

  1. Acute Peritonitis and Nonspecific Resistance Factors in the Administration of Ozonized Perfluorane (Experimental Study

    Directory of Open Access Journals (Sweden)

    A. M. Golubev

    2008-01-01

    Full Text Available Objective: to study the effect of ozonized perfluorane on the natural course of acute of fecal peritonitis and congenital (nonspecific immunity factors during its intraperitoneal administration. Materials and methods. Perfluorane and saline solution were ozonized bubbling with a mixture of ozone and oxygen at a rate of 0.5 l/min and at a preset ozone concentration of 3000 flg/l on a Medozons — BM AOT — H-01-Arz-91 ozonator (OAO «Arzamasskiy Priborostroitelnyi Zavod» for 15 minutes. The concentration of ozone was measured in the solutions on a NF 254/1 spectrophotometer. Experiments were carried out on 200 non-inbred albino male rats in 4 series of experiments. After simulating fecal peritonitis by the procedure developed by S. S. Remennik, the animals were intraperitoneally injected ozonized perfluorane (Series 1, ozonized saline solution (Series 2, perfluorane (Series 3, and saline solution (Series 4 on the basis of 1.5 ml per 100 g of weight. Nine intact rats were used as a control. Results. The congenital immunity parameters (phagocytic block, intracellular and serum bactericidal activities were studied. An association was found between the clinical course and the degree of nonspecific immunity suppression. The ozonized perfluorane was ascertained to have a more significant protective action on nonspecific immunity factors than perfluorane or the ozonized saline solution. The factors under study were significantly decreased when saline solution was administered, and with this there was a mass mortality of Series 4 rats on days 2—14 of the experiment. Conclusion. The therapeutic effect of the ozonized perfluorane is due to the activation of phagocytic mononuclear leukocytes and their increased count, to the antibacterial activity of ozone and the protective action on the nonspecific link of the body’s immunological resistance.

  2. Timing of ischemic onset estimated from the electrocardiogram is better than historical timing for predicting outcome after reperfusion therapy for acute anterior myocardial infarction: a DANish trial in Acute Myocardial Infarction 2 (DANAMI-2) substudy

    DEFF Research Database (Denmark)

    Sejersten, Maria; Ripa, Rasmus S; Grande, Peer

    2007-01-01

    BACKGROUND: Acute treatment strategy and subsequently prognosis are influenced by the duration of ischemia in patients with ST-elevation acute myocardial infarction (AMI). However, timing of ischemia may be difficult to access by patient history (historical timing) alone. We hypothesized that an ......BACKGROUND: Acute treatment strategy and subsequently prognosis are influenced by the duration of ischemia in patients with ST-elevation acute myocardial infarction (AMI). However, timing of ischemia may be difficult to access by patient history (historical timing) alone. We hypothesized...

  3. Experimental models of acute infection and Toll-like receptor driven septic shock.

    Science.gov (United States)

    Ferstl, Ruth; Spiller, Stephan; Fichte, Sylvia; Dreher, Stefan; Kirschning, Carsten J

    2009-01-01

    Mainly Gram-negative and Gram-positive bacterial infections, but also other infections such as with fungal or viral pathogens, can cause the life-threatening clinical condition of septic shock. Transgression of the host immune response from a local level limited to the pathogen's place of entry to the systemic level is recognised as a major mode of action leading to sepsis. This view has been established upon demonstration of the capacity of specific pathogen-associated molecular patterns (PAMPs) to elicit symptoms of septic shock upon systemic administration. Immune stimulatory PAMPs are agonists of soluble, cytoplasmic, as well as/or cell membrane-anchored and/or -spanning pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs). However, reflection of pathogen-host crosstalk triggering sepsis pathogenesis upon an infection by a host response to challenge with an isolated PAMP is incomplete. Therefore, an experimental model more reflective of pathogen-host interaction requires experimental host confrontation with a specific pathogen in its viable form resulting in a collective stimulation of a variety of specific PRRs. This chapter describes methods to analyse innate pathogen sensing by the host on both a cellular and systemic level.

  4. Intracoronary levosimendan during ischemia prevents myocardial apoptosis.

    Directory of Open Access Journals (Sweden)

    Markus eMalmberg

    2012-02-01

    Full Text Available Background. Levosimendan is a calcium-sensitizing inotropic agent that prevents myocardial contractile depression following cardiac surgery. Levosimendan has also anti-apoptotic properties, but the role of this mechanism is not clear. We studied whether levosimendan prevents cardiomyocyte apoptosis and post-operative stunning after either intracoronary administration or intravenous infusion in an experimental model. Methods. Pigs (n=24 were subjected to 40 minutes of global, cardioplegic ischemia under cardiopulmonary bypass and 240 minutes of reperfusion. L-IV group received intravenous infusion of levosimendan (65 μg/kg 40 minutes before ischemia and L-IC group received levosimendan (65 μg/kg during ischemia administered intracoronary. Control group was operated without levosimendan. Echocardiography was performed to all animals. Apoptosis was determined from transmyocardial biopsies taken from left ventricle using TUNEL assay and immunohistochemistry of active caspace-3. Results. Apoptosis was induced after ischemia-reperfusion in all groups (pre L-IV 0.002±0.004 % vs. post L-IV 0.020±0.017 % p=0.02, pre L-IC 0.001±0.004 % vs. post L-IC 0.020±0.017 % p<0.001, pre control 0.007±0.013 % vs. post control 0.062±0.044 % p=0.01. The amount of apoptosis was higher in the controls, compared with the L-IV (p=0.03 and the L-IC (p=0.03 groups. Longitudinal left ventricular contraction was significantly reduced in the L-IC and the control groups when compared to the L-IV group (L-IV 0.75±0.12 mm vs. L-IC 0.53±0.11 mm p=0.003, L-IV vs. control 0.54±0.11 p=0.01. Conclusions. Both intracoronary administration and pre-ischemic intravenous infusion of levosimendan equally prevented apoptosis, but intravenous administration was required for optimal preservation of the post-operative systolic left ventricle function.

  5. Multi-site laser Doppler flowmetry for assessing collateral flow in experimental ischemic stroke: Validation of outcome prediction with acute MRI.

    Science.gov (United States)

    Cuccione, Elisa; Versace, Alessandro; Cho, Tae-Hee; Carone, Davide; Berner, Lise-Prune; Ong, Elodie; Rousseau, David; Cai, Ruiyao; Monza, Laura; Ferrarese, Carlo; Sganzerla, Erik P; Berthezène, Yves; Nighoghossian, Norbert; Wiart, Marlène; Beretta, Simone; Chauveau, Fabien

    2017-06-01

    High variability in infarct size is common in experimental stroke models and affects statistical power and validity of neuroprotection trials. The aim of this study was to explore cerebral collateral flow as a stratification factor for the prediction of ischemic outcome. Transient intraluminal occlusion of the middle cerebral artery was induced for 90 min in 18 Wistar rats. Cerebral collateral flow was assessed intra-procedurally using multi-site laser Doppler flowmetry monitoring in both the lateral middle cerebral artery territory and the borderzone territory between middle cerebral artery and anterior cerebral artery. Multi-modal magnetic resonance imaging was used to assess acute ischemic lesion (diffusion-weighted imaging, DWI), acute perfusion deficit (time-to-peak, TTP), and final ischemic lesion at 24 h. Infarct volumes and typology at 24 h (large hemispheric versus basal ganglia infarcts) were predicted by both intra-ischemic collateral perfusion and acute DWI lesion volume. Collateral flow assessed by multi-site laser Doppler flowmetry correlated with the corresponding acute perfusion deficit using TTP maps. Multi-site laser Doppler flowmetry monitoring was able to predict ischemic outcome and perfusion deficit in good agreement with acute MRI. Our results support the additional value of cerebral collateral flow monitoring for outcome prediction in experimental ischemic stroke, especially when acute MRI facilities are not available.

  6. Diagnostic radiology of apoplexy - imaging of cerebral ischemia

    International Nuclear Information System (INIS)

    Rieber, A.; Tomczak, R.; Brambs, H.J.

    1998-01-01

    The recent enhancements achieved in CT and MR imaging techniques have launched a debate about the techniques preferrably to be applied for diagnostic evaluation of acute cerebral stroke. At present, CT still is the modality of choice for primary evaluation of cerebral ischemia, due to relative cost-effectiveness, high availability, and the capability to reliably differentiate ischemia from hemorrhage. MRI on the other hand is superior to CT in detecting and imaging the infarction area within the first few hours, especially if the technique of diffusion-weighted sequencing is applied. Current research focuses on determining whether MRI with perfusion and diffusion-weighted sequencing will yield images distinctly showing the penumbra on the one hand, and the damaged brain tissue on the other. It remains to be seen whether improved tomographic imaging will lead to novel approaches for therapy. (orig./CB) [de

  7. Hepatoprotective effect of Solanum xanthocarpum fruit extract against CCl4 induced acute liver toxicity in experimental animals.

    Science.gov (United States)

    Gupta, Ramesh K; Hussain, Talib; Panigrahi, G; Das, Avik; Singh, Gireesh Narayan; Sweety, K; Faiyazuddin, Md; Rao, Chandana Venkateswara

    2011-12-01

    To investigate the hepatoprotective potential of Solanum xanthocarpum (Solanaceae) (S. xanthocarpum) in experimental rats to validate its traditional claim. 50% ethanolic fruit extract of S. xanthocarpum (SXE, 100, 200 or 400 mg/kg body weight) was administered daily for 14 days in experimental animals. Liver injury was induced chemically, by CCl(4) administration (1 mL/kg i. p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), Serum alkaline phosphatise (SALP) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were screened along with histopathological studies. Obtained results demonstrated that the treatment with SXE significantly (P<0.05-<0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore, SXE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed that SXE attenuated the hepatocellular necrosis and led to reduction of inflammatory cells inflltration. The results of this study strongly indicate the protective effect of SXE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scientifically support its traditional use. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  8. Nonhuman primate models of focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Jingjing Fan

    2017-01-01

    Full Text Available Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

  9. [The effect of nitrates on the outcome of acute experimental ischemic stroke].

    Science.gov (United States)

    Kuzenkov, V S; Krushinskiĭ, A L; Reutov, V P

    2012-01-01

    Effects of nitrates NaNO(3), KNO(3), Mg(NO(3)) 2 on animals (Wistar rats) were studied on the basis of the experimental model of ischemic stroke induced by the occlusion of two carotid arteries. The animals were divided into two groups: the main group (n=60) and the control group (n=30). Three series of experiments were conducted. In each experiment, the rats of the main group were treated with one of nitrates and the control group was treated with physiological solution. It has been shown that nitrates exert either positive or negative effect depending on the cation type, nitrate concentration and the duration of their action on the dynamics of neurologic disturbances. Conditions of the development of neuroprotective effect of nitrates are discussed.

  10. Melatonin attenuates lung injury in a hind limb ischemia–reperfusion rat model

    Directory of Open Access Journals (Sweden)

    Hamed Takhtfooladi

    2015-01-01

    Full Text Available Objective: This study evaluated the protective antioxidant effect of melatonin on lung injury as a remote organ after skeletal muscle ischemia–reperfusion in rats. Methods: Thirty male Wistar rats were allocated randomly into three experimental groups: operated with no ischemia (Sham group, ischemia–reperfusion group and ischemia–reperfusion + melatonin group. Hind limb ischemia was induced by clamping the femoral artery. After 2 h ischemia, the clamp was removed and the animal underwent 24 h reperfusion. Rats in the ischemia–reperfusion + melatonin group received melatonin (10 mg/kg i.v., immediately before the clamp was removed. At the end of the trial, animals were euthanized and the lungs were removed for water content determination, histopathological and biochemical studies. Results: In the ischemia–reperfusion + melatonin group, tissues showed less intense histological abnormalities such as neutrophilic infiltration, intra-alveolar hemorrhage and edema compared with the ischemia–reperfusion group. Histopathologically, there was a significant difference (P < 0.05 between the two groups. The lung water content in the ischemia–reperfusion + melatonin group was significantly lower than the ischemia–reperfusion group (P < 0.05. Lung tissue myeloperoxidase (MPO activity and nitric oxide (NO level were significantly (P < 0.05 increased by ischemia–reperfusion. The increase in these parameters was reduced by melatonin.Comparing the ischemia–reperfusion + melatonin group with the sham group, no significant increase in all analyzed aspects of the research was observed. Conclusions: These findings suggest that melatonin has preventive effects in lung tissue injury after transient femoral artery occlusion. Keywords: Melatonin, Ischemia–reperfusion, Lung remote injury, Histopathology, Myeloperoxidase, Nitric oxide

  11. PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia

    Directory of Open Access Journals (Sweden)

    Raimundo M. G. del Moral

    2013-01-01

    Full Text Available We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN and other renal lesions related to prolonged cold ischemia/reperfusion (IR in kidneys preserved at 4°C in University of Wisconsin (UW solution. Material and Methods. We used 30 male Parp1+/+ wild-type and 15 male Parp10/0 knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinylbutoxyl]-1(2H-isoquinolinone (DPQ at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ. We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp10/0 knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

  12. Study on the Renal Anemia: Experimental Study in Acute Renal Anemia

    International Nuclear Information System (INIS)

    Yoon, Zo Eun

    1969-01-01

    The double tracer study on erythrokinetics was carried out experimentally with radioactive iron( 59 Fe) and chromium ( 51 Cr) in rabbits. The 0.1% cantharidin solution and 1% pot. perchlomate solution was given subcutaneously to 20 rabbits respectively. 3 and 6 days after injection, the blood chemistry, urine examination, ferrokinetics and apparent half survival time of RBC were ( 51 Cr T-1/2) determined. Following were the results: 1) Red blood cell hematocrit and hemoglobin values were moderately reduced and B.U.N. and serum creatinine values were slightly increased in the cantharidin group, while B.U.N. and serum creatinine values were within normal limits in the pot. perchlomate group. Reticulocyte values were slightly increased in the cantharidin group, while was normal range in the pot. perchlomate group. 2) Blood chemistry finding was not significant statistically in both experimental groups, but serum iron value was moderately reduced in both group. 3) Plasma volume was unchanged in both group, but red cell volume and whole blood volume were slightly reduced in both groups. 4) Results of ferrokinetics were as follows: i) The plasma iron disappearance rate was delayed in both groups. Plasma iron turnover rate, red cell iron utilization and red cell iron turnover rate were decreased in both groups, and then red cell iron turnover rate was more decreased than plasma iron turnover rate in both groups. Circulating red cell iron was slightly increased in cantharidin group and red cell iron concentration was within normal range in both groups. ii) P.I.T.R.-R.C.I.T. value moderately increased in the cantharidin group and slightly increased in the pot. perchlomate group. Reticulocyte index, red cell iron turnover index, plasma iron turnover index and effective erythropoiesis index were wholly reduced in both groups. iii) The red cell life span was slightly shortened in the cantharidin group while was within normal range in pot. perchlomate group. The pathologic

  13. Research on acute and chronic toxity of the experimental drug Аmprolinsyl

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    B. Gutyj

    2017-02-01

    membranes of hepatocytes, which indicates increased activity of aminotransferases.When investigating the chronic toxicity of Amprolinsyl it was found that at doses of 1/50 LD50, and 1/100 LD50 the drug had no effect on the results of functional tests, due to the normal functioning of the liver tissue and the lack of negative impact on animals in the 3rd and 4th groups. Administration of the the drug at doses of 1/20, 1/50 and 1/100 LD50 over 30 days did not significantly affect the functional state of the internal organs of the experimental animals. When investigating the morphological blood parameters of the rats following oral administration of Amprolinsyl at different doses a downward trend in the haemoglobin and colour index value and a likely reduction in the number of white blood cells, compared to the control group was observed in all experimental groups. According to the values of haematological and biochemical parameters, it was established that in spite of the low toxicityof Amprolinsyl at doses of 1/20 and 1/50 LD50 the drug had an effect on lipid metabolism, as was shown following the increase of glycerol.

  14. In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed.

    Science.gov (United States)

    Vainchtein, I D; Vinet, J; Brouwer, N; Brendecke, S; Biagini, G; Biber, K; Boddeke, H W G M; Eggen, B J L

    2014-10-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) characterized by loss of myelin accompanied by infiltration of T-lymphocytes and monocytes. Although it has been shown that these infiltrates are important for the progression of MS, the role of microglia, the resident macrophages of the CNS, remains ambiguous. Therefore, we have compared the phenotypes of microglia and macrophages in a mouse model for MS, experimental autoimmune encephalomyelitis (EAE). In order to properly discriminate between these two cell types, microglia were defined as CD11b(pos) CD45(int) Ly-6C(neg) , and infiltrated macrophages as CD11b(pos) CD45(high) Ly-6C(pos) . During clinical EAE, microglia displayed a weakly immune-activated phenotype, based on the expression of MHCII, co-stimulatory molecules (CD80, CD86, and CD40) and proinflammatory genes [interleukin-1β (IL-1β) and tumour necrosis factor- α (TNF-α)]. In contrast, CD11b(pos) CD45(high) Ly-6C(pos) infiltrated macrophages were strongly activated and could be divided into two populations Ly-6C(int) and Ly-6C(high) , respectively. Ly-6C(high) macrophages contained less myelin than Ly-6C(int) macrophages and expression levels of the proinflammatory cytokines IL-1β and TNF-α were higher in Ly-6C(int) macrophages. Together, our data show that during clinical EAE, microglia are only weakly activated whereas infiltrated macrophages are highly immune reactive. © 2014 Wiley Periodicals, Inc.

  15. Multifocal electroretinogram for functional evaluation of retinal injury following ischemia-reperfusion in pigs

    DEFF Research Database (Denmark)

    Morén, Håkan; Gesslein, Bodil; Andreasson, Sten

    2010-01-01

    Multifocal electroretinogram (mfERG) has the power to discriminate between localized functional losses and overall retinal changes when evaluating retinal injury. So far, full-field ERG has been the gold standard for examining retinal ischemia and the effects of different neuroprotectants...... in experimental conditions. The aim of the present study was to establish mfERG, with simultaneous fundus monitoring, for analyzing the localized functional response in the retina after ischemia-reperfusion in the porcine eye....

  16. Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice

    NARCIS (Netherlands)

    J.R. Mitchell (James); M. Verweij (Marielle); K. Brand (Karl); H.W.M. van de Ven (Marieke); N.N.T. Goemaere (Natascha); S. van den Engel (Sandra); T. Chu (Timothy); F. Forrer (Flavio); C. Müller (Cristina); M. de Jong (Marion); W.F.J. van IJcken (Wilfred); J.N.M. IJzermans (Jan); J.H.J. Hoeijmakers (Jan); R.W.F. de Bruin (Ron)

    2010-01-01

    textabstractDietary restriction (DR) extends lifespan and increases resistance to multiple forms of stress, including ischemia reperfusion injury to the brain and heart in rodents. While maximal effects on lifespan require long-term restriction, the kinetics of onset of benefits against acute stress

  17. Cerebral blood flow in cerebral ischemia. A review (with 1 color plate)

    DEFF Research Database (Denmark)

    Lassen, N A

    1978-01-01

    In the majority of apoplexy patients the absence of a primary haemorrhage points to acute vascular occclusion with regional ischemia as the initiating event. Yet, in many such cases in particular with transient symptoms, no occlusions can be found angiographically. This along with other evidences...... and of metabolic integrity of tissue areas be possible as a prerequisite for rational therapy....

  18. Dynamic assessment of acute blunt cerebral contusions and lacerations with CT perfusion: an experimental study

    International Nuclear Information System (INIS)

    Yuan Tao; Quan Guanmin; Liu Huaijun; Gao Guodong; Lei Jianming

    2009-01-01

    Objective: To explore the dynamic changes of blood perfusion in traumatic cerebral contusion and laceration of experimental model. Methods: Impact-acceleration head traumatic cerebral contusion and laceration models of 40 rabbits were established. CTP was made for all animals at 1, 3, 6, 12, 24, 48 and 72 h after head injury. The original images were transferred to workstation for postprocessing. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) of central area, peripheral area of contusion and laceration, and their mirror areas were measured on the section in which lesions were in their maximal area. The CTP parameters among different areas were compared with paired samples t test. The evolvement of CBF, CBV and MTT of cerebral contusion and laceration areas were recorded as well. Then, the histological abnormalities of central and peripheral areas were observed separately by referring to corresponding CTP maps. Results: Experimental models were successfully made in 35 rabbits. Abnormal signal intensity was detected on their T 2 WI and DWI images, which was consistent with brain contusion. For CTP parameters: (1) The CBF of central area of the lesions decreased markedly after trauma and reached its nadir at 12 h. Then the CBF of central area rose slowly from 24 h. The value of CBF of the central area at 1, 3, 6, 12, 24 and 72 h were (27.58±18.70), (20.64±6.50), (23.38± 7.53), (22.14±10.25), (25.08±11.01), (43.08±18.33) and (54.79± 14.63) ml·min -1 ·100 g -1 respectively. Whereas the CBF value of the corresponding mirror areas were (62.28±25.46), (60.67±16.19), (67.00±21.34), (74.46±20.11), (66.73±11.68), (81.63± 10.99) and 86.16±10.57) ml·min -1 ·100 g -1 respectively. There was significant difference of CBF between the central and the mirror areas (t=4.41, 5.57, 5.47, 6.02, 6.44, 4.81, 10.60 respectively, P 0.05). (2) The CBV of central area of the lesions also decreased obviously after trauma and reached its

  19. Role of morphine preconditioning and nitric oxide following brain ischemia reperfusion injury in mice

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    Maedeh Arabian

    2015-01-01

    Full Text Available Objective(s: Morphine dependence (MD potently protects heart against ischemia reperfusion (IR injury through specific signaling mechanisms, which are different from the pathways involved in acute morphine treatment or classical preconditioning. Since opioid receptor density changes post cerebral ischemia strongly correlated with brain histological damage, in the present study, we tried to elucidate the possible role of opioid receptors in IR injury among morphine-dependent mice. Materials and Methods: Accordingly, incremental doses (10 mg/kg/day to 30 mg/kg/day of morphine sulphate were subcutaneously administered for 5 days before global brain ischemia induction through bilateral common carotid artery occlusion. Animals were received naloxone (5 mg/kg or L-NAME (20 mg/kg 30 min after the last morphine dose. Twenty four hr after the ischemia induction, Retention trial of passive avoidance test and western blot analysis were done. histological analysis (TUNEL and NISSL staining performed 72 hr after ischemia. Results: MD improved post ischemia memory performance (P

  20. Intestinal ischemia-reperfusion injury augments intestinal mucosal injury and bacterial translocation in jaundiced rats.

    Science.gov (United States)

    Yüksek, Yunus Nadi; Kologlu, Murat; Daglar, Gül; Doganay, Mutlu; Dolapci, Istar; Bilgihan, Ayse; Dolapçi, Mete; Kama, Nuri Aydin

    2004-01-01

    The aim of this study was to evaluate local effects and degree of bacterial translocation related with intestinal ischemia-reperfusion injury in a rat obstructive jaundice model. Thirty adult Sprague-Dawley rats (200-250 g) were divided into three groups; including Group 1 (jaundice group), Group 2 (jaundice-ischemia group) and Group 3 (ischemia group). All rats had 2 laparotomies. After experimental interventions, tissue samples for translocation; liver and ileum samples for histopathological examination, 25 cm of small intestine for mucosal myeloperoxidase and malondialdehyde levels and blood samples for biochemical analysis were obtained. Jaundiced rats had increased liver enzyme levels and total and direct bilirubin levels (p<0.05). Intestinal mucosal myeloperoxidase and malondialdehyde levels were found to be high in intestinal ischemia-reperfusion groups (p<0.05). Intestinal mucosal damage was more severe in rats with intestinal ischemia-reperfusion after bile duct ligation (p<0.05). Degree of bacterial translocation was also found to be significantly high in these rats (p<0.05). Intestinal mucosa is disturbed more severely in obstructive jaundice with the development of ischemia and reperfusion. Development of intestinal ischemia-reperfusion in obstructive jaundice increases bacterial translocation.

  1. Comparison of acute effect of systemic versus intravitreal infliximab treatment in an experimental model of endotoxin-induced uveitis.

    Science.gov (United States)

    Yuksel, Erdem; Hasanreisoglu, Berati; Yuksel, Nilay; Yilmaz, Guldal; Ercin, Ugur; Bilgihan, Ayse

    2014-02-01

    In this study, we investigated the efficacy of systemic and intravitreal (IV) infliximab treatments and compared these 2 different treatment modalities in an experimental model of endotoxin-induced uveitis (EIU). Twenty-four white New Zealand rabbits were equally divided into 4 groups. Group 1 received IV injection of lipopolysaccharide (LPS), group 2 received IV injections of LPS and saline, group 3 received IV LPS and IV 2 mg/0.1 cc infliximab, and group 4 received IV LPS and 5 mg/kg intravenous infliximab. Inflammation was determined with objective and subjective tests. The subjective test was clinical determination of uveitis, the objective tests were determination of protein concentrations and tumor necrosis factor alpha (TNF-α) levels and histopathology. Clinical examination score was lower in group 3 and group 4 (4±0.6 and 3.5±1.6, respectively) when compared with group 1 (P=0.02; P=0.04, respectively) and group 2. In group 3 and 4, the aqueous and vitreous protein and TNF-α concentration measured significantly lower than group 1 and 2. In histopathologic examination, there was no statistically significant difference between group 1, 2, and 3 (3.5±0.5, 3.6±0.5, 3.6±0.5, respectively). However, the lowest histopathologic inflammation was determined in group 4 (2.5±0.5) (compared with group 1 and group 3, respectively; P=0.03; P=0.014). In a rabbit model of experimental EIU, intravenous administration of infliximab was more effective than IV route in an acute period.

  2. Cocktail treatment, a promising strategy to treat acute cerebral ischemic stroke?

    Directory of Open Access Journals (Sweden)

    Li-jun Liang

    2016-01-01

    Full Text Available Up to now, over 1,000 experimental treatments found in cells and rodents have been difficult to translate to human ischemic stroke. Since ischemia and reperfusion, two separate stages of ischemic stroke, have different pathophysiological mechanisms leading to brain injury, a combination of protective agents targeting ischemia and reperfusion respectively may obtain substantially better results than a single agent. Normobaric hyperoxia (NBO has been shown to exhibit neuro- and vaso-protective effects by improving tissue oxygenation when it is given during ischemia, however the effect of NBO would diminish when the duration of ischemia and reperfusion was extended. Therefore, during reperfusion drug treatment targeting inflammation, oxidative stress and free radical scavenger would be a useful adjuvant to extend the therapeutic window of tissue plasminogen activator, the only United States Food and Drug Administration (FDA approved treatment for acute ischemic stroke. In this review, we discussed the neuro- and vaso-protective effects of NBO and recent finding of combining NBO with other drugs.

  3. Relation of immediate and delayed thallium-201 distribution to localization of iodine-125 antimyosin antibody in acute experimental myocardial infarction

    International Nuclear Information System (INIS)

    Khaw, B.A.; Strauss, H.W.; Pohost, G.M.; Fallon, J.T.; Katus, H.A.; Haber, E.

    1983-01-01

    Thallium-201 (TI-201) distribution in acute experimental myocardial infarction (MI) (n . 18) was compared with cardiac-specific antimyosin Fab (AM-Fab) uptake, a specific marker for myocardial necrosis. When antimyosin was injected 4 hours after ligation with TI-201 administered 23 hours 55 minutes later and measurement of myocardial distribution determined 5 minutes after intravenous administration of TI-201, (1) TI-201 distribution closely correlated with microsphere regional blood flow, and (2) an inverse exponential relation to iodine-125 (I-125) AM-Fab uptake was apparent. In another group of 4 animals, TI-201 and AM-Fab were administered intravenously 4 hours after MI, and 36 hours later myocardial distribution was measured. This delayed TI-201 distribution had a close inverse linear correlation with I-125 AM-Fab uptake. This inverse linear relation also was apparent in 28-hour-old MIs in dogs (n . 4) where collateral circulation had been established. TI-201 was administered intravenously at 27 hours after MI, and TI-201 distribution was determined 1 hour later. The present study demonstrated that whereas immediate TI-201 distribution is flow-limited, delayed TI-201 distribution is a marker of cell viability which, due to prolonged circulation time and redistribution, is not flow-limited

  4. Detection of parenchymal abnormalities in experimentally induced acute pyelonephritis in rabbits using contrast-enhanced ultrasonography, CT, and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jeong Ah; Kim, Bo Hyun; Kim, Seung Kwon; Seo, Jin Won [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Jong Sung [Laboratory Animal Research Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2016-12-15

    We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) in detecting acute pyelonephritis (APN) using the rabbit kidney model and compared it with CT and MRI. This study was approved by the Institutional Review Board. In a total of 20 New Zealand White rabbits, APN was induced experimentally. CEUS, CT, and MRI were performed on the first, third, and seventh postoperative days. After imaging studies, the subjects were sacrificed and the pathological diagnosis of APN was confirmed in each animal by a pathologist. Imaging studies were obtained in eight animals, including eight CEUS, four computed tomography (CT), and four magnetic resonance imaging (MRI) images. CEUS depicted diffuse renal enlargement (7), diffuse heterogeneous parenchymal enhancement (6), and focal areas of decreased parenchymal enhancement (6). These findings were well correlated with the CT and MRI findings in five cases in which these studies were available. CT and MRI showed diffuse renal enlargement, diffuse heterogeneous parenchymal enhancement, focal areas of decreased parenchymal enhancement, focal contour bulging, and the finding of perinephric spread of infection. In a rabbit model, CEUS could depict the parenchymal lesions of APN similar to CT or MRI; however, it was limited in depicting the perinephric extension of inflammation.

  5. Brain Network Response to Acupuncture Stimuli in Experimental Acute Low Back Pain: An fMRI Study

    Directory of Open Access Journals (Sweden)

    Yu Shi

    2015-01-01

    Full Text Available Most neuroimaging studies have demonstrated that acupuncture can significantly modulate brain activation patterns in healthy subjects, while only a few studies have examined clinical pain. In the current study, we combined an experimental acute low back pain (ALBP model and functional magnetic resonance imaging (fMRI to explore the neural mechanisms of acupuncture analgesia. All ALBP subjects first underwent two resting state fMRI scans at baseline and during a painful episode and then underwent two additional fMRI scans, once during acupuncture stimulation (ACUP and once during tactile stimulation (SHAM pseudorandomly, at the BL40 acupoint. Our results showed that, compared with the baseline, the pain state had higher regional homogeneity (ReHo values in the pain matrix, limbic system, and default mode network (DMN and lower ReHo values in frontal gyrus and temporal gyrus; compared with the OFF status, ACUP yielded broad deactivation in subjects, including nearly all of the limbic system, pain status, and DMN, and also evoked numerous activations in the attentional and somatosensory systems; compared with SHAM, we found that ACUP induced more deactivations and fewer activations in the subjects. Multiple brain networks play crucial roles in acupuncture analgesia, suggesting that ACUP exceeds a somatosensory-guided mind-body therapy for ALBP.

  6. Electroacupuncture acutely improves cerebral blood flow and attenuates moderate ischemic injury via an endothelial mechanism in mice.

    Directory of Open Access Journals (Sweden)

    Ji Hyun Kim

    Full Text Available Electroacupuncture (EA is a novel therapy based on traditional acupuncture combined with modern eletrotherapy that is currently being investigated as a treatment for acute ischemic stroke. Here, we studied whether acute EA stimulation improves tissue and functional outcome following experimentally induced cerebral ischemia in mice. We hypothesized that endothelial nitric oxide synthase (eNOS-mediated perfusion augmentation was related to the beneficial effects of EA by interventions in acute ischemic injury. EA stimulation at Baihui (GV20 and Dazhui (GV14 increased cerebral perfusion in the cerebral cortex, which was suppressed in eNOS KO, but there was no mean arterial blood pressure (MABP response. The increased perfusion elicited by EA were completely abolished by a muscarinic acetylcholine receptor (mAChR blocker (atropine, but not a β-adrenergic receptor blocker (propranolol, an α-adrenergic receptor blocker (phentolamine, or a nicotinic acetylcholine receptor (nAChR blocker (mecamylamine. In addition, EA increased acetylcholine (ACh release and mAChR M3 expression in the cerebral cortex. Acute EA stimulation after occlusion significantly reduced infarct volume by 34.5% when compared to a control group of mice at 24 h after 60 min-middle cerebral artery occlusion (MCAO (moderate ischemic injury, but not 90-min MCAO (severe ischemic injury. Furthermore, the impact of EA on moderate ischemic injury was totally abolished in eNOS KO. Consistent with a smaller infarct size, acute EA stimulation led to prominent improvement of neurological function and vestibule-motor function. Our results suggest that acute EA stimulation after moderate focal cerebral ischemia, but not severe ischemia improves tissue and functional recovery and ACh/eNOS-mediated perfusion augmentation might be related to these beneficial effects of EA by interventions in acute ischemic injury.

  7. Optimal use of atherectomy in critical limb ischemia.

    Science.gov (United States)

    Rundback, John H; Herman, Kevin Chaim

    2014-09-01

    Critical limb ischemia (CLI) is the most severe and debilitating form of peripheral arterial disease and is associated with high rates of limb loss and cardiovascular mortality. The unique physical environment of tibial occlusive disease underlying most CLI cases limits treatment options and long-term durability, with resulting frequent rates of persistent obstruction, restenosis, and reintervention. Atherectomy represents a potential strategy to improve acute and late results when treating patients with CLI. Available atherectomy devices each have specific performance characteristics, evidentiary rationale, and limitations that mandate a clear understanding of the optimal albeit evolving use of this category of interventional tools. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Functional tests for myocardial ischemia

    International Nuclear Information System (INIS)

    Levinson, J.R.; Guiney, T.E.; Boucher, C.A.

    1991-01-01

    Functional tests for myocardial ischemia are numerous. Most depend upon a combination of either exercise or pharmacologic intervention with analysis of the electrocardiogram, of regional perfusion with radionuclide imaging, or of regional wall motion with radionuclide imaging or echocardiography. While each test has unique features, especially at the research level, they are generally quite similar in clinical practice, so the clinician is advised to concentrate on one or two in which local expertise is high.22 references

  9. Myocardial ischemia in Kawasaki disease

    International Nuclear Information System (INIS)

    Fukuda, Tsuyoshi

    1993-01-01

    The detection of myocardial ischemia is essential for evaluation of patients with Kawasaki disease, especially who have had coronary artery lesions. To evaluate the clinical efficacy of Tl-201 single photon emission computed tomography (SPECT) after dipyridamole infusion (maximum dose 0.70 mg/kg) for detecting myocardial ischemia, 44 patients with Kawasaki disease aged 7.7±4.8 years at the study and 10 age matched controls were observed. In the Kawasaki disease group, significant coronary artery stenosis was observed in 14, coronary aneurysm without stenosis in 18, the regression of the coronary aneurysms in 2 and without coronary lesions in 10 patients. In 24 of 44 patients, treadmill exercise stress test was also performed at the same period. Myocardial ischemic changes were observed in 11 patients, all combined with significant coronary artery stenosis. The sensitivity of SPECT for detection of overall coronary stenosis was 79%, coronary that of treadmill exercise test was only 33% (p<0.001). Furthermore, among the patients having significant coronary stenosis, the severity score was significantly elevated in patients who had electrocardiographic abnormal Q wave compared to those without abnormal Q wave (51.0±38.8 versus 20.0±12.1, p<0.05). These data suggest that the pharmacological stress scintigraphy using dipyridamole injection provides not only the accurate detection but quantitative evaluation of myocardial ischemia in these patients. This noninvasive technique may become one of the most useful index for detection and follow-up of myocardial ischemia in Kawasaki disease. (author)

  10. Real time monitoring of rat liver energy state during ischemia.

    Science.gov (United States)

    Barbiro, E; Zurovsky, Y; Mayevsky, A

    1998-11-01

    Hepatic failure is one of the major problems developed during the posttransplantation period. A possible cause of hepatic failure is the prolonged ischemia induced during the implantation procedure. Hepatic ischemia leads to a reduction in oxygen supply, ATP level decline, liver metabolism impairment, and finally organ failure. The purpose of this study was to estimate the functional state of the liver by monitoring liver blood flow and the mitochondrial NADH redox state simultaneously and continuously during in situ liver ischemia followed by reperfusion. Measurements were performed using the multiprobe developed in our laboratory consisting of fibers for the measurement of relative liver blood flow (laser Doppler flowmetry) and mitochondrial redox state (NADH fluorescence). The experimental procedure included the temporary interruption of blood flow to the liver using three types of ischemia, hepatic artery occlusion, portal vein occlusion, and simultaneous occlusion of hepatic artery and portal vein, followed by a reperfusion period. These preliminary experiments showed a significant decrease in liver blood flow, following the three types of liver ischemia, and a significant increase in NADH levels. The probe used in this study incorporates the advantage of monitoring NADH and liver blood flow simultaneously and continuously from the same area on the surface of the liver. Since each of these two parameters is not calibrated in absolute units, the simultaneous monitoring decreases possible artifacts. Also, it will allow us to determine of the coupling between tissue blood flow and oxidative phosphorylation. It is believed that the measurements of respiratory chain dysfunction might predict organ viability in clinical organ transplantation situations. Using this probe may also help to decrease the variability in liver blood flow monitoring since liver blood flow monitoring is supported simultaneously with the mitochondrial redox state, which supplies the

  11. Selective Cannabinoid 2 Receptor Stimulation Reduces Tubular Epithelial Cell Damage after Renal Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Pressly, Jeffrey D; Mustafa, Suni M; Adibi, Ammaar H; Alghamdi, Sahar; Pandey, Pankaj; Roy, Kuldeep K; Doerksen, Robert J; Moore, Bob M; Park, Frank

    2018-02-01

    Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), which is an increasing problem in the clinic and has been associated with elevated rates of mortality. Therapies to treat AKI are currently not available, so identification of new targets that can be modulated to ameliorate renal damage upon diagnosis of AKI is essential. In this study, a novel cannabinoid receptor 2 (CB2) agonist, SMM-295 [3'-methyl-4-(2-(thiophen-2-yl)propan-2-yl)biphenyl-2,6-diol], was designed, synthesized, and tested in vitro and in silico. Molecular docking of SMM-295 into a CB2 active-state homology model showed that SMM-295 interacts well with key amino acids to stabilize the active state. In human embryonic kidney 293 cells, SMM-295 was capable of reducing cAMP production with 66-fold selectivity for CB2 versus cannabinoid receptor 1 and dose-dependently increased mitogen-activated protein kinase and Akt phosphorylation. In vivo testing of the CB2 agonist was performed using a mouse model of bilateral IRI, which is a common model to mimic human AKI, where SMM-295 was immediately administered upon reperfusion of the kidneys after the ischemia episode. Histologic damage assessment 48 hours after reperfusion demonstrated reduced tubular damage in the presence of SMM-295. This was consistent with reduced plasma markers of renal dysfunction (i.e., creatinine and neutrophil gelatinase-associated lipocalin) in SMM-295-treated mice. Mechanistically, kidneys treated with SMM-295 were shown to have elevated activation of Akt with reduced terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling (TUNEL)-positive cells compared with vehicle-treated kidneys after IRI. These data suggest that selective CB2 receptor activation could be a potential therapeutic target in the treatment of AKI. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  12. ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4) is a new acute-phase protein isolated from cattle during experimental infection

    DEFF Research Database (Denmark)

    Pineiro, M.; Andres, M.; Iturralde, M.

    2004-01-01

    We have isolated from calf serum a protein with an apparent M, of 120,000. The protein was detected by using antibodies against major acute-phase protein in pigs with acute inflammation. The amino acid sequence of an internal fragment revealed that this protein is the bovine counterpart of ITIH4......, and Peptostreptococcus indolicus to induce an acute-phase reaction. All animals developed moderate to severe clinical mastitis and exhibited remarkable increases in ITIH4 concentration in serum (from 3 to 12 times the initial values, peaking at 48 to 72 h after infection) that correlated with the severity of the disease....... Animals with experimental infections with bovine respiratory syncytial virus (BRSV) also showed increases in ITIH4 concentration (from two- to fivefold), which peaked at around 7 to 8 days after inoculation. Generally, no response was seen after a second infection of the same animals with the virus...

  13. August rats are more resistant to arrhythmogenic effect of myocardial ischemia and reperfusion than Wistar rats.

    Science.gov (United States)

    Belkina, L M; Kirillina, T N; Pshennikova, M G; Arkhipenko, Yu V

    2002-06-01

    As differentiated from Wistar rats, myocardial ischemia and reperfusion produce no ventricular fibrillation in August rats. Pretreatment with nitric oxide synthase inhibitor Nw-nitro-L-arginine increased mortality rate in August rats with acute myocardial infarction from 20 to 40%. Under these conditions mortality rate in Wistar rats increased from 50 to 71%. Interstrain differences in the resistance of these animals to the arrhythmogenic effect of ischemia are probably associated with higher activity of the nitric oxide system in August rats compared to Wistar rats.

  14. Experimental pancreatitis in the rat: role of bile reflux in sodium taurocholate-induced acute haemorrhagic pancreatitis

    NARCIS (Netherlands)

    Lange, J. F.; van Gool, J.; Tytgat, G. N.

    1986-01-01

    Mortality of sodium taurocholate-induced acute haemorrhagic pancreatitis in the rat was prevented by biliary diversion. Bile reflux into the pancreas after the induction of pancreatitis is postulated to be a major factor affecting mortality of this popular model of acute pancreatitis. The reduction

  15. Low-methoxyl lemon pectin attenuates inflammatory responses and improves intestinal barrier integrity in caerulein-induced experimental acute pancreatitis

    NARCIS (Netherlands)

    Sun, Yajun; He, Yue; Wang, Fei; Zhang, Hao; de Vos, Paul; Sun, Jia

    Scope: Acute pancreatitis (AP) is a common clinical acute abdominal disease. The intestinal injury associated with AP will aggravate the condition retroactively. This study investigates whether the low-methoxyl pectin (LMP) isolated from lemon could attenuate AP and associated intestinal injury.

  16. Inhibition of cyclooxygenase-2 in experimental severe acute pancreatitis Inibição da Ciclo-Oxigenase-2 na pancreatite aguda grave experimental

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    José Luiz Jesus de Almeida

    2006-08-01

    Full Text Available BACKGROUND: The standard treatment for acute pancreatitis (AP is still based on supportive care. The search for a new drug that could change the natural history of the disease is a continuing challenge for many researchers. The aim of this study is to evaluate the effect of a cyclooxygenase-2 (COX-2 inhibitor on experimental AP in rats. METHODS: The animals were divided into 2 groups: Group 1 (n = 30-animals with taurocholate-induced AP treated with parecoxib (40 mg/kg. Group 2 (n = 30-animals with taurocholate-induced AP that received saline. The COX-2 inhibitor (parecoxib was injected immediately after AP induction, through the penis dorsal vein. The parameters evaluated were histology, serum levels of amylase, IL-6 and IL-10, and mortality rate. RESULTS: The serum levels of IL-6 and IL-10 in the parecoxib-treated group were lower than the control group. The amylase serum levels and the mortality rate remained unchanged in the treated animals. Histologic morphology also was unaltered, except for fat necrosis, which was higher in parecoxib-treated rats. CONCLUSION: Inhibition of Cox-2 decreases the systemic release of inflammatory cytokines, but has a poor effect on the direct pancreas injury caused by taurocholate.INTRODUÇÃO: O tratamento padrão para a pancreatite aguda permanece baseado em medidas de suporte. A busca por uma droga que altere a história natural da doença ainda é um desafio para muitos pesquisadores. O objetivo deste estudo é avaliar o efeito de um inibidor da COX-2 na pancreatite aguda grave experimental (PA em ratos. MÉTODO: Os animais foram divididos em dois Grupos: Grupo 1 (n=30 - animais com PA induzida por taurocolato e tratados com parecoxib (40mg/Kg. Grupo 2 (n=30 - animais com PA induzida por taurocolato que receberam solução salina. O inibidor de COX-2 (parecoxib foi injetado imediatamente após a indução, através da veia dorsal do pênis. Os parâmetros avaliados foram histologia, níveis séricos de

  17. Effect of neonatal asphyxia on the impairment of the auditory pathway by recording auditory brainstem responses in newborn piglets: a new experimentation model to study the perinatal hypoxic-ischemic damage on the auditory system.

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    Francisco Jose Alvarez

    Full Text Available Hypoxia-ischemia (HI is a major perinatal problem that results in severe damage to the brain impairing the normal development of the auditory system. The purpose of the present study is to study the effect of perinatal asphyxia on the auditory pathway by recording auditory brain responses in a novel animal experimentation model in newborn piglets.Hypoxia-ischemia was induced to 1.3 day-old piglets by clamping 30 minutes both carotid arteries by vascular occluders and lowering the fraction of inspired oxygen. We compared the Auditory Brain Responses (ABRs of newborn piglets exposed to acute hypoxia/ischemia (n = 6 and a control group with no such exposure (n = 10. ABRs were recorded for both ears before the start of the experiment (baseline, after 30 minutes of HI injury, and every 30 minutes during 6 h after the HI injury.Auditory brain responses were altered during the hypoxic-ischemic insult but recovered 30-60 minutes later. Hypoxia/ischemia seemed to induce auditory functional damage by increasing I-V latencies and decreasing wave I, III and V amplitudes, although differences were not significant.The described experimental model of hypoxia-ischemia in newborn piglets may be useful for studying the effect of perinatal asphyxia on the impairment of the auditory pathway.

  18. Intoxicação experimental aguda por samambaia (Pteridium aquilinum em bovinos Experimental acute poisoning by bracken fern (Pteridium aquilinum in cattle

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    Bruno L. Anjos

    2009-09-01

    .6, 10.2, and 10.6g/kg body weight totaling at the end of the experiment, respectively, 59.3%, 63.3%, 47.4%, and 47.5% of bracken fern in relation to their body weight. The disease was characterized by fever up to 42.5°C and varying degrees of hemorrhages observed clinically, at necropsy and on histological examination. Death occurred 6-7 days after the onset of fever. The hematological changes consisted mainly of marked thrombocytopenia and neutropenia. Two of the four affected calves had mild anemia. The deficits in secondary hemostasis were mild in each case. There were no significant changes thus permitting to rule out the role of secondary hemostasis in the pathogenesis of the hemorrhages in the bracken fern poisoning. The measurement of fibrin degradation products in the serum showed conflicting results and did no allow for a solid conclusion regarding the role of disseminated intravascular coagulation in the pathogenesis of the hemorrhages in fern poisoning. The cytology and the histopathology of bone marrow from the four poisoned calves revealed marked decrease in the numbers of hematopoietic cells from the three marrow lineages, which characterizes marrow failure due to aplasia; it was concluded that the events of the primary hemostasis due to thrombocytopenia are responsible for the hemorrhages. In blood culture from three affected calves there was growth of Klebsiella oxytoca, Staphylococcus hyicus and Staphylococcus aureus, indicating that septicemia, facilitated by neutropenia could have a role in the death of cattle acutely poisoned due to the ingestion of P. aquilinum. Additional points of the interest in the acute experimental poisoning by bracken fern in cattle reported here were the development of hematuria and the so called laryngeal form.

  19. The Effect of PM 10 on Ischemia- Reperfusion Induced Arrhythmias in Rats

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    Esmat Radmanesh

    Full Text Available ABSTRACT Epidemiological studies show that particulate matter (PM is the principal instigator of some adverse clinical symptoms involving cardiovascular diseases. PM exposure can increase experimental infarct size and potentiate myocardial ischemia and arrhythmias in experimental MI models such as ischemia-reperfusion (I/R injury.The present study was aimed to evaluate the effects of particulate matter (PM10 on ischemia- reperfusion induced arrhythmias with emphasis on the protective role of VA as an antioxidant on them. Male Wistar rats were divided into 8 groups (n=10: Control, VAc, Sham, VA, PM1 (0.5 mg/kg, PM2 (2.5 mg/kg, PM3 group (5 mg/kg, PM3 + VA group. Within 48 hours, PM10 was instilled into trachea in two stages. Then the hearts were isolated, transferred to a Langendorff apparatus, and subjected to global ischemia (30 minutes followed by reperfusion (60 minutes. The ischemia- reperfusion induced ventricular arrhythmias were assessed according to the Lambeth conventions.In the present study,the number, incidence and duration of arrhythmiasduring30 minutes ischemia were demonstrated to be more than those in the reperfusion stage. PM exposure increased significantly the number, incidence and duration of arrhythmias in the ischemia and reperfusion duration. Vanillic acid reduced significantly the number, incidence and duration of arrhythmias during the ischemia and reperfusion period.In summary, the results of this study demonstrated that the protective and dysrhythmic effects of VA in the PM exposure rats in I/R model are probably related to its antioxidant properties.

  20. Efficacy and Safety of Platelet Glycoprotein Receptor Blockade in Aged and Comorbid Mice With Acute Experimental Stroke.

    Science.gov (United States)

    Kraft, Peter; Schuhmann, Michael K; Fluri, Felix; Lorenz, Kristina; Zernecke, Alma; Stoll, Guido; Nieswandt, Bernhard; Kleinschnitz, Christoph

    2015-12-01

    Despite the medical and socioeconomic effect of ischemic stroke and extensive preclinical research, treatment options for ischemic stroke are limited. We recently identified and characterized essential steps of thrombus formation in stroke and demonstrated that inhibition of the platelet glycoprotein (GP) receptors Ib and VI, but not IIb/IIIa, protects young and healthy mice from ischemic neurodegeneration. Whether these findings translate to the clinic remains unclear. Considering that the typical stroke patient is elderly with comorbidity, we aimed to analyze the efficacy and safety of novel preclinical antithrombotics in adult and comorbid mice with acute experimental stroke. We subjected adult, healthy, atherosclerotic (Ldlr(-/-)), diabetic (streptozotocin treated), and hypertensive (RenTgMK) mice to a 60-minute transient middle cerebral artery occlusion. Animals were pretreated with anti-GPVI antibodies or treated 1 hour after stroke induction with anti-GPIb or anti-GPIIb/IIIa antigen-binding fragments, respectively. Isotype treatment served as control. Twenty-four hours after transient middle cerebral artery occlusion, we visually assessed the intracerebral hemorrhage rate and measured infarct volumes (using 2,3,5-triphenyltetrazolium chloride-stained brain slices) and functional outcome (using Bederson and grip-test scores). GPIb and GPVI inhibition protected the mice from ischemic stroke without increasing bleeding complications. In contrast, GPIIb/IIIa inhibition was not protective but increased the intracerebral hemorrhage rate. Inhibition of early steps of thrombus formation protects adult and comorbid mice from ischemic stroke. The use of clinically meaningful mouse strains might improve the translation of preclinical stroke research to the clinic. © 2015 American Heart Association, Inc.

  1. Cardioprotective Effects of LCZ696 (Sacubitril/Valsartan After Experimental Acute Myocardial Infarction

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    Masanobu Ishii, MD

    2017-12-01

    Full Text Available LCZ696 (sacubitril/valsartan can lower the risk of cardiovascular events in chronic heart failure. However, it is unclear whether LCZ696 can improve prognosis in patients with acute myocardial infarction (MI. The present study shows that LCZ696 can prevent cardiac rupture after MI, probably due to the suppression of pro-inflammatory cytokines, matrix metalloproteinase-9 activity and aldosterone production, and enhancement of natriuretic peptides in mice. These findings suggest the mechanistic insight of cardioprotective effects of LCZ696 against acute MI, resulting in the belief that LCZ696 might be useful clinically to improve survival after acute MI.

  2. Hypoxia inducible factor 1-alpha (HIF-1 alpha is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival.

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    Elisa Conde

    Full Text Available Acute tubular necrosis (ATN caused by ischemia/reperfusion (I/R during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α, using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant.

  3. Global brain ischemia and reperfusion.

    Science.gov (United States)

    White, B C; Grossman, L I; O'Neil, B J; DeGracia, D J; Neumar, R W; Rafols, J A; Krause, G S

    1996-05-01

    Brain damage accompanying cardiac arrest and resuscitation is frequent and devastating. Neurons in the hippocampus CA1 and CA4 zones and cortical layers III and V are selectively vulnerable to death after injury by ischemia and reperfusion. Ultrastructural evidence indicates that most of the structural damage is associated with reperfusion, during which the vulnerable neurons develop disaggregation of polyribosomes, peroxidative damage to unsaturated fatty acids in the plasma membrane, and prominent alterations in the structure of the Golgi apparatus that is responsible for membrane assembly. Reperfusion is also associated with vulnerable neurons with prominent production of messenger RNAs for stress proteins and for the proteins of the activator protein-1 complex, but these vulnerable neurons fail to efficiently translate these messages into the proteins. The inhibition of protein synthesis during reperfusion involves alteration of translation initiation factors, specifically serine phosphorylation of the alpha-subunit of eukaryotic initiation factor-2 (elF-2 alpha). Growth factors--in particular, insulin--have the potential to reverse phosphorylation of elF-2 alpha, promote effective translation of the mRNA transcripts generated in response to ischemia and reperfusion, enhance neuronal defenses against radicals, and stimulate lipid synthesis and membrane repair. There is now substantial evidence that the insulin-class growth factors have neuron-sparing effects against damage by radicals and ischemia and reperfusion. This new knowledge may provide a fundamental basis for a rational approach to "cerebral resuscitation" that will allow substantial amelioration of the often dismal neurologic outcome now associated with resuscitation from cardiac arrest.

  4. Mechanisms of Acupuncture Therapy for Cerebral Ischemia: an Evidence-Based Review of Clinical and Animal Studies on Cerebral Ischemia.

    Science.gov (United States)

    Zhu, Wen; Ye, Yang; Liu, Yi; Wang, Xue-Rui; Shi, Guang-Xia; Zhang, Shuai; Liu, Cun-Zhi

    2017-12-01

    Ischemic stroke is a major cause of mortality and disability worldwide. As a part of Traditional Chinese Medicine (TCM), acupuncture has been shown to be effective in promoting recovery after stroke. In this article, we review the clinical and experimental studies that demonstrated the mechanisms of acupuncture treatment for cerebral ischemia. Clinical studies indicated that acupuncture activated relevant brain regions, modulated cerebral blood flow and related molecules in stroke patients. Evidence from laboratory indicated that acupuncture regulates cerebral blood flow and metabolism after the interrupt of blood supply. Acupuncture regulates multiple molecules and signaling pathways that lead to excitoxicity, oxidative stress, inflammation, neurons death and survival. Acupuncture also promotes neurogenesis, angiogenesis as well as neuroplasticity after ischemic damage. The evidence provided from clinical and laboratory suggests that acupuncture induces multi-level regulation via complex mechanisms and a single factor may not be enough to explain the beneficial effects against cerebral ischemia.

  5. Effects of hyper- and hypo- thyroidism on oxidative stress of the eye in experimental acute anterior uveitis.

    Science.gov (United States)

    Bilgihan, K; Bilgihan, A; Diker, S; Ataoglu, O; Dolapci, M; Akata, F; Hasanreisôglu, B; Turkozkan, N

    1996-02-01

    Glutathione peroxidase activities and malondialdehyde levels were measured in the homogenated anterior segment of rat eyes with endotoxin induced acute anterior uveitis in euthyroid, hyperthyroid and hypothyroid rats. Malondialdehyde concentrations were found to be significantly increased (p 0.05). These results suggest that excess or deficiency of the thyroid hormones cause alterations in the malondialdehyde levels and glutathione peroxidase activities of the rat eyes in endotoxin induced uveitis, and hyperthyroidism may increase the oxidative stress in endotoxin induced acute anterior uveitis.

  6. Chick embryo partial ischemia model: a new approach to study ischemia ex vivo.

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    Syamantak Majumder

    Full Text Available BACKGROUND: Ischemia is a pathophysiological condition due to blockade in blood supply to a specific tissue thus damaging the physiological activity of the tissue. Different in vivo models are presently available to study ischemia in heart and other tissues. However, no ex vivo ischemia model has been available to date for routine ischemia research and for faster screening of anti-ischemia drugs. In the present study, we took the opportunity to develop an ex vivo model of partial ischemia using the vascular bed of 4(th day incubated chick embryo. METHODOLOGY/PRINCIPAL FINDINGS: Ischemia was created in chick embryo by ligating the right vitelline artery using sterile surgical suture. Hypoxia inducible factor- 1 alpha (HIF-1alpha, creatine phospho kinase-MB and reactive oxygen species in animal tissues and cells were measured to confirm ischemia in chick embryo. Additionally, ranolazine, N-acetyl cysteine and trimetazidine were administered as an anti-ischemic drug to validate the present model. Results from the present study depicted that blocking blood flow elevates HIF-1alpha, lipid peroxidation, peroxynitrite level in ischemic vessels while ranolazine administration partially attenuates ischemia driven HIF-1alpha expression. Endothelial cell incubated on ischemic blood vessels elucidated a higher level of HIF-1alpha expression with time while ranolazine treatment reduced HIF-1alpha in ischemic cells. Incubation of caprine heart strip on chick embryo ischemia model depicted an elevated creatine phospho kinase-MB activity under ischemic condition while histology of the treated heart sections evoked edema and disruption of myofibril structures. CONCLUSIONS/SIGNIFICANCE: The present study concluded that chick embryo partial ischemia model can be used as a novel ex vivo model of ischemia. Therefore, the present model can be used parallel with the known in vivo ischemia models in understanding the mechanistic insight of ischemia development and in

  7. Bumetanide promotes neural precursor cell regeneration and dendritic development in the hippocampal dentate gyrus in the chronic stage of cerebral ischemia

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    Wang-shu Xu

    2016-01-01

    Full Text Available Bumetanide has been shown to lessen cerebral edema and reduce the infarct area in the acute stage of cerebral ischemia. Few studies focus on the effects of bumetanide on neuroprotection and neurogenesis in the chronic stage of cerebral ischemia. We established a rat model of cerebral ischemia by injecting endothelin-1 in the left cortical motor area and left corpus striatum. Seven days later, bumetanide 200 µg/kg/day was injected into the lateral ventricle for 21 consecutive days with a mini-osmotic pump. Results demonstrated that the number of neuroblasts cells and the total length of dendrites increased, escape latency reduced, and the number of platform crossings increased in the rat hippocampal dentate gyrus in the chronic stage of cerebral ischemia. These findings suggest that bumetanide promoted neural precursor cell regeneration, dendritic development and the recovery of cognitive function, and protected brain tissue in the chronic stage of ischemia.

  8. Magnetic resonance imaging and histologic findings of acute and subacute stage of experimental cerebral fat embolism in cats

    International Nuclear Information System (INIS)

    Kim, Hak Jin; Lee, Chang Hun; Lee, Suk Hong; Rark, Byung Rae; Kim, Sang Sik; Kim, Yong Woo

    2002-01-01

    To determine the magnetic resonance imaging (MRI) findings and natural history of cerebral fat embolism in a cat model, and to correlate the MRI and histologic findings. Using the femoral arterial approach, the internal carotid artery of 11 cats was injected with 0.1 ml of triolein, T2-weighted (T2WI), T1-weighted (T1WI) and Gd-enhanced T1-weighted (Gd-T1WI) images were obtained serially at 2 hours, 1 and 4 days and 1,2 and 3 weeks after embolization. Any abnormal signal intensity (SI) was evaluated. After MR imaging at 3 weeks, brain tissue was obtained for light microscopic (LM) examination using hematoxylin-eosin and Luxol fast blue staining, and for electron microscopic (EM) examination. The histologic and MRI findings were correlated. At 2 hours, lesions showed high SI at T2WI, iso-or low SI at T1WI, and strong enhancement at Gd-T1WI. The high SI seen at T2WI decreased thereafter, and most lesions became iso-intense. At week 3, however, small focal areas of high SI were seen in the grey matter of eight cats and in the white matter of three. The low SI noted at acute-stage T1WI subsequently became normal, though in the areas in which T2WI had depicted high SI, focal areas of low SI remained. Lesion enhancement demonstrated by Gd-T1WI decreased continuously from day 1, and at week 3, weak enhancement was seen at the margin of the remained hypointense lesions in the gray matter in five cats. At LM examination with hematoxylin-eosin staining revealed normal histologic findings in the greater park of an embolized lesion. Cystic change was observed in the gray matter of eight cats, and in the gray and white matter of three of the eight. At LM examination, Luxol fast blue, staining demonstrated demyelination around the cystic change occurring in the matter, and EM examination of the embolized cortex revealed sporadic intracapillary fat vacuoles (n=11) and disruption of the blood-brain barrier (n=4). Most lesions were normal, however, and perivascular interstitial

  9. Diagnosis of myocardial ischemia combining multiphase postmortem CT-angiography, histology, and postmortem biochemistry.

    Science.gov (United States)

    Vanhaebost, Jessica; Ducrot, Kewin; de Froidmont, Sébastien; Scarpelli, Maria Pia; Egger, Coraline; Baumann, Pia; Schmit, Gregory; Grabherr, Silke; Palmiere, Cristian

    2017-02-01

    The aim of this study was to assess whether the identification of pathological myocardial enhancement at multiphase postmortem computed tomography angiography was correlated with increased levels of troponin T and I in postmortem serum from femoral blood as well as morphological findings of myocardial ischemia. We further aimed to investigate whether autopsy cases characterized by increased troponin T and I concentrations as well as morphological findings of myocardial ischemia were also characterized by pathological myocardial enhancement at multiphase postmortem computed tomography angiography. Two different approaches were used. In one, 40 forensic autopsy cases that had pathological enhancement of the myocardium (mean Hounsfield units ≥95) observed at postmortem angiography were retrospectively selected. In the second approach, 40 forensic autopsy cases that had a cause of death attributed to acute myocardial ischemia were retrospectively selected. The preliminary results seem to indicate that the identification of a pathological enhancement of the myocardium at postmortem angiography is associated with the presence of increased levels of cardiac troponins in postmortem serum and morphological findings of ischemia. Analogously, a pathological enhancement of the myocardium at postmortem angiography can be retrospectively found in the great majority of autopsy cases characterized by increased cardiac troponin levels in postmortem serum and morphological findings of myocardial ischemia. Multiphase postmortem computed tomography angiography is a useful tool in the postmortem setting for investigating ischemically damaged myocardium.

  10. Neuroprotection of Catalpol for Experimental Acute Focal Ischemic Stroke: Preclinical Evidence and Possible Mechanisms of Antioxidation, Anti-Inflammation, and Antiapoptosis

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    Xia-wei Zheng

    2017-01-01

    Full Text Available Neuroprotection is defined as using a therapy that affects the brain tissue in the still-viable ischemic penumbra to salvage or delay the infarction. Catalpol, the main active principle of the root of Radix Rehmanniae, was reported to have pleiotropic neuroprotective effects in neurodegenerative diseases including ischemic stroke. Here, we evaluated the neuroprotective effects of catalpol in experimental acute ischemic stroke. Studies on catalpol in animal models of acute ischemic stroke were identified from 6 databases. Twenty-five studies involving 805 animals were included. Twelve comparisons showed significant effects of catalpol on decreasing infarct size according to 2,3,5-triphenyltetrazolium chloride staining compared with the control (P<0.05. One study reported significant effect of catalpol on reducing infarct size according to magnetic resonance imaging scan compared with the control (P<0.05. Meta-analysis of these studies indicated that catalpol significantly improved the neurological function score according to Zea Longa score, Bederson score, balance beam-walking test, adhesive removal test, bar-grasping score, and corner test compared with the control (P<0.05. In conclusion, catalpol exerted neuroprotective effects for experimental acute focal ischemic stroke, largely through reducing oxidative reactions, inhibiting apoptosis, and repressing inflammatory reactions and autophagy. However, these apparently positive findings should be interpreted with caution because of the methodological flaws.

  11. Optical Coherence Tomography Study of Experimental Anterior Ischemic Optic Neuropathy and Histologic Confirmation

    Science.gov (United States)

    Ho, Joyce K.; Stanford, Madison P.; Shariati, Mohammad A.; Dalal, Roopa; Liao, Yaping Joyce

    2013-01-01

    Purpose. The optic nerve is part of the central nervous system, and interruption of this pathway due to ischemia typically results in optic atrophy and loss of retinal ganglion cells. In this study, we assessed in vivo retinal changes following murine anterior ischemic optic neuropathy (AION) by using spectral-domain optical coherence tomography (SD-OCT) and compared these anatomic measurements to that of histology. Methods. We induced ischemia at the optic disc via laser-activated photochemical thrombosis, performed serial SD-OCT and manual segmentation of the retinal layers to measure the ganglion cell complex (GCC) and total retinal thickness, and correlated these measurements with that of histology. Results. There was impaired perfusion and leakage at the optic disc on fluorescein angiography immediately after AION and severe swelling and distortion of the peripapillary retina on day-1. We used SD-OCT to quantify the changes in retinal thickness following experimental AION, which revealed significant thickening of the GCC on day-1 after ischemia followed by gradual thinning that plateaued by week-3. Thickness of the peripapillary sensory retina was also increased on day-1 and thinned chronically. This pattern of acute retinal swelling and chronic thinning on SD-OCT correlated well with changes seen in histology and corresponded to loss of retinal ganglion layer cells after ischemia. Conclusions. This was a serial SD-OCT quantification of acute and chronic changes following experimental AION, which revealed changes in the GCC similar to that of human AION, but over a time frame of weeks rather than months. PMID:23887804

  12. Memantine mediates neuroprotection via regulating neurovascular unit in a mouse model of focal cerebral ischemia.

    Science.gov (United States)

    Chen, Zheng-Zhen; Yang, Dan-Dan; Zhao, Zhan; Yan, Hui; Ji, Juan; Sun, Xiu-Lan

    2016-04-01

    Memantine is a low-moderate affinity and uncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonist, which is also a potential neuroprotectant in acute ischemic stroke for its particular action profiles. The present study was to reveal the mechanisms involved in the neuroprotection of memantine. We used a mouse model of permanent focal cerebral ischemia via middle cerebral artery occlusion to verify our hypothesis. 2,3,5-Triphenyltetrazolium chloride staining was used to compare infarct size. The amount of astrocytes and the somal volume of the microglia cell body were analyzed by immunohistochemistry and stereological estimates. Western blotting was used to determine the protein expressions. Memantine prevented cerebral ischemia-induced brain infarct and neuronal injury, and reduced oxygen-glucose deprivation-induced cortical neuronal apoptosis. Moreover, memantine reduced the amount of the damaged astrocytes and over activated microglia after 24h of ischemia. In the early phase of ischemia, higher production of MMP-9 was observed, and thereby collagen IV was dramatically disrupted. Meanwhile, the post-synaptic density protein 95(PSD-95) was also severely cleavaged. Memantine decreased MMP-9 secretion, prevented the degradation of collagen IV in mouse brain. PSD-95 cleavage was also inhibited by memantine. These results suggested that memantine exerted neuroprotection effects in acute ischemic brain damage, partially via improving the functions of neurovascular unit. Taking all these findings together, we consider that memantine might be a promising protective agent against ischemic stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Silent ischemia in patients after uncomplicated myocardial infarction

    International Nuclear Information System (INIS)

    Samarzija, M.; Tezak, S.

    1994-01-01

    The purpose of this study was to determine the frequency and importance of silent ischemia in patients (pts) after the acute myocardial infarction (A MI) as well as to establish diagnostic and prognostic value of exercise stress test (EST), Holter (H) monitoring and thallium-201 (Tl) scintigraphy. All the three tests were performed 2-4 months following the AMI. The criterion for diagnosing myocardial ischemia on EST and H is 1 mm or more of horizontal or down-sloping ST depression. Additional criteria for Holter imply the ischemic episode should last one minute and be separated from other episodes by at least one minute. Planar thallium images were performed 5-10 minute after the stress test; the delayed images were obtained after 3-6 hours. Visual and quantitative methods were employed in the analysis of TI-scintigraphy. Scintigraphy was considered positive if exercise- induced perfusion defects showed redistribution. The study included 74 asymptomatic patients after the AMI. The patients were divided into two groups by results of quantitative Tl-scintigraphy: Group I - 44 pts with silent ischemia, Group II - 30 pts without ischemia. In Group I, out of 44 pts, 9 had a positive exercise stress, 4 showed a painless ST depression on Holter and 7 had both tests positive, whereas 24 pts had only scintigraphy positive. In Group II one patient had positive EST and H. Sensitivity and specificity were determined by results of coronary arteriography performed on 33 pts: EST (Se=40%, Sp=80%), H (Se=219, Sp=100%) and scintigraphy (Se=93%, Sp =80%). During the follow-up period lasting at least 12 months, in Group I 3 pts died, 1 developed a new myocardial infarction and 15 pts had painful ischemic occurrences. In Group II only 3 pts developed symptoms of angina pectoris. Tl-scintigraphy was the only non-invasive test showing significant correlation with the follow-up outcomes. The diagnostic and prognostic superiority of Tl-scintigraphy justifies its value as the initial

  14. Myocardial perfusion in silent myocardial ischemia

    International Nuclear Information System (INIS)

    Narita, Michihiro; Kurihara, Tadashi; Murano, Kenichi; Usami, Masahisa

    1989-01-01

    To investigate myocardial perfusion in silent myocardial ischemia, we performed exercise stress myocardial tomography with thallium-201 (Tl) in 85 patients with coronary artery disease (CAD). Exercise stress myocardial tomography was obtained both immediately after exercise and three hours later. Patients were classified into two groups according to the presence (Symptomatic Group, n=36) or absence (Silent Group, n=49) of chest pain during exercise stress. Clinical features (age, gender and history of myocardial infarction) and arteriographically determined severity of CAD were the same in both groups. The extent of myocardial ischemia (% Ischemia) estimated by exercise stress myocardial tomography was the same in each group (30±10 % in Silent Group, 28±12 % in Symptomatic Group, NS). The severity of exercise-induced myocardial ischemia was expressed as a minimal value of myocardial Tl washout rate (minimal WOR) of each patient. Although exercise heart rate was identical in both groups, minimal WOR in Silent Group was significantly higher than that of Symptomatic Group (4±10% vs -16±14%, p<0.001). The study in patients who exhibited both silent and symptomatic ischemia showed the same results. These findings suggest that the severity of ischemia is a fundamental factor in determining the presence or absence of pain during exercise induced ischemia. (author)

  15. Antioxidant and antiapoptotic effects of erdosteine in a rat model of ovarian ischemia-reperfusion injury

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    Vedat Ugurel

    2017-01-01

    Full Text Available Objective(s: To evaluate the protective effect of erdosteine, an antiapoptotic and antioxidant agent, on torsion–detorsion evoked histopathological changes in experimental ovarian ischemia-reperfusion (IR injury. Materials and Methods: Eighteen female Wistar albino rats were used in control, IR, and IR+Edosteine (IR-E groups, (n=6 in each. The IR-E group received the erdosteine for seven days before the induction of torsion/retorsion, (10 mg/kg/days. The IR and IR-E groups were exposed to right unilateral adnexal torsion for 3 hr. Three hours later, re-laparotomy was performed, and the right ovaries were surgically excised. Oxidant and antioxidants levels were determined in serum. The ovarian tissue samples were received and fixed with 10% neutral buffered formalin. The sections were stained with H&E, anti-PCNA, and TUNEL. Results: The IR group were showed severe acute inflammation, polynuclear leukocytes and macrophages, stromal oedema and haemorrhage. Treatment with erdosteine in rats significantly retained degenerative changes in the ovaryPCNA (+ cell numbers were significantly decreased in the IR and IR-E groups unlike the control group. However, its numbers were significantly increased in the IR-E group unlike the IR group. TUNEL (+ cell numbers were significantly increased in the IR group unlike the control and the IR-E groups. In erdosteine treated group, TUNEL (+ cells were detected significantly less than the IR group (P

  16. The experimental investigation of fibrinolytic system under the influence of flocalin in conditions of acute hypoxic kidney injury

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    A. I. Gozhenko

    2017-08-01

    Full Text Available In the experiments on rats subjected to acute hypoxic histochemical nephropathy, caused by sodium nitrite and 2,4-dinitrophenol, fibrinolytic activities of blood plasma, urine, renal cortex, medulla, and papilla after treatment with flocalin – the activator of KATP channels, were studied­. It was shown that in the conditions of acute kidney hypoxic injury flocalin administration resulted in the increase and essential restoration of fibrinolysis in blood plasma diminished under hypoxia, which was due to the growth of non-enzymatic fibrinolysis, whereas in urine and renal medulla the appreciable increase of enzymatic fibrinolytic activity took place. Moreover, the treatment of hypoxic nephropathy animals by flocalin resulted in the marked restoration of kidney ion regulatory and protein excretory functions that proves the positive influence of KATP channels activation on the one of the biochemical mechanisms of acute kidney injury as well as the protective effect of flocalin in relation to tubular cells of nephron. The obtained results testify to the beneficial effects of KATP channels activation in the conditions of acute hypoxic kidneys injury.

  17. IMAGE ANALYSIS IN GOMORI´S TRICHROME STAIN OF SKELETAL MUSCLES SUBJECTED TO ISCHEMIA AND REPERFUSION INJURY

    OpenAIRE

    Doris Haydee Rosero Salazar; Liliana Janeth Flórez Elvira

    2016-01-01

    Conditions that produce ischemia and reperfusion injury include orthopedic surgeries, vascular diseases and accidents in remote places in which use of a manual tourniquet is required. Tissues under such stress suffer the consequences of evidenced by changes in their normal microscopic organization that can be reversible or irreversible according to the time and severity of lesion. An experimental model of ischemia has been designed taking into account the characteristics similar to a surgical...

  18. Level of the proteins of the acute phase as criterions of the antibacterial therapy effectiveness in the E.coli associated experimental peritonitis

    Directory of Open Access Journals (Sweden)

    V. V. Minukhin

    2013-08-01

    Full Text Available Introduction. Peritonitis is accompanied by increase of acute-phase proteins levels. C – reactive protein (CRP is acute – phase protein which is produced in human organism in response to tissue injury, infection or inflammation. CRP is produced in small quantities (<1mg/l under normal conditions. Measurement of CRP levels in serum is used for setting of the diagnosis and diseases monitoring as well as efficacy of their treatment. Seromucoid (orosomucoid, alpha-1 acid glucoprotein is one of acute – phase proteins. Levels of serum orosomucoid are elevated since onset of the inflammatory process due to microbial contamination develops in peritonitis. Levels of alpha – 1 acid glucoprotein is elevated during acute phase of inflammation. Alpha – 1 acid glucoprotein is one of main acute – phase proteins. Aim of the study. To determinate levels of seromucoid and CRP in serum of experimental animals and to evaluate the duration of the inflammatory process and the efficacy of antimicrobial therapy in mice with experimentally induced peritonitis. Material and methods of study. Levels of CRP were determined with the use of a half – quantitative immunoturbidimetric method. Levels of seromucoids were determined by means of the immunoturbidimetric method. Levels of CRP and seromucoid were determined in serum obtained from mice in which experimental peritonitis were induced by Escherichia coli. Mice were divided into 6 groups depending on methods of treatment: the 1st group: Amikacin; the 2nd group: gatifloxacin; the 3rd group: Amikacin combined with Gatiflocsacin; the 4th group: Amikacin combined with Bacteriophagum Coli-Proteicum; the 5th group: Gatiflocsacin combined with Bacteriophagum Coli-Proteicum; the 6th group: Amikacin combined with Gatiflocsacin and Bacteriophagum Coli-Proteicum; Studies were conducted on the 3rd and the 5th day after the start of antimicrobial therapy. Results of study. Studies showed that the positive CRP test and the

  19. The MASP family of Trypanosoma cruzi: changes in gene expression and antigenic profile during the acute phase of experimental infection.

    Directory of Open Access Journals (Sweden)

    Sara Lopes dos Santos

    Full Text Available Trypanosoma cruzi is the etiological agent of Chagas disease, a debilitating illness that affects millions of people in the Americas. A major finding of the T. cruzi genome project was the discovery of a novel multigene family composed of approximately 1,300 genes that encode mucin-associated surface proteins (MASPs. The high level of polymorphism of the MASP family associated with its localization at the surface of infective forms of the parasite suggests that MASP participates in host-parasite interactions. We speculate that the large repertoire of MASP sequences may contribute to the ability of T. cruzi to infect several host cell types and/or participate in host immune evasion mechanisms.By sequencing seven cDNA libraries, we analyzed the MASP expression profile in trypomastigotes derived from distinct host cells and after sequential passages in acutely infected mice. Additionally, to investigate the MASP antigenic profile, we performed B-cell epitope prediction on MASP proteins and designed a MASP-specific peptide array with 110 putative epitopes, which was screened with sera from acutely infected mice.We observed differential expression of a few MASP genes between trypomastigotes derived from epithelial and myoblast cell lines. The more pronounced MASP expression changes were observed between bloodstream and tissue-culture trypomastigotes and between bloodstream forms from sequential passages in acutely infected mice. Moreover, we demonstrated that different MASP members were expressed during the acute T. cruzi infection and constitute parasite antigens that are recognized by IgG and IgM antibodies. We also found that distinct MASP peptides could trigger different antibody responses and that the antibody level against a given peptide may vary after sequential passages in mice. We speculate that changes in the large repertoire of MASP antigenic peptides during an infection may contribute to the evasion of host immune responses during the

  20. Local lysis with Alteplase for the treatment of acute embolic leg ischemia following the use of the Duett {sup trademark} closure device: preliminary results; Lokale Alteplase-Lyse zur Therapie der akuten embolischen Beinischaemie nach Einsatz des Duett {sup trademark} -Verschluss-Systems: vorlaeufige Ergebnisse

    Energy Technology Data Exchange (ETDEWEB)

    Schuermann, K.; Buecker, A.; Wingen, M.; Tacke, J.; Wein, B.; Guenther, R.W. [Klinik fuer Radiologische Diagnostik des Universitaetsklinikums der RWTH Aachen (Germany); Janssens, U. [Medizinische Klinik I (Kardiologie) des Universitaetsklinikums der RWTH Aachen (Germany)

    2004-04-01

    Purpose: To analyze retrospectively the result of the alteplase lysis therapy of embolic complications following the use of the Duett closure device. Methods and Materials: For 3.5 years, the Duett closure device was used in 1,398 angiographies to close the femoral puncture site. The Duett device consists of a balloon and a liquid procoagulant containing collagen and thrombin, which is injected into the puncture tract under endovascular balloon protection of the arterial puncture site. In 9 patients (0.64%), the procoagulant was incidentally injected into the femoral artery causing acute leg ischemia. Eight patients received local lysis therapy with alteplase via a contralateral femoral access. One patient underwent surgery. On average, 21 mg alteplase (4-35 mg) were administered within 14 h (4-21 h). The course of the lysis was followed angiographyically and clinically. All patients were inteerviewed by telephone 23 months (4-35 months) later.Results: In 3 patients, lysis was complete. In 5 patients, only little thrombotic material remained. In all patients, symptoms of ischemia resolved completely within the first hours after initiation of lysis. In 5 cases, bleeding occurred at the puncture site closed with the Duett device during lysis, including development of a false aneurysm in 2 cases. Complications led to premature termination (n=2) or interruption of the lysis (n=3). All complications were treated conservatively. Clinically, long-term sequelae were paresthesia and hypoesthesia in the lower leg and foot in 2 patients treated with lysis, and in the patient who underwent surgery. (orig.) [German] Ziel: Das Ergebnis der Alteplase-Lysetherapie von Embolien nach Einsatz des Duett-Verschluss-Systems wurde retrospektiv untersucht. Methoden: Innerhalb von 3,5 Jahren wurde nach 1398 Angiographien das Duett-System zum Verschluss der femoralen Punktionsstelle eingesetzt. Das System besteht aus einem Ballon und einem fluessigen Prokoagulans (Kollagen, Thrombin), das

  1. Leg ischemia post-varicocelectomy

    Directory of Open Access Journals (Sweden)

    Al-Wahbi AM

    2016-03-01

    Full Text Available Abdullah M Al-Wahbi1, Shaza Elmoukaied2 1Division of Vascular Surgery, Department of Surgery, King Abdulaziz Medical City, Riyadh, Saudi Arabia; 2Department of Surgery, Dr Sulaiman Al Habib Hospital, Riyadh, Saudi Arabia Abstract: Varicocelectomy is the most commonly performed operation for the treatment of male infertility. Many surgical approaches are used as each of them has advantages over the other and is preferred by surgeons. Vascular injury has never been reported as a complication of varicocelectomy apart from testicular artery injury. We present a 36-year-old male who developed leg ischemia post-varicocelectomy due to common femoral artery injury. He was successfully treated by using a vein graft. Keywords: varicocele, varicocelectomy, complications, vascular injuries

  2. Temporary intestinal ischemia for radiation protection

    International Nuclear Information System (INIS)

    Lote, K.

    1983-01-01

    The most important determinant of cellular radiosensivity is the tissue oxygen content at the time of irradiation. The purpose of the present experimental work was to assess a new iscemia-inducing method in order to reduce normal tissue radiation damage during radiotherapy. Temporary ischemia was induced in a cat small intestine by degraded starch microspheres. Regional arterial and tissue blod flow immediately fell by 85% with subsequent normalization within 26 minutes after microsphere injection. No tendency of small vessel thrombosis caused by starch sphere embolization in combination with previous or current intestinal irradiation was detected. Starch sphere remenants were rapidly engulfed by, and persisted within tissue macrophages for 14 days without causing intestinal inflammatory reactions. In vitro studies showed that human platelets neither adhered to nor were aggregated by starch microspheres. The new method, wich occlude arteriolar vessels distal to the mesentric arterial arcades and thus largely excludes collateral blood flow, seems suited to provide effictive and selective feline small intestinal hypoxic radiation protection. This conclusion may also be valid in man

  3. Myocardial ischemia and angina pectoris. The clinical problem in patients

    Energy Technology Data Exchange (ETDEWEB)

    Selwyn, A.P.; Fox, K.M.; Jonathan, A.; Lavender, P.; Watson, I.

    1981-02-01

    Ambulatory monitoring of ST segment changes was performed in 60 patients presenting with angina, positive ECG stress tests and coronary artery disease, 85% of ischemic ECG events were asymptomatic, 37% occurred with no increase in heart rate and 15% of episodes either lasted 20 minutes or more or fluctuated in severity. A controlled pilot study in ten patients showed depression. Radionuclide studies in 50 patients with angina and coronary artery disease have shown that stress (i.e., atrial pacing) produced different patterns of disturbed regional myocardial perfusion related to the patient's exercise capacity and eventually leading to a decrease in regional myocardial perfusion during the ischemic episode. ST segment depression appeared only after the decrease in regional myocardial perfusion. These findings combined with past research suggest that patients with angina and coronary artery disease can suffer frequent asymptomatic disturbances of the regional myocardial perfusion. The frequency of these episodes and the time course for the recovery of the metabolic consequences mean that segments of ventricular myocardium may be constantly abnormal. The relative importance of changes in coronary tone and malfunction of platelets in the diseased coronary tree needs to be examined in clinical research. Pilot studies of antiplatelet agents have shown a significant beneficial effect on episodes of ischemia occurring at night and those occurring without any increase in heart rate. The techniques and observations in these patients with coronary artery disease all suggest that acute transient regional myocardial ischemia is caused by a variety of mechanisms. Further research using objective methods is required to discover the causes of ischemia and to rationalize treatment.

  4. Characterization of Microparticles after Hepatic Ischemia-Reperfusion Injury

    Science.gov (United States)

    Freeman, Christopher M.; Quillin, Ralph C.; Wilson, Gregory C.; Nojima, Hiroyuki; Johnson, Bobby L.; Sutton, Jeffrey M.; Schuster, Rebecca M.; Blanchard, John; Edwards, Michael J.; Caldwell, Charles C.; Lentsch, Alex B.

    2014-01-01

    Background Hepatic ischemia-reperfusion (I/R) is a well-studied model of liver injury and has demonstrated a biphasic injury followed by recovery and regeneration. Microparticles (MPs) are a developing field of study and these small membrane bound vesicles have been shown to have effector function in other physiologic and pathologic states. This study was designed to quantify the levels of MPs from various cell origins–platelets, neutrophils, and endolethial cells–following hepatic ischemia-reperfusion injury. Methods A murine model was used with mice undergoing 90 minutes of partial hepatic ischemia followed by various times of reperfusion. Following reperfusion, plasma samples were taken and MPs of various cell origins were labeled and levels were measured using flow cytometry. Additionally, cell specific MPs were further assessed by Annexin V, which stains for the presence of phosphatidylserine, a cell surface marker linked to apoptosis. Statistical analysis was performed using one-way analysis of variance with subsequent Student-Newman-Keuls test with data presented as the mean and standard error of the mean. Results MPs from varying sources show an increase in circulating levels following hepatic I/R injury. However, the timing of the appearance of different MP subtypes differs for each cell type. Platelet and neutrophil-derived MP levels demonstrated an acute elevation following injury whereas endothelial-derived MP levels demonstrated a delayed elevation. Conclusion This is the first study to characterize circulating levels of cell-specific MPs after hepatic I/R injury and suggests that MPs derived from platelets and neutrophils serve as markers of inflammatory injury and may be active participants in this process. In contrast, MPs derived from endothelial cells increase after the injury response during the reparative phase and may be important in angiogenesis that occurs in the regenerating liver. PMID:24879335

  5. Therapeutic hypothermia reduces intestinal ischemia/reperfusion ...

    African Journals Online (AJOL)

    The detached intestinal epithelial cells in hypothermia group showed ... of apoptosis than those in normothermia group at 4 h (17.30 ± 2.56 vs. ... intestinal ischemia/reperfusion (IR) injury, which could be attenuated by therapeutic hypothermia.

  6. Effects of acute and chronic experimental contamination on direct cesium 137 uptake by the eel, Anguilla anguilla L

    International Nuclear Information System (INIS)

    Foulquier, Luc; Lambrechts, Alain.

    1982-03-01

    This study covers the effects of different types of contamination on direct cesium 137 uptake by the eel. In the first experiment (acute contamination), simulating a waste discharge, the fish were kept in water with a rapidly decreasing cesium 137 activity. In a second experiment (chronic contamination), the water activity increased constantly, simulating increasing waste frequency and activity levels. Irrespective of the type of contamination, radiocesium retention by eels is low ( [fr

  7. Experimental Justification of Enteral Lavage by Osmotically Active Solution in Acute Intestinal Obstruction Complicated by Intraabdominal Hypertension

    OpenAIRE

    Lukoyanychev E.E.; Ryabkov M.G.; Kudykin M.N.

    2011-01-01

    The aim of the study is to determine the influence of intra-enteric pressure level on the mechanism causing decompensation of microcirculation defects in the wall of a small intestine and to assess the effectiveness of enteral lavage by hydroxyethyl amylum in case of an increased intra-enteric pressure in acute intestinal obstruction. Materials and Methods. The experiment was carried out on 54 laboratory animals. In I series of the experiment (36 non-pedigree dogs) the processes of microc...

  8. Mesenchymal Stem Cells From Bone Marrow, Adipose Tissue, and Lung Tissue Differentially Mitigate Lung and Distal Organ Damage in Experimental Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Silva, Johnatas D; Lopes-Pacheco, Miquéias; Paz, Ana H R; Cruz, Fernanda F; Melo, Elga B; de Oliveira, Milena V; Xisto, Débora G; Capelozzi, Vera L; Morales, Marcelo M; Pelosi, Paolo; Cirne-Lima, Elizabeth; Rocco, Patricia R M

    2018-02-01

    Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome. Animal study and primary cell culture. Laboratory investigation. Seventy-five Wistar rats. Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium). Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1β, keratinocyte-derived chemokine, transforming growth factor-β, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue

  9. Influence of matrix nature on the functional efficacy of biomedical cell product for the regeneration of damaged liver (experimental model of acute liver failure

    Directory of Open Access Journals (Sweden)

    S. V. Gautier

    2017-01-01

    Full Text Available Aim. A comparative analysis of the functional efficacy of biomedical cell products (BMCP for the regeneration of damaged liver based on biopolymer scaffolded porous and hydrogel matrices was performed on the experimental model of acute liver failure. Materials and methods. Matrices allowed for clinical use were employed for BMCP in the form of a sponge made from biopolymer nanostructured composite material (BNCM based on a highly purified bacterial copolymers of poly (β-hydroxybutyrate-co-β-oxyvalerate and polyethylene glycol and a hydrogel matrix from biopolymer microheterogeneous collagen-containing hydrogel (BMCH. Cellular component of BMCP was represented by liver cells and multipotent mesenchymal bone marrow stem cells. The functional efficacy of BMCP for the regeneration of damaged liver was evaluated on the experimental model of acute liver failure in Wistar rats (n = 40 via biochemical, morphological, and immunohistochemical methods. Results. When BMCP was implanted to regenerate the damaged liver on the basis of the scaffolded BNCM or hydrogel BMCH matrices, the lethality in rats with acute liver failure was absent; while in control it was 66.6%. Restoration of the activity of cytolytic enzyme levels and protein-synthetic liver function began on day 9 after modeling acute liver failure, in contrast to the control group, where recovery occurred only by days 18–21. Both matrices maintained the viability and functional activity of liver cells up to 90 days with the formation of blood vessels in BMCP. The obtained data confirm that scaffolded BNCM matrix and hydrogel BMCH matrix retain for a long time (up to 90 days the vital activity of the adherent cells in the BMCP composition, which allows using them to correct acute liver failure. At the same time, hydrogel matrix due to the presence of bioactive components contributes to the creation of the best conditions for adhesion and cell activity which accelerate the regeneration processes

  10. Body mass index and risk for mental stress induced ischemia in coronary artery disease.

    Science.gov (United States)

    Soufer, Robert; Fernandez, Antonio B; Meadows, Judith; Collins, Dorothea; Burg, Matthew M

    2016-05-19

    Acute emotionally reactive mental stress (MS) can provoke prognostically relevant deficits in cardiac function and myocardial perfusion, and chronic inflammation increases risk for this ischemic phenomenon. We have described parasympathetic withdrawal and generation of inflammatory factors in MS. Adiposity is also associated with elevated markers of chronic inflammation. High body mass index (BMI) is frequently used as a surrogate for assessment of excess adiposity, and associated with traditional CAD risk factors, and CAD mortality. BMI is also associated with autonomic dysregulation, adipose tissue derived proinflammatory cytokines, which are also attendant to emotion provoked myocardial ischemia. Thus, we sought to determine if body mass index (BMI) contributes to risk of developing myocardial isch