WorldWideScience

Sample records for suggesting myocardial ischemia

  1. Myocardial Ischemia

    Science.gov (United States)

    ... pectoris: Chest pain caused by myocardial ischemia. www.uptodate.com/home. Accessed June 1, 2015. Deedwania PC. Silent myocardial ischemia: Epidemiology and pathogenesis. www.uptodate.com/home. Accessed June 1, 2015. Mann DL, ...

  2. Myocardial Ischemia

    Science.gov (United States)

    ... occurs when blood flow to the heart muscle (myocardium) is obstructed by a partial or complete blockage of a coronary artery by a buildup of plaques (atherosclerosis). If the plaques rupture, you can have a heart attack (myocardial infarction). Myocardial ischemia occurs when blood flow ...

  3. Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy

    NARCIS (Netherlands)

    van den Heuvel, AFM; van Veldhuisen, DJ; van der Wall, EE; Blanksma, PK; Siebelink, HMJ; Vaalburg, WM; van Gilst, WH; Crijns, HJGM

    OBJECTIVES We performed positron emission tomography (PET) to evaluate myocardial ischemia in patients with idiopathic dilated cardiomyopathy (IDC). BACKGROUND Patients with IDC have anatomically normal coronary arteries, and it has been assumed that myocardial ischemia does not occur. METHODS We

  4. Silent myocardial ischemia during coronary angioplasty.

    Science.gov (United States)

    Dellborg, M; Emanuelsson, H; Swedberg, K

    1993-01-01

    Silent myocardial ischemia is a marker in patients with coronary artery disease identifying those at high risk for subsequent cardiac events. During provoked myocardial ischemia some patients with angina pectoris do not develop chest pain. Are there clinical, angiographic or electrocardiographic differences between patients with chest pain as compared with patients without chest pain during provoked myocardial ischemia? Coronary angioplasty is a well-established method for the treatment of coronary stenosis, but it is also an interesting model for the study of myocardial ischemia as a result of coronary occlusion. We monitored 114 patients with angina pectoris during coronary angioplasty with dynamic, computerized vectorcardiography. During inflation of the balloon 33 of 114 patients had silent ischemia. Patients with silent myocardial ischemia had similar reasons for terminating the preangioplasty exercise test and where on similar anti-ischemic drug regimes. Silent myocardial ischemia was significantly associated with a history of diabetes, presence of collaterals, a history of less severe previous angina and less ST segment changes during angioplasty as compared with patients with painful ischemia. It is suggested that during coronary angioplasty silent ischemia may be caused by a less severe degree of ischemia, possibly as a result of the protective effect of collaterals.

  5. Spatial Organization of Acute Myocardial Ischemia

    Science.gov (United States)

    Aras, Kedar; Burton, Brett; Swenson, Darrell; MacLeod, Rob

    2016-01-01

    Introduction Myocardial ischemia is a pathological condition initiated by supply and demand imbalance of the blood to the heart. Previous studies suggest that ischemia originates in the subendocardium, i.e., that nontransmural ischemia is limited to the subendocardium. By contrast, we hypothesized that acute myocardial ischemia is not limited to the subendocardium and sought to document its spatial distribution in an animal preparation. The goal of these experiments was to investigate the spatial organization of ischemia and its relationship to the resulting shifts in ST segment potentials during short episodes of acute ischemia. Methods We conducted acute ischemia studies in open-chest canines (N=19) and swines (N=10), which entailed creating carefully controlled ischemia using demand, supply or complete occlusion ischemia protocols and recording intramyocardial and epicardial potentials. Elevation of the potentials at 40% of the ST segment between the J-point and the peak of the T-wave (ST40%) provided the metric for local ischemia. The threshold for ischemic ST segment elevations was defined as two standard deviations away from the baseline values. Results The relative frequency of occurrence of acute ischemia was higher in the subendocardium (78% for canines and 94% for swines) and the mid-wall (87% for canines and 97% for swines) in comparison with the subepicardium (30% for canines and 22% for swines). In addition, acute ischemia was seen arising throughout the myocardium (distributed pattern) in 87% of the canine and 94% of the swine episodes. Alternately, acute ischemia was seen originating only in the subendocardium (subendocardial pattern) in 13% of the canine episodes and 6% of the swine episodes (p < 0.05). Conclusions Our findings suggest that the spatial distribution of acute ischemia is a complex phenomenon arising throughout the myocardial wall and is not limited to the subendocardium. PMID:26947437

  6. Transient myocardial ischemia after myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H

    1995-01-01

    Ambulatory ST-segment monitoring is a relatively new device in the evaluation of myocardial ischemia. The method is unique in allowing us to continuously examine the patient over an extended period of time in a changing environmental milieu. In survivors of acute myocardial infarction the prevale...

  7. Cardiac metabolism in myocardial ischemia.

    Science.gov (United States)

    Rosano, Giuseppe M C; Fini, Massimo; Caminiti, Giuseppe; Barbaro, Giuseppe

    2008-01-01

    Myocardial ischemia occurs for a mismatch between blood flow and metabolic requirements, when the rate of oxygen and metabolic substrates delivery to the myocardium is insufficient to meet the myocardial energy requirements for a given myocardial workload. During ischemia, substantial changes occur in cardiac energy metabolism, as a consequence of the reduced oxygen availability. Some of these metabolic changes are beneficial and may help the heart adapt to the ischemic condition. However, most of the changes are maladaptive and contribute to the severity of the ischemic injury leading stunned or hibernating myocardium, cell death and ultimately to contractile disfunction. Dramatic changes in cardiac metabolism and contractile function, also occur during myocardial reperfusion as a consequence of the generation of oxygen free radicals, loss of cation homeostasis, depletion of energy stores, and changes in subcellular activities. The reperfusion injury may cause in the death of cardiac myocytes that were still viable immediately before myocardial reperfusion. This form of myocardial injury, by itself can induce cardiomyocyte death and increase infarct size. During acute ischemia the relative substrate concentration is the prime factor defining preference and utilization rate. Allosteric enzyme regulation and protein phosphorylation cascades, partially controlled by hormones such as insulin, modulate the concentration effect; together they provide short-term adjustments of cardiac energy metabolism. The expression of metabolic genes is also dynamically regulated in response to developmental and (patho)physiological conditions, leading to long-term adjustments. Specific nuclear receptor transcription factors and co-activators regulate the expression of these genes. Understanding the functional role of these changes is critical for developing the concept of metabolic intervention for heart disease. The paper will review the alterations in energy metabolism that occur

  8. Silent ischemia and severity of pain in acute myocardial infarction

    DEFF Research Database (Denmark)

    Nielsen, F E; Nielsen, S L; Knudsen, F

    1991-01-01

    An overall low tendency to complain of pain, due to a low perception of pain, has been suggested in the pathogenesis of silent ischemia, independent of the extent of the diseased coronaries and a history of previous acute myocardial infarction. This hypothesis has been tested indirectly...... in this retrospective study by comparison of the use of analgesics during admission for a first acute myocardial infarction with the occurrence of silent ischemia at exertion tests four weeks after discharge from hospital. The study did not show a lower use of analgesics in patients with silent ischemia, but this may...

  9. Constrictive pericarditis causing a positive TI-201 SPECT stress test for myocardial ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Matthews, R.J.; Lightfoote, J.; Grusd, R.S. (Diagnostic Imaging of Southern California Medical Group, Sherman Oaks (USA))

    1990-08-01

    A case of constritive pericarditis was demonstrated by a positive thallium SPECT stress test for myocardial ischemia. After pericardiectomy, the repeat thallium stress test was normal. The disappearance of the criteria for a positive test suggests that constrictive pericarditis can cause myocardial ischemia, which can be demonstrated by thallium SPECT stress testing.

  10. Cardiac MRI for myocardial ischemia.

    LENUS (Irish Health Repository)

    Daly, Caroline

    2013-01-01

    Proper assessment of the physiologic impact of coronary artery stenosis on the LV myocardium can affect patient prognosis and treatment decisions. Cardiac magnetic resonance imaging (CMR) assesses myocardial perfusion by imaging the myocardium during a first-pass transit of an intravenous gadolinium bolus, with spatial and temporal resolution substantially higher than nuclear myocardial perfusion imaging. Coupled with late gadolinium enhancement (LGE) imaging for infarction during the same imaging session, CMR with vasodilating stress perfusion imaging can qualitatively and quantitatively assess the myocardial extent of hypoperfusion from coronary stenosis independent of infarcted myocardium. This approach has been validated experimentally, and multiple clinical trials have established its diagnostic robustness when compared to stress single-photon emission computed tomography. In specialized centers, dobutamine stress CMR has been shown to have incremental diagnostic value above stress echocardiography due to its high imaging quality and ability to image the heart with no restriction of imaging window. This paper reviews the technical aspects, diagnostic utility, prognostic values, challenges to clinical adaptation, and future developments of stress CMR imaging.

  11. The efficacy of nisoldipine on myocardial perfusion in patients with silent myocardial ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Junichi; Muto, Hiroshi; Naitou, Katsutoshi [Toho University, Tokyo (Japan). Omori Hospital] [and others

    1997-06-01

    Patients who had old myocardial infarction associated with myocardial viability and ischemia were divided into a pain-free group and a pain-positive group of nine patients each. The improvement of myocardial perfusion with nisoldipine therapy was compared between the two groups using exercise-load Tl-201 myocardial SPECT (myocardial SPECT). The exercise time was significantly prolonged from 505 seconds to 607 seconds after administration of nisoldipine in the pain-positive group (p<0.05), but there was no change in the pain-free group. The extent score of the full circumference of the left ventricle, the severity score, and the %Tl uptake of the infarcted region were significantly improved in both groups by administration of nisoldipine. These findings suggested that nisoldipine caused a decrease in the myocardial oxygen requirements associated with reduction of the afterload and coronary artery dilatation in the pain-positive group, but mainly caused coronary dilatation in the pain-free group. Since myocardial perfusion also improved after nisoldipine administration in the pain-free group, the possibility that calcium antagonists can be used for prophylactic treatment of asymptomatic myocardial ischemia was suggested. (author)

  12. Caffeine reduces dipyridamole-induced myocardial ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Smits, P.; Aengevaeren, W.R.; Corstens, F.H.; Thien, T. (Univ. of Nijmegen (Netherlands))

    1989-10-01

    The mechanism of action of coronary vasodilation after dipyridamole may be based on inhibition of cellular uptake of circulating endogenous adenosine. Since caffeine has been reported to be a competitive antagonist of adenosine we studied the effect of caffeine on the outcome of dipiridamole-{sup 201}Tl cardiac imaging in one patient. During caffeine abstinence dipyridamole induced myocardial ischemia with down-slope ST depressions on the ECG, and reversible perfusion defects on the scintigrams. When the test was repeated 1 wk later on similar conditions, but now shortly after infusion of caffeine (4 mg/kg), the ECG showed nodepressions, and the scintigrams only slight signs of ischemia. We conclude that when caffeine abstinence is not sufficient, the widespread use of coffee and related products may be responsible for false-negative findings in dipyridamole-201Tl cardiac imaging.

  13. Increases in myeloperoxidase levels after exercise in myocardial perfusion scintigraphy are not induced by myocardial ischemia

    NARCIS (Netherlands)

    van der Zee, P. M.; Meuwese, M. C.; Verberne, H. J.; de Ruijter, M.; van Straalen, J. P.; Fischer, J. C.; Sturk, A.; van Eck-Smit, B. L. F.; Stroes, E. S. G.; de Winter, R. J.

    2008-01-01

    Background: Increased systemic levels of myeloperoxidase (MPO) have been reported in patients with acute myocardial ischemia. We studied the association between exercise-induced myocardial ischemia measured by myocardial perfusion scintigraphy (MPS) and the magnitude and time course of changes in

  14. Myocardial ischemia in hypertrophic cardiomyopathy; Isquemia miocardica na cardiomiopatia hipertrofica

    Energy Technology Data Exchange (ETDEWEB)

    Lima Filho, Moyses de Oliveira; Figueiredo, Geraldo L.; Simoes, Marcus V.; Pyntia, Antonio O.; Marin Neto, Jose Antonio [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Div. de Cardiologia

    2000-08-01

    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)

  15. Electrocardiography as a tool for validating myocardial ischemia-reperfusion procedures in mice.

    Science.gov (United States)

    Preda, Mihai B; Burlacu, Alexandrina

    2010-12-01

    This paper evaluates the modifications induced by ischemia and ischemia-reperfusion in mice after permanent or transient, respectively, ligation of the left coronary artery and establishes a correlation among the extent of ischemia, electrocardiograph features, and infarct size. The left coronary artery was ligated 1 mm distal from the tip of the left auricle. Histologic analysis revealed that 30-min ischemia (n = 9) led to infarction involving 9.7% ± 0.5% of the left ventricle, whereas 1-h ischemia (n = 9) resulted in transmural infarction of 16.1% ± 4.6% of the left ventricle. In contrast, 24-h ischemia (n = 8) and permanent ischemia (n = 8) induced similarly sized infarcts (33% ± 2% and 31.8% ± 0.7%, respectively), suggesting ineffective reperfusion after 24-h ischemia. Electrocardiography revealed that ligation of the left coronary artery led to ST height elevation (204 compared with 14 μV) and QTc prolongation (136 compared with 76 ms). Both parameters rapidly normalized on reperfusion, demonstrating that electrocardiography was important for validating correct ligation and reperfusion. In addition, electrocardiography predicted the severity of the myocardial damage induced by ischemia. Our results show that electrocardiographic changes present after 30-min ischemia were reversed on reperfusion; however, prolonged ischemia induced pathologic electrocardiographic patterns that remained even after reperfusion. The mouse model of myocardial ischemia-reperfusion can be improved by using electrocardiography to validate ligation and reperfusion during surgery and to predict the severity of infarction.

  16. Gadolinium decreases inflammation related to myocardial ischemia and reperfusion injury

    Directory of Open Access Journals (Sweden)

    Nicolosi Alfred C

    2009-12-01

    control and GdCl3 treated rats. Likewise, IL-8 levels increased throughout the 3 hour time period in the Sham group. There was no difference in IL-8 detected in the myocardium after 120 min reperfusion between groups. In contrast, after 120 min reperfusion GdCl3 decreased the myocardial tissue levels of macrophage secreted cytokines, GM-CSF and IL-1. Conclusion GdCl3 treatment prior to ischemia and reperfusion injury decreased circulating monocytes and neutrophils, macrophage secreted cytokines, and leukocyte infiltration into injured myocardium. These results suggest GdCl3 decreased monoctye and neutrophil migration and activation and may be a novel treatment for inflammation during ischemia and reperfusion.

  17. Etanercept Attenuates Myocardial Ischemia/Reperfusion Injury by Decreasing Inflammation and Oxidative Stress

    Science.gov (United States)

    Yang, Mei; Chen, Jianchang; Zhao, Jing; Meng, Mei

    2014-01-01

    The protective role of etanercept in myocardial ischemia/reperfusion is not well understood. The aim of this study was to investigate whether etanercept modulates neutrophil accumulation, TNF-α induction and oxidative stress in an ischemia/reperfusion injured rat heart model. Rats were randomly exposed to sham operation, myocardial ischemia/reperfusion (MI/R) alone, MI/R+ etanercept. The results demonstrated that compared to MI/R, etanercept reduced myocardial infarction area, myocardial myeloperoxidase (MPO) levels, serum creatinine kinase (CK) and lactate dehydrogenase (LDH) levels, and both serum and myocardial TNF-α production. Etanercept also markedly enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reduced the level of malondialdehyde (MDA) in MI/R rats. In summary, our data suggested that etanercept has protective effects against MI/R injury in rats, which may be attributed to attenuating inflammation and oxidative stress. PMID:25260027

  18. Role of cytokines in myocardial ischemia and reperfusion

    Directory of Open Access Journals (Sweden)

    H. S. Sharma

    1997-01-01

    Full Text Available Mediators of myocardial inflammation, predominantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the inflammation may result in deleterious complications for myocardial infarction. The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of literature suggests that inflammatory mediators could play a crucial role in ischemia–reperfusion injury. Furthermore, ischemia–reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypoxia causes a series of well documented changes in cardiomyocytes that includes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypoxic cardiomyocytes produce interleukin-6 (IL-6 which could contribute to the myocardial dysfunction observed in ischemia reperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-α (TNF-α, transforming growth factor-β1 (TGF-β1 as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF, in the heart. Intrestingly, these multipotent cytokines (e.g. TNF-α may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have included a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart.

  19. Metabolic and neurohumoral aspects of acute myocardial ischemia in man

    NARCIS (Netherlands)

    W.J. Remme (Willem)

    1990-01-01

    textabstractThis thesis aims at defining the relevance and applicability of some metabolic aspects of acute myocardial ischemia to delineate occurrence and extent of the latter in man. Studies focus on myocardial lactate metabolism and adenine nucleotide catabolism, correlate changes with other

  20. Liraglutide-induced reduction of myocardial ischemia- reperfusion ...

    African Journals Online (AJOL)

    bulldog clamp was loosened, and myocardial perfusion was ... [6]. Statistical analysis. SPSS version 20 statistical package was used for statistical analyses. Data were analysed for statistical significance using ANOVA. P < 0.05 ... Table 1: Mass of myocardial ischemia and infarction areas of rats (mean ± SD, n = 6). Group.

  1. Evaluation of myocardial ischemia by multiple detector computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Fabio Vieira, E-mail: rccury@me.com [Hospital do Coracao (HCor), Sao Paulo, SP (Brazil); Cury, Roberto Caldeira [Hospital Samaritano, Sao Paulo, SP (Brazil)

    2015-01-15

    For years, cardiovascular diseases have been the leading cause of death worldwide, bringing on important social and economic consequences. Given this scenario, the search for a method capable of diagnosing coronary artery diseases in an early and accurate way is increasingly higher. The coronary computed tomography angiogram is already widely established for the stratification of coronary artery diseases, and, more recently, the computed tomography myocardial perfusion imaging has been providing relevant information by correlating ischemia and the coronary anatomy. The objective of this review is to describe the evaluation of myocardial ischemia by multiple detector computed tomography. This study will resort to controlled clinical trials that show the possibility of a single method to identify the atherosclerotic load, presence of coronary artery luminal narrowing and possible myocardial ischemia, by means of a fast, practical and reliable method validated by a multicenter study. (author)

  2. Purkinje fibers after myocardial ischemia-reperfusion.

    Science.gov (United States)

    García Gómez-Heras, Soledad; Álvarez-Ayuso, Lourdes; Torralba Arranz, Amalia; Fernández-García, Héctor

    2015-07-01

    The purpose of this study was to evaluate the effects of ischemia-reperfusion on Purkinje fibers, comparing them with the adjacent cardiomyocytes. In a model of heterotopic heart transplantation in pigs, the donor heart was subjected to 2 hours of ischemia (n=9), preserved in cold saline, and subjected to 24 hours of ischemia with preservation in Wisconsin solution, alone (n=6), or with an additive consisting of calcium (n=4), Nicorandil (n=6) or Trolox (n=7). After 2 hours of reperfusion, we evaluated the recovery of cardiac electrical activity and took samples of ventricular myocardium for morphological study. The prolonged ischemia significantly affected atrial automaticity and A-V conduction in all the groups subjected to 24 hours of ischemia, as compared to 2 hours. There were no significant differences among the groups that underwent prolonged ischemia. Changes in the electrical activity did not correlate with the morphological changes. In the Purkinje fibers, ischemia-reperfusion produced a marked decrease in the glycogen content in all the groups. In the gap junctions the immunolabeling of connexin-43 decreased significantly, adopting a dispersed distribution, and staining the sarcolemma adjacent to the connective tissue. These changes were less marked in the group preserved exclusively with Wisconsin solution, despite the prolonged ischemia. The addition of other substances did not improve the altered morphology. In all the groups, the injury appeared to be more prominent in the Purkinje fibers than in the neighboring cardiomyocytes, indicating the greater susceptibility of the former to ischemia-reperfusion injury.

  3. Effect of thrombolytic therapy on postinfarction myocardial ischemia

    DEFF Research Database (Denmark)

    Mickley, H; Junker, A; Møller, M

    1994-01-01

    In patients with acute myocardial infarction a substantial reduction in mortality can be achieved by early intravenous thrombolytic therapy. The beneficial effect of thrombolysis on left ventricular function is relatively small, and it seems unlikely that this minor improvement alone can...... be responsible for the reduction in cardiac death. So far it has not been clearly established how thrombolytic therapy affects postinfarction myocardial ischemia. From studies evaluating ST segment changes on exercise testing or ambulatory monitoring it is concluded that thrombolysis probably results...

  4. Ultrasound imaging of propagation of myocardial contraction for non-invasive identification of myocardial ischemia

    Science.gov (United States)

    Matsuno, Yuya; Taki, Hirofumi; Yamamoto, Hiroaki; Hirano, Michinori; Morosawa, Susumu; Shimokawa, Hiroaki; Kanai, Hiroshi

    2017-07-01

    Non-invasive identification of ischemic regions is important for diagnosis and treatment of myocardial infarction. In the present study, ultrasound measurement was applied to the interventricular septum of three open-chest swine hearts. The properties of the myocardial contraction response of the septum were compared between normal and acute ischemic conditions, where the acute ischemic condition of the septum originated from direct avascularization of the left anterior descending (LAD) coronary artery. The result showed that the contraction response propagated from the basal side to the apical side along the septum. The estimated propagation velocities in the normal and acute ischemic conditions were 3.6 and 1.9 m/s, respectively. This finding indicates that acute ischemia which occurred 5 s after the avascularization of the LAD promptly suppressed the propagation velocity through the ventricular septum to about half the normal velocity. It was suggested that the myocardial ischemic region could be identified using the difference in the propagation velocity of the myocardial response to contraction.

  5. Energy Drinks and Myocardial Ischemia: A Review of Case Reports.

    Science.gov (United States)

    Lippi, Giuseppe; Cervellin, Gianfranco; Sanchis-Gomar, Fabian

    2016-07-01

    The use and abuse of energy drinks (EDs) is constantly increasing worldwide. We performed a systematic search in Medline, Scopus and Web of Science to identify evidence about the potential link between these beverages and myocardial ischemia. Overall, 8 case reports could be detected, all of which described a realistic association between large intake of EDs and episodes of myocardial ischemia. Interestingly, no additional triggers of myocardial ischemia other than energy drinks could be identified in the vast majority of cases. Some plausible explanations can be brought in support of this association. Most of the biological effects of EDs are seemingly mediated by a positive inotropic effect on cardiac function, which entails increase in heart rate, cardiac output and contractility, stroke volume and arterial blood pressure. Additional biological abnormalities reported after EDs intake include increased platelet aggregation, endothelial dysfunction, hyperglycemia as well as an increase in total cholesterol, triglycerides and low-density lipoprotein cholesterol. Although a causal relationship between large consumption of EDs and myocardial ischemia cannot be definitely established so far, concerns about the cardiovascular risk of excessive consumption of these beverages are seemingly justified.

  6. Myocardial Ischemia Screening in Middle-Aged and Elderly Men

    Czech Academy of Sciences Publication Activity Database

    Boudík, F.; Reissigová, Jindra; Tomečková, Marie; Anger, Z.; Bultas, J.; Šimek, S.

    2010-01-01

    Roč. 17, č. 4 (2010), s. 352-356 ISSN 1667-8982 R&D Projects: GA MŠk(CZ) 1M06014 Institutional research plan: CEZ:AV0Z10300504 Keywords : body surface mapping * stress ECG test * myocardial ischemia * risk factors Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.028, year: 2010

  7. Depressive symptoms are associated with mental stress-induced myocardial ischemia after acute myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Jingkai Wei

    Full Text Available Depression is an adverse prognostic factor after an acute myocardial infarction (MI, and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI.We studied 98 patients (49 women and 49 men age 38-60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task, and after exercise or pharmacological stress. A summed difference score (SDS, obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores.There was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [β = 0.17, 95% CI: (0.04, 0.30, p = 0.01] and cognitive symptoms [β = 0.31, 95% CI: (0.07, 0.56, p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress.Among young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological stress.

  8. In vivo study of myocardial elastography under graded ischemia conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Wei-Ning; Provost, Jean; Konofagou, Elisa E [Department of Biomedical Engineering, Columbia University, New York, NY (United States); Fujikura, Kana [Department of Radiology, Columbia University, New York, NY (United States); Wang Jie, E-mail: ek2191@columbia.edu [Department of Medicine, Columbia University, New York, NY (United States)

    2011-02-21

    The capability of currently available echocardiography-based strain estimation techniques to fully map myocardial abnormality at early stages of myocardial ischemia is yet to be investigated. In this study, myocardial elastography (ME), a radio-frequency (RF)-based strain imaging technique that maps the full 2D transmural angle-independent strain tensor in standard echocardiographic views at both high spatial and temporal resolution is presented. The objectives were to (1) evaluate the performance of ME on mapping the onset, extent and progression of myocardial ischemia at graded coronary constriction levels (from partial to complete coronary flow reduction), and (2) validate the accuracy of the strain estimates against sonomicrometry (SM) measurements. A non-survival canine ischemic model (n = 5) was performed by gradually constricting the left anterior descending (LAD) coronary blood flow from 0% (baseline blood flow) to 100% (zero blood flow) at 20% increments. An open-architecture ultrasound system was used to acquire RF echocardiograms in a standard full short-axis view at the frame rate of 211 fps, at least twice higher than what is typically used in conventional echocardiographic systems, using a previously developed, fully automated composite technique. Myocardial deformation was estimated by ME and validated against sonomicrometry. ME estimates and maps transmural (1) 2D displacements using RF cross-correlation and recorrelation; and (2) 2D polar (radial and circumferential) strains, derived from 2D (i.e. both lateral and axial) displacement components, at high accuracy. Full-view strain images were shown and found to reliably depict decreased myocardial function in the region at risk at increased levels of coronary flow reduction. The ME radial strain was deemed to be a more sensitive, quantitative, regional measure of myocardial ischemia as a result of coronary flow reduction when compared to the conventional wall motion score index and ejection fraction

  9. In vivo study of myocardial elastography under graded ischemia conditions

    Science.gov (United States)

    Lee, Wei-Ning; Provost, Jean; Fujikura, Kana; Wang, Jie; Konofagou, Elisa E.

    2011-02-01

    The capability of currently available echocardiography-based strain estimation techniques to fully map myocardial abnormality at early stages of myocardial ischemia is yet to be investigated. In this study, myocardial elastography (ME), a radio-frequency (RF)-based strain imaging technique that maps the full 2D transmural angle-independent strain tensor in standard echocardiographic views at both high spatial and temporal resolution is presented. The objectives were to (1) evaluate the performance of ME on mapping the onset, extent and progression of myocardial ischemia at graded coronary constriction levels (from partial to complete coronary flow reduction), and (2) validate the accuracy of the strain estimates against sonomicrometry (SM) measurements. A non-survival canine ischemic model (n = 5) was performed by gradually constricting the left anterior descending (LAD) coronary blood flow from 0% (baseline blood flow) to 100% (zero blood flow) at 20% increments. An open-architecture ultrasound system was used to acquire RF echocardiograms in a standard full short-axis view at the frame rate of 211 fps, at least twice higher than what is typically used in conventional echocardiographic systems, using a previously developed, fully automated composite technique. Myocardial deformation was estimated by ME and validated against sonomicrometry. ME estimates and maps transmural (1) 2D displacements using RF cross-correlation and recorrelation; and (2) 2D polar (radial and circumferential) strains, derived from 2D (i.e. both lateral and axial) displacement components, at high accuracy. Full-view strain images were shown and found to reliably depict decreased myocardial function in the region at risk at increased levels of coronary flow reduction. The ME radial strain was deemed to be a more sensitive, quantitative, regional measure of myocardial ischemia as a result of coronary flow reduction when compared to the conventional wall motion score index and ejection fraction

  10. IDENTIFIKASI SINYAL ECG IRAMA MYOCARDIAL ISCHEMIA DENGAN PENDEKATAN FUZZY LOGIC

    Directory of Open Access Journals (Sweden)

    Azhar A N

    2009-07-01

    Full Text Available The heart is one of vital organs in human body. Incidence of heart disease can be fatal for the patient. Myocardial ischemia, the disease that is often suffered by the human, is a disease due to clogged heart arteries blood vessels. One of the ways to detect this disease is by reading the graph output of electrocardiogram (ECG signal. ECG signal represents the condition and activity of the heart. Specialized knowledge, accuration and expertise are required to read ECG graph. To help expert or doctor, expert system based on artificial intelligent, such as Fuzzy Logic approach, can be applied to improve diagnostic accuracy and thoroughness. Fuzzy logic can be applied because of it flexibility to understand the linguistic variables used in identifying myocardial ischemia disease.

  11. Coronary vasodilator reserve persists despite tachycardia and myocardial ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Bristow, J.D.; McFalls, E.O.; Anselone, C.G.; Pantely, G.A. (Oregon Health Sciences Univ., Portland (USA))

    1987-08-01

    During myocardial ischemia, the authors tested whether coronary blood flow measured with radioactive microspheres labeled with {sup 141}Ce, {sup 51}Cr, {sup 103}Ru, and {sup 95}Nb would increase in response to tachycardia thereby employing known coronary flow reserve. The authors instrumented the left anterior descending (LAD) coronary circulation in anesthetized pigs and performed three sets of experiments while coronary pressure was controlled and several heart rate increases were produced. (1) Pacing-induced tachycardia at normal LAD pressure was characterized by increased LAD flow and myocardial oxygen consumption, without production of lactate. (2) Tachycardia at a mean LAD pressure of 38 mmHg was associated with a lower, fixed coronary flow and oxygen consumption. Lactate was produced at all rates and local myocardial function declined progressively. (3) Coronary flow at low LAD pressure doubled during tachycardia when intracoronary adenosine was added. The increase to the subepicardium was >100%, whereas subendocardial flow changed little. There is persistent coronary flow reserve during moderately severe myocardial ischemia, even when metabolic demand is increased by tachycardia. This reserve, however, is predominantly subepicardial.

  12. Effect of Glucocorticoids on Ultrastructure of Myocardial Muscle in the Course of Experimentally Induced Acute Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Piotr Kuropka

    2017-01-01

    Full Text Available The search for effective methods of myocardial cytoprotection against ischemia is the most significant issue in modern cardiology and cardiac surgery. Glucocorticoids are deemed very strong modulators of inflammatory response and thus can potentially protect heart muscle from postreperfusion injury and myocardial ischemia during cardiac surgery. Ultrastructural examination of the left ventricle heart samples revealed that the intravenous application of dexamethasone and hydrocortisone proved to exert cytoprotective effect on cardiomyocytes during experimentally induced acute ischemia in rats.

  13. HIF-1α signaling activation by post-ischemia treatment with astragaloside IV attenuates myocardial ischemia-reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Jingwen Si

    Full Text Available In this study, we evaluated the effect of astragaloside IV (Ast IV post-ischemia treatment on myocardial ischemia-reperfusion (IR injury (IRI. We also examined whether hypoxia inducible factor-1α (HIF-1α and its downstream gene-inducible nitric oxide (NO synthase (iNOS play roles in the cardioprotective effect of Ast IV. Cultured cardiomyocytes and perfused isolated rat hearts were exposed to Ast IV during reperfusion in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2-MeOE2. The post-ischemia treatment with Ast IV protected cardiomyocytes from the apoptosis and death induced by simulated IRI (SIRI. Additionally, in cardiomyocytes, 2-MeOE2 and HIF-1α siRNA treatment each not only abolished the anti-apoptotic effect of post-ischemia treatment with Ast IV but also reversed the upregulation of HIF-1α and iNOS expression. Furthermore, after treatment with Ast IV, post-ischemic cardiac functional recovery and lactate dehydrogenase (LDH release in the coronary flow (CF were improved, and the myocardial infarct size was decreased. Moreover, the number of apoptotic cells was reduced, and the upregulation of the anti-apoptotic protein Bcl2 and downregulation of the pro-apoptotic protein Caspase3 were reversed. 2-MeOE2 reversed these effects of Ast IV on IR-injured hearts. These results suggest that post-ischemia treatment with Ast IV can attenuate IRI by upregulating HIF-1α expression, which transmits a survival signal to the myocardium.

  14. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

    Science.gov (United States)

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-01-01

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

  15. Chest Pain and Mental Stress Induced Myocardial Ischemia: Sex Differences.

    Science.gov (United States)

    Pimple, Pratik; Hammadah, Muhammad; Wilmot, Kobina; Ramadan, Ronnie; Mheid, Ibhar Al; Levantsevych, Oleksiy; Sullivan, Samaah; Garcia, Ernest V; Nye, Jonathon; Shah, Amit J; Ward, Laura; Mehta, Puja; Raggi, Paolo; Bremner, J Douglas; Quyyumi, Arshed A; Vaccarino, Viola

    2017-12-07

    Mental stress-induced myocardial ischemia (MSIMI) is a frequent phenomenon in patients with coronary artery disease. Women with coronary artery disease tend to have more MSIMI and more chest pain/anginal symptoms than men, but whether the association between MSIMI and angina burden differs in women and men, is unknown. This was a cross-sectional study with experimental manipulation of 950 individuals with stable coronary artery disease. Chest pain/angina frequency in the previous 4 weeks was assessed with the Seattle Angina Questionnaire's angina-frequency subscale. MSIMI was assessed with myocardial perfusion imaging during mental stress (standardized public speaking task). Presence of MSIMI was based on expert readers and established criteria. A conventional (exercise or pharmacological) stress test was used as a control condition. Overall, 338 individuals (37%) reported angina; 112 (12%) developed MSIMI, and 256 (29%) developed conventional stress ischemia. Women who reported angina had almost double the probability to develop MSIMI (19% vs. 10%), adjusted prevalence rate ratio (PRR)= 1.90, 95% CI: 1.04-3.46), while there was no such difference in men (11% vs. 11%, adjusted PRR= 1.09, 95% CI: 0.66-1.82). No association was found between angina symptoms and conventional stress ischemia for either women or men. Results for ischemia as a continuous variable were similar. In women, but not in men, anginal symptoms may be a marker of vulnerability towards ischemia induced by psychological stress. These results highlight the psychosocial origins of angina in women, and may have important implications for the management and prognosis of women with angina. Copyright © 2017. Published by Elsevier Inc.

  16. Ischemic QRS prolongation as a biomarker of severe myocardial ischemia.

    Science.gov (United States)

    Almer, Jakob; Jennings, Robert B; Maan, Arie C; Ringborn, Michael; Maynard, Charles; Pahlm, Olle; Arheden, Håkan; Wagner, Galen S; Engblom, Henrik

    2016-01-01

    Previous studies have shown that QRS prolongation is a sign of depressed collateral flow and increased rate of myocardial cell death during coronary occlusion. The aims of this study were to evaluate ischemic QRS prolongation as a biomarker of severe ischemia by establishing the relationship between prolongation and collateral flow experimentally in a dog model, and test if the same pattern of ischemic QRS prolongation occurs in man. Degree of ischemic QRS prolongation was measured using a novel method in dogs (n=23) and patients (n=52) during coronary occlusion for 5min. Collateral arterial flow was assessed in the dogs. There was a significant correlation between QRS prolongation and collateral flow in dogs (r=0.61, p=0.008). Magnitude and temporal evolution of prolongation during ischemia were similar for dogs and humans (p=0.202 and p=0.911). Quantification of ischemic QRS prolongation could potentially be used as a biomarker for severe myocardial ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. [Silent myocardial ischemia in patients with transient ischemic attacks].

    Science.gov (United States)

    Sánchez Valiente, S; Mostacero, E; del Río, A; Morales, F

    1994-10-01

    Given evidence that ischemic heart disease is the most frequent cause of death in patients with cerebrovascular disease, we used ergometrics to screen 80 patients with TIA for silent myocardial ischemia (SMI) at the neurological unit of Hospital Clínico Universitario in Zaragoza, Spain. The patients were compared with a control group of 80 with no signs of heart disease. Neither the patients nor the controls had ever shown clinical signs of coronary ischemia and their baseline electrocardiograms were normal. Stress test results were positive in 25 (31%) of the TIA patients, and in 4 (5%) (p Hiperlipidemia (75% testing positive versus 43% negative, p < 0.01) and diabetes (31% testing positive versus 13% negative, p < 0.01) were the risk factors statistically related with a positive stress test.

  18. Detection of myocardial ischemia with myocardial perfusion SPECT in patients with diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Seo, J. H.; Jeong, S. Y.; Bae, J. H.; Anh, B. C.; Lee, J.; Lee, K. B [Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2004-07-01

    Diabetes mellitus(DM) is a critical disease associated with higher rates of cardiovascular morbidity and mortality. Atherosclerosis accounts for 65-80% of all deaths in diabetic patients and patients with DM are known to show high prevalence of coronary artery diseases(CAD). We evaluated the incidence of scintigraphic evidence of CAD in diabetic patients and results were compared with cardiovascular symptoms and clinical factors. 169 patients with DM(mean age 629years, 68 males) were referred for evaluation of CAD between Jan 2002 and Dec 2003. 101(60%) patients were with chest pain and 68(40%) were asymptomatic. Patients underwent exercise(n=6) or adenosine stress(n=163) SPECT myocardial perfusion imaging(MPI). Exclusion criteria included history of documented myocardial infarction, prior revascularization, clinically significant valvular heart disease, left-bundle branch block on rest ECG. We evaluated symptoms associated with cardiac problem and other clinical and laboratory data to reveal correlation with presence of CAD. MPI were assessed visually and semi-quantitatively with C-Equal program. Myocardial ischemia was detected in 52(31%) patients. Among them, 41 had 1-vessel and 9 had 2-vessel disease. In 52 patients with ischemia, 28(54%) were male and 24(46%) were female. 20/68(29%) asymptomatic and 32/101(32%) symptomatic patients had ischemia. Higher prevalence of neuropathy, hypertension, higher blood glucose level, HbA1c and CRP was noted in patients with myocardial ischemia. Serum levels of cholesterol and LDL was not significantly different between patients with ischemia and with normal MPI findings. Abnormal MPI findings were not related with gender and age. These results show a high prevalence of abnormal MPI results in diabetic patients regardless of symptoms. Screening stress MPI in diabetic patients should be indicated irrespective of symptoms, especially in patients with neuropathy, hypertension, higher level of blood glucose, or increased CRP.

  19. Increased cardiac BNP expression associated with myocardial ischemia

    DEFF Research Database (Denmark)

    Goetze, J P; Christoffersen, Christina; Perko, M

    2003-01-01

    without coronary artery disease. BNP mRNA was quantified by real-time PCR, and plasma BNP and proBNP concentrations were measured with radioimmunoassays. Quantitative analysis of BNP mRNA in atrial and ventricular biopsies from coronary bypass grafting patients revealed close associations of plasma BNP...... and proBNP concentrations to ventricular, but not atrial, BNP mRNA levels. Plasma BNP and proBNP concentrations were markedly increased in patients with coronary artery disease but without concomitant left ventricular dysfunction. These results are compatible with the notion that myocardial ischemia, even...

  20. [The protective effects of IPC on isolated myocardial ischemia/reperfusion injury in rats].

    Science.gov (United States)

    Cao, Xia; Gu, Xin-quan; Yang, Shi-jie; Zhang, Hui-qing

    2003-05-01

    To investigate the protective effects and mechanism of IPC on myocardial ischemia/reperfusion injury. Effects of IPC on arrhythmia and coronary blood flow and the release of AST, CPK, LDH, SOD and LFO at different time after ischemia/reperfusion injury in rat Langendorff hearts were studied. IPC decreased the release of AST, CPK and LDH and increased myocardial SOD activity and decreased LPO level. IPC also inhibited ischemia/reperfusion arrhythmias and increased coronary blood flow. The results showed that IPC had well protective effects on myocardial ischemia/reperfusion injury.

  1. Phellinus linteus Mycelium Alleviates Myocardial Ischemia-Reperfusion Injury through Autophagic Regulation

    Science.gov (United States)

    Su, Hsing-Hui; Chu, Ya-Chun; Liao, Jiuan-Miaw; Wang, Yi-Hsin; Jan, Ming-Shiou; Lin, Chia-Wei; Wu, Chiu-Yeh; Tseng, Chin-Yin; Yen, Jiin-Cherng; Huang, Shiang-Suo

    2017-01-01

    The incidence of myocardial ischemia-reperfusion (IR) injury is rapidly increasing around the world and this disease is a major contributor to global morbidity and mortality. It is known that regulation of programmed cell death including apoptosis and autophagy reduces the impact of myocardial IR injury. In this study, the cardioprotective effects and underlying mechanisms of Phellinus linteus (Berk. and Curt.) Teng, Hymenochaetaceae (PL), a type of medicinal mushroom, were examined in rats subjected to myocardial IR injury. The left main coronary artery of rats was ligated for 1 h and reperfused for 3 h. The arrhythmia levels were monitored during the entire process and the infarct size was evaluated after myocardial IR injury. Furthermore, the expression levels of proteins in apoptotic and autophagic pathways were observed. Pretreatment with PL mycelium (PLM) significantly reduced ventricular arrhythmia and mortality due to myocardial IR injury. PLM also significantly decreased myocardial infarct size and plasma lactate dehydrogenase level after myocardial IR injury. Moreover, PLM administration resulted in decreased caspase 3 and caspase 9 activation and increased Bcl-2/Bax ratio. Phosphorylation level of AMPK was elevated while mTOR level was reduced. Becline-1 and p62 levels decreased. These findings suggest that PLM is effective in protecting the myocardium against IR injury. The mechanism involves mediation through suppressed pro-apoptotic signaling and regulation of autophagic signaling, including stimulation of AMPK-dependent pathway and inhibition of beclin-1-dependent pathway, resulting in enhancement of protective autophagy and inhibition of excessive autophagy. PMID:28420993

  2. Lactation protects against myocardial ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Shekarforoush, S; Safari, F

    2015-12-01

    Some researchers have reported that lactation is effective in reducing cardiovascular disease risk factors. The purpose of this study was to investigate whether lactation may improve intrinsic tolerance against ischemia reperfusion (IR) injury. The rats were randomly divided into two groups (n = 8 in each group). In the lactation (Lact) group, the surgery was performed on postpartum day 21 (at the end of lactation period) and the results were compared with those of virgin female rats (control group). Cardiac IR injury was induced by means of left anterior descending coronary artery occlusion for 30 min followed by reperfusion for 120 min. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. At the end of the experiment, Mean arterial pressure in the control group was significantly lower than that in the Lact group. Myocardial infarct size was significantly reduced in the Lact group (23 ± 3% vs. 45 ± 8%, p Lactation reduced the extent of myocardial injury induced by ischemia and reperfusion. So, lactation may increase cardiac tolerance to ischemic injury.

  3. Myocardial metabolic abnormalities in hypertrophic cardiomyopathy assessed by iodine-123-labeled beta-methyl-branched fatty acid myocardial scintigraphy and its relation to exercise-induced ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Matsuo, Shinro; Nakamura, Yasuyuki; Takahashi, Masayuki; Mitsunami, Kenichi; Kinoshita, Masahiko [Shiga Univ. of Medical Science, Otsu (Japan)

    1998-03-01

    Reversible thallium-201 ({sup 201}Tl) abnormalities during exercise stress have been used as markers of myocardial ischemia in hypertrophic cardiomyopathy (HCM) and are most likely to identify relatively underperfused myocardium. Although metabolic abnormalities in HCM were reported, the relationship between impaired energy metabolism and exercise-induced ischemia has not been fully elucidated as yet. To assess the relationship between myocardial perfusion abnormalities and fatty acid metabolic abnormalities, 28 patients with HCM underwent exercise {sup 201}Tl and rest {sup 123}I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy. Perfusion abnormalities were observed by exercise {sup 201}Tl in 19/28 patients with HCM. {sup 123}I-BMIPP uptake was decreased compared with delayed {sup 201}Tl in 106/364 (29%) of the total myocardial segments (p<0.01, McNemar symmetry test). Such disparity between {sup 123}I-BMIPP and {sup 201}Tl was observed more often in the 49/75 (65%) segments with reversible exercise {sup 201}Tl defects (p<0.001). Our results indicate that exercise-induced myocardial ischemia exists in HCM, resulting in metabolic abnormalities. The combination of {sup 123}I-BMIPP and {sup 201}Tl suggests that myocardial ischemia may play an important role in metabolic abnormalities in HCM. (author)

  4. 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

    2017-01-01

    BACKGROUND: Terminal "QRS distortion" on the electrocardiogram (ECG) (based on Sclarovsky-Birnbaum's Grades of Ischemia Score) is a sign of severe ischemia, associated with adverse cardiovascular outcome in ST-segment elevation myocardial infarction (STEMI). In addition, ECG indices of the acuten......BACKGROUND: Terminal "QRS distortion" on the electrocardiogram (ECG) (based on Sclarovsky-Birnbaum's Grades of Ischemia Score) is a sign of severe ischemia, associated with adverse cardiovascular outcome in ST-segment elevation myocardial infarction (STEMI). In addition, ECG indices...... of the acuteness of ischemia (based on Anderson-Wilkins Acuteness Score) indicate myocardial salvage potential. We assessed whether severe ischemia with or without acute ischemia is predictive of infarct size (IS), myocardial salvage index (MSI) and left ventricular ejection fraction (LVEF) in anterior versus......, and 5 (6%) patients with severe and acute ischemia. In patients with anterior STEMI (n=35), ECG measures of severity and acuteness of ischemia identified significant and stepwise differences in myocardial damage and function. Patients with severe and non-acute ischemia had the largest IS, smallest MSI...

  5. Mechanisms of load dependency of myocardial ischemia reperfusion injury

    Science.gov (United States)

    Mozaffari, Mahmood S; Liu, Jun Yao; Abebe, Worku; Baban, Babak

    2013-01-01

    Coronary artery disease and associated ischemic heart disease are prevalent disorders worldwide. Further, systemic hypertension is common and markedly increases the risk for heart disease. A common denominator of systemic hypertension of various etiologies is increased myocardial load/mechanical stress. Thus, it is likely that high pressure/mechanical stress attenuates the contribution of cardioprotective but accentuates the contribution of cardiotoxic pathways thereby exacerbating the outcome of an ischemia reperfusion insult to the heart. Critical events which contribute to cardiomyocyte injury in the ischemic-reperfused heart include cellular calcium overload and generation of reactive oxygen/nitrogen species which, in turn, promote the opening of the mitochondrial permeability transition pore, an important event in cell death. Increasing evidence also indicates that the myocardium is capable of mounting a robust inflammatory response which contributes importantly to tissue injury. On the other hand, cardioprotective maneuvers of ischemic preconditioning and postconditioning have led to identification of complex web of signaling pathways (e.g., reperfusion injury salvage kinase) which ultimately converge on the mitochondria to exert cytoprotection. The present review is intended to briefly describe mechanisms of cardiac ischemia reperfusion injury followed by a discussion of our work focused on how pressure/mechanical stress modulates endogenous cardiotoxic and cardioprotective mechanisms to ultimately exacerbate ischemia reperfusion injury. PMID:24224132

  6. The Influence of Endothelial Function and Myocardial Ischemia on Peak Oxygen Consumption in Patients with Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Simon L. Bacon

    2012-01-01

    Full Text Available Impaired endothelial function has been shown to limit exercise in coronary artery disease (CAD patients and has been implicated in myocardial ischemia. However, the association of endothelial function and ischemia on peak exercise oxygen consumption (VO2 has not been previously reported. A total of 116 CAD patients underwent standard exercise stress testing, during which VO2 was measured. On a separate day, endothelial-dependent and -independent function were assessed by ultrasound using flow-mediated arterial vasodilation (FMD and sublingual glyceryl trinitrate administration (GTNMD of the brachial artery. Patients with exercise-induced myocardial ischemia had lower FMD than nonischemic patients (3.64±0.57 versus 4.98±0.36, P=.050, but there was no difference in GTNMD (14.11±0.99 versus 15.47±0.63, P=.249. Analyses revealed that both FMD (P=.006 and GTNMD (P=.019 were related to peak VO2. However, neither the presence of ischemia (P=.860 nor the interaction of ischemia with FMD (P=.382 and GTNMD (P=.151 was related to peak VO2. These data suggest that poor endothelial function, potentially via impaired NO production and smooth muscle dysfunction, may be an important determinant of exercise capacity in patients with CAD, independent of myocardial ischemia.

  7. Myocardial ischemia-reperfusion injury, antioxidant enzyme systems, and selenium: a review.

    Science.gov (United States)

    Venardos, Kylie M; Perkins, Anthony; Headrick, John; Kaye, David M

    2007-01-01

    Coronary heart disease (CHD) remains the greatest killer in the Western world, and although the death rate from CHD has been falling, the current increased prevalence of major risk factors including obesity and diabetes, suggests it is likely that CHD incidence will increase over the next 20 years. In conjunction with preventive strategies, major advances in the treatment of acute coronary syndromes and myocardial infarction have occurred over the past 20 years. In particular the ability to rapidly restore blood flow to the myocardium during heart attack, using interventional cardiologic or thrombolytic approaches has been a major step forward. Nevertheless, while 'reperfusion' is a major therapeutic aim, the process of ischemia followed by reperfusion is often followed by the activation of an injurious cascade. While the pathogenesis of ischemia-reperfusion is not completely understood, there is considerable evidence implicating reactive oxygen species (ROS) as an initial cause of the injury. ROS formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks, all potentially damaging to normal cellular function. ROS have been shown to be generated following routine clinical procedures such as coronary bypass surgery and thrombolysis, due to the unavoidable episode of ischemia-reperfusion. Furthermore, they have been associated with poor cardiac recovery post-ischemia, with recent studies supporting a role for them in infarction, necrosis, apoptosis, arrhythmogenesis and endothelial dysfunction following ischemia-reperfusion. In normal physiological condition, ROS production is usually homeostatically controlled by endogenous free radical scavengers such as superoxide dismutase, catalase, and the glutathione peroxidase and thioredoxin reductase systems. Accordingly, targeting the generation of ROS with various antioxidants has been shown to reduce injury following oxidative stress, and improve

  8. A possible relationship between gluconeogenesis and glycogen metabolism in rabbits during myocardial ischemia

    Directory of Open Access Journals (Sweden)

    RAQUEL R. DE AGUIAR

    2017-08-01

    Full Text Available ABSTRACT Ischemia is responsible for many metabolic abnormalities in the heart, causing changes in organ function. One of modifications occurring in the ischemic cell is changing from aerobic to anaerobic metabolism. This change causes the predominance of the use of carbohydrates as an energy substrate instead of lipids. In this case, the glycogen is essential to the maintenance of heart energy intake, being an important reserve to resist the stress caused by hypoxia, using glycolysis and lactic acid fermentation. In order to study the glucose anaerobic pathways utilization and understand the metabolic adaptations, New Zealand white rabbits were subjected to ischemia caused by Inflow occlusion technique. The animals were monitored during surgery by pH and lactate levels. Transcription analysis of the pyruvate kinase, lactate dehydrogenase and phosphoenolpyruvate carboxykinase enzymes were performed by qRT-PCR, and glycogen quantification was determined enzymatically. Pyruvate kinase transcription increased during ischemia, followed by glycogen consumption content. The gluconeogenesis increased in control and ischemia moments, suggesting a relationship between gluconeogenesis and glycogen metabolism. This result shows the significant contribution of these substrates in the organ energy supply and demonstrates the capacity of the heart to adapt the metabolism after this injury, sustaining the homeostasis during short-term myocardial ischemia.

  9. Compound danshen dripping pills modulate the perturbed energy metabolism in a rat model of acute myocardial ischemia

    Science.gov (United States)

    Guo, Jiahua; Yong, Yonghong; Aa, Jiye; Cao, Bei; Sun, Runbin; Yu, Xiaoyi; Huang, Jingqiu; Yang, Na; Yan, Lulu; Li, Xinxin; Cao, Jing; Aa, Nan; Yang, Zhijian; Kong, Xiangqing; Wang, Liansheng; Zhu, Xuanxuan; Ma, Xiaohui; Guo, Zhixin; Zhou, Shuiping; Sun, He; Wang, Guangji

    2016-01-01

    The continuous administration of compound danshen dripping pills (CDDP) showed good efficacy in relieving myocardial ischemia clinically. To probe the underlying mechanism, metabolic features were evaluated in a rat model of acute myocardial ischemia induced by isoproterenol (ISO) and administrated with CDDP using a metabolomics platform. Our data revealed that the ISO-induced animal model showed obvious myocardial injury, decreased energy production, and a marked change in metabolomic patterns in plasma and heart tissue. CDDP pretreatment increased energy production, ameliorated biochemical indices, modulated the changes and metabolomic pattern induced by ISO, especially in heart tissue. For the first time, we found that ISO induced myocardial ischemia was accomplished with a reduced fatty acids metabolism and an elevated glycolysis for energy supply upon the ischemic stress; while CDDP pretreatment prevented the tendency induced by ISO and enhanced a metabolic shift towards fatty acids metabolism that conventionally dominates energy supply to cardiac muscle cells. These data suggested that the underlying mechanism of CDDP involved regulating the dominant energy production mode and enhancing a metabolic shift toward fatty acids metabolism in ischemic heart. It was further indicated that CDDP had the potential to prevent myocardial ischemia in clinic. PMID:27905409

  10. Prevalence of Ischemia on Myocardial Perfusion Scintigraphy of Pre- and Postmenopausal Women

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Daniel Augusto Message dos, E-mail: danielmessage@cardiol.br; Navarro, Wendy Yasdin Sierraalta; Alexandre, Leonardo Machado; Cestari, Priscila Feitosa; Smanio, Paola Emanuela Poggio [Instituto Dante Pazzanese de Cardiologia, São Paulo, SP (Brazil)

    2013-12-15

    In postmenopausal women, the presence of risk factors for coronary artery disease (CAD) increases. However, the difference in prevalence of ischemia between pre- and postmenopausal women with multiple risk factors for CAD has not been well established. To compare the prevalence of ischemia on Tc{sup 99m}-sestamibi myocardial perfusion scintigraphy (MPS) in pre-and postmenopausal women, and to evaluate whether menopause can be considered an independent risk predictor of ischemia in women with multiple risk factors for CAD. This study retrospectively assessed 500 MPS of pre- and postmenopausal women with multiple risk factors for CAD. Statistical analysis was performed by using Fisher exact test and univariate and multivariate analysis, a p value ≤ 0.05 being considered significant. Postmenopausal women represented 55.9% of the sample; 83.3% were hypertensive; 28.9%, diabetic; 32.1%, smokers; 25%, obese; 61.2% had high cholesterol levels; and 34.3% had known CAD. Postmenopausal women were more often hypertensive, diabetic and dyslipidemic, and had lower functional capacity on exercise testing (p = < 0.005). The presence of ischemia on MPS did not significantly differ between the pre- and postmenopausal groups (p = 0.395). The only variable associated with ischemia on MPS was known CAD (p = 0.004). The results suggest that, in women with multiple risk factors for CAD, menopause was not an independent predictor of ischemia on MPS. Those data support the idea that the investigation of ischemia via MPS in women with multiple risk factors for CAD should begin prior to menopause.

  11. 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

    Circadian rhythms have been demonstrated in acute myocardial infarction (AMI) and in other clinical cardiac dysfunctions. The purpose of this study was to elucidate whether a circadian pattern of transient myocardial ischemia exists after first AMI. Prospectively, 24-hour ambulatory ST-segment mo...

  12. Screening of Bioactive Ingredients in Ligusticum Chuanxiong Hort for Protection against Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Xu Liu

    2016-12-01

    Full Text Available Background/Aims: To study the spectrum-effect relationship and effective components of Ligusticum Chuanxiong Hort. (LCH on the protection of canine myocardial ischemia. Methods: Fingerprint spectrum of LCH extracts was developed using high performance liquid chromatography (HPLC, and a canine model of acute myocardial ischemia was established by ligating the coronary artery. Bivariate correlation analysis and multivariate regression analysis were used to correlate the pharmacodynamics of LCH extract and its common peaks in HPLC. Results: The bioactive components of LCH were ligustrazine, ferulic acid, cnidilide and ligustilide. Ligustrazine and ferulic acid could significantly reduce serum lactic acid in canine model of acute myocardial ischemia, while ligustilide could significantly reduce the elevation of serum free fatty acid. Conclusions: The spectrum-effect relationship study shows that the effective components of LCH are ligustrazine, ferulic acid, cnidilide and ligustilide, which have protective effect on myocardial ischemia.

  13. Cardioprotective Effect of Electroacupuncture Pretreatment on Myocardial Ischemia/Reperfusion Injury via Antiapoptotic Signaling

    Directory of Open Access Journals (Sweden)

    Sheng-feng Lu

    2016-01-01

    Full Text Available Objectives. Our previous study has used RNA-seq technology to show that apoptotic molecules were involved in the myocardial protection of electroacupuncture pretreatment (EAP on the ischemia/reperfusion (I/R animal model. Therefore, this study was designed to investigate how EAP protects myocardium against myocardial I/R injury through antiapoptotic mechanism. Methods. By using rats with myocardial I/R, we ligated the left anterior descending artery (LAD for 30 minutes followed by 4 hr of reperfusion after EAP at the Neiguan (PC6 acupoint for 12 days; we employed arrhythmia scores, serum myocardial enzymes, and cardiac troponin T (cTnT to evaluate the cardioprotective effect. Heart tissues were harvested for western blot analyses for the expressions of pro- and antiapoptotic signaling molecules. Results. Our preliminary findings showed that EAP increased the survival of the animals along with declined arrhythmia scores and decreased CK, LDH, CK-Mb, and cTnT levels. Further analyses with the heart tissues detected reduced myocardial fiber damage, decreased number of apoptotic cells and the protein expressions of Cyt c and cleaved caspase 3, and the elevated level of Endo G and AIF after EAP intervention. At the same time, the protein expressions of antiapoptotic molecules, including Xiap, BclxL, and Bcl2, were obviously increased. Conclusions. The present study suggested that EAP protected the myocardium from I/R injury at least partially through the activation of endogenous antiapoptotic signaling.

  14. Toll-like receptors: new players in myocardial ischemia/reperfusion injury.

    Science.gov (United States)

    Ha, Tuanzhu; Liu, Li; Kelley, Jim; Kao, Race; Williams, David; Li, Chuanfu

    2011-10-01

    Innate immune and inflammatory responses have been implicated in myocardial ischemia/reperfusion (I/R) injury. However, the mechanisms by which innate immunity and inflammatory response are involved in myocardial I/R have not been elucidated completely. Recent studies highlight the role of Toll-like receptors (TLRs) in the induction of innate immune and inflammatory responses. Growing evidence has demonstrated that TLRs play a critical role in myocardial I/R injury. Specifically, deficiency of TLR4 protects the myocardium from ischemic injury, whereas modulation of TLR2 induces cardioprotection against ischemic insult. Importantly, cardioprotection induced by modulation of TLRs involves activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, suggesting that there is a crosstalk between TLRs and PI3K/Akt signaling pathways. In addition, TLRs also associate with other coreceptors, such as macrophage scavenger receptors in the recognition of their ligands. TLRs are also involved in the induction of angiogenesis, modulation of stem cell function, and expression of microRNA, which are currently important topic areas in myocardial I/R. Understanding how TLRs contribute to myocardial I/R injury could provide basic scientific knowledge for the development of new therapeutic approaches for the treatment and management of patients with heart attack.

  15. Cardioprotection with forsythoside B in rat myocardial ischemia-reperfusion injury: relation to inflammation response.

    Science.gov (United States)

    Jiang, W-L; Fu, F-H; Xu, B-M; Tian, J-W; Zhu, H-B; Jian-Hou

    2010-07-01

    The present study was undertaken to examine the effect of forsythoside B (FB) on rat myocardial ischemia-reperfusion (I/R) model and elucidate the potential mechanism. Left ventricular systolic pressure (LVSP) and +/-dp/dt(max) were detected. Blood samples were collected to determine serum levels of troponin T (Tn-T), TNF-alpha and IL-6. Hearts were harvested to assess histopathological change and infarct size, determine content of MDA, myeloperoxidase (MPO), SOD and GPx activities, analyze expression of high-mobility group box 1 (HMGB1), phosphor-I kappaB-alpha and phosphor-nuclear factor kappaB (NF-kappaB) in ischemic myocardial tissue by Western blot. Compared with control group, rats treatment with FB showed a significant recovery in myocardial function with improvement of LVSP and +/-dp/dt(max). The myocardial infarct volume, serum levels of Tn-T, TNF-alpha and IL-6, content of MDA and MPO activity in myocardial tissue were all reduced, protein expression of HMGB1, phosphor-I kappaB-alpha and phosphor-NF-kappaB were down-regulated, while attenuated the decrease of SOD and GPx activities. Besides, the infiltration of polymorph nuclear leukocytes (PMNs) and histopathological damages in myocardium were decreased in FB treated groups. These findings suggested that FB rescued cardiac function from I/R injury by limiting inflammation response and its antioxidant properties. (c) 2009 Elsevier GmbH. All rights reserved.

  16. Assessment of dyssynchronous wall motion during acute myocardial ischemia using velocity vector imaging.

    Science.gov (United States)

    Masuda, Kasumi; Asanuma, Toshihiko; Taniguchi, Asuka; Uranishi, Ayumi; Ishikura, Fuminobu; Beppu, Shintaro

    2008-03-01

    (r = 0.74, p < 0.001 with a linear regression). The assessment of VVI at MVO permits easy detection of dyssynchronous wall motion during acute myocardial ischemia that cannot be diagnosed by conventional measurement of systolic wall thickness. The spatial extent of inward motion at MVO suggests the size of the risk area.

  17. Peak enhancement ratio of myocardium to aorta for identification of myocardial ischemia using dynamic myocardial computed tomography perfusion imaging.

    Science.gov (United States)

    Tanabe, Yuki; Kido, Teruhito; Kurata, Akira; Yokoi, Takahiro; Fukuyama, Naoki; Uetani, Teruyoshi; Nishiyama, Hikaru; Kawaguchi, Naoto; Tahir, Enver; Miyagawa, Masao; Mochizuki, Teruhito

    2017-12-01

    This study aimed to evaluate the feasibility of peak enhancement (PE) ratio of myocardium to aorta (PER) derived from stress dynamic computed tomography myocardial perfusion imaging (CTP) for the detection of myocardial ischemia assessed by magnetic resonance (MR) imaging. Forty-four patients who underwent stress dynamic CTP and MR imaging were retrospectively evaluated. From the time-attenuation curve, myocardial PE, PER, and myocardial blood flow (MBF) were calculated on a segment-based analysis. The correlation between myocardial and aortic PE was assessed by Spearman's correlation, and the differences in myocardial PE and PER between normal and ischemic myocardium were assessed by the Mann-Whitney U-test. The diagnostic accuracies of myocardial PE, PER, and MBF for detecting myocardial ischemia were compared by receiver operating characteristic analysis. Of 704 segments, 258 segments (37%) were diagnosed as myocardial ischemia with MR imaging. Myocardial and aortic PE were significantly correlated in both normal and ischemic segments (r=0.76 and 0.58; pmyocardial PE and PER of ischemic segments were significantly lower than those of normal segments (pmyocardial PE, 78% (67-88%) and 82% (95% CI, 70-91%) for PER, and 81% (95% CI, 73-87%) and 85% (95% CI, 79-92%) for MBF. There was a significantly larger area under the curve for PER (0.87; 95% CI, 0.84-0.90) and MBF (0.88; 95%CI, 0.85-0.91), compared to myocardial PE (0.75; 95% CI, 0.70-0.79) (pmyocardial ischemia, comparable to that of MBF. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  18. Does exercise conditioning delay progression of myocardial ischemia in coronary atherosclerotic heart disease?

    Science.gov (United States)

    Froelicher, V F

    1977-01-01

    The data regarding the effect of physical of physical conditioning on the progression of myocardial is chemia, although suggestive of a favorable influence, are in no way definitive. Efforts to alter the physical activity habits of our population should not supersede efforts directed to alter the major risk factors. The emphasis in the prevention of coronary atherosclerotic heart disease for the general public should be on the well established cardinal risk factors, that is, hypercholesterolemia, hypertension, and cigarette smoking. The National Postinfarction Rehabilitation Study, when completed, may demonstrate how physical conditioning influences the progression of myocardial ischemia. However, "moderate activity is a part of a balanced satisfying living and is the safe and sane hygienic prescription of the thoughtful physician for his patients, the high risk and the healthy alike.

  19. Transportation or noise is associated with tolerance to myocardial ischemia and reperfusion injury.

    Science.gov (United States)

    Rowland, R T; Cleveland, J C; Upadhya, P; Harken, A H; Brown, J M

    2000-03-01

    Myocardial stress can result in myocellular phenotypic changes including enhanced activity of antioxidant enzyme systems. Accordingly, endogenous tissue antioxidant enzyme activity has been associated with resistance to cardiac ischemia and reperfusion injury. The present study was designed to determine if environmental perturbations could alter myocardial antioxidant enzyme (catalase) activity and function after ischemia. Isolated perfused rat hearts (Langendorff apparatus, 37 degrees C) were subjected to 20 min global ischemia (37 degrees C) and 40 min reperfusion. Rats studied immediately following shipment had increased myocardial catalase activity (1330 +/- 3.5 U/g, P construction-related noise levels in excess of 90 dB (A scale) had increased myocardial catalase activity (1140 +/- 3.3 U/g, P noise levels for 2 days exhibited increased myocardial catalase activity (1125 +/- 30 U/g, P < 0.05) and myocardial ischemia and reperfusion injury tolerance (DP 62 +/- 1.7 mm Hg, P < 0.05). We conclude that variations in environmental conditions can relate to changes in antioxidant defense mechanisms and tolerance to myocardial ischemia and reperfusion injury in the rat. Copyright 2000 Academic Press.

  20. Exercise myocardial perfusion scintigraphy is useful for evaluating myocardial ischemia even in the elderly

    Energy Technology Data Exchange (ETDEWEB)

    Kurata, Chinori; Uehara, Akihiko; Sugi, Toshihiko; Yamazaki, Keisuke [Hamamatsu Univ. School of Medicine, Shizuoka (Japan); Tawarahara, Kei; Mikami, Tadashi; Matoh, Fumitaka; Odagiri, Keiichi

    2000-06-01

    Pharmacologic stress testing is recommended to elderly patients as a valuable alternative to exercise testing. We examined whether exercise testing is as useful for evaluating myocardial ischemia in the elderly as in the young. The consecutive 1,508 patients who underwent exercise {sup 201}Tl single-photon emission computed tomography (SPECT) were divided into six age groups: 6-29 years (n=56), 30-44 (n=143), 45-54 (n=311), 55-64 (n=498), 65-74 (n=402), and 75-88 (n=98). Both heart rate and rate-pressure product at peak exercise were significantly lower in patients aged 75-88 than in the other five groups. The frequency of ischemic ST depression was higher in patients aged 75-88 than in those aged 6-74, although the difference was not significant. Moreover, the frequency of {sup 201}Tl transient defect was significantly higher in patients aged 75-88 than in those aged 6-74. On the other hand, the sensitivity of ischemic ST depression for {sup 201}Tl transient defect was similar among the six groups, but the specificity was significantly lower in patients aged 75-88 than in those aged 6-74. In conclusion, exercise {sup 201}Tl SPECT is useful for evaluating myocardial ischemia even in the elderly, but exercise electrocardiography has limitations such as lower specificity in the elderly than {sup 201}Tl SPECT. (author)

  1. The elusive role of myocardial perfusion imaging in stable ischemic heart disease: Is ISCHEMIA the answer?

    Science.gov (United States)

    Xie, Joe X; Winchester, David E; Phillips, Lawrence M; Hachamovitch, Rory; Berman, Daniel S; Blankstein, Ron; Di Carli, Marcelo F; Miller, Todd D; Al-Mallah, Mouaz H; Shaw, Leslee J

    2017-10-01

    The assessment of ischemia through myocardial perfusion imaging (MPI) is widely accepted as an index step in the diagnostic evaluation of stable ischemic heart disease (SIHD). Numerous observational studies have characterized the prognostic significance of ischemia extent and severity. However, the role of ischemia in directing downstream SIHD care including coronary revascularization has remained elusive as reductions in ischemic burden have not translated to improved clinical outcomes in randomized trials. Importantly, selection bias leading to the inclusion of many low risk patients with minimal ischemia have narrowed the generalizability of prior studies along with other limitations. Accordingly, an ongoing randomized controlled trial entitled ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) will compare an invasive coronary revascularization strategy vs a conservative medical therapy approach among stable patients with moderate to severe ischemia. The results of ISCHEMIA may have a substantial impact on the management of SIHD and better define the role of MPI in current SIHD pathways of care.

  2. Localization of post-infarction myocardial ischemia by /sup 201/Tl emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Spielmann, R.P.; Heinemann, H.; Montz, R.; Nienaber, C.A.

    1985-12-01

    In 41 patients with a history of a single myocardial infarction, the location of myocardial ischemia was studied by /sup 201/Tl emission computed tomography immediately and 3 h after intravenous dipyridamole. Peri-infarctional ischemia without distant ischemia was observed in 15 patients. The occurrence of distant ischemia was found to be dependent on the severity of stenosis in non-infarct coronary vessels. Twelve (86%) of 14 patients with non-infarct stenosis of 75% or greater had distant ischemia, but only 1 (4%) of 27 patients with non-infarct stenosis of less than 75%. In the presence of distant ischemia, peri-infarctional ischemia was in 11 patients (85%) associated with collaterals supplying the infarct zone, whereas in 13 (87%) of the patients with peri-infarctional ischemia only, incomplete obstruction of the infarct vessel was observed. It is concluded that, by the distinction between peri-infarctional and distant ischemia, the presence of significant stenosis in non-infarct vessels can be non-invasively predicted from tomographic thallium scintigraphy with dipyridamole.

  3. The Cardioprotective Effects of Citric Acid and L-Malic Acid on Myocardial Ischemia/Reperfusion Injury

    Science.gov (United States)

    Tang, Xilan; Liu, Jianxun; Dong, Wei; Li, Peng; Li, Lei; Lin, Chengren; Zheng, Yongqiu; Hou, Jincai; Li, Dan

    2013-01-01

    Organic acids in Chinese herbs, the long-neglected components, have been reported to possess antioxidant, anti-inflammatory, and antiplatelet aggregation activities; thus they may have potentially protective effect on ischemic heart disease. Therefore, this study aims to investigate the protective effects of two organic acids, that is, citric acid and L-malic acid, which are the main components of Fructus Choerospondiatis, on myocardial ischemia/reperfusion injury and the underlying mechanisms. In in vivo rat model of myocardial ischemia/reperfusion injury, we found that treatments with citric acid and L-malic acid significantly reduced myocardial infarct size, serum levels of TNF-α, and platelet aggregation. In vitro experiments revealed that both citric acid and L-malic acid significantly reduced LDH release, decreased apoptotic rate, downregulated the expression of cleaved caspase-3, and upregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation injury. These results suggest that both citric acid and L-malic acid have protective effects on myocardial ischemia/reperfusion injury; the underlying mechanism may be related to their anti-inflammatory, antiplatelet aggregation and direct cardiomyocyte protective effects. These results also demonstrate that organic acids, besides flavonoids, may also be the major active ingredient of Fructus Choerospondiatis responsible for its cardioprotective effects and should be attached great importance in the therapy of ischemic heart disease. PMID:23737849

  4. Salidroside attenuates myocardial ischemia-reperfusion injury via PI3K/Akt signaling pathway.

    Science.gov (United States)

    Xu, Mao-Chun; Shi, Hai-Ming; Gao, Xiu-Fang; Wang, Hao

    2013-01-01

    To investigate the cardioprotective effects of salidroside on myocardial ischemia-reperfusion injury (IRI) in rabbits and the underlying action mechanisms in PI3K/Akt signaling pathway, a rabbit ischemia/reperfusion model was created by ligating the left anterior descending coronary arterial branch for 30 min and by releasing the ligature to allow reperfusion for 120 min. Salidroside or salidroside+PI3K inhibitor (LY294002) was administered via intracoronary injections at the onset of reperfusion. Apoptosis of cardiomyocytes was assessed by terminal dUTP nick-end labeling assay, and the expression of apoptosis-related proteins was observed by immunohistochemistry. The expressions of total Akt and phosphorylated Akt (p-Akt) were detected by western blot analysis. The results showed that intracoronary injection of salidroside at the onset of reperfusion markedly reduced the apoptosis of cardiomyocytes, significantly increasing Bcl-2 and p-Akt proteins expressions and decreasing Bax and caspase-3 expressions in the hearts subjected to ischemia followed by 120-min reperfusion. However, the anti-apoptotic effect induced by salidroside was inhibited by LY294002, which blocked the activation of Akt. These results suggested that intracoronary administration of salidroside at the onset of reperfusion could significantly reduce the IRI-induced apoptosis of cardiomyocytes, and this protective mechanism seemed to be mediated by the PI3K-Akt signaling pathway.

  5. [Changes of myocardial enzymes related to glycolysis and fatty acid metabolism in chronic myocardial ischemia: experiment with pigs].

    Science.gov (United States)

    Gong, Jing; Wang, Hong-yue; Pu, Jie-lin; Zheng, Ying-li; Shen, Rui; Yang, Min-fu; He, Zuo-xiang

    2008-08-12

    To investigate the changes myocardial enzymes related to glycolysis and fatty acid metabolism in chronic myocardial ischemia and to evaluate the relationship between the gene expression of glycolytic metabolism related enzymes and myocardial viability. Fourteen Chinese experimental pigs underwent placement of arterial ring into the left anterior descending coronary artery so as to establish models of myocardial ischemia and infarction. (18)F-2-deoxy-2-fluoro-D-glucose single photon emission computed tomography was conducted to observe the viability of the myocardium. One week later the pigs were killed with their hearts taken out. Specimens of ischemic zone, infarction zone, and non-ischemic zone were obtained. RT-PCR was used to detect the mRNA expression of glucose transporter (GLUT) 1, GLUT4, medium-chain acyl-CoA dehydrogenase (MCAD), and heart-fatty acid binding protein (H-FABP). Immunohistochemistry was used to examine the protein expression of Glut1 and Glut4. Periodic Acid Schiff-hematoxylin staining was conducted to detect the glycogen. Pathological examination showed 5 pigs with myocardial infarction and 5 pigs with ischemia. In the pigs with ischemia, the mRNA expression levels of GLUT1 and GLUT4 in the ischemic zone were 9466 +/- 9033 and 60 398 +/- 64 699 respectively, both significantly higher than those in the control zone (5854 +/- 5287 and 34 188 +/- 44 714 respectively, P = 0.043, P = 0.043). the RNA expression of H-FABP in the ischemic zone was 18 123 +/- 15 925, significantly lower than that in the control zone (50 718 +/- 62 412, P = 0.043), and there was no significant difference in the mRNA expression level of MCAD. In the pigs with infarction the mRNA expression of level of H-FABP in the infarction zone was 21 919 +/- 15 224, significantly lower than that in the control zone (87 545 +/- 92 990, P = 0.043), and there were not significant differences in the mRNA expression levels of the GLUT1, GLUT4, and MCAD genes (all P > 0.05). The m

  6. Transmural heterogeneity of myocardial contraction and ischemia. Diagnosis and clinical implications.

    Science.gov (United States)

    Colonna, P; Cadeddu, C; Montisci, R; Chen, L; Meloni, L; Iliceto, S

    2000-03-01

    Myocardial contraction behaves heterogeneously, being greater in subendocardial than in subepicardial layers. Similarly, during acute myocardial ischemia or infarction, the subendocardium is the first myocardial layer to suffer. Conventional two-dimensional echocardiography cannot distinguish the transmural extension of myocardial ischemia or infarction, showing akinesia also when only the subendocardium is affected. Novel ultrasonographic techniques (like tissue characterization with integrated backscatter or Doppler tissue imaging) and nuclear magnetic resonance tagging can investigate myocardial contraction in different transmural layers and distinguish subendocardial from transmural ischemia or infarction. With the advent of thrombolysis and primary angioplasty in the acute phase of myocardial infarction a correct diagnosis of the extension of myocardial necrosis cannot ignore its transmural wavefront development. The salvage of the subepicardial layer does not give direct information on overall myocardial thickening but is one of the major determinants of overall left ventricular dysfunction and size. Although it is still necessary to investigate this phenomenon, new ultrasonographic techniques give us important information and more opportunities to appropriate diagnosis and future treatment of cardiac patients.

  7. Coxsackie and adenovirus receptor (CAR) is a modifier of cardiac conduction and arrhythmia vulnerability in the setting of myocardial ischemia

    Science.gov (United States)

    Marsman, Roos F.J.; Bezzina, Connie R.; Freiberg, Fabian; Verkerk, Arie O.; Adriaens, Michiel E.; Podliesna, Svitlana; Chen, Chen; Purfürst, Bettina; Spallek, Bastian; Koopmann, Tamara T.; Baczko, Istvan; dos Remedios, Cristobal G.; George, Alfred L.; Bishopric, Nanette H.; Lodder, Elisabeth M.; de Bakker, Jacques M.T.; Fischer, Robert; Coronel, Ruben; Wilde, Arthur A.M.; Gotthardt, Michael; Remme, Carol Ann

    2014-01-01

    Objectives To investigate the modulatory effect of the Coxsackie and adenovirus receptor (CAR) on ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. Background A heritable component in risk for ventricular fibrillation (VF) during myocardial infarction (MI) has been well established. A recent genome-wide association study (GWAS) for VF during acute MI has led to the identification of a locus on chromosome 21q21 (rs2824292) in the vicinity of the CXADR gene. CXADR encodes the coxsackie and adenovirus receptor (CAR), a cell adhesion molecule predominantly located at intercalated discs of the cardiomyocyte. Methods The correlation between CAR transcript levels and rs2824292 genotype was investigated in human left ventricular samples. Electrophysiological studies and molecular analyses were performed CAR haploinsufficient mice (CAR+/−). Results In human left ventricular samples, the risk allele at the chr21q21 GWAS locus was associated with lower CXADR mRNA levels, suggesting that decreased cardiac levels of CAR predispose to ischemia-induced VF. Hearts from CAR+/− mice displayed ventricular conduction slowing in addition to an earlier onset of ventricular arrhythmias during the early phase of acute myocardial ischemia following LAD ligation. Connexin43 expression and distribution was unaffected, but CAR+/− hearts displayed increased arrhythmia susceptibility upon pharmacological electrical uncoupling. Patch-clamp analysis of isolated CAR+/− myocytes showed reduced sodium current magnitude specifically at the intercalated disc. Moreover, CAR co-precipitated with NaV1.5 in vitro, suggesting that CAR affects sodium channel function through a physical interaction with NaV1.5. Conclusion We identify CAR as a novel modifier of ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. Genetic determinants of arrhythmia susceptibility (such as CAR) may constitute future targets for risk

  8. Impact of coronary revascularization on the clinical and scintigraphic outlook of patients with myocardial ischemia.

    Science.gov (United States)

    Nudi, Francesco; Procaccini, Enrica; Versaci, Francesco; Giordano, Alessandro; Pinto, Annamaria; Neri, Giandomenico; Frati, Giacomo; Schillaci, Orazio; Nudi, Alessandro; Tomai, Fabrizio; Biondi-Zoccai, Giuseppe

    2017-06-01

    The impact of coronary revascularization on outcomes and ischemic burden among patients with objective proof of ischemia is not yet established. We appraised the impact of revascularization on outcomes and residual ischemia in patients with objective evidence of ischemia at myocardial perfusion scintigraphy (MPS). We queried our database for stable patients with myocardial ischemia at MPS, excluding those with prior myocardial infarction, systolic dysfunction, or cardiomyopathy. The impact of revascularization (defined as revascularization as first follow-up event) on outcomes and changes in myocardial ischemia at repeat MPS was appraised with propensity-matched analyses. From 6195 patients, propensity matching yielded 1262 pairs of patients undergoing revascularization versus not undergoing revascularization. After 35.2 ± 23.9 months, revascularization was associated with lower risks of cardiac death [2 (0.2%) versus 10 (0.8%) in those not revascularized, P = 0.038] and of the composite of cardiac death or myocardial infarction [17 (1.3%) versus 37 (2.9%), P = 0.007]. In addition, revascularization was associated with a higher rate of improvement in ischemia degree after 28.1 ± 20.7 months of follow-up (P revascularization versus 136 (42.0%) in the nonrevascularization group. Conversely, revascularization did not prove impactful on follow-up MPS in patients with only minimal or mild ischemia at baseline MPS (P revascularization was associated with a better clinical prognosis and a lower ischemic burden at repeat MPS.

  9. Temporal Trends in the Prevalence, Severity, and Localization of Myocardial Ischemia and Necrosis at Myocardial Perfusion Imaging After Myocardial Infarction.

    Science.gov (United States)

    Nudi, Francesco; Schillaci, Orazio; Di Belardino, Natale; Versaci, Francesco; Tomai, Fabrizio; Pinto, Annamaria; Neri, Giandomenico; Procaccini, Enrica; Nudi, Alessandro; Frati, Giacomo; Biondi-Zoccai, Giuseppe

    2017-10-15

    The definition, presentation, and management of myocardial infarction (MI) have changed substantially in the last decade. Whether these changes have impacted on the presence, severity, and localization of necrosis at myocardial perfusion imaging (MPI) has not been appraised to date. Subjects undergoing MPI and reporting a history of clinical MI were shortlisted. We focused on the presence, severity, and localization of necrosis at MPI with a retrospective single-center analysis. A total of 10,476 patients were included, distinguishing 5 groups according to the period in which myocardial perfusion scintigraphy had been performed (2004 to 2005, 2006 to 2007, 2008 to 2009, 2010 to 2011, 2012 to 2013). Trend analysis showed over time a significant worsening in baseline features (e.g., age, diabetes mellitus, and Q waves at electrocardiogram), whereas medical therapy and revascularization were offered with increasing frequency. Over the years, there was also a lower prevalence of normal MPI (from 16.8% to 13.6%) and ischemic MPI (from 35.6% to 32.8%), and a higher prevalence of ischemic and necrotic MPI (from 12.0% to 12.7%) or solely necrotic MPI (from 35.7% to 40.9%, p necrosis (from 19.8% to 8.2%) and moderate necrosis (from 8.5% to 7.8%, p = 0.028). These trends were largely confirmed at regional level and after propensity score matching. In conclusion, the outlook of stable patients with previous MI has substantially improved in the last decade, with a decrease in the severity of residual myocardial ischemia and necrosis, despite an apparent worsening in baseline features. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Serum YKL-40 for monitoring myocardial ischemia after revascularization in patients with stable coronary artery disease

    DEFF Research Database (Denmark)

    Harutyunyan, Marina Jurjevna; Johansen, Julia S; Mygind, Naja D

    2014-01-01

    AIM: The aim was to investigate the inflammatory biomarker YKL-40 as a monitor of myocardial ischemia in patients with coronary artery disease (CAD). METHODS: A total of 311 patients with stable CAD were included. Blood samples were taken at baseline, the day after coronary angiography and/or after...... percutaneous coronary intervention and after 6 months. RESULTS: A total of 148 (48%) patients were revascularized and 163 patients underwent only coronary angiography. In the entire population, serum YKL-40 increased significantly from baseline to 6 months (p = 0.05). This tendency was seen...... of disease progression but not of myocardial ischemia in patients with stable CAD....

  11. Availability of a baseline Electrocardiogram changes the application of the Sclarovsky-Birnbaum Myocardial Ischemia Grade

    DEFF Research Database (Denmark)

    Carlsen, Esben A; Bang, Lia E; Køber, Lars

    2014-01-01

    BACKGROUND AND AIMS: The electrocardiogram (ECG) based Sclarovsky-Birnbaum Ischemia Grade may be used to determine the prognosis of patients with ST-elevation myocardial infarction (STEMI). However, application of the method is based on assumption of the baseline QRS morphology. Thus, the aims...... of this study were to determine if the baseline QRS morphology was correctly assumed based on an ECG recorded during induced ischemia, and if reference to the baseline ECG altered the designated Ischemia Grade. METHODS: Sixty-three patients with chronic ischemic heart disease that underwent elective...... percutaneous transluminal coronary angioplasty were included. Baseline ECG and ECG during the procedure were recorded. In the latter, Ischemia Grade was classified according to assumed baseline QRS morphology. Then the baseline ECG was used as reference and Ischemia Grade was determined based on change from...

  12. Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury

    OpenAIRE

    Nicholas Chun; Haddadin, Ala S.; Junying Liu; Yunfang Hou; Wong, Karen A.; Daniel Lee; Rushbrook, Julie I.; Karan Gulaya; Roberta Hines; Tamika Hollis; Beatriz Nistal Nuno; Mangi, Abeel A.; Sabet Hashim; Marcela Pekna; Amy Catalfamo

    2017-01-01

    The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R) is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the classical and lectin pathways are crucial. Whether factor B (fB), a component of the alternative complement pathway required for amplification of complement cascade activation, participates in the pathophysiology of myocardial I/R injury has not been...

  13. Compound danshen dripping pills modulate the perturbed energy metabolism in a rat model of acute myocardial ischemia

    OpenAIRE

    Jiahua Guo; Yonghong Yong; Jiye Aa; Bei Cao; Runbin Sun; Xiaoyi Yu; Jingqiu Huang; Na Yang; Lulu Yan; Xinxin Li; Jing Cao; Nan Aa; Zhijian Yang; Xiangqing Kong; Liansheng Wang

    2016-01-01

    The continuous administration of compound danshen dripping pills (CDDP) showed good efficacy in relieving myocardial ischemia clinically. To probe the underlying mechanism, metabolic features were evaluated in a rat model of acute myocardial ischemia induced by isoproterenol (ISO) and administrated with CDDP using a metabolomics platform. Our data revealed that the ISO-induced animal model showed obvious myocardial injury, decreased energy production, and a marked change in metabolomic patter...

  14. Spinal cord stimulation reduces ventricular arrhythmias during acute ischemia by attenuation of regional myocardial excitability.

    Science.gov (United States)

    Howard-Quijano, Kimberly; Takamiya, Tatsuo; Dale, Erica A; Kipke, Jasmine; Kubo, Yukiko; Grogan, Tristan; Afyouni, Andyshea; Shivkumar, Kalyanam; Mahajan, Aman

    2017-08-01

    Myocardial ischemia creates autonomic nervous system imbalance and can trigger cardiac arrhythmias. We hypothesized that neuromodulation by spinal cord stimulation (SCS) will attenuate local cardiac sympathoexcitation from ischemia-induced increases in afferent signaling, reduce ventricular arrhythmias, and improve myocardial function during acute ischemia. Yorkshire pigs ( n = 20) were randomized to SCS (50 Hz at 200-μs duration, current 90% motor threshold) or sham operation (sham) for 30 min before ischemia. A four-pole SCS lead was placed percutaneously in the epidural space (T 1 -T 4 ), and a 56-electrode mesh was placed over the heart for high-resolution electrophysiological recordings, including activation recovery intervals (ARIs), activation time, repolarization time, and dispersion of repolarization. Electrophysiological and hemodynamic measures were recorded at baseline, after SCS/sham, during acute ischemia (300-s coronary artery ligation), and throughout reperfusion. SCS 1 ) reduced sympathoexcitation-induced ARI and repolarization time shortening in the ischemic myocardium; 2 ) attenuated increases in the dispersion of repolarization; 3 ) reduced ventricular tachyarrythmias [nonsustained ventricular tachycardias: 24 events (3 sham animals) vs. 1 event (1 SCS animal), P spinal cord stimulation decreased sympathetic nerve activation regionally in ischemic myocardium with no effect on normal myocardium, demonstrating that the antiarrhythmic effects of spinal cord stimulation are likely due to attenuation of local sympathoexcitation in the ischemic myocardium and not changes in global myocardial electrophysiology. Copyright © 2017 the American Physiological Society.

  15. Quantifying QRS changes during myocardial ischemia: Insights from high frequency electrocardiography.

    Science.gov (United States)

    Amit, Guy; Granot, Yair; Abboud, Shimon

    2014-01-01

    Over four decades of high frequency electrocardiography research have provided a body of knowledge about QRS changes during myocardial ischemia, and the techniques to measure and quantify them. High-frequency QRS (HFQRS) components, being closely related to the pattern of ventricular depolarization, carry valuable clinical information. Changes in HFQRS amplitude and morphology have been shown to be sensitive diagnostic markers of myocardial ischemia, often superior to measures of ST-T segment changes. Clinical studies in patients undergoing exercise testing have consistently demonstrated the incremental diagnostic value of HFQRS analysis in detection of demand ischemia. In 6 studies that evaluated the HyperQ™ technology, the average sensitivity and specificity of HFQRS analysis were 75%±6% and 80%±6%, respectively, compared to average sensitivity 48%±16% and average specificity 70%±15% of ST segment analysis. In patients with acute supply ischemia, recent studies characterized and quantified the ischemic HFQRS patterns. HFQRS morphology index was found to be higher in patients with acute coronary syndrome (ACS), compared to non-ischemic, with good sensitivity in patients without ST elevation. These research findings may be translated into commercially-available ECG systems and be used in clinical practice for improved diagnosis and monitoring of myocardial ischemia. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Stronger correlation with myocardial ischemia of high-sensitivity troponin T than other biomarkers.

    Science.gov (United States)

    Pipikos, Theodore; Kapelouzou, Alkistis; Tsilimigras, Diamantis I; Fostinis, Yannis; Pipikou, Marina; Theodorakos, Athanassios; Pavlidis, Antonis N; Kontogiannis, Christos; Cokkinos, Dennis V; Koutelou, Maria

    2018-01-29

    Acute myocardial infarction (AMI) is considered a major cause of death and disability. Myocardial perfusion scintigraphy (MPS) as a non-invasive diagnostic imaging procedure and certain biomarkers associated with myocardial ischemia (ISCH), such as ischemia-modified albumin (IMA), neuropeptide Y (NPY), N-terminal pro b-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) could probably aid in the detection of myocardial infarction. Between December 2011 and June 2012, we prospectively analyzed patients who underwent a MPS study with the clinical question of myocardial ISCH. An exercise test was performed along with a MPS. Blood was drawn from the patients before exercise and the within 3 minutes from achieving maximum load and was analyzed for the aforementioned biomarkers. A total of 71 patients (56 men and 15 women) were enrolled with a mean age of 61 ± 12 years. Twenty-six patients (36.6%) showed reduced uptake on stress MPS images that normalized at rest, a finding consistent with ISCH. Between ISCH and non-ISCH groups, only hsTnT levels showed a significant difference with the highest levels pertaining to the former group both before (0.0075 ng/ml vs 0.0050 ng/ml, P = 0.023) and after stress exercise (0.0085 vs 0.0050, P = 0.015). The most prominent differences were seen in higher stages of the Bruce protocol (stress duration > 9.05 minutes - P insults, serum hsTnT holds a greater ability of detecting not only myocardial infarction but also less severe ischemia. Further studies with larger cohorts of patients are warranted in order to better define the role of hsTnT as a screening tool for myocardial ischemia.

  17. Induced coronary spasm without electrocardiographic signs or symptoms of myocardial ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Cipriano, P.R.

    1983-03-01

    Angiographic studies have shown that coronary artery spasm can be induced with ergonovine maleate. Coronary artery spasm induced by ergonovine maleate in these studies was nearly always accompanied by chest pain and electrocardiographic changes of myocardial ischemia. This report demonstrates that coronary artery spasm induced by ergonovine maleate may be diagnosed by angiography in the absence of these signs or symptoms.

  18. Myocardial perfusion scintigraphy in the detection of silent ischemia in asymptomatic diabetic patients

    Energy Technology Data Exchange (ETDEWEB)

    Oki, Glaucia Celeste Rossatto [Clinica Diagnoson and Hospital Aristides Maltez, Salvador, BA (Brazil). Servicos de Medicina Nuclear; Pavin, Elizabeth Joao; Parisi, Maria Candida R. [Universidade Estadual de Campinas (Unicamp), Campinas, SP (Brazil). Department of Internal Medicine. Service of Endocrinology; Coelho, Otavio Rizzi; Almeida, Raitany C. [Universidade Estadual de Campinas (Unicamp), Campinas, SP (Brazil). Department of Internal Medicine. Service of Cardiology; Etchebehere, Elba Cristina Sa de Camargo; Ramos, Celso Dario, E-mail: cdramos@unicamp.br [Universidade Estadual de Campinas (Unicamp), Campinas, SP (Brazil). Department of Radiology. Service of Nuclear Medicine; Camargo, Edwaldo Eduardo [Hospital Sirio-Libanes, Campinas, SP (Brazil). Service of Nuclear Medicine

    2013-01-15

    Objective: This study was aimed to evaluate myocardial perfusion in asymptomatic patients with type 1 (DM1) and type 2 diabetes mellitus (DM2) without previous diagnoses of coronary artery disease (CAD) or cerebral infarction. Materials and Methods: Fifty-nine consecutive asymptomatic patients (16 DM1, 43 DM2) underwent myocardial perfusion scintigraphy with {sup 99m}Tc-sestamibi (MPS). They were evaluated for body mass index, metabolic control of DM, type of therapy, systemic arterial hypertension, dyslipidemia, nephropathy, retinopathy, peripheral neuropathy, smoking, and familial history of CAD. Results: MPS was abnormal in 15 patients (25.4%): 12 (20.3%) with perfusion abnormalities, and 3 with isolated left ventricular dysfunction. The strongest predictors for abnormal myocardial perfusion were: age 60 years and above (p = 0.017; odds ratio [OR] = 6.0), peripheral neuropathy (p = 0.028; OR = 6.1), nephropathy (p = 0.031; OR = 5.6), and stress ECG positive for ischemia (p = 0.049; OR = 4.08). Conclusion: Silent myocardial ischemia occurs in more than one in five asymptomatic diabetic patients. The strongest predictors of ischemia in this study were: patient age, peripheral neuropathy, nephropathy, retinopathy and a stress ECG positive for ischemia. (author)

  19. Myocardial ischemia and reperfusion injury: Studies using transgenic and knockout mice

    NARCIS (Netherlands)

    Jong, W. M. C.; ten Cate, H.; Reitsma, P. H.; de Winter, R. J.

    2005-01-01

    Transgenic and knockout mice are created and used for a large variety of research objectives. This overview describes the (genetically modified) mouse models that have been used to study the development of myocardial ischemia and reperfusion injury. The role of cytokines, chemokines, leukocytes,

  20. Melatonin reduces cardiac morbidity and markers of myocardial ischemia after elective abdominal aortic aneurism repair

    DEFF Research Database (Denmark)

    Gögenür, Ismail; Kücükakin, Bülent; Panduro Jensen, Leif

    2014-01-01

    The aim was to examine the effect of perioperative melatonin treatment on clinical cardiac morbidity and markers of myocardial ischemia in patients undergoing elective surgery for abdominal aortic aneurism. Reperfusion injury results in increased cardiac morbidity in patients undergoing surgery f...

  1. 1H NMR-derived metabolomics of filtered serum of myocardial ischemia in unstable angina patients.

    Science.gov (United States)

    Ameta, Keerti; Gupta, Ashish; Ameta, Deepak; Sethi, Rishi; Kumar, Deepak; Ahmad, Israr; Mahdi, Abbas Ali

    2016-05-01

    Despite continuing research for development of accurate biomarkers of myocardial ischemia in unstable angina, lack of biochemical biomarkers is alarming. We sought to develop accurate biomarkers using high throughput proton nuclear magnetic resonance ((1)H NMR) spectroscopy and filtered serum (lacking proteins and lipoproteins) based metabolomics for detecting myocardial ischemia in unstable angina patients with utmost precision. Study includes 127 filtered serum samples from myocardial ischemia in unstable angina patients (UA; n=65) and healthy controls (HC; n=62). High resolution NMR spectra were obtained to highlight metabolic perturbations of small metabolites. A supervised orthogonal partial least square discriminant analysis was applied to generate a prediction model. Receiver operating characteristic (ROC) curve analysis was performed to reveal the clinical utility of signature biomarkers. Five biomarkers--valine, alanine, glutamine, inosine and adenine--could differentiate 95% of UA from HC with 96% sensitivity and 95% specificity. (1)H NMR-based filtered serum metabolic profiling appears to be an assuring, least invasive and faster way to screen and identify myocardial ischemia in unstable angina patients. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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%.

  3. Activity Exerted by a Testosterone Derivative on Myocardial Injury Using an Ischemia/Reperfusion Model

    Science.gov (United States)

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Betty, Sarabia-Alcocer; Monica, Velázquez-Sarabia Betty

    2014-01-01

    Some reports indicate that several steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the activity exerted by the testosterone derivatives on cardiac injury caused by ischemia/reperfusion (I/R). Analyzing these data, in this study, a new testosterone derivative was synthetized with the objective of evaluating its effect on myocardial injury using an ischemia/reperfusion model. In addition, perfusion pressure and coronary resistance were evaluated in isolated rat hearts using the Langendorff technique. Additionally, molecular mechanism involved in the activity exerted by the testosterone derivative on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in the absence or presence of the following compounds: flutamide, prazosin, metoprolol, nifedipine, indomethacin, and PINANE TXA2. The results showed that the testosterone derivative significantly increases (P = 0.05) the perfusion pressure and coronary resistance in isolated heart. Other data indicate that the testosterone derivative increases left ventricular pressure in a dose-dependent manner (0.001–100 nM); however, this phenomenon was significantly inhibited (P = 0.06) by indomethacin and PINANE-TXA2  (P = 0.05) at a dose of 1 nM. In conclusion, these data suggest that testosterone derivative induces changes in the left ventricular pressure levels through thromboxane receptor activation. PMID:24839599

  4. Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Nicholas Chun

    Full Text Available The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the classical and lectin pathways are crucial. Whether factor B (fB, a component of the alternative complement pathway required for amplification of complement cascade activation, participates in the pathophysiology of myocardial I/R injury has not been addressed. We induced regional myocardial I/R injury by transient coronary ligation in WT C57BL/6 mice, a manipulation that resulted in marked myocardial necrosis associated with activation of fB protein and myocardial deposition of C3 activation products. In contrast, in fB-/- mice, the same procedure resulted in significantly reduced myocardial necrosis (% ventricular tissue necrotic; fB-/- mice, 20 ± 4%; WT mice, 45 ± 3%; P < 0.05 and diminished deposition of C3 activation products in the myocardial tissue (fB-/- mice, 0 ± 0%; WT mice, 31 ± 6%; P<0.05. Reconstitution of fB-/- mice with WT serum followed by cardiac I/R restored the myocardial necrosis and activated C3 deposition in the myocardium. In translational human studies we measured levels of activated fB (Bb in intracoronary blood samples obtained during cardio-pulmonary bypass surgery before and after aortic cross clamping (AXCL, during which global heart ischemia was induced. Intracoronary Bb increased immediately after AXCL, and the levels were directly correlated with peripheral blood levels of cardiac troponin I, an established biomarker of myocardial necrosis (Spearman coefficient = 0.465, P < 0.01. Taken together, our results support the conclusion that circulating fB is a crucial pathophysiological amplifier of I/R-induced, complement-dependent myocardial necrosis and identify fB as a potential therapeutic target for prevention of human myocardial I/R injury.

  5. Toll-like receptor 3 plays a role in myocardial infarction and ischemia/reperfusion injury.

    Science.gov (United States)

    Lu, Chen; Ren, Danyang; Wang, Xiaohui; Ha, Tuanzhu; Liu, Li; Lee, Eric J; Hu, Jing; Kalbfleisch, John; Gao, Xiang; Kao, Race; Williams, David; Li, Chuanfu

    2014-01-01

    Innate immune and inflammatory responses mediated by Toll like receptors (TLRs) have been implicated in myocardial ischemia/reperfusion (I/R) injury. This study examined the role of TLR3 in myocardial injury induced by two models, namely, myocardial infarction (MI) and I/R. First, we examined the role of TLR3 in MI. TLR3 deficient (TLR3(-/-)) and wild type (WT) mice were subjected to MI induced by permanent ligation of the left anterior descending (LAD) coronary artery for 21days. Cardiac function was measured by echocardiography. Next, we examined whether TLR3 contributes to myocardial I/R injury. TLR3(-/-) and WT mice were subjected to myocardial ischemia (45min) followed by reperfusion for up to 3days. Cardiac function and myocardial infarct size were examined. We also examined the effect of TLR3 deficiency on I/R-induced myocardial apoptosis and inflammatory cytokine production. TLR3(-/-) mice showed significant attenuation of cardiac dysfunction after MI or I/R. Myocardial infarct size and myocardial apoptosis induced by I/R injury were significantly attenuated in TLR3(-/-) mice. TLR3 deficiency increases B-cell lymphoma 2 (BCL2) levels and attenuates I/R-increased Fas, Fas ligand or CD95L (FasL), Fas-Associated protein with Death Domain (FADD), Bax and Bak levels in the myocardium. TLR3 deficiency also attenuates I/R-induced myocardial nuclear factor KappaB (NF-κB) binding activity, Tumor necrosis factor alpha (TNF-α) and Interleukin-1 beta (IL-1β) production as well as I/R-induced infiltration of neutrophils and macrophages into the myocardium. TLR3 plays an important role in myocardial injury induced by MI or I/R. The mechanisms involve activation of apoptotic signaling and NF-κB binding activity. Modulation of TLR3 may be an effective approach for ameliorating heart injury in heart attack patients. © 2013.

  6. 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 prevalence...... of transient myocardial ischemia was found between the 3 recordings (17, 17 and 20%), and most ischemic episodes were silent (98, 100 and 97%). In the early postinfarction period, a peak of ischemic activity was demonstrated between 6 P.M. and midnight (40 of 93 episodes [43%]). Over time, the maximal...

  7. EphrinA1-Fc attenuates myocardial ischemia/reperfusion injury in mice.

    Directory of Open Access Journals (Sweden)

    Augustin DuSablon

    Full Text Available EphrinA1, a membrane-bound receptor tyrosine kinase ligand expressed in healthy cardiomyocytes, is lost in injured cells following myocardial infarction. Previously, we have reported that a single intramyocardial injection of chimeric ephrinA1-Fc at the time of ischemia reduced injury in the nonreperfused myocardium by 50% at 4 days post-MI by reducing apoptosis and inflammatory cell infiltration. In a clinically relevant model of acute ischemia (30min/reperfusion (24hr or 4 days injury, we now demonstrate that ephrinA1-Fc reduces infarct size by 46% and completely preserves cardiac function (ejection fraction, fractional shortening, and chamber dimensions in the short-term (24hrs post-MI as well as long-term (4 days. At 24 hours post-MI, diminished serum inflammatory cell chemoattractants in ephrinA1-Fc-treated mice reduces recruitment of neutrophils and leukocytes into the myocardium. Differences in relative expression levels of EphA-Rs are described in the context of their putative role in mediating cardioprotection. Validation by Western blotting of selected targets from mass spectrometry analyses of pooled samples of left ventricular tissue homogenates from mice that underwent 30min ischemia and 24hr of reperfusion (I/R indicates that ephrinA1-Fc administration alters several regulators of signaling pathways that attenuate apoptosis, promote autophagy, and shift from FA metabolism in favor of increased glycolysis to optimize anaerobic ATP production. Taken together, reduced injury is due a combination of adaptive metabolic reprogramming, improved cell survival, and decreased inflammatory cell recruitment, suggesting that ephrinA1-Fc enhances the capacity of the heart to withstand an ischemic insult.

  8. Diabetic Inhibition of Preconditioning- and Postconditioning-Mediated Myocardial Protection against Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Xia Yin

    2012-01-01

    Full Text Available Ischemic preconditioning (IPC or postconditioning (Ipost is proved to efficiently prevent ischemia/reperfusion injuries. Mortality of diabetic patients with acute myocardial infarction was found to be 2–6 folds higher than that of non-diabetic patients with same myocardial infarction, which may be in part due to diabetic inhibition of IPC- and Ipost-mediated protective mechanisms. Both IPC- and Ipost-mediated myocardial protection is predominantly mediated by stimulating PI3K/Akt and associated GSK-3β pathway while diabetes-mediated pathogenic effects are found to be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. Therefore, this review briefly introduced the general features of IPC- and Ipost-mediated myocardial protection and the general pathogenic effects of diabetes on the myocardium. We have collected experimental evidence that indicates the diabetic inhibition of IPC- and Ipost-mediated myocardial protection. Increasing evidence implies that diabetic inhibition of IPC- and Ipost-mediated myocardial protection may be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. Therefore any strategy to activate PI3K/Akt and associated GSK-3β pathway to release the diabetic inhibition of both IPC and Ipost-mediated myocardial protection may provide the protective effect against ischemia/reperfusion injuries.

  9. Cardioprotective Effect of the Aqueous Extract of Lavender Flower against Myocardial Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Dong Wang

    2014-01-01

    Full Text Available This study was conducted to evaluate the cardioprotective property of the aqueous extract of lavender flower (LFAE. The myocardial ischemia/reperfusion (I/R injury of rat was prepared by Langendorff retrograde perfusion technology. The heart was preperfused with K-H solution containing LFAE for 10 min before 20 minutes global ischemia, and then the reperfusion with K-H solution was conducted for 45 min. The left ventricular developed pressure (LVDP and the maximum up/downrate of left ventricular pressure (±dp/dtmax were recorded by physiological recorder as the myocardial function and the myocardial infarct size was detected by TTC staining. Lactate dehydrogenase (LDH and creatine kinase (CK activities in the effluent were measured to determine the myocardial injury degree. The superoxide anion dismutase (SOD and malondialdehyde (MDA in myocardial tissue were detected to determine the oxidative stress degree. The results showed that the pretreatment with LFAE significantly decreased the myocardial infarct size and also decreased the LDH, CK activities, and MDA level, while it increased the LVDP, ±dp/dtmax, SOD activities, and the coronary artery flow. Our findings indicated that LFAE could provide protection for heart against the I/R injury which may be related to the improvement of myocardial oxidative stress states.

  10. Comparison of adenosine-induced myocardial ischemia and atherosclerosis measured by coronary calcium tomography

    Energy Technology Data Exchange (ETDEWEB)

    Cho, I. H.; Chun, K. A.; Won, K. C.; Lee, H. W.; Hong, K. L.; Park, J. S.; Shin, D. K.; Kim, Y. C.; Sim, B. S. [Yeungnam University Medical Center, Daegu (Korea, Republic of)

    2005-07-01

    Coronary artery calcium shows a anatomic information and coronary atherosclerotic burde, but myocardial perfusion SPECT shows a physiologic significance of coronary stenosis and stress induced ischemia. Both are valuable in the noninvasive assessment of patients with suspected coronary artery disease. There has been little evaluation regarding the relationship between CAC and adenosine-induced ischemia and how to integrate CAC with myocardial perfusion SPECT. We assessed the relationship between adenosine-induced myocardial ischemia on myocardial perfusion single-photon emission computed tomography (MPS) and magnitude of coronary calcification (CAC) by MDCT in patients undergoing both tests. A total of 111 patients underwent adenosine-induced MPS and CAC within 2days. Coronary angiography was done in 55 patients. The frequency of ischemia by MPS was compared to the magnitude of CAC. Among 56 patients with ischemic MPS, the CAC scores were >0 in 87.5%, >100 in 76.8%, and > 400 in 50.0%. Of 25 normal MPS, the CAC scores were >0 in 70.9%. >100 in 34.5%, and > 400 in 14.5%, respectively. Of 38 patient with coronary artery stenosis proved by coronary angiography, the CAC scores were >0 in 92.1%, >100 in 78.9%, and > 400 in 50.0 %, respectively. Of 12 patient without coronary artery stenosis, the CAC scores were >100 in 66.7%, and > 400 in 41.7%. Ischemic MPS is associated with a high likelihood of subclinical atherosclerosis by CAC, but it can be also seen for CAC scores <100. The patient without significant coronary artery stenosis, however, may have extensive atherosclerosis by CAC criteria. Although, low CAC scores appear to obviate the need for subsequent testing, but MPS is still needed to diagnosis the myocardial ischemia.

  11. Exercise may cause myocardial ischemia at the anaerobic threshold in cardiac rehabilitation programs.

    Science.gov (United States)

    Fuchs, A R C N; Meneghelo, R S; Stefanini, E; De Paola, A V; Smanio, P E P; Mastrocolla, L E; Ferraz, A S; Buglia, S; Piegas, L S; Carvalho, A A C

    2009-03-01

    Myocardial ischemia may occur during an exercise session in cardiac rehabilitation programs. However, it has not been established whether it is elicited when exercise prescription is based on heart rate corresponding to the anaerobic threshold as measured by cardiopulmonary exercise testing. Our objective was to determine the incidence of myocardial ischemia in cardiac rehabilitation programs according to myocardial perfusion SPECT in exercise programs based on the anaerobic threshold. Thirty-nine patients (35 men and 4 women) diagnosed with coronary artery disease by coronary angiography and stress technetium-99m-sestamibi gated SPECT associated with a baseline cardiopulmonary exercise test were assessed. Ages ranged from 45 to 75 years. A second cardiopulmonary exercise test determined training intensity at the anaerobic threshold. Repeat gated-SPECT was obtained after a third cardiopulmonary exercise test at the prescribed workload and heart rate. Myocardial perfusion images were analyzed using a score system of 6.4 at rest, 13.9 at peak stress, and 10.7 during the prescribed exercise (P exercise was defined as a difference > or = 2 between the summed stress score and summed rest score. Accordingly, 25 (64%) patients were classified as ischemic and 14 (36%) as nonischemic. MIBI-SPECT showed myocardial ischemia during exercise within the anaerobic threshold. The 64% prevalence of ischemia observed in the study should not be looked on as representative of the whole population of patients undergoing exercise programs. Changes in patient care and exercise programs were implemented as a result of our finding of ischemia during the prescribed exercise.

  12. Relationship between coronary contrast-flow quantitative flow ratio and myocardial ischemia assessed by SPECT MPI

    Energy Technology Data Exchange (ETDEWEB)

    Smit, Jeff M.; Rosendael, Alexander R. van; Jukema, J.W.; Delgado, Victoria; Bax, Jeroen J.; Scholte, Arthur J. [Leiden University Medical Center, Department of Cardiology, Leiden (Netherlands); Koning, Gerhard [Medis Medical Imaging Systems B.V., Leiden (Netherlands); Dibbets-Schneider, Petra [Leiden University Medical Center, Department of Nuclear Medicine, Leiden (Netherlands); Mertens, Bart J. [Leiden University Medical Center, Department of Medical Statistics, Leiden (Netherlands); Reiber, Johan H.C. [Medis Medical Imaging Systems B.V., Leiden (Netherlands); Leiden University Medical Center, Department of Radiology, Leiden (Netherlands)

    2017-10-15

    A new method has been developed to calculate fractional flow reserve (FFR) from invasive coronary angiography, the so-called ''contrast-flow quantitative flow ratio (cQFR)''. Recently, cQFR was compared to invasive FFR in intermediate coronary lesions showing an overall diagnostic accuracy of 85%. The purpose of this study was to investigate the relationship between cQFR and myocardial ischemia assessed by single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI). Patients who underwent SPECT MPI and coronary angiography within 3 months were included. The cQFR computation was performed offline, using dedicated software. The cQFR computation was based on 3-dimensional quantitative coronary angiography (QCA) and computational fluid dynamics. The standard 17-segment model was used to determine the vascular territories. Myocardial ischemia was defined as a summed difference score ≥2 in a vascular territory. A cQFR of ≤0.80 was considered abnormal. Two hundred and twenty-four coronary arteries were analysed in 85 patients. Overall accuracy of cQFR to detect ischemia on SPECT MPI was 90%. In multivariable analysis, cQFR was independently associated with ischemia on SPECT MPI (OR per 0.01 decrease of cQFR: 1.10; 95% CI 1.04-1.18, p = 0.002), whereas clinical and QCA parameters were not. Furthermore, cQFR showed incremental value for the detection of ischemia compared to clinical and QCA parameters (global chi square 48.7 to 62.6; p <0.001). A good relationship between cQFR and SPECT MPI was found. cQFR was independently associated with ischemia on SPECT MPI and showed incremental value to detect ischemia compared to clinical and QCA parameters. (orig.)

  13. The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression.

    Science.gov (United States)

    Wang, Yiming; Zhang, Hongming; Chai, Fangxian; Liu, Xingde; Berk, Michael

    2014-12-04

    Major depressive disorder (MDD) is an independent risk factor for coronary heart disease (CHD), and influences the occurrence and prognosis of cardiovascular events. Although there is evidence that antidepressants may be cardioprotective after acute myocardial infarction (AMI) comorbid with MDD, the operative pathophysiological mechanisms remain unclear. Our aim was therefore to explore the molecular mechanisms of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 in a rat model of depression during myocardial ischemia/reperfusion (I/R). Rats were divided randomly into 3 groups (n = 8): D group (depression), DI/R group (depression with myocardial I/R) and escitalopram + DI/R group. The rats in all three groups underwent the same chronic mild stress and separation for 21 days, at the same time, in the escitalopram + DI/R group, rats were administered escitalopram by gavage (10 mg/kg/day). Ligation of the rat's left anterior descending branch was done in the myocardial I/R model. Following which behavioral tests were done. The size of the myocardial infarction was detected using 1.5% TTC dye. The Tunel method was used to detect apoptotic myocardial cells, and both the Rt-PCR method and immunohistochemical techniques were used to detect the expression of Bcl-2 and Bax. Compared with the D and DI/R groups, rats in Escitalopram + DI/R group showed significantly increased movements and sucrose consumption (P escitalopram + DI/R group was significantly decreased (P escitalopram + DI/R groups (P escitalopram + DI/R group were significantly decreased (P escitalopram + DI/R group (P escitalopram. This suggests that clinically escitalopram may have a direct cardioprotective after acute myocardial infarction.

  14. Myocardial perfusion abnormality and effects of Ca channel blockers on myocardial ischemia in patients with hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Yoko [Kyoto Prefectural Univ. of Medicine (Japan)

    1997-03-01

    The purpose of this study was to investigate the frequency of myocardial ischemia and characteristic regions of myocardial hypoperfusion during stress in patients with hypertrophic cardiomyopathy. Furthermore, the effects of Ca channel blocker (verapamil, diltiazem) on myocardial ischemia were studied. One hundred patients with hypertrophic cardiomyopathy underwent exercise {sup 201}Tl SPECT. Sixty-eight patients had one or more {sup 201}Tl abnormalities. Of the 68 patients with {sup 201}Tl abnormalities, 56 had reversible {sup 201}Tl abnormalities and 12 had fixed defect. {sup 201}Tl abnormalities were frequently distributed in the anterior and posterior areas of junction between the ventricular septum and the free wall and the apex. Of the 56 patients with reversible {sup 201}Tl abnormalities, 40 patients underwent one more exercise {sup 201}Tl SPECT after 8 weeks of oral administration of verapamil or diltiazem. The {sup 201}Tl defect was visually scored as the defect score. Transient dilation index was calculated as an index of subendocardial ischemia. The mean defect score decreased significantly from 9.80{+-}4.35 to 5.50{+-}4.63 after verapamil and from 9.90{+-}5.17 to 5.50{+-}4.89 after diltiazem. Mean transient dilation index decreased from 1.20{+-}0.12 to 1.08{+-}0.09 after treatment with verapamil and from 1.16{+-}0.10 to 1.02{+-}0.09 after treatment with diltiazem. (K.H.)

  15. Mild troponin I elevation does not predict ischemia on myocardial perfusion imaging

    Directory of Open Access Journals (Sweden)

    Le Dung Ha

    2017-08-01

    Full Text Available IntroductionData are limited on the degree of mild troponin I elevation and clinical risk factors in predicting myocardial ischemia.MethodsHospitalized adult patients who underwent myocardial perfusion imaging (MPI from 2015 to 2016 at Rochester General Hospital and had mild troponin I elevation (>0.1 and <1.5 ng/mL were included. Predictors of outcomes were determined using logistic regression model.ResultsOne hundred and sixty-six patients with mild troponin I elevation who underwent MPI were followed. Mean age was 69.6 ± 12.5 years and 53.0% of the patients were female. Fourteen patients (8.4% presented with typical chest pain (CP, 60 patients (36.1% had atypical CP and 92 patients (55.4% had no CP on presentation. MPI was positive for ischemia in 45 patients (27.1%. There was no difference in peak troponin I level with ischemia versus no ischemia on MPI (0.34 ng/dL [0.13-0.69] vs. 0.23 ng/dL [0.14-0.50], p value 0.254. Atypical CP did not predict the presence of ischemia on MPI (odds ratio [OR] 1.97, 95% confidence interval [CI] 0.91-4.26. Coronary artery disease (CAD history (age and sex adjusted p value 0.013, diabetes (adjusted p value 0.036, creatinine ≥2 mg/dL (adjusted p value 0.019 and dialysis (adjusted p value 0.006 were statistically significant predictors of ischemia on MPI.ConclusionsIn patients presenting with mild troponin I elevation, peak troponin I level did not predict ischemia on MPI. The presence of CAD history, diabetes, elevated creatinine and dialysis were predictors of ischemia on MPI.

  16. Changes in vasodilation following myocardial ischemia/reperfusion in rats

    DEFF Research Database (Denmark)

    Kristiansen, Sarah Brøgger; Sheykhzade, Majid; Edvinsson, Lars

    2017-01-01

    BACKGROUND: Blockage of a coronary artery, usually caused by arteriosclerosis, can lead to life threatening acute myocardial infarction. Opening with PCI (percutaneous coronary intervention), may be lifesaving, but reperfusion might exacerbate the cellular damage, and changes in the endothelium a...

  17. Effect of controlled hypotension on myocardial ischemia marker in eye-nose related surgery.

    Science.gov (United States)

    Jin, Yuexi; Jiang, Wanna; Ye, Wenlian; Jiang, Aifen; Liu, Le

    2016-11-01

    We aimed to investigate the effect of different controlled hypotension levels on myocardial enzymes and myocardial ischemia protein in elderly hypertension patients, and then provide clinical evidence of suitable controlled hypotension level for them. Then, 45 elderly hypertension patients received elective eye-nose related surgery with nasal endoscope, who were randomly and evenly divided into three groups, including A, B and C groups, with mean arterial pressure (MAP) decreased by 20%, 30% and 40% respectively. The change of myocardial enzymes, myocardial ischemia modified albumin, score of surgical field quality and 12-lead electrocardiogram at different perioperative points were recorded. Then operative time, urine output and postoperative adverse complications of the patients were recorded too. Myocardial enzymes of group C were higher than that of both group A and B at T4, T5 points (pControlled hypotension with MAP reduced by 30% brings minimum myocardial damage and fewer complications, while meeting the demand of surgical field. Thus it is an ideal controlled hypotension level and can be used for elderly hypertension patients safely.

  18. Effect of digoxin on the extent of injury and the severity of arrhythmias during acute myocardial ischemia and infarction in the dog.

    Science.gov (United States)

    Lynch, J J; Lucchesi, B R

    1988-02-01

    Recently, this laboratory has demonstrated an enhanced susceptibility toward the development of lethal ventricular arrhythmias occurring in response to acute posterolateral ischemia in dogs with previous anterior myocardial infarction in the presence of therapeutic serum concentrations of digoxin. In the present study, acute posterolateral myocardial ischemia was produced in the absence of previous myocardial infarction in 15 digoxin-pretreated (1.19 +/- 0.21 ng/ml serum digoxin, 5-7 days pretreatment) and 11 vehicle-pretreated dogs. The incidences of sudden ventricular fibrillation and of 24 h arrhythmic mortality in response to posterolateral ischemia were 4/15 (27%) vs. 1/11 (9%) (p = 0.23) and 7/15 (47%) vs. 4/11 (36%) (p = 0.27) for digoxin- vs. vehicle-pretreated dogs, respectively. Ventricular ectopic activity at 24 and 48 h after the onset of posterolateral ischemia was reduced significantly by both intravenous lidocaine (1.0-5.0 mg/kg) and verapamil (50.0-500.0 micrograms/kg) in the vehicle-pretreated dogs, whereas neither antiarrhythmic agent significantly suppressed ventricular ectopy in the digoxin-pretreated dogs. The mean sizes for developing posterolateral myocardial infarctions (percentage of left ventricle) were greater for the digoxin-pretreatment group (31.9 +/- 2.8%) vs. vehicle-pretreatment group (14.8 +/- 2.0%, p less than 0.001). These findings suggest that uncomplicated acute myocardial ischemia in the presence of serum concentrations of digoxin that are considered clinically therapeutic may result in the development of larger areas of developing myocardial infarction and in the occurrence of ventricular arrhythmias that are less sensitive to suppression with conventional antiarrhythmic agents.

  19. Iodine 123-phenylpentadecanoic acid myocardial scintigraphy: usefulness in the identification of myocardial ischemia.

    Science.gov (United States)

    Kennedy, P L; Corbett, J R; Kulkarni, P V; Wolfe, C L; Jansen, D E; Hansen, C L; Buja, L M; Parkey, R W; Willerson, J T

    1986-11-01

    In this study, we tested the hypothesis that myocardial ischemia induced by exercise in patients is associated with diminished metabolism and/or delayed clearance of an intravenously injected fatty acid, iodine 123-labeled phenylpentadecanoic acid (IPPA). Fifteen normal volunteers and 18 patients with significant coronary heart disease (CHD) received IPPA during exercise. In the patients with CHD, radionuclide ventriculograms were also obtained during exercise. The normal volunteers had relatively uniform initial left ventricular segmental IPPA activity after exercise and uniform IPPA clearance in the interval from 4 to 20 min immediately after exercise. In contrast, the patients with CHD had increased initial left ventricular segmental IPPA activity (63%, p less than .001) and delayed IPPA clearance (44%, p less than .01) in segments supplied by significantly narrowed coronary arteries. Based on analysis with the mean values +/- 1 SD for initial IPPA activity, clearance, or both in normal volunteers, the sensitivity and specificity of exercise IPPA scintigraphy for detecting CHD were 89% and 67%, respectively; when +/- 2 SD differences from the mean values in the normal volunteers were considered, the sensitivity and specificity were 72% and 100%, respectively. Among the total of 27 noninfarcted left ventricular segments supplied by significantly narrowed coronary arteries in the study patients, 26 (96%) had an abnormality (mean +/- 1 SD) of either initial IPPA activity or clearance compared with corresponding segments in the normal volunteers and/or with other left ventricular segments in the same image that were not supplied by significantly narrowed coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Dorsal spinal cord stimulation obtunds the capacity of intrathoracic extracardiac neurons to transduce myocardial ischemia.

    Science.gov (United States)

    Ardell, Jeffrey L; Cardinal, René; Vermeulen, Michel; Armour, J Andrew

    2009-08-01

    Populations of intrathoracic extracardiac neurons transduce myocardial ischemia, thereby contributing to sympathetic control of regional cardiac indices during such pathology. Our objective was to determine whether electrical neuromodulation using spinal cord stimulation (SCS) modulates such local reflex control. In 10 anesthetized canines, middle cervical ganglion neurons were identified that transduce the ventricular milieu. Their capacity to transduce a global (rapid ventricular pacing) vs. regional (transient regional ischemia) ventricular stress was tested before and during SCS (50 Hz, 0.2 ms duration at 90% MT) applied to the dorsal aspect of the T1 to T4 spinal cord. Rapid ventricular pacing and transient myocardial ischemia both activated cardiac-related middle cervical ganglion neurons. SCS obtunded their capacity to reflexly respond to the regional ventricular ischemia, but not rapid ventricular pacing. In conclusion, spinal cord inputs to the intrathoracic extracardiac nervous system obtund the latter's capacity to transduce regional ventricular ischemia, but not global cardiac stress. Given the substantial body of literature indicating the adverse consequences of excessive adrenergic neuronal excitation on cardiac function, these data delineate the intrathoracic extracardiac nervous system as a potential target for neuromodulation therapy in minimizing such effects.

  1. Therapy insight: prophylaxis, monitoring and treatment of perioperative myocardial ischemia with emphasis on urological surgery.

    Science.gov (United States)

    Winkler, Mathias H; Mayer, Eric K; Hrouda, David; Doyle, Patrick

    2007-06-01

    Unrecognized or silent perioperative myocardial ischemia is common in patients who undergo high-risk surgery, including cystectomy, and could predict cardiac morbidity and mortality in postoperative patients. This disorder is not merely a marker of extensive coronary disease but has a close association with perioperative myocardial infarction (PMI). In a review of published data, including meta-analyses, in the context of high-risk urological surgery, up to 50% of PMIs were found to go unrecognized if only clinical signs and symptoms are considered. Prevention and treatment of these previously unrecognized cardiac events might significantly reduce long-term morbidity and mortality. The emergence of reliable markers of PMI, such as increased levels of troponin I, could help in the detection of events that would have otherwise remained unnoticed. In this Review we examine the effect of these developments in the context of high-risk urological surgery. Changes to preoperative assessment, perioperative management, and prophylaxis of PMI are critically assessed. We performed a prospective audit using postoperative troponin I levels to assess the rate of silent perioperative myocardial ischemia and infarction. An increasingly proactive attitude towards perioperative monitoring for myocardial ischemia and infarction has evolved, and postoperative serial screening with troponin I might be beneficial in high-risk patients undergoing major urological surgery.

  2. 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

  3. Increase in experimental infarct size with digoxin in a canine model of myocardial ischemia-reperfusion injury.

    Science.gov (United States)

    Lynch, J J; Simpson, P J; Gallagher, K P; McClanahan, T B; Lee, K A; Lucchesi, B R

    1988-06-01

    In the present study, dogs were pretreated with intravenous digoxin, 0.0125 mg/kg/day, for 6 to 7 consecutive days to achieve clinically relevant serum concentrations; untreated animals were used as control subjects. After pretreatment, nine digoxin-pretreated dogs and nine control dogs were anesthetized and subjected to a 60-minute occlusion of the left circumflex coronary artery, followed by 6 hours of reperfusion. Anatomic myocardial infarct size, expressed as a percentage of the areas at risk of infarction and as a percentage of the total left ventricle were: 20.2 +/- 3.3% control vs 35.4 +/- 6.2% digoxin-pretreated (p less than 0.05) and 8.6 +/- 1.3% control vs 14.7 +/- 2.5% digoxin-pretreated (p less than 0.05), respectively (2.04 +/- 0.37 ng/ml serum digoxin). Regional myocardial blood flow in the nonischemic and ischemic zones tended to be lower in digoxin-pretreated than in control animals at baseline testing and were significantly reduced in the anterior subendocardial sites of digoxin-pretreated dogs during ischemia and reperfusion. These data suggest that an exacerbation or enhancement of myocardial ischemia-reperfusion injury may occur in the presence of clinically observable serum digoxin concentrations.

  4. [Histoautoradiographic study of the heart in experimental myocardial ischemia].

    Science.gov (United States)

    Makhova, A N; Shliapnikov, V N

    1979-01-01

    Autoradiographic examinations of the heart muscle in experimental myocardial necroses using 3H-thymidine, revealed a high DNA synthesis in the connective tissue cells in the zone of necrosis in the acute period of infarction and its subsequent decrease. Deviations from this regularity were observed when relapses of necrosis developed. The activation of DNA synthesis occurred to a lesser extent in stromal cells of the periinfarction and remote zones of the heart. Muscle cells incorporated 3H-thymidine extremely rarely. When myocardial infarction was combined with aterosclerosis, relapses of necrosis occurred frequently, and morphological changes in many arteries and veins were accompanied by 3H-thymidine incorporation into the nuclei of the endothelium, smooth cells and adventitial cells. Inhibition of DNA synthesis in connective tissue cells of various heart zones was observed in cases of combined myocardial infarction and aterosclerosis and hypertension.

  5. PET/CT Imaging in Mouse Models of Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Sara Gargiulo

    2012-01-01

    Full Text Available Different species have been used to reproduce myocardial infarction models but in the last years mice became the animals of choice for the analysis of several diseases, due to their short life cycle and the possibility of genetic manipulation. Many techniques are currently used for cardiovascular imaging in mice, including X-ray computed tomography (CT, high-resolution ultrasound, magnetic resonance imaging, and nuclear medicine procedures. Cardiac positron emission tomography (PET allows to examine noninvasively, on a molecular level and with high sensitivity, regional changes in myocardial perfusion, metabolism, apoptosis, inflammation, and gene expression or to measure changes in anatomical and functional parameters in heart diseases. Currently hybrid PET/CT scanners for small laboratory animals are available, where CT adds high-resolution anatomical information. This paper reviews mouse models of myocardial infarction and discusses the applications of dedicated PET/CT systems technology, including animal preparation, anesthesia, radiotracers, and images postprocessing.

  6. 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...

  7. The uncoordinated-5 homolog B (UNC5B receptor increases myocardial ischemia-reperfusion injury.

    Directory of Open Access Journals (Sweden)

    David Köhler

    Full Text Available The UNC5 receptor family are chemorepulsive neuronal guidance receptors with additional functions outside the central nervous system. Previous studies have implicated that the UNC5B receptor influences the migration of leukocytes into sites of tissue inflammation. Given that this process is a critical step during the pathophysiology of myocardial ischemia followed by reperfusion (IR we investigated the role of UNC5B during myocardial IR. In initial in-vitro experiments, the functional inhibition of UNC5B resulted in a significant reduction of chemotactic migration of neutrophils. In-vivo, using a model of acute myocardial ischemia in UNC5B(+/- and wild type (WT animals, we found a significant reduction of infarct sizes in UNC5B(+/- animals. This was associated with significantly reduced levels of troponin-I and IL-6 in UNC5B(+/- mice. The repression of UNC5B using siRNA and the functional inhibition of UNC5B significantly dampened the extent of myocardial IR injury. Following depletion of neutrophils, we were not able to observe any further reduction in infarct size through functional inhibition of UNC5B in WT and UNC5B(+/- mice. In summary our studies demonstrate an important role for UNC5B during myocardial IR injury, and that UNC5B might be a potential therapeutic target to control reperfusion injury in the future.

  8. The Uncoordinated-5 Homolog B (UNC5B) Receptor Increases Myocardial Ischemia-Reperfusion Injury

    Science.gov (United States)

    Köhler, David; Streißenberger, Ariane; König, Klemens; Granja, Tiago; Roth, Judith M.; Lehmann, Rainer; de Oliveira Franz, Claudia Bernardo; Rosenberger, Peter

    2013-01-01

    The UNC5 receptor family are chemorepulsive neuronal guidance receptors with additional functions outside the central nervous system. Previous studies have implicated that the UNC5B receptor influences the migration of leukocytes into sites of tissue inflammation. Given that this process is a critical step during the pathophysiology of myocardial ischemia followed by reperfusion (IR) we investigated the role of UNC5B during myocardial IR. In initial in-vitro experiments, the functional inhibition of UNC5B resulted in a significant reduction of chemotactic migration of neutrophils. In-vivo, using a model of acute myocardial ischemia in UNC5B+/− and wild type (WT) animals, we found a significant reduction of infarct sizes in UNC5B+/− animals. This was associated with significantly reduced levels of troponin-I and IL-6 in UNC5B+/− mice. The repression of UNC5B using siRNA and the functional inhibition of UNC5B significantly dampened the extent of myocardial IR injury. Following depletion of neutrophils, we were not able to observe any further reduction in infarct size through functional inhibition of UNC5B in WT and UNC5B+/− mice. In summary our studies demonstrate an important role for UNC5B during myocardial IR injury, and that UNC5B might be a potential therapeutic target to control reperfusion injury in the future. PMID:23936025

  9. The influence of clopidogrel on ischemia diagnosed by myocardial perfusion stress testing.

    Science.gov (United States)

    Jovin, Ion S; Ebisu, Keita A; Oprea, Adriana D; Brandt, Cynthia A; Natale, Donna; Finta, Laurie A; Dziura, James; Wackers, Frans J

    2016-08-01

    Clopidogrel is a platelet adenosine receptor antagonist which can influence coronary vascular tone and thus can potentially interfere with myocardial perfusion imaging. We investigated whether clopidogrel can hamper the diagnosis of ischemia in patients undergoing myocardial perfusion testing. Data from a database of 6349 myocardial perfusion stress tests were analyzed. Using a propensity analysis, patients who were taking clopidogrel were compared with patients not taking clopidogrel for the presence of reversible perfusion defects on myocardial single-photon emission computed tomography scans. Of the 6349 tests, the stress technique was adenosine in 2713 patients and exercise in 3636. At the time of the stress test, 277 (4.3%) of the patients were taking clopidogrel. The odds ratio (OR) for patients taking clopidogrel to have a reversible perfusion defect was 2.75 (95% confidence interval [CI] 2.09-3.62; P clopidogrel, the OR was 1.06 (CI 0.76-1.49; P = .73) for patients undergoing adenosine stress tests and 1.60 (CI 0.85-3.00; P = .14) for patients undergoing exercise stress tests. We found no evidence that the use of clopidogrel decreases the likelihood of ischemia on adenosine or exercise stress myocardial perfusion scans.

  10. Introduction to the role of oxygen radicals in myocardial ischemia and infarction.

    Science.gov (United States)

    Kloner, R A

    1988-01-01

    There has been considerable interest over the past several years concerning the role of oxygen radicals in myocardial ischemia-reperfusion injury. The purpose of the following symposium will be to review recent advances in the understanding of oxygen free radical damage to the heart. Included in the symposium are descriptions of the biochemistry of free radicals and evidence of their direct toxic effects on the heart, as well as discussions concerning the effect of oxygen free radical scavengers on myocardial infarct size, the stunned myocardium, and cardiac preservation during surgery.

  11. Intra-myocardial growth hormone administration ameliorates arrhythmogenesis during ischemia-reperfusion in rats.

    Science.gov (United States)

    Kontonika, Marianthi; Barka, Eleonora; Roumpi, Maria; Vilaeti, Agapi D; Baltogiannis, Giannis G; Vlahos, Antonios P; Agathopoulos, Simeon; Kolettis, Theofilos M

    Growth hormone, currently under evaluation for the prevention of left ventricular remodeling post-myocardial infarction, displays antiarrhythmic properties in the acute setting. However, it is uncertain whether these actions are retained after ischemia/reperfusion. Using implanted telemetry transmitters, we examined the effects of prolonged, intra-myocardial growth hormone administration in conscious rats. During a 24-h observation period, ventricular tachyarrhythmias and sympathetic activation were attenuated in treated rats, whereas infarct-size was unchanged. These findings call for further study on the antiarrhythmic effects of growth hormone and on the underlying mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Intravenous infusion of bone marrow mesenchymal stem cells improves myocardial function in a rat model of myocardial ischemia.

    Science.gov (United States)

    Wang, Tong; Tang, Wanchun; Sun, Shijie; Ristagno, Giuseppe; Huang, Zitong; Weil, Max Harry

    2007-11-01

    We investigated the effects of three different sites for delivery of bone marrow mesenchymal stem cells (MSCs) in a rat model of myocardial ischemia. Prospective, randomized, controlled study. University affiliated research institute. Male Sprague-Dawley rats. A thoracotomy was performed under general anesthesia. Myocardial ischemia was induced by ligation of the left anterior descending coronary artery. One month later, animals were randomized to receive 5 x 10(6) MSCs labeled with PKH26 in phosphate buffer solution or phosphate buffer solution alone as a placebo by injection into right femoral vein, directly into the left ventricular (LV) cavity, or into the ischemic zone in the anterior ventricular free wall. Echocardiographically measured myocardial function, including ejection fraction and fractional shortening, was quantitated 2 wks and 4 wks after administering MSCs or phosphate buffer solution. Hemodynamics, including cardiac index, LV dP/dt40, LV negative dP/dt, and LV diastolic pressure were measured 4 wks after administering MSCs or phosphate buffer solution. MSCs were counted in 5-microm sections obtained with cryostat from each harvested heart. Significant improvements in ejection fraction, fractional shortening, cardiac index, LV dP/dt40, LV negative dP/dt, and LV diastolic pressure followed injection of MSCs, regardless of the site of injection. However, the number of MSCs counted in the heart sections was significantly greater after direct myocardial injection. Independently of the site of injection and regardless of the different concentration of bone marrow mesenchymal stem cells identified in the myocardium, myocardial function was comparably improved in all groups of animals treated with MSCs.

  13. Ratio of the value of the blood pressure and myocardial ischemia in critical patients

    Directory of Open Access Journals (Sweden)

    Juan Luis Barrios-Morocho

    2016-04-01

    Full Text Available Objective: To know the relationship between the values of the pressure blood and myocardial ischemia in critical patients older than 65 years who were admitted in emergency to a hospital of medium complexity of social security. Material and methods: Cross-sectional, retrospective, explanatory and observational study. Sampling not probabilistic in 192 critical patients (priority I and II, older than 65 years, which were admitted by emergency to the Hospital II Vitarte EsSalud, since January 2014 to October 2015, with at least one determination of Troponin I at admission in emergency. Ranges of Spearman correlation Test and Test of binary logistic were used to calculate the risk of occurrence of myocardial ischemia in relation to systolic or diastolic blood pressure values. Results: There was a negative correlation between the value of the diastolic blood pressure with the presence of ischemia myocardial (Rho of Spearman = - 0,155; p = 0,032, statistically significant. It was risk found risk of ischemia myocardial in patients with diastolic hypotension OR: 2,545; IC: 1,051-6,163; NC: 95%; and with normal OR diastolic pressure values: 3,320; IC: 1,479-7,452; NC: 95%. Conclusions: Changes in blood pressure are usually presented in critically ill patients, having to take into account the assessment of cardiac enzymes, when diastolic blood pressure values are below normal values. Although the results are clearly predictive, they can't be generalized given our non-random sample, and restricted to over 65 years old.

  14. Neural control hierarchy of the heart has not evolved to deal with myocardial ischemia.

    Science.gov (United States)

    Kember, G; Armour, J A; Zamir, M

    2013-08-01

    The consequences of myocardial ischemia are examined from the standpoint of the neural control system of the heart, a hierarchy of three neuronal centers residing in central command, intrathoracic ganglia, and intrinsic cardiac ganglia. The basis of the investigation is the premise that while this hierarchical control system has evolved to deal with "normal" physiological circumstances, its response in the event of myocardial ischemia is unpredictable because the singular circumstances of this event are as yet not part of its evolutionary repertoire. The results indicate that the harmonious relationship between the three levels of control breaks down, because of a conflict between the priorities that they have evolved to deal with. Essentially, while the main priority in central command is blood demand, the priority at the intrathoracic and cardiac levels is heart rate. As a result of this breakdown, heart rate becomes less predictable and therefore less reliable as a diagnostic guide as to the traumatic state of the heart, which it is commonly used as such following an ischemic event. On the basis of these results it is proposed that under the singular conditions of myocardial ischemia a determination of neural control indexes in addition to cardiovascular indexes has the potential of enhancing clinical outcome.

  15. [Formula Optimization in Renshen Jianxin Capsule Based on Uniform Design and Anti-myocardial Ischemia Effect].

    Science.gov (United States)

    Yang, Chua-hua; Li, Yun-lun; Jiang, Hai-qiang; Nie, Lei; Ju, Jiang-qing; Li, Shuai; Ding, Xue-yi; Zhang, Shi-jun

    2015-09-01

    To realize quadratic formula optimization of Renshen Jianxin Capsule (RJC) by screening Chinese herbs with major anti-myocardial ischemia effect in RJC and optimize their optimal dosages. By following "uniform design-pharmacodynamic experiment-mathematical modeling-formula optimization", authors employed U10(10(8)) uniform design in the experiment. Eight Chinese herbs contained in RJC were taken as observatory factors. Electrocardiograph (ECG) changes of myocardial ischemia induced by isoproterenol were taken as pharmacodynamic indices. The mathematical model between herbal factors and pharmacodynamic indices was established using stepwise regression analysis to screen Chinese herbs with major anti-myocardial ischemia effect. Their optimal dosages were optimized using the grid algorithm. The regression equation was y =1. 7889 -0. 3247 Ginseng xSalvia Miltiorrhiza -0. 0663 Astragalus membranaceus xOriental Waterplantain tuber. Forecasting factors included were Ginseng, Salvia Miltiorrhiza, Astragalus membranaceus, and Oriental Waterplantain tuber. The optimal formula dosage calculated by the grid algorithm was Ginseng 1. 62 g, Astragalus membranaceus 4. 62 g, Salvia Miltiorrhiza 2. 43 g, and Oriental Waterplantain tuber 1. 66 g. Uniform design combined with stepwise regression analysis and grid algorithm were able to realize quadratic formula optimization of RJC.

  16. Myocardial ischemia and cytokine response are associated with subsequent onset of infections after noncardiac surgery.

    Science.gov (United States)

    Spies, Claudia D; Kern, Hartmut; Schröder, Torsten; Sander, Michael; Sepold, Henning; Lang, Philip; Stangl, Karl; Behrens, Steffen; Sinha, Pranav; Schaffartzik, Walter; Wernecke, Klaus-Dieter; Kox, Wolfgang J; Jain, Uday

    2002-07-01

    Postoperative myocardial ischemia (POMI) is prevalent among patients after major noncardiac surgery. Surgery, as well as POMI, may modulate the immune system, potentially worsening patient outcome. We sought to investigate the modulation of soluble interleukin (IL)-6 and IL-10 by POMI and its association with increased postoperative infection rates. Two-hundred-three patients undergoing elective major abdominal, vascular, and orthopedic surgery participated in this prospective observational study. Perioperative management was standardized. Hemodynamic variables were kept within 20% of baseline. POMI was assessed by Holter electrocardiography starting at least 8 h before the induction of anesthesia and continued until 96 h after surgery. Twelve-lead electrocardiograms, cardiac enzymes, and immune variables were obtained at the time of admission to the hospital, before surgery, before the induction of anesthesia, after surgery, at the time of admission to the intensive care unit, and 6, 12, 18, 24, 36, 48, 72, 96, 120, 144, and 168 h after surgery. Infections were diagnosed according to the Centers for Disease Control criteria. The incidence of POMI was 27%, and the majority of cases (76%) occurred within the first 24 h after surgery. IL-6 and IL-10 levels significantly increased during surgery but did not differ between the POMI and Non-POMI groups. However, in the subset of patients who developed severe infections or sepsis (n = 47) a median of 3 days (range, 1-8 days) after surgery, the intraoperative increases of IL-6 and IL-10 in the POMI group were, respectively, 3 and 10 times higher compared with the increase in the Non-POMI group. By using a multifactorial analysis in these patients with severe infections, the type of surgical trauma was associated with an increased IL-6 response, whereas the increase in IL-10 was attributed to POMI. These findings suggest that immediate cytokine responses due to POMI and type of surgery might be relevant for the later onset

  17. shRNA interference of NLRP3 inflammasome alleviate ischemia reperfusion-induced myocardial damage through autophagy activation.

    Science.gov (United States)

    Meng, Zhu; Song, Mei-Yan; Li, Chuan-Fang; Zhao, Jia-Qi

    2017-12-16

    Myocardial ischemia-reperfusion (I/R) injury always occur during the recovery of myocardial blood supply with high morbidity and mortality. Although, various therapeutic schedules were applied in clinic, there are real problems that have to be resolved on curative effect. Nod-like receptor protein 3 (NLRP3) inflammasome has moderation effects on cellular damage and inflammatory reaction after I/R injury. Our research aims to investigate a more effective approach to restrain the activation of NLRP3 inflammasome in treating myocardial I/R injury. Results indicated that cell viability, Bax/Bcl-2 expression were affected hardly by sh-NLRP3 transfection in normal cells. However, the decreased cell viability and increased Bax/Bcl-2 expression level caused by I/R were remarkably suppressed through sh-NLRP3 transfection. Besides that, the reduced levels of pro-autophagy proteins (Beclin1, Agt7, LC3II/LC3I) while enhanced level of anti-autophagy protein (p62) and apoptosis-related proteins (Bax/Bcl-2) were significantly repressed via sh-NLRP3 transfection. Nevertheless, the autophagy inhibitor 3 MA could reverse the results. Moreover, in vivo experiment suggested that NLRP3 was up-regulated in wild type (WT) rats with I/R injury. The expansion of infarct size induced by ischemia was tremendously constricted in NLRP3 knockout (KO) rats. NLRP3 silence had nearly no impact on myocardial enzymes (AST, LDH and CK) expressions, inflammatory factors (TNF-α and IL-1β) expressions and cell apoptosis in rats without I/R injury. Nonetheless, the elevated levels of myocardial enzymes, inflammatory factors and cell apoptosis caused by I/R injury were vastly inhibited in NLRP3 KO rats. Furthermore, NLRP3 KO itself would lead to higher level of pro-autophagy proteins (Beclin1, Agt7, LC3II/LC3I) while lower level of anti-autophagy protein (p62) in vivo. The decreased expressions of pro-autophagy proteins while increased expressions of anti-autophagy protein induced by I/R injury were

  18. Effects and Mechanisms of Chinese Herbal Medicine in Ameliorating Myocardial Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Qing Liu

    2013-01-01

    Full Text Available Myocardial ischemia-reperfusion (MIR injury is a major contributor to the morbidity and mortality associated with coronary artery disease, which accounts for approximately 450,000 deaths a year in the United States alone. Chinese herbal medicine, especially combined herbal formulations, has been widely used in traditional Chinese medicine for the treatment of myocardial infarction for hundreds of years. While the efficacy of Chinese herbal medicine is well documented, the underlying molecular mechanisms remain elusive. In this review, we highlight recent studies which are focused on elucidating the cellular and molecular mechanisms using extracted compounds, single herbs, or herbal formulations in experimental settings. These studies represent recent efforts to bridge the gap between the enigma of ancient Chinese herbal medicine and the concepts of modern cell and molecular biology in the treatment of myocardial infarction.

  19. Myocardial strain may be useful in differentiating Takotsubo cardiomyopathy from left anterior descending coronary artery ischemia.

    Science.gov (United States)

    Cai, LiYing; Addetia, Karima; Medvedofsky, Diego; Spencer, Kirk T

    2017-03-01

    Stress-induced cardiomyopathy (SCM) is characterized by transient apical wall motion abnormalities of the left ventricle (LV) in the absence of obstructive coronary artery disease. Although the echocardiographic findings of SCM mimic those of left anterior descending coronary artery ischemia or infarction (LAD), the regional LV wall motion pattern and degree of RV involvement may differ. We sought to systematically assess regional LV and RV function with myocardial strain imaging to assess if ventricular involvement may differ between SCM and LAD. This was a retrospective cohort study, with 3 groups: patients with SCM (n=55), patients with LAD (n=36), and 37 normal subjects. All the patients had a comprehensive transthoracic echocardiographic examination, including assessment of longitudinal strain (LS). Global LV longitudinal strain was markedly decreased in both the SCM and LAD groups. However, SCM patients differed by more severe involvement the mid-inferolateral, mid-inferior, apical-lateral, and apical-inferior segments. When compared to the LAD patients, SCM patients had significantly more RV involvement both visually and quantitatively (27-42% versus 0-25%). Predictors of SCM included visually reduced RV systolic function, abnormal TAPSE, RVS' and RV LS in the apical segment. Of the LV variables, regional LS in the mid-inferior and apical-inferior segments could differentiate the groups. Our results suggest that RV involvement and the pattern of LV regional LS abnormalities may help differentiate SCM from LAD disease during echocardiographic imaging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Protection against myocardial ischemia-reperfusion injury in clinical practice.

    Science.gov (United States)

    Garcia-Dorado, David; Rodríguez-Sinovas, Antonio; Ruiz-Meana, Marisol; Inserte, Javier

    2014-05-01

    Even when reperfusion therapy is applied as early as possible, survival and quality of life are compromised in a considerable number of patients with ST-segment elevation acute myocardial infarction. Some cell death following transient coronary occlusion occurs during reperfusion, due to poor handling of calcium in the sarcoplasmic reticulum-mitochondria system, calpain activation, oxidative stress, and mitochondrial failure, all promoted by rapid normalization of intracellular pH. Various clinical trials have shown that infarct size can be limited by nonpharmacological strategies--such as ischemic postconditioning and remote ischemic conditioning--or by drugs--such as cyclosporine, insulin, glucagon-like peptide-1 agonists, beta-blockers, or stimulation of cyclic guanosine monophosphate synthesis. However, some clinical studies have yielded negative results, largely due to a lack of consistent preclinical data or a poor design, especially delayed administration. Large-scale clinical trials are therefore necessary, particularly those with primary clinical variables and combined therapies that consider age, sex, and comorbidities, to convert protection against reperfusion injury into a standard treatment for patients with ST-segment elevation acute myocardial infarction. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  1. Clinical assessment of left ventricular systolic torsion: effects of myocardial infarction and ischemia.

    Science.gov (United States)

    Bansal, Manish; Leano, Rodel L; Marwick, Thomas H

    2008-08-01

    The helical arrangement of myocardial fibers leads to left ventricular (LV) torsion, a vital contributor to systolic and diastolic function. Rotation and torsion can now be measured; we sought to determine the utility of torsion as a marker of LV function at rest and after stress in patients with myocardial infarctions (MIs) and ischemia. Dobutamine echocardiography was performed in 125 patients. After the exclusion of 40 patients with suboptimal images, LV systolic rotation and torsion were measured offline using speckle-tracking echocardiography in 44 patients with and 41 without prior MIs. Hemodynamic findings and the extent of infarction and ischemia were correlated with length-corrected torsion measurements at baseline and at peak-dose dobutamine. Resting global and regional LV systolic torsion were significantly reduced in patients with compared with those without previous MIs (1.16 +/- 1.15 degrees /cm vs 3.16 +/- 1.3 degrees /cm, P anteroapical or inferoposterior infarcts (1.81 +/- 1.13 degrees /cm vs 2.27 +/- 1.18 degrees /cm, P = NS) and no differences in regional torsion. Torsion was most impaired in patients with multiple areas of infarction (1.03 +/- 0.89 degrees /cm, P < .001). However, dobutamine-induced ischemia (2.59 +/- 1.14 ischemic segments) had no effect on global and regional systolic torsion at peak dose or change in torsion from rest to peak dose. The influence of MI on LV systolic torsion appears to be related to infarct size rather than site, and torsion was an independent determinant of resting function. LV torsion was not significantly influenced by stress-induced myocardial ischemia.

  2. 45. Ezetimibe and statins yields on silent holter ambulatory myocardial ischemia

    Directory of Open Access Journals (Sweden)

    W. Kadro

    2016-07-01

    Full Text Available Further cholestrol lowering may affect silent ischemia detected on holter monitoring. Cholesterol lowering is associated with a reduction in cardiovascular morbidity and mortality. Statins are the main drugs for cholesterol lowering. Ezetimibe when added to statins gives further reduction in cholesterol but its long-term effect on cardiovascular morbidity and mortality and ischemic events is not known. This study sought to determine whether further cholesterol lowering with ezitimibe will also results in a reduction of myocardial ischemia during daily life. We enrolled 50 patients with proven stable coronary artery disease (CAD and at least one episode of ST-segment depression on ambulatory ECG monitoring. All of them were receiving optimal therapy for CAD including statin therapy for cholesterol reduction. 25 patients were randomized to continue their statin therapy (Statin only group and 25 to recieve statin plus ezitimibe 10 mg/day (ezitimibe group. Serum cholesterol and LDL cholesterol levels and ambulatory monitoring were repeated after 4–6 months of therapy. The two groups were comparable with respect to baseline characteristics, number of episodes of ST-segment depression, and baseline serum cholesterol levels. The ezitimibe group had lower mean total and LDL cholesterol levels at study end and experienced a significant reduction in the number of episodes of ST-segment depression compared with the statin only group. ST-segment depression was completely resolved in 13 of 25 patients (52% in the ezitimibe group versus 3 of 25 (12% in the statin only group. The ezitimibe group exhibited a highly significant reduction in ambulatory ischemia (P < .001. By logistic regression, treatment with ezitimibe was an independent predictor of ischemia resolution. Further cholesterol lowering with ezitimibe can result in reduction or resolution of myocardial ischemia recorded as episodes of ST-segment depression in ambulatory monitoring of the ECG.

  3. [Intracoronary and hypodermic injection of granulocyte colony-stimulating factor improved cardiac function in Swine with chronic myocardial ischemia].

    Science.gov (United States)

    Huang, Rong-chong; Yao, Kang; Lu, Hao; Yang, Jun; Shi, Hong-cheng; Zhang, Yi-qi; Huang, Zhe-yong; Zhang, Shu-ning; Yang, Shan; Sun, Ai-jun; Zou, Yun-zeng; Ge, Jun-bo

    2009-08-01

    To compare the efficacy and feasibility between intracoronary and hypodermic injection of granulocyte colony-stimulating factor (G-CSF) on improving cardiac function in a Swine model of chronic myocardial ischemia. Eighteen Swine underwent placement of ameroid constrictor on left circumflex coronary artery. The presence of myocardial ischemia was verified at four weeks after the operation, and the animals were then randomly assigned into three groups (n = 6 each): (1) administration of vehicle (control), (2) hypodermic injection of G-CSF (5 microgxkg(-1)x;d(-1)) for five days (IH), and (3) intracoronary injection of a bonus G-CSF (60 microg/kg) (IC). Coronary angiogram, cardiac MRI, and (18)F-FDG-SPECT/(99m)Tc-SPECT (DISA-SPECT) measurements were performed at pre-administration and at 4 weeks post administration. Global heart function such as left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVSDV) and left ventricular ejection fraction (LVEF), myocardial perfusion, myocardial viability and myocardial infarct area were evaluated. Myocardial vWF, Bcl-2 and Bax expressions were detected by Western blot and RT-PCR. MRI data showed that left ventricular dilation and dysfunction were similarly prevented in IH and IC G-CSF treated animals at eight weeks after the operation. SPECT revealed that both IH and IC G-CSF equally improved the regional contractility of chronic myocardial ischemia and increased myocardial viability. Myocardial infarct size was also reduced after both G-CSF treatments as detected by MRI. Intracoronary injection of G-CSF did not lead to angiogenesis in other organs. G-CSF treatments were also associated with a significant reduction in myocardial apoptosis and significant increase in angiogenesis. Both intracoronary and hypodermic injection of G-CSF were safe and feasible and could equally improve cardiac function and increase angiogenesis in this Swine model of chronic myocardial ischemia.

  4. A Biomimic Reconstituted High Density Lipoprotein Nanosystem for Enhanced VEGF Gene Therapy of Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Xiaotian Sun

    2015-01-01

    Full Text Available A biomimic reconstituted high density lipoprotein (rHDL based system, rHDL/Stearic-PEI/VEGF complexes, was fabricated as an advanced nanovector for delivering VEGF plasmid. Here, Stearic-PEI was utilized to effectively condense VEGF plasmid and to incorporate the plasmid into rHDL. The rHDL/Stearic-PEI/VEGF complexes with diameter under 100 nm and neutral surface charge demonstrated enhanced stability under the presence of bovine serum albumin. Moreover, in vitro cytotoxicity and transfection assays on H9C2 cells further revealed their superiority, as they displayed lower cytotoxicity with much higher transfection efficiency when compared to PEI 10K/VEGF and Lipos/Stearic-PEI/VEGF complexes. In addition, in vivo investigation on ischemia/reperfusion rat model implied that rHDL/Stearic-PEI/VEGF complexes possessed high transgene capacity and strong therapeutic activity. These findings indicated that rHDL/Stearic-PEI/VEGF complexes could be an ideal gene delivery system for enhanced VEGF gene therapy of myocardial ischemia, which might be a new promising strategy for effective myocardial ischemia treatment.

  5. Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning

    DEFF Research Database (Denmark)

    Schmidt, Michael Rahbek; Smerup, M; Konstantinov, I E

    2006-01-01

    Remote ischemic preconditioning reduces myocardial infarction (MI) in animal models. We tested the hypothesis that the systemic protection thus induced is effective when ischemic preconditioning is administered during ischemia (PerC) and before reperfusion and examined the role of the K(+)-depend...

  6. Effects of ischemia and coronary reperfusion on myocardial digoxin uptake.

    Science.gov (United States)

    Beller, G A; Smith, T W; Hood, W B

    1975-12-01

    The effects of coronary reperfusion on the uptake of digoxin by ischemic myocardium were studied in 17 open chest dogs undergoing anterior wall infarction produced by snaring confluent branches of the left coronary arterial system. Epicardial electrograms delineated ischemic, border and nonischemic zones. The hearts were reperfused by snare release after 1, 2 and 6 hours of occlusion. After 15 minutes of reperfusion, 1.0 mg of tritiated digoxin (3H-digoxin) was given intravenously, and 2 hours later the hearts were excised and endocardial and epicardial samples from each zone were analyzed for 3H-digoxin concentration. In another group of eight dogs regional myocardial blood flow was assessed utilizing 15 mu of radio-labeled microspheres administered during occlusion and reperfusion. In five dogs with 1 hour of coronary occlusion and subsequent reperfusion, 3H-digoxin uptake was comparable in endocardial and epicardial layers of all three zones. In six dogs undergoing reperfusion after 2 hours of occlusion, mean 3H-digoxin concentration was significantly (P less than 0.001) reduced from the mean nonischemic concentration, by 54 percent in endocardial and 35 percent in epicardial layers of the ischemic zone. Border zone endocardial and epicardial 3H-digoxin uptake was reduced by 21 percent and 16 percent, respectively (P less than 0.05). In six dogs undergoing reperfusion after 6 hours of occlusion, 3H-digoxin uptake in the ischemic zone was significantly (P less than 0.001) reduced by 85 percent in endocardial and 60 percent in epicardial layers from the concentration in the nonischemic zone. Border zone uptake was decreased by 54 percent in endocardial and 36 percent in epicardial regions (P less than 0.01). These alterations of in vivo digoxin binding could not be explained by impaired reflow of blood to ischemic myocardium. We conclude that coronary reperfusion after 2 to 6 hours of occlusion is associated with a marked reduction in myocardial digoxin uptake

  7. Myocardial bridging causing ischemia and recurrent chest pain: a case report

    Directory of Open Access Journals (Sweden)

    Abdou Mohamed

    2011-07-01

    Full Text Available Abstract Background Myocardial bridging is present when a segment of a major epicardial coronary artery runs intramurally through the myocardium. It usually has a benign prognosis, but in some cases myocardial ischemia, infarction and sudden cardiac death have been reported. We are here reporting a case of myocardial bridging which was complicated with recurrent chest pain and transient ST-segment elevation during exercise treadmill test. Case presentation A 40 year-old-man presented with recurrent retrosternal chest pain of 2 months duration. He had history of smoking and was obese, otherwise no physical abnormalities were detected by examination. Electrocardiogram and blood tests were normal apart from impaired glucose tolerance with elevated triglycerides and decreased level of high density lipoprotein cholesterol. While doing exercise treadmill test, the patient developed chest pain and significant ST-segment elevation in almost all precordial leads that persisted for about 15 minutes through recovery. We decided to admit the patient to the coronary care unit for further management and to perform coronary angiogram. Myocardial bridging was observed in the mid segment of the left anterior descending coronary artery. Medical treatment was decided. At one year follow up, our patient was healthy and had no cardiac complaints. In conclusion, myocardial bridging may predispose to coronary vasospasm that may leads to ischemic complications.

  8. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Tong, Chao; Peng, Chuan; Wang, Lianlian; Zhang, Li; Yang, Xiaotao; Xu, Ping; Li, Jinjin; Delplancke, Thibaut; Zhang, Hua; Qi, Hongbo

    2016-03-03

    Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice.

  9. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Chao Tong

    2016-03-01

    Full Text Available Background: Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV administration dose of lycopene protects against myocardial infarction (MI in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS production and related signaling pathways during myocardial I/R. Methods: In this study, we established both in vitro hypoxia/reoxygenation (H/R cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Results: Lycopene treatment (1 μM before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Conclusion: Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice.

  10. Metabonomic analysis of Allium macrostemon Bunge as a treatment for acute myocardial ischemia in rats.

    Science.gov (United States)

    Li, Fang; Xu, Qian; Zheng, Ting; Huang, Fang; Han, Lintao

    2014-01-01

    Myocardial ischemia (MI) refers to a pathological state of the heart caused by reduced cardiac blood perfusion, which leads to a decreased oxygen supply in the heart and an abnormal myocardial energy metabolism. Acute myocardial ischemia (AMI) has posed a significant health risk for humans. Allium macrostemon Bunge (AMB), a popular traditional Chinese medicine, is used for MI treatment. The therapeutic effects of AMB were assessed and the detailed mechanisms of AMB for AMI treatment were investigated. We characterized the metabonomic variations in rats from the sham surgery, AMI, and AMB-pretreated AMI groups through a combination of nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analysis. Thirty-five metabolites including carbohydrates, a range of amino acids, and organic acids were detected. The (1)H NMR spectra of the rat serum were analyzed using the principal component analysis (PCA) and orthogonal projection to latent structures discriminate analysis (OPLS-DA). Results showed that AMI induced some physiological changes in rats and also led to metabolic disorders related to glycolysis promotion, amino acid metabolism disruption, and other metabolite metabolism perturbation. AMB pretreatment reduced the AMI injury and maintained metabolic balance, possibly by limiting the change in energy metabolism and regulating amino acid metabolism. These findings provide a comprehensive insight on the metabolic response of AMI rats to AMB pretreatment and are important for the use of AMB for AMI therapy. Published by Elsevier B.V.

  11. Inhibition of KV7 channels protects against myocardial ischemia and reperfusion injury

    DEFF Research Database (Denmark)

    Hedegaard, Elise Røge; Johnsen, Jacob; Povlsen, Jonas Agerlund

    2015-01-01

    the expression of the KV7 channels in rat hearts by reverse transcriptse PCR. The effect of the KV7 channel inhibitors, XE991 and linopirdine, and the KV7 channel opener, flupirtine on myocardial IR injury in isolated hearts and coronary arteries from Wistar rats was examined. Hearts were subjected to no......Aims: KV7 channel are activated by ischemia and mediate hypoxic vasodilatation. We investigated the effect of KV7 channel modulation on cardiac ischemia and reperfusion (IR) injury and the interaction with cardioprotection by ischemic preconditioning (IPC). Methods and Results: We investigated.......1, KV7.4 and KV7.5 were expressed in rat coronary arteries and all KV7 subtypes (KV7.1-5) in the left and right ventricles of the heart. KV7 channel blockade by XE991 and linopirdine reduced infarct size additive to infarct reduction by IPC. Flupirtine abolished infarct size reduction by IPC...

  12. Influence of electrode misplacement on the electrocardiographic signs of inferior myocardial ischemia.

    Science.gov (United States)

    Rudiger, Alain; Schöb, Lukas; Follath, Ferenc

    2003-11-01

    Electrocardiographic (ECG) artifacts resulting from misplacements of electrodes are frequent, difficult to detect, and can become of clinical importance. We investigated 2 healthy volunteers and 3 patients with ECG signs of inferior myocardial scars. We exchanged the peripheral electrodes in a defined manner and investigated the resulting ECG for morphology and possible diagnostic errors. In the volunteers, ECG signs of inferior ischemia could be produced. In the patients with ischemic heart disease, normal ECG without signs of ischemia resulted by placing the electrode of the left leg to the left arm. The automatic ECG analyzer was not helpful in detecting artifacts by misplaced electrodes. A very low amplitude of the QRS complex in lead I, II, or III was pathognomonic for electrode misplacement in half of the cases. ECG artifacts must also be suspected when abnormal QRS- or P-axis occur or when QRS morphology does not match with the clinical presentation of the patient.

  13. Sulfonylurea Receptor 1 Subunits of ATP-Sensitive Potassium Channels and Myocardial Ischemia/Reperfusion Injury

    Science.gov (United States)

    Lefer, David J.; Nichols, Colin G.; Coetzee, William A.

    2009-01-01

    KATP channels are generally cardioprotective under conditions of metabolic impairment, consisting of pore-forming (Kir6.1 and/or Kir6.2) and sulphonylurea-binding, modulatory subunits (SUR1, SUR2A or SUR2B). Cardiovascular KATP channels are generally thought to consist of Kir6.2/SUR2A subunits (in the case of heart muscle) or Kir6.1/SUR2B subunits (smooth muscle), whereas SUR1-containing channels have well-documented roles in pancreatic insulin release. Recent data, however, demonstrated the presence of SUR1 subunits in mouse cardiac tissue (particularly in atria) and a surprising protection from myocardial ischemia/reperfusion in SUR1-null mice. Here we review some of the extra-pancreatic roles assigned to SUR1 subunits and consider whether these might be involved in the sequelae of ischemia/reperfusion. PMID:19577714

  14. Myocardial capillary permeability for small hydrophilic indicators during normal physiological conditions and after ischemia and reperfusion

    DEFF Research Database (Denmark)

    Svendsen, J H

    1991-01-01

    these PdS values Pd values between 1.57.10(-5) and 1.92.10(-5) cm.s-1 were calculated, in accordance with values obtained by other methods. Similar data have been obtained in myocardium of patients undergoing coronary angiography. Oxygen derived free radicals seems to participate in reperfusion injury...... including microvascular alterations. In open chest dogs transitory increases in capillary extraction fraction and PdS for small hydrophilic solutes were seen following 20 minutes of regional myocardial ischemia and reperfusion. This response could be inhibited by treatment directed against superoxide...

  15. Comparison of cardioprotective and anti-inflammatory effects of ischemia pre- and postconditioning in rats with myocardial ischemia-reperfusion injury.

    Science.gov (United States)

    Xiong, Jun; Wang, Qiang; Xue, Fu-Shan; Yuan, Yuan-Jing; Li, Shan; Liu, Jian-Hua; Liao, Xu; Zhang, Yan-Ming

    2011-06-01

    To compare cardioprotective and anti-inflammatory effects of ischemia preconditioning (IPC) and ischemia postconditioning (IPOC) in a rat myocardial ischemia-reperfusion injury (IRI) model. Forty Sprague-Dawley rats were randomly divided equally into four groups. In the groups other than the sham group, the left anterior descending coronary artery was ligated for 30 min followed by a 180 min reperfusion in vivo. The control group was subjected to no additional intervention, the IPC group to three cycles of 5 min ischemia separated by 5 min reperfusion before the index ischemia and the IPOC group to three cycles of 10 s ischemia separated by 10 s reperfusion immediately after the end of the index ischemia. Hemodynamic changes during the ischemia and reperfusion were recorded. At 180 min of reperfusion, serum concentrations of troponin I (TnI), tumor necrosis factor α (TNF-α) and high-mobility group box 1 (HMGB-1) were assayed, and the infarction size was assessed by Evans blue and triphenyltetrazolium chloride staining. Compared to the control group, infarct size and serum concentrations of TnI, TNF-α and HMGB1 at 180 min of reperfusion were significantly reduced in the IPC and IPOC groups. However, infarct size and serum concentrations of TNF-α and HMGB1 at 180 min of reperfusion were significantly increased in the IPOC group compared to the IPC group. In the rats with myocardial IRI in vivo, both IPC and IPOC can produce significant cardioprotective and anti-inflammatory effects. However, cardioprotective and anti-inflammatory effects provided by IPOC are weaker than with IPC.

  16. Viscerosomatic interaction induced by myocardial ischemia in conscious dogs

    National Research Council Canada - National Science Library

    Patricia A. Gwirtz; Jerry Dickey; David Vick; Maurice A. Williams; Brian Foresman

    2007-01-01

    ...–T5 region that can be detected by palpatory means. This is consistent with theories of manual medicine suggesting that disturbances in visceral organ physiology can cause increases in skeletal muscle tone in specific muscle groups...

  17. Postoperative real-time electrocardiography monitoring detects myocardial ischemia: a case report.

    Science.gov (United States)

    Yang, Homer; Fayad, Ashraf; Chaput, Alan; Oake, Stuart; Chan, Adrian D C; Crossan, Mary Lou

    2017-04-01

    This case report outlines the utility and challenges of remote continuous postoperative electrocardiography ECG) monitoring, which is routed through a secure smartphone to provide real-time detection and management of myocardial ischemia. A 42-yr-old male with previous myocardial infarction and angioplasty underwent a radical prostatectomy. At three hours and 45 min postoperatively, remote real-time ECG monitoring was initiated upon the patient's arrival on a regular surgical ward. Monitor alerts were routed to a study clinician's smartphone. About six hours postoperatively, alarms were received and horizontal ST segment depressions were observed. A 12-lead ECG validated the ST segment changes, prompting initiation of a metoprolol iv and a red blood cell transfusion. Approximately seven hours and 30 min postoperatively, the ST segments normalized. The patient was discharged on postoperative day 3 and followed for four years without any sequelae. This case report illustrates the use of remote ECG monitoring and clinician response in real time with the use of a smartphone. With each alert, a small ECG strip is transmitted to the smartphone for viewing. In our view, this technology and management system provides a possible means to interrupt myocardial ischemic cascades in real time and prevent postoperative myocardial infarction.

  18. N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy

    Directory of Open Access Journals (Sweden)

    Sheng Wang

    2017-01-01

    Full Text Available Background. Excessive autophagy is a major mechanism of myocardial ischemia reperfusion injury (I/RI in diabetes with enhanced oxidative stress. Antioxidant N-acetylcysteine (NAC reduces myocardial I/RI. It is unknown if inhibition of autophagy may represent a mechanism whereby NAC confers cardioprotection in diabetes. Methods and Results. Diabetes was induced in Sprague-Dawley rats with streptozotocin and they were treated without or with NAC (1.5 g/kg/day for four weeks before being subjected to 30-minute coronary occlusion and 2-hour reperfusion. The results showed that cardiac levels of 15-F2t-Isoprostane were increased and that autophagy was evidenced as increases in ratio of LC3 II/I and protein P62 and AMPK and mTOR expressions were significantly increased in diabetic compared to nondiabetic rats, concomitant with increased postischemic myocardial infarct size and CK-MB release but decreased Akt and eNOS activation. Diabetes was also associated with increased postischemic apoptotic cell death manifested as increases in TUNEL positive cells, cleaved-caspase-3, and ratio of Bax/Bcl-2 protein expression. NAC significantly attenuated I/RI-induced increases in oxidative stress and cardiac apoptosis, prevented postischemic autophagy formation in diabetes, and reduced postischemic myocardial infarction (all p<0.05. Conclusions. NAC confers cardioprotection against diabetic heart I/RI primarily through inhibiting excessive autophagy which might be a major mechanism why diabetic hearts are less tolerant to I/RI.

  19. Visualization of network target crosstalk optimizes drug synergism in myocardial ischemia.

    Directory of Open Access Journals (Sweden)

    Xiaojing Wan

    Full Text Available Numerous drugs and compounds have been validated as protecting against myocardial ischemia (MI, a leading cause of heart failure; however, synergistic possibilities among them have not been systematically explored. Thus, there appears to be significant room for optimization in the field of drug combination therapy for MI. Here, we propose an easy approach for the identification and optimization of MI-related synergistic drug combinations via visualization of the crosstalk between networks of drug targets corresponding to different drugs (each drug has a unique network of targets. As an example, in the present study, 28 target crosstalk networks (TCNs of random pairwise combinations of 8 MI-related drugs (curcumin, capsaicin, celecoxib, raloxifene, silibinin, sulforaphane, tacrolimus, and tamoxifen were established to illustrate the proposed method. The TCNs revealed a high likelihood of synergy between curcumin and the other drugs, which was confirmed by in vitro experiments. Further drug combination optimization showed a synergistic protective effect of curcumin, celecoxib, and sililinin in combination against H₂O₂-induced ischemic injury of cardiomyocytes at a relatively low concentration of 500 nM. This result is in agreement with the earlier finding of a denser and modular functional crosstalk between their networks of targets in the regulation of cell apoptosis. Our study offers a simple approach to rapidly search for and optimize potent synergistic drug combinations, which can be used for identifying better MI therapeutic strategies. Some new light was also shed on the characteristic features of drug synergy, suggesting that it is possible to apply this method to other complex human diseases.

  20. PI3Kgamma protects from myocardial ischemia and reperfusion injury through a kinase-independent pathway.

    Directory of Open Access Journals (Sweden)

    Bernhard J Haubner

    Full Text Available BACKGROUND: PI3Kgamma functions in the immune compartment to promote inflammation in response to G-protein-coupled receptor (GPCR agonists and PI3Kgamma also acts within the heart itself both as a negative regulator of cardiac contractility and as a pro-survival factor. Thus, PI3Kgamma has the potential to both promote and limit M I/R injury. METHODOLOGY/PRINCIPAL FINDINGS: Complete PI3Kgamma-/- mutant mice, catalytically inactive PI3KgammaKD/KD (KD knock-in mice, and control wild type (WT mice were subjected to in vivo myocardial ischemia and reperfusion (M I/R injury. Additionally, bone-marrow chimeric mice were constructed to elucidate the contribution of the inflammatory response to cardiac damage. PI3Kgamma-/- mice exhibited a significantly increased infarction size following reperfusion. Mechanistically, PI3Kgamma is required for activation of the Reperfusion Injury Salvage Kinase (RISK pathway (AKT/ERK1/2 and regulates phospholamban phosphorylation in the acute injury response. Using bone marrow chimeras, the cardioprotective role of PI3Kgamma was mapped to non-haematopoietic cells. Importantly, this massive increase in M I/R injury in PI3Kgamma-/- mice was rescued in PI3Kgamma kinase-dead (PI3KgammaKD/KD knock-in mice. However, PI3KgammaKD/KD mice exhibited a cardiac injury similar to wild type animals, suggesting that specific blockade of PI3Kgamma catalytic activity has no beneficial effects. CONCLUSIONS/SIGNIFICANCE: Our data show that PI3Kgamma is cardioprotective during M I/R injury independent of its catalytic kinase activity and that loss of PI3Kgamma function in the hematopoietic compartment does not affect disease outcome. Thus, clinical development of specific PI3Kgamma blockers should proceed with caution.

  1. All-Trans Retinoic Acid Ameliorates Myocardial Ischemia/Reperfusion Injury by Reducing Cardiomyocyte Apoptosis

    Science.gov (United States)

    Zhao, Xiaoran; Yang, Ke; Lu, Lin; Zhang, Fengru; Shen, Weifeng; Zhang, Ruiyan

    2015-01-01

    Myocardial ischemia/reperfusion (I/R) injury interferes with the restoration of blood flow to ischemic myocardium. Oxidative stress-elicited apoptosis has been reported to contribute to I/R injury. All-trans retinoic acid (ATRA) has anti-apoptotic activity as previously reported. Here, we investigated the effects and the mechanism of action of ATRA on myocardial I/R injury both in vivo and in vitro. In vivo, ATRA reduced the size of the infarcted area (17.81±1.05% vs. 24.41±1.03%, PATRA on myocardial I/R injury was related to its anti-apoptotic effects. The anti-apoptotic effects of ATRA were associated with partial inhibition of reactive oxygen species (ROS) production and significantly less phosphorylation of mitogen-activated protein kinases (MAPKs) including p38, JNK, and ERK. Western blot analysis also revealed that ATRA pre-treatment increased a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) expression (0.65 ± 0.20 vs. 0.41±0.02 in vivo) and reduced the level of receptor for advanced glycation end-products (RAGE) (0.38 ± 0.17 vs. 0.52 ± 0.11 in vivo). Concomitantly, the protective role of ATRA on I/R injury was not observed in RAGE-KO mice. The current results indicated that ATRA could prevent myocardial injury and reduced cardiomyocyte apoptosis after I/R effectively. One possible mechanism underlying these effects is that ATRA could increase ADAM10 expression and thus cleave RAGE, which is the main receptor up-stream of MAPKs in myocardial I/R injury, resulting in the down-regulation of MAPK signaling and protective role on myocardial I/R injury. PMID:26186635

  2. Traditional Chinese Medicine Shuang Shen Ning Xin Attenuates Myocardial Ischemia/Reperfusion Injury by Preserving of Mitochondrial Function

    Directory of Open Access Journals (Sweden)

    Xueli Li

    2014-01-01

    Full Text Available To investigate the potential cardioprotective effects of Shuang Shen Ning Xin on myocardial ischemia/reperfusion injury. Wistar rats were treated with trimetazidine (10 mg/kg/day, ig, Shuang Shen Ning Xin (22.5, 45 mg/kg/day, ig, or saline for 5 consecutive days. Myocardial ischemia/reperfusion injury was induced by ligation of the left anterior descending coronary artery for 40 min and reperfusion for 120 min on the last day of administration. It is found that Shuang Shen Ning Xin pretreatment markedly decreased infarct size and serum LDH levels, and this observed protection was associated with reduced myocardial oxidative stress and cardiomyocyte apoptosis after myocardial ischemia/reperfusion injury. In addition, further studies on mitochondrial function showed that rats treated with Shuang Shen Ning Xin displayed decreased mitochondrial swelling and cytosolic cytochrome c levels, which were accompanied by a preservation of complex I activities and inhibition of mitochondrial permeability transition. In conclusion, the mitochondrial protective effect of Shuang Shen Ning Xin could be a new mechanism, by which Shuang Shen Ning Xin attenuates myocardial ischemia/reperfusion injury.

  3. 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.

  4. Assessment of Myocardial Ischemia in Obese Individuals Undergoing Physical Stress Echocardiography (PSE

    Directory of Open Access Journals (Sweden)

    Mara Graziele Maciel Silveira

    2015-05-01

    Full Text Available Background: Physical stress echocardiography is an established methodology for diagnosis and risk stratification of coronary artery disease in patients with physical capacity. In obese (body mass index ≥ 30 kg/m2 the usefulness of pharmacological stress echocardiography has been demonstrated; however, has not been reported the use of physical stress echocardiography in this growing population group. Objective: To assess the frequency of myocardial ischemia in obese and non-obese patients undergoing physical stress echocardiography and compare their clinical and echocardiographic differences. Methods: 4,050 patients who underwent treadmill physical stress echocardiography were studied according to the Bruce protocol, divided into two groups: obese (n = 945; 23.3% and non-obese (n = 3,105; 76.6%. Results: There was no difference regarding gender. Obese patients were younger (55.4 ± 10.9 vs. 57.56 ± 11.67 and had a higher frequency of hypertension (75.2% vs. 57, 2%; p < 0.0001, diabetis mellitus (15.2% vs. 10.9%; p < 0.0001, dyslipidemia (59.5% vs 51.9%; p < 0.0001, family history of coronary artery disease (59.3% vs. 55.1%; p = 0.023 and physical inactivity (71.4% vs. 52.9%, p < 0.0001. The obese had greater aortic dimensions (3.27 vs. 3.14 cm; p < 0.0001, left atrium (3.97 vs. 3.72 cm; p < 0.0001 and the relative thickness of the ventricule (33.7 vs. 32.8 cm; p < 0.0001. Regarding the presence of myocardial ischemia, there was no difference between groups (19% vs. 17.9%; p = 0.41. In adjusted logistic regression, the presence of myocardial ischemia remained independently associated with age, female gender, diabetes and hypertension. Conclusion: Obesity did not behave as a predictor of the presence of ischemia and the physical stress echocardiography. The application of this assessment tool in large scale sample demonstrates the feasibility of the methodology, also in obese.

  5. Assessment of Myocardial Ischemia in Obese Individuals Undergoing Physical Stress Echocardiography (PSE).

    Science.gov (United States)

    Silveira, Mara Graziele Maciel; Sousa, Antônio Carlos Sobral; Santos, Marcos Antônio Almeida; Tavares, Irlaneide da Silva; Andrade, Stephanie Macedo; Melo, Luiza Dantas; Andrade, Loren Suyane Oliveira de; Santos, Emmanuel Lima Almeida; Oliveira, Joselina Luzia Menezes

    2015-05-01

    Physical stress echocardiography is an established methodology for diagnosis and risk stratification of coronary artery disease in patients with physical capacity. In obese (body mass index ≥ 30 kg/m2) the usefulness of pharmacological stress echocardiography has been demonstrated; however, has not been reported the use of physical stress echocardiography in this growing population group. To assess the frequency of myocardial ischemia in obese and non-obese patients undergoing physical stress echocardiography and compare their clinical and echocardiographic differences. 4,050 patients who underwent treadmill physical stress echocardiography were studied according to the Bruce protocol, divided into two groups: obese (n = 945; 23.3%) and non-obese (n = 3,105; 76.6%). There was no difference regarding gender. Obese patients were younger (55.4 ± 10.9 vs. 57.56 ± 11.67) and had a higher frequency of hypertension (75.2% vs. 57, 2%; p diabetis mellitus (15.2% vs. 10.9%; p < 0.0001), dyslipidemia (59.5% vs 51.9%; p < 0.0001), family history of coronary artery disease (59.3% vs. 55.1%; p = 0.023) and physical inactivity (71.4% vs. 52.9%, p < 0.0001). The obese had greater aortic dimensions (3.27 vs. 3.14 cm; p < 0.0001), left atrium (3.97 vs. 3.72 cm; p < 0.0001) and the relative thickness of the ventricule (33.7 vs. 32.8 cm; p < 0.0001). Regarding the presence of myocardial ischemia, there was no difference between groups (19% vs. 17.9%; p = 0.41). In adjusted logistic regression, the presence of myocardial ischemia remained independently associated with age, female gender, diabetes and hypertension. Obesity did not behave as a predictor of the presence of ischemia and the physical stress echocardiography. The application of this assessment tool in large scale sample demonstrates the feasibility of the methodology, also in obese.

  6. 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.

  7. Plasma osteoprotegerin is related to carotid and peripheral arterial disease, but not to myocardial ischemia in type 2 diabetes mellitus

    Science.gov (United States)

    2011-01-01

    Background Cardiovascular disease (CVD) is frequent in type 2 diabetes mellitus patients due to accelerated atherosclerosis. Plasma osteoprotegerin (OPG) has evolved as a biomarker for CVD. We examined the relationship between plasma OPG levels and different CVD manifestations in type 2 diabetes. Methods Type 2 diabetes patients without known CVD referred consecutively to a diabetes clinic for the first time (n = 305, aged: 58.6 ± 11.3 years, diabetes duration: 4.5 ± 5.3 years) were screened for carotid arterial disease, peripheral arterial disease, and myocardial ischemia by means of carotid artery ultrasonography, peripheral ankle and toe systolic blood pressure measurements, and myocardial perfusion scintigraphy (MPS). In addition, plasma OPG concentrations and other CVD-related markers were measured. Results The prevalence of carotid arterial disease, peripheral arterial disease, and myocardial ischemia was 42%, 15%, and 30%, respectively. Plasma OPG was significantly increased in patients with carotid and peripheral arterial disease compared to patients without (p < 0.001, respectively), however, this was not the case for patients with myocardial ischemia versus those without (p = 0.71). When adjusted for age, HbA1c and U-albumin creatinine ratio in a multivariate logistic regression analysis, plasma OPG remained strongly associated with carotid arterial disease (adjusted OR: 2.12; 95% CI: 1.22-3.67; p = 0.008), but not with peripheral arterial disease or myocardial ischemia. Conclusions Increased plasma OPG concentration is associated with carotid and peripheral arterial disease in patients with type 2 diabetes, whereas no relation is observed with respect to myocardial ischemia on MPS. The reason for this discrepancy is unknown. Trial registration number at http://www.clinicaltrial.gov: NCT00298844 PMID:21838881

  8. Suv39h1 Protects from Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Bo Yang

    2014-04-01

    Full Text Available Background: Patients with diabetes are at increased risk of ischemic events. Suv39h1 is a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9, which is associated with the suppression of inflammatory genes in diabetes. However, the role of Suv39h1 in myocardial ischemia/reperfusion (I/R injury under diabetic condition has not been evaluated. Methods: To generate diabetic model, male SD rats were fed with 60% fat diet followed by intraperitoneal injection with 40mg/kg streptozotocin. Adenovirus encoding Suv39h1 gene was used for Suv39h1 overexpression. Each rat received injections of adenovirus at five myocardial sites. Three days after gene transfection, each rat was subjected to left main coronary artery occlusion and reperfusion. After 30 min ischemia and reperfusion for 4 h, the rats were euthanized for real-time PCR, Western blot, immunohistochemical staining, and morphometric analysis. Results: Delivery of Ad-Suv39h1 into the hearts of diabetic rats could markedly increase Suv39h1 expression. Up-regulation of Suv39h1 significantly reduced infarct size and tissue damage after I/R injury, which was associated with protection from apoptosis of cardiac myocytes and reduction of inflammatory response. In addition, compared with injury group, Ad-Suv39h1 led to a decreased activity of mitogen-activated protein kinase family and its down-steam transcriptional factor NF-κB. Conclusion: Overexpression of Suv39h1 results in the de-activation of proinflammatory pathways and reduced apoptosis and myocardial injury. Therefore, Suv39h1 might represent a novel therapeutic strategy to reduce I/R injury under diabetic condition.

  9. A computer heart model incorporating anisotropic propagation. IV. Simulation of regional myocardial ischemia.

    Science.gov (United States)

    Dubé, B; Gulrajani, R M; Lorange, M; LeBlanc, A R; Nasmith, J; Nadeau, R A

    1996-04-01

    The main goal of this study was to simulate clinical body surface potential maps, recorded during percutaneous transluminal coronary angioplasty protocols, using a realistic geometry computer heart model. Other objectives were to address the question of reciprocal ST-segment changes observed in the 12-lead electrocardiogram during ischemia and to verify the hypothesis that the shortening of the QRS duration observed in left anterior descending (LAD) coronary artery occlusion may be explained by conduction delay in the septal His-Purkinje system. Simulation was achieved by first introducing into the heart model three transmural zones of mild, moderate, and severe ischemia for assumed occlusions in the LAD, left circumflex, and right coronary arteries. The heart model was then excited, in turn, with these three zones present for assumed occlusions in the LAD, left circumflex, and right coronary arteries. Myocardial conduction velocities in the regions of moderate and severe ischemia were assumed to be reduced to 75 and 50% of normal, respectively. Model action potentials in the mild, moderate, and severely ischemic zones were also altered to reflect known ischemic changes in these action potentials. Body surface potential maps and electrocardiograms were computed by placing the heart inside a numerical torso model. Simulated map patterns during both ST-segment and QRS were qualitatively similar to clinical maps. Reciprocal ST-segment depression was observed for all three occlusions in remote leads that did not overlie the ischemic zones. QRS shortening due to septal His-Purkinje conduction delay was verified. The simulation results attest to the model's ability to reproduce body surface potential distributions recorded following percutaneous transluminal coronary angioplasty protocols. The simulations also showed that reciprocal ST-segment changes occur as a natural consequence of the primary ischemic region and that there is no need to invoke a second region of

  10. Taxol prevents myocardial ischemia-reperfusion injury by inducing JNK-mediated HO-1 expression.

    Science.gov (United States)

    Cao, Huaming; Wang, Yiping; Wang, Qiang; Wang, Ruxing; Guo, Suxia; Zhao, Xiaoxi; Zhang, Yu; Tong, Debing; Yang, Zhenyu

    2016-01-01

    Ischemia/hypoxia and reperfusion impair mitochondria and produce a large amount of reactive oxygen species (ROS), which lead to mitochondrial and brain damage. Furthermore, heme oxygenase-1 (HO-1) as a cytoprotective gene protects cells against ROS-induced cell death in ischemia-reperfusion injury. Induction of HO-1 is involved in cytoprotective effects of taxol. We hypothesize that taxol protects cardiac myocytes possibly by preserving myocardial mitochondrial function and inducing HO-1 expression through the JNK pathway. In this project, the perfused Langendorff hearts isolated from rats were randomly divided into five groups: control, ischemic, ischemic + taxol (0.1 μM), ischemic + taxol (0.3 μM), and ischemic + taxol (1 μM). Briefly, following a 15 min equilibration period, the control group was subject to normoxic perfusion for 120 min; the ischemia group, normoxic reperfusion for 120 min after 30 min ischemia; the taxol groups, normoxic reperfusion for 120 min after 30-min ischemia with taxol (0.1, 0.3, or 1 μM). The microtubule disruption score, ROS levels, and the activity of mitochondrial electron transport chain complexes I and III were examined by using immunohistochemical methods and free radical detection kits. Western blot assay was employed to study the underlying mechanisms. After Taxol treatment (0.1 µM), the ischemic microtubule disruption score was reduced to 9.8 ± 1.9%. The study revealed that 0.1, 0.3, and 1 μM taxol reduced the level of ROS by 33, 46 and 51%, respectively (p HO-1 increased with taxol treatments, which could be inhibited by the specific inhibitor of JNK, SP600125. Taxol stabilized microtubules and effectively reduced ROS levels during ischemia. It also preserved the activity of mitochondrial complexes I and III. Interestingly, taxol induced the expression of HO-1 via the JNK pathway in cardiac myocytes.

  11. Guanxin Danshen Formulation Protects against Myocardial Ischemia Reperfusion Injury-Induced Left Ventricular Remodeling by Upregulating Estrogen Receptor β

    Directory of Open Access Journals (Sweden)

    Xuehong Deng

    2017-11-01

    Full Text Available Background: Guanxin Danshen formulation (GXDSF is a traditional Chinese herbal recipe recorded in the Chinese Pharmacopeia since 1995 edition, which consists of Salviae miltiorrhizae Radix et Rhizoma, Notoginseng Radix et Rhizoma and Dalbergiae odoriferae Lignum. Our previous research suggested GXDSF had positive effect on cardiovascular disease. Therefore, the aim of this study was to elucidate the effects of GXDSF on myocardial ischemia reperfusion injury-induced left ventricular remodelling (MIRI-LVR.Methods: The effects of GXDSF on cardiac function were detected by haemodynamics and echocardiograms. The effects of GXDSF on biochemical parameters (AST, LDH and CK-MB were analyzed. Histopathologic examinations were performed to evaluate the effect of GXDSF on cardiac structure. In addition, the Traditional Chinese Medicine Systems Pharmacology (TCMSP database was used to predict the main target of GXDSF. Target validation was conducted by using western blots and immunofluorescent double staining assays.Results: We found that +dp/dt and LVSP were significantly elevated in the GXDSF-treated groups compared with the MIRI-LVR model group. Left ventricular ejection fraction (LVEF and left ventricular fractional shortening (LVFS were increased in the GXDSF-treated groups compared with the model group. All biochemical parameters (AST, LDH and CK-MB were considerably decreased in the GXDSF-treated groups compared with the model group. Fibrosis parameters (collagen I and III, α-SMA, and left ventricular fibrosis percentage were decreased to different degrees in the GXDSF-treated groups compared with the model group, and the collagen III/I ratio was elevated by the same treatments. TCMSP database prediction and western blot results indicated that estrogen receptor β (ERβ could be the main target of GXDSF. PHTPP, a selective antagonist of ERβ, could inhibit the expression of ERβ and the phosphorylation of PI3K and Akt in myocardial tissue induced by

  12. Coxsackie and adenovirus receptor is a modifier of cardiac conduction and arrhythmia vulnerability in the setting of myocardial ischemia.

    NARCIS (Netherlands)

    Marsman, R.F.; Bezzina, C.R.; Freiberg, F.; Verkerk, A.O.; Adriaens, M.E.; Podliesna, S.; Chen, C.; Purfurst, B.; Spallek, B.; Koopmann, T.T.; Baczko, I.; Remedios, C.G. Dos; George AL, J.r.; Bishopric, N.H.; Lodder, E.M.; Bakker, J.M. de; Fischer, R.; Coronel, R.; Wilde, A.A.; Gotthardt, M.; Remme, C.A.

    2014-01-01

    OBJECTIVES: The aim of this study was to investigate the modulatory effect of the coxsackie and adenovirus receptor (CAR) on ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. BACKGROUND: A heritable component in the risk of ventricular fibrillation during

  13. Coxsackie and Adenovirus Receptor Is a Modifier of Cardiac Conduction and Arrhythmia Vulnerability in the Setting of Myocardial Ischemia

    NARCIS (Netherlands)

    Marsman, Roos F. J.; Bezzina, Connie R.; Freiberg, Fabian; Verkerk, Arie O.; Adriaens, Michiel E.; Podliesna, Svitlana; Chen, Chen; Purfürst, Bettina; Spallek, Bastian; Koopmann, Tamara T.; Baczko, Istvan; dos Remedios, Cristobal G.; George, Alfred L.; Bishopric, Nanette H.; Lodder, Elisabeth M.; de Bakker, Jacques M. T.; Fischer, Robert; Coronel, Ruben; Wilde, Arthur A. M.; Gotthardt, Michael; Remme, Carol Ann

    2014-01-01

    Objectives The aim of this study was to investigate the modulatory effect of the coxsackie and adenovirus receptor (CAR) on ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. Background A heritable component in the risk of ventricular fibrillation during

  14. Relevance of tissue Doppler in the quantification of stress echocardiography for the detection of myocardial ischemia in clinical practice

    Directory of Open Access Journals (Sweden)

    Sicari Rosa

    2005-01-01

    Full Text Available Abstract In the present article we review the main published data on the application of Tissue Doppler Imaging (TDI to stress echocardiography for the detection of myocardial ischemia. TDI has been applied to stress echocardiography in order to overcome the limitations of visual analysis for myocardial ischemia. The introduction of a new technology for clinical routine use should pass through the different phases of scientific assessment from feasibility studies to large multicenter studies, from efficacy to effectiveness studies. Nonetheless the pro-technology bias plays a major role in medicine and expensive and sophisticated techniques are accepted before their real usefulness and incremental value to the available ones is assessed. Apparently, TDI is not exempted by this approach : its applications are not substantiated by strong and sound results. Nonetheless, conventional stress echocardiography for myocardial ischemia detection is heavily criticized on the basis of its subjectivity. Stress echocardiography has a long lasting history and the evidence collected over 20 years positioned it as an established tool for the detection and prognostication of coronary artery disease. The quantitative assessment of myocardial ischemia remains a scientific challenge and a clinical goal but time has not come for these newer ultrasonographic techniques which should be restricted to research laboratories.

  15. Relevance of tissue Doppler in the quantification of stress echocardiography for the detection of myocardial ischemia in clinical practice

    Science.gov (United States)

    Sicari, Rosa

    2005-01-01

    In the present article we review the main published data on the application of Tissue Doppler Imaging (TDI) to stress echocardiography for the detection of myocardial ischemia. TDI has been applied to stress echocardiography in order to overcome the limitations of visual analysis for myocardial ischemia. The introduction of a new technology for clinical routine use should pass through the different phases of scientific assessment from feasibility studies to large multicenter studies, from efficacy to effectiveness studies. Nonetheless the pro-technology bias plays a major role in medicine and expensive and sophisticated techniques are accepted before their real usefulness and incremental value to the available ones is assessed. Apparently, TDI is not exempted by this approach : its applications are not substantiated by strong and sound results. Nonetheless, conventional stress echocardiography for myocardial ischemia detection is heavily criticized on the basis of its subjectivity. Stress echocardiography has a long lasting history and the evidence collected over 20 years positioned it as an established tool for the detection and prognostication of coronary artery disease. The quantitative assessment of myocardial ischemia remains a scientific challenge and a clinical goal but time has not come for these newer ultrasonographic techniques which should be restricted to research laboratories. PMID:15679889

  16. Polymeric gene delivery of ischemia-inducible VEGE significantly attenuates infarct size and apoptosis following myocardial infarct.(Clinical report)

    National Research Council Canada - National Science Library

    Yockman, J.W; Choi, D; Whitten, M.G; Chang, C.W; Kastenmeier, A; Erickson, H; Albanil, A; Lee, M; Kim, S.W; Bull, D.A

    2009-01-01

    ... cell protective effects. (6,7) Vascular endothelial growth factor (VEGF), one of the number of angiogenic growth factors, has been shown to preserve myocardial function in the setting of ischemia-reperfusion and to inhibit apoptosis in some systems. (8,9) Furthermore, myocyte-secreted VEGF, acting via autocrine and paracrine pathways, has been shown to...

  17. Inhibition of endoplasmic reticulum stress by neuregulin-1 protects against myocardial ischemia/reperfusion injury.

    Science.gov (United States)

    Fang, Shan-Juan; Li, Peng-Yang; Wang, Chun-Mei; Xin, Yi; Lu, Wei-Wei; Zhang, Xiao-Xia; Zuo, Song; Ma, Chang-Sheng; Tang, Chao-Shu; Nie, Shao-Ping; Qi, Yong-Fen

    2017-02-01

    Neuregulin-1 (NRG-1), an endogenously produced polypeptide, is the ligand of cardiomyocyte ErbB receptors, with cardiovascular protective effects. In the present study, we explored whether the cardioprotective effect of NRG-1 against I/R injury is mediated by inhibiting myocardial endoplasmic reticulum (ER) stress. In vitro, NRG-1 directly inhibited the upregulation of ER stress markers such as glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved caspase-12 induced by the ER stress inducers tunicamycin or dithiothreitol in both neonatal and adult ventricular myocytes. Attenuating ErbB signals by an ErbB inhibitor AG1478 or ErbB4 knockdown and preincubation with phosphoinositide 3-kinase inhibitors all reversed the effect of NRG-1 inhibiting ER stress in cultured neonatal rat cardiomyocytes. Concurrently, cardiomyocyte ER stress and apoptosis induced by hypoxia-reoxygenation were decreased by NRG-1 treatment in vitro. Furthermore, in an in vivo rat model of myocardium ischemia/reperfusion (I/R), intravenous NRG-1 administration significantly decreased ER stress and myocardial infarct size induced by I/R. NRG-1 could protect the heart against I/R injury by inhibiting myocardial ER stress, which might be mediated by the phosphoinositide 3-kinase/Akt signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Punicalagin Pretreatment Attenuates Myocardial Ischemia-Reperfusion Injury via Activation of AMPK.

    Science.gov (United States)

    Ding, Mingge; Wang, Yin; Sun, Di; Liu, Zhenghua; Wang, Jie; Li, Xing; Huo, Cong; Jia, Xin; Chen, Wei; Fu, Feng; Wang, Xiaoming

    2017-01-01

    Punicalagin (PUN), a major bioactive component in pomegranate juice, has been proven to exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) insult via anti-oxidant properties. This study aims to investigate whether PUN provides cardioprotection against myocardial I/R (MI/R) injury and the underlying mechanisms. PUN (30[Formula: see text]mg/kg/d) or vehicle was intragastrically administered to Sprague-Dawley rats for one week before the operation. MI/R was induced by ligating the left anterior descending coronary artery for 30[Formula: see text]min and subsequent reperfusion for 3[Formula: see text]h. PUN pretreatment conferred cardioprotective effects against MI/R injury by improving cardiac function, limiting infarct size, reducing serum creatine kinase-MB and lactate dehydrogenase activities, and suppressing cardiomyocyte apoptosis. Moreover, PUN pretreatment inhibited I/R-induced myocardial oxidative stress as evidenced by decreased generation of superoxide content and malonaldialdehyde formation and increased antioxidant capability. Furthermore, PUN pretreatment increased adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation in I/R hearts. AMPK inhibitor compound c inhibited PUN-enhanced AMPK phosphorylation, and blunted PUN-mediated anti-oxidative effects and cardioprotection. These results indicate for the first time that PUN pretreatment protect against I/R-induced oxidative stress and myocardial injury via activation of AMPK.

  19. Cardioprotective Effects of Astragalin against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart.

    Science.gov (United States)

    Qu, Daoxu; Han, Jichun; Ren, Huanhuan; Yang, Wenxiao; Zhang, Xinjie; Zheng, Qiusheng; Wang, Dong

    2016-01-01

    This study aims to evaluate the cardioprotective effects of astragalin against myocardial ischemia/reperfusion (I/R) injury in isolated rat heart. The cardioprotective effects of astragalin on myocardial I/R injury were investigated on Langendorff apparatus. Adult male Sprague-Dawley rats were randomly divided into five groups. The results showed that astragalin pretreatment improved myocardial function. Compared with I/R group, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in coronary flow decreased in astragalin pretreatment groups, whereas superoxide dismutase (SOD) activity and glutathione/glutathione disulfide (GSH/GSSG) ratio significantly increased. The levels of malondialdehyde (MDA), intracellular reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) decreased in astragalin-treated groups. The infarct size (IS) and apoptosis rate in hearts from astragalin-treated groups were lower than those in hearts from the I/R group. Western blot analysis also revealed that astragalin preconditioning significantly reduced Bax level, whereas Bcl-2 was increased in the myocardium. Therefore, astragalin exhibited cardioprotective effects via its antioxidative, antiapoptotic, and anti-inflammatory activities.

  20. Brief Myocardial Ischemia Produces Cardiac Troponin I Release and Focal Myocyte Apoptosis in the Absence of Pathological Infarction in Swine

    Directory of Open Access Journals (Sweden)

    Brian R. Weil, PhD

    2017-04-01

    Full Text Available Summary: In a porcine model of brief ischemia leading to reversible stunning in the absence of tissue necrosis, we demonstrated delayed release of cardiac troponin I (cTnI that exceeded the 99th percentile for normal animals 60 min after reperfusion and rose to readily detectable levels 24 h later. Although tissue analysis at 60 min showed no evidence of infarction, TUNEL staining demonstrated isolated myocytes undergoing apoptosis, which was absent after 24 h. These results demonstrate that cTnI elevations occur after ischemia of a duration that is insufficient to produce myocyte necrosis and reflect myocyte injury associated with apoptosis in the absence of pathological evidence of infarction. Key Words: cardiac troponin I, cardiomyocyte apoptosis, myocardial ischemia, myocardial stunning

  1. Myocardial Bridge

    Science.gov (United States)

    ... Sudden Cardiac Arrest Valve Disease Vulnerable Plaque Myocardial Bridge Related terms: myocardium, coronary arteries, myocardial ischemia Your ... surface of the heart. What is a myocardial bridge? A myocardial bridge is a band of heart ...

  2. Myocardial uptake of {sup 99m}Tc-annexin-V and {sup 111}In-antimyosin-antibodies after ischemia-reperfusion in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarda-Mantel, Laure [Universite Denis Diderot-Paris 7, UMR S773, Paris (France); AP-HP, Groupe Hospitalier Bichat-Beaujon, Service de Medecine Nucleaire, Paris (France); INSERM, U773, Paris (France); Hopital Bichat, Service de Medecine Nucleaire, Paris (France); Hervatin, Florence [Universite Denis Diderot-Paris 7, UMR S773, Paris (France); CEA, DSV/DRM/SHFJ, Orsay (France); Michel, Jean-Baptiste; Louedec, Liliane [INSERM, U698, Paris (France); Martet, Genevieve [Universite Denis Diderot-Paris 7, UMR S773, Paris (France); INSERM, U773, Paris (France); Rouzet, Francois; Lebtahi, Rachida; Merlet, Pascal; Le Guludec, Dominique [Universite Denis Diderot-Paris 7, UMR S773, Paris (France); AP-HP, Groupe Hospitalier Bichat-Beaujon, Service de Medecine Nucleaire, Paris (France); INSERM, U773, Paris (France); Khaw, Ban-An [Bouve College of Pharmacy and Health Sciences, Center for Drug Targeting and Analysis, Boston, MA (United States)

    2008-01-15

    Phosphatidylserin exposure on cell surfaces occurs early during apoptosis and is detected in vivo by using {sup 99m}Tc-annexin-V (ANX). Cardiomyocyte membrane disruption is detected in vivo by using {sup 111}In-antimyosin-antibodies (AM). We aimed to determine if ANX and AM allow evaluation of the time-course of these two distinct cell death events after myocardial ischemia-reperfusion. Coronary tying (20 min) followed by reperfusion (IR) was performed in 31 rats. Twelve of the rats were injected with ANX, 11 with AM, and eight with both tracers. Myocardial uptake of tracers was studied 1-2 h, 4 h, or 24 h after IR by scintigraphy (ANX, n = 14) and autoradiography (all cases), and compared to histology and Apostain staining. Scintigraphy was positive in all rats 2 h after IR and in three of five rats at 24 h. On autoradiography, ANX activity was intense in myocardial lesions as early as 1 h post-IR, whereas AM activity was mild at 2 h then increased at 4 h post-IR. ANX and AM uptakes evolved from mid-myocardium to endocardial and epicardial regions from 2 h to 24 h post-IR. Apostain staining was significant in myocardial lesions (p < 10{sup 6} compared to six sham-operated rats). On histology, myocardial lesion was characterized by interstitial oedema, myocytes necrosis, and dramatic thinning at 24 h. These data suggest that ANX and AM allow temporal and regional evaluations of PS exposure and membrane disruption, respectively, during myocytes death after 20-min myocardial ischemia followed by reperfusion. Also, (i) apoptosis starts very early in injured myocardium, (ii) myocyte necrosis occurs later (3-4 h post-reperfusion), and (iii) most dead cells are removed from mid-myocardium between 6 h and 24 h after reperfusion. (orig.)

  3. Simulated microgravity increases myocardial susceptibility to ischemia-reperfusion injury via a deficiency of AMP-activated protein kinase.

    Science.gov (United States)

    Lu, Yuan-Ming; Jiao, Bo; Lee, Jun; Zhang, Lin; Yu, Zhi-Bin

    2017-01-01

    Gravitation is an important factor in maintaining cardiac contractility. Our study investigated whether simulated microgravity increases myocardial susceptibility to ischemia-reperfusion (IR) injury. Using the Langendorff-perfused heart model with 300 beats/min pacing, 4-week tail suspension (SUS) and control (CON) male Sprague-Dawley rats (n = 10 rats/group) were subjected to 60 min of left anterior descending coronary artery (LAD) occlusion followed by 120 min of reperfusion. Left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP), creatine kinase (CK) and lactate dehydrogenase (LDH) activity, and infarct size were assessed. Data demonstrated that there were significantly increased LVEDP, CK, LDH, and infarct size in SUS compared with CON (P < 0.05), accompanied by decreased LVESP (P < 0.05). Furthermore, TUNEL-positive cardiomyocytes were higher in SUS than that in CON (P < 0.01), and AMP-activated protein kinase (AMPK) phosphorylation and Bcl-2/Bax in SUS were less compared with CON (P < 0.05). Similarly, isolated hearts pre-treated with A-769662 exhibited better recovery of cardiac function, increased AMPK phosphorylation, and reduced necrosis and apoptosis. Furthermore, AMPKα protein showed a significant suppression in 4-week hindlimb unweighting rats. These results suggest that AMPK deficiency increases myocardial susceptibility to IR injury in rats subjected to simulated microgravity.

  4. Effects of Nitrate Intake on Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Sajad Jeddi

    Full Text Available Abstract Background: Coronary artery disease is 2-3 times more common in diabetic individuals. Dietary nitrate/nitrite has beneficial effects in both diabetes and cardiovascular disease. It also has protective effects against myocardial ischemia-reperfusion (IR injury in healthy animals. However, the effects of nitrate on myocardial IR injury in diabetic rats have not yet been investigated. Objective: We examined the effects of dietary nitrate on myocardial IR injury in streptozotocin-nicotinamide-induced diabetic rats. Method: Rats were divided into four groups (n=7 in each group: control, control+nitrate, diabetes, and diabetes+nitrate. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Nitrate (sodium nitrate was added to drinking water (100 mg/L for 2 months. The hearts were perfused in a Langendorff apparatus at 2 months and assessed before (baseline and after myocardial IR for the following parameters: left ventricular developed pressure (LVDP, minimum and maximum rates of pressure change in the left ventricle (±dP/dt, endothelial nitric oxide (NO synthase (eNOS and inducible NO synthase (iNOS mRNA expression, and levels of malondialdehyde (MDA and NO metabolites (NOx. Results: Recovery of LVDP and ±dP/dt was lower in diabetic rats versus controls, but almost normalized after nitrate intake. Diabetic rats had lower eNOS and higher iNOS expression both at baseline and after IR, and dietary nitrate restored these parameters to normal values after IR. Compared with controls, heart NOx level was lower in diabetic rats at baseline but was higher after IR. Diabetic rats had higher MDA levels both at baseline and after IR, which along with heart NOx levels decreased following nitrate intake. Conclusion: Dietary nitrate in diabetic rats provides cardioprotection against IR injury by regulating eNOS and iNOS expression and inhibiting lipid peroxidation in the heart.

  5. Selective cyclooxygenase-2 inhibition protects against myocardial damage in experimental acute ischemia

    Directory of Open Access Journals (Sweden)

    Alberto Carnieto Jr.

    2009-03-01

    Full Text Available BACKGROUND: Acute myocardial infarction is associated with tissue inflammation. Early coronary reperfusion clearly improves the outcome but may help propagate the inflammatory response and enhance tissue damage. Cyclooxygenase-2 is an enzyme that catalyzes the initial step in the formation of inflammatory prostaglandins from arachidonic acid. Cyclooxygenase-2 levels are increased when ischemic cardiac events occur. The overall function of COX-2 in the inflammatory process generated by myocardial ischemic damage has not yet been elucidated. GOAL: The objective of this study was to determine whether a selective cyclooxygenase-2 inhibitor (rofecoxib could alter the evolution of acute myocardial infarction after reperfusion. METHODS AND RESULTS: This study was performed with 48 mongrel dogs divided into two groups: controls and those treated with the drug. All animals were prepared for left anterior descending coronary artery occlusion. The dogs then underwent 180 minutes of coronary occlusion, followed by 30 minutes of reperfusion. Blood samples were collected from the venous sinus immediately before coronary occlusion and after 30 minutes of reperfusion for measurements of CPK-MB, CPK-MBm and troponin I. During the experiment we observed the mean blood pressure, heart rate and coronary flow. The coronary flow and heart rate did not change, but in the control group, there was blood pressure instability, in addition to maximal levels of CPK-MB post-infarction. The same results were observed for CPK-MBm and troponin I. CONCLUSION: In a canine model of myocardial ischemia-reperfusion, selective inhibition of Cyclooxygenase-2 with rofecoxib was not associated with early detrimental effects on the hemodynamic profile or the gross extent of infarction; in fact, it may be beneficial by limiting cell necrosis.

  6. Thioredoxin-interacting protein and myocardial mitochondrial function in ischemia-reperfusion injury.

    Science.gov (United States)

    Yoshioka, Jun; Lee, Richard T

    2014-02-01

    Cellular metabolism and reactive oxygen species (ROS) formation are interrelated processes in mitochondria and are implicated in a variety of human diseases including ischemic heart disease. During ischemia, mitochondrial respiration rates fall. Though seemingly paradoxical, reduced respiration has been observed to be cardioprotective due in part to reduced generation of ROS. Enhanced myocardial glucose uptake is considered beneficial for the myocardium under stress, as glucose is the primary substrate to support anaerobic metabolism. Thus, inhibition of mitochondrial respiration and uncoupling oxidative phosphorylation can protect the myocardium from irreversible ischemic damage. Growing evidence now positions the TXNIP/thioredoxin system at a nodal point linking pathways of antioxidant defense, cell survival, and energy metabolism. This emerging picture reveals TXNIP's function as a regulator of glucose homeostasis and may prove central to regulation of mitochondrial function during ischemia. In this review, we summarize how TXNIP and its binding partner thioredoxin act as regulators of mitochondrial metabolism. While the precise mechanism remains incompletely defined, the TXNIP-thioredoxin interaction has the potential to affect signaling that regulates mitochondrial bioenergetics and respiratory function with potential cardioprotection against ischemic injury. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia

    Science.gov (United States)

    Kimura, M; Toyoda, M; Gojo, S; Itakura, Y; Kami, D; Miyoshi, S; Kyo, S; Ono, M; Umezawa, A

    2012-01-01

    Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC) transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP)-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion. PMID:24693195

  8. Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia

    Directory of Open Access Journals (Sweden)

    Kimura M

    2012-01-01

    Full Text Available Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion.

  9. Do N-acetylcystein, beta-glucan, and coenzyme Q10 mollify myocardial ischemia-reperfusion injury?

    Science.gov (United States)

    Bolcal, Cengiz; Yildirim, Vedat; Doganci, Suat; Sargin, Murat; Aydin, Ahmet; Kuralay, Erkan; Ozal, Ertugrul; Demirkilic, Ufuk; Oz, Bilgehan Savas; Sayal, Ahmet; Tatar, Harun

    2007-01-01

    N-acetylcysteine, beta-glucan, and coenzyme Q10 have been shown to have antioxidant and anti-inflammatory effects on reperfusion injury. The aim of our study was to determine and evaluate the effects of these agents on myocardial ischemia-reperfusion injury. Forty-four New Zealand white rabbits, all female, weighing 2.4 to 4.1 kg (mean, 3.6 kg) were used in the study. Four study groups of 11 animals were arranged by randomization. The groups were the control group (group C), a group premedicated with coenzyme Q10 (group Q), a group premedicated with beta-glucan (group betaT), and a group premedicated with N-acetylcysteine (group N). After exploration of the heart, a basal myocardial biopsy was taken from the anteroapical left ventricle, and the first blood sampling was done before ischemia. For the ischemia-reperfusion experiments, the major left anterior descending artery was occluded after baseline measurements. After a 45-minute transient ischemic period, the heart was perfused for 120 minutes. After perfusion, the second myocardial biopsy was taken from the anteroapical left ventricle, and the second blood sampling was done. Blood and tissue analysis were performed and evaluated statistically. Baseline and reperfusion levels of glutathione peroxidase, superoxide dismutase, malonyldialdehyde, and nitric oxide changed significantly. While malonyldialdehyde levels increased in group C, they decreased in the other study groups (P =.001). The increases in glutathione peroxidase and superoxide dismutase levels were significant in all groups except group C (P =.0001 and P <.05, respectively). Levels of nitric oxide were found to be decreased in group C, whereas they increased in the other groups (P =.001). Antioxidant medication may help in lowering the risk of myocardial ischemia-reperfusion injury. All the medications in our study are shown to have effective roles in preventing ischemia-reperfusion injury to some extent through their antioxidant properties.

  10. Alcohol and the Heart: A Proteomics Analysis of Pericardium and Myocardium in a Swine Model of Myocardial Ischemia.

    Science.gov (United States)

    Elmadhun, Nassrene Y; Sadek, Ahmed A; Sabe, Ashraf A; Lassaletta, Antonio D; Sellke, Frank W

    2015-11-01

    Previous studies have demonstrated that moderate alcohol consumption is cardioprotective and reduces postoperative pericardial adhesions; however, the mechanism is not fully understood. Using proteomic analysis, we sought to objectively investigate the effects of daily moderate alcohol consumption in the pericardium and myocardium in a swine model of chronic myocardial ischemia. Fourteen swine underwent placement of an ameroid constrictor to induce chronic myocardial ischemia. Animals were supplemented with 90 mL of ethanol daily (ETOH) or 80 g of sucrose of equal caloric value (SUC). After 7 weeks, the ischemic myocardium and pericardium were harvested for proteomics analysis. Pericardial proteomics analysis yielded 397 proteins, of which 23 were unique to SUC and 52 were unique to ETOH. Of the 322 common proteins, 71 were statistically significant and 23 were characterized (p Alcohol supplementation increased structural proteins, and decreased immune protease inhibitors and coagulation proteins in the pericardium (p Alcohol supplementation decreased cardiac remodeling proteins, cell death proteins and motor proteins, and increased metabolic proteins (p alcohol consumption affects numerous pathways that contribute to cardioprotection, including cardiac remodeling, metabolism, and cell death. Our findings reveal the biosignature of myocardial and pericardial protein expression in the setting of chronic myocardial ischemia and daily moderate alcohol consumption. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  11. c-Jun DNAzymes inhibit myocardial inflammation, ROS generation, infarct size, and improve cardiac function after ischemia-reperfusion injury.

    Science.gov (United States)

    Luo, Xiao; Cai, Hong; Ni, Jun; Bhindi, Ravinay; Lowe, Harry C; Chesterman, Colin N; Khachigian, Levon M

    2009-11-01

    Coronary reperfusion has been the mainstay therapy for reduced infarct size after a heart attack. However, this intervention also results in myocardial injury by initiating a marked inflammatory reaction, and new treatments are keenly sought. The basic-region leucine zipper protein, c-Jun is poorly expressed in the normal myocardium and is induced within 24 hours after myocardial ischemia-reperfusion injury. Synthetic catalytic DNA molecules (DNAzymes) targeting c-Jun (Dz13) reduce infarct size in the area-at-risk (AAR) regardless of whether it is delivered intramyocardially at the initiation of ischemia or at the time of reperfusion. Dz13 attenuates neutrophil infiltration, c-Jun and ICAM-1 expression in vascular endothelium, cardiomyocyte apoptosis, and the generation of reactive oxygen species in the reperfused myocardium. It inhibits infiltration into the AAR of complement 3 (C3), C3a receptor (C3aR), membrane attack complex-1 (Mac-1), or matrix metalloproteinase-2 (MMP-2) positive inflammatory cells. Dz13 also improves cardiac function without influencing myocardial vascularity or fibrosis. These findings demonstrate the regulatory role of c-Jun in the pathogenesis of myocardial inflammation and infarction following ischemia-reperfusion injury, and inhibition of this process using catalytic DNA.

  12. Lipoxin A4 Preconditioning and Postconditioning Protect Myocardial Ischemia/Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Qifeng Zhao

    2013-01-01

    Full Text Available This study aims to investigate the pre- and postconditioning effects of lipoxin A4 (LXA4 on myocardial damage caused by ischemia/reperfusion (I/R injury. Seventy-two rats were divided into 6 groups: sham groups (C1 and C2, I/R groups (I/R1 and I/R2, and I/R plus LXA4 preconditioning and postconditioning groups (LX1 and LX2. The serum levels of IL-1β, IL-6, IL-8, IL-10, TNF-α, and cardiac troponin I (cTnI were measured. The content and the activity of Na+-K+-ATPase as well as the superoxide dismutase (SOD, and malondialdehyde (MDA levels were determined. Along with the examination of myocardium ultrastructure and ventricular arrhythmia scores (VAS, connexin 43 (Cx43 expression were also detected. Lower levels of IL-1β, IL-6, IL-8, TNF-α, cTnI, MDA content, and VAS and higher levels of IL-10, SOD activity, Na+-K+-ATPase content and activity, and Cx43 expression appeared in LX groups than I/R groups. Besides, H&E staining, TEM examination as well as analysis of gene, and protein confirmed that LXA4 preconditioning was more effective than postconditioning in preventing arrhythmogenesis via the upregulation of Cx43. That is, LXA4 postconditioning had better protective effect on Na+-K+-ATPase and myocardial ultrastructure.

  13. Coronary arterial BK channel dysfunction exacerbates ischemia/reperfusion-induced myocardial injury in diabetic mice.

    Science.gov (United States)

    Lu, Tong; Jiang, Bin; Wang, Xiao-Li; Lee, Hon-Chi

    2016-09-01

    The large conductance Ca(2+)-activated K(+) (BK) channels, abundantly expressed in coronary artery smooth muscle cells (SMCs), play a pivotal role in regulating coronary circulation. A large body of evidence indicates that coronary arterial BK channel function is diminished in both type 1 and type 2 diabetes. However, the consequence of coronary BK channel dysfunction in diabetes is not clear. We hypothesized that impaired coronary BK channel function exacerbates myocardial ischemia/reperfusion (I/R) injury in streptozotocin-induced diabetic mice. Combining patch-clamp techniques and cellular biological approaches, we found that diabetes facilitated the colocalization of angiotensin II (Ang II) type 1 receptors and BK channel α-subunits (BK-α), but not BK channel β1-subunits (BK-β1), in the caveolae of coronary SMCs. This caveolar compartmentation in vascular SMCs not only enhanced Ang II-mediated inhibition of BK-α but also produced a physical disassociation between BK-α and BK-β1, leading to increased infarct size in diabetic hearts. Most importantly, genetic ablation of caveolae integrity or pharmacological activation of coronary BK channels protected the cardiac function of diabetic mice from experimental I/R injury in both in vivo and ex vivo preparations. Our results demonstrate a vascular ionic mechanism underlying the poor outcome of myocardial injury in diabetes. Hence, activation of coronary BK channels may serve as a therapeutic target for cardiovascular complications of diabetes.

  14. Effects of local radiofrequency denervation on ventricular electrophysiological properties in normal and acute myocardial ischemia heart.

    Science.gov (United States)

    Huang, Y; Wang, D-N; Liu, P; Song, Y; Cui, H-M; Zhang, J-Y; Blackwell, J; Liao, D-N

    2016-06-01

    To observe the effects of local radiofrequency denervation on ventricular effective refractory periods, electrical alternans and ventricular arrhythmia susceptibility post myocardial infarction. Thirty-four mongrel dogs were randomly divided into the normal heart group (n = 16, 8 in sham and 8 in local sympathetic denervation - LSD) and the acute myocardial ischemia (AMI) group (n = 18, 9 in control and 9 in LSD). The left cardiac sympathetic nerve was denervated with irrigated catheter radiofrequency ablation. Left ventricular effective refractory periods (ERP), monophasic action potential duration at 90% (APD90) and APD alternans were measured at baseline and 2 hours after LSD in the normal heart group. AMI was induced by ligating the left anterior descending coronary artery 2 hours after LSD was performed. Then APD90, the occurrence of ventricular arrhythmias (VAs) were measured. Compared with baseline, LSD significantly prolonged ventricular ERP and APD90 at all sites (p LSD group, whereas no significant change was shown in the sham group. But their spatial dispersions did not change in both groups. APD alternans occurred at shorter pacing cycle length at each site after LAD→LSD when compared to the sham group (p LSD group than in the control group (p LSD may have a beneficial impact on ventricular arrhythmias induced by AMI through modulation of autonomic tone.

  15. Electrophysiological, haemodynamic, and mitochondrial alterations induced by levobupivacaine during myocardial ischemia in a pig model: protection by lipid emulsions?

    Science.gov (United States)

    Mamou, Zahida; Descotes, Jacques; Chevalier, Philippe; Bui-Xuan, Bernard; Romestaing, Caroline; Timour, Quadiri

    2015-10-01

    Accidental intravascular or high-dose injection of local anesthetics (LA) can result in serious, potentially life-threatening complications. Indeed, adequate supportive measures and the administration of lipid emulsions are required in such complications. The study's objectives were threefold: (i) evaluate the myocardial toxicity of levobupivacaine when administered intravenously; (ii) investigate levobupivacaine toxicity on cardiomyocytes mitochondrial functions and cellular structure; (iii) assess the protective effects of a lipid emulsion in the presence or absence of myocardial ischemia. Domestic pigs randomized into two groups of 24 animals each, with either preserved coronary circulation or experimental myocardial ischemia. Six animals from each group received either: (i) single IV injection of saline, (ii) lipid emulsion (Intralipid(®) ), (iii) levobupivacaine, (iv) combination levobupivacaine-Intralipid(®) . Serially measured endpoints included: heart rate, duration of the monophasic action potentials (dMAP), mean arterial pressure, and peak of the time derivative of left ventricular pressure (LV dP/dtmax ). In addition, the following cardiomyocytes mitochondrial functions were measured: reactive oxygen species (ROS) production, oxidative phosphorylation, and calcium retention capacity (CRC) as well as the consequences of ROS production on lipids, proteins, and DNA. IV injection of levobupivacaine induced sinus bradycardia and reduced dMAP and LV dP/dtmax . At the mitochondrial level, oxygen consumption and CRC were decreased. In contrast, ROS production was increased leading to enhanced lipid peroxidation and structural alterations of proteins and DNA. Myocardial ischemia was associated with global worsening of all changes. Intralipid(®) quickly improved haemodynamics. However, beneficial effects of Intralipid(®) were less clear after myocardial ischemia. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  16. Myocardial capillary permeability after regional ischemia and reperfusion in the in vivo canine heart. Effect of superoxide dismutase

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Bjerrum, P J; Haunsø, S

    1991-01-01

    This study assesses the effect of the superoxide anion scavenger superoxide dismutase on myocardial capillary permeability-surface area (PS) products for small hydrophilic molecules after ischemia and reperfusion. Open-chest dogs underwent a 20-minute occlusion of the left anterior descending...... the start of reperfusion. In 13 dogs, no scavenger treatment was given (nonprotected control group), whereas eight dogs were treated systemically with 15,000 units/kg superoxide dismutase during 1 hour, starting 20 minutes before ischemia. In the control group, three dogs developed reperfusion ventricular...

  17. Endurance exercise accelerates myocardial tissue oxygenation recovery and reduces ischemia reperfusion injury in mice.

    Directory of Open Access Journals (Sweden)

    Yuanjing Li

    Full Text Available Exercise training offers cardioprotection against ischemia and reperfusion (I/R injury. However, few essential signals have been identified to underscore the protection from injury. In the present study, we hypothesized that exercise-induced acceleration of myocardial tissue oxygenation recovery contributes to this protection. C57BL/6 mice (4 weeks old were trained on treadmills for 45 min/day at a treading rate of 15 m/min for 8 weeks. At the end of 8-week exercise training, mice underwent 30-min left anterior descending coronary artery occlusion followed by 60-min or 24-h reperfusion. Electron paramagnetic resonance oximetry was performed to measure myocardial tissue oxygenation. Western immunoblotting analyses, gene transfection, and myography were examined. The oximetry study demonstrated that exercise markedly shortened myocardial tissue oxygenation recovery time following reperfusion. Exercise training up-regulated Kir6.1 protein expression (a subunit of ATP-sensitive K(+channel on vascular smooth muscle cells, VSMC sarc-K(ATP and protected the heart from I/R injury. In vivo gene transfer of dominant negative Kir6.1AAA prolonged the recovery time and enlarged infarct size. In addition, transfection of Kir6.1AAA increased the stiffness and reduced the relaxation capacity in the vasculature. Together, our study demonstrated that exercise training up-regulated Kir6.1, improved tissue oxygenation recovery, and protected the heart against I/R injury. This exercise-induced cardioprotective mechanism may provide a potential therapeutic intervention targeting VSMC sarc-K(ATP channels and reperfusion recovery.

  18. Assessment of myocardial ischemia and viability using tissue Doppler and deformation imaging: the lessons from the experimental studies.

    Science.gov (United States)

    Thibault, H; Derumeaux, G

    2008-01-01

    Tissue Doppler imaging and strain rate imaging are quantitative methods for assessing myocardial function and have been shown to overcome the limitations of current ultrasound methods in assessing the complex changes in regional myocardial function that occur in differing ischemic substrates. Tissue Doppler imaging (TDI) measures in real time the myocardial velocity gradient which is an index of myocardial deformation. Strain and strain rate (SR) imaging has been shown to be a sensitive technique for quantifying regional myocardial deformation. Strain rate is less load-dependent that strain and provides therefore a better measure of contractility. In the setting of ischemia, experimental studies have shown that strain imaging was an accurate method for quantitative evaluation of regional myocardial function and may yield important physiological data. In myocardial infarction, transmural extension of scar distribution in the infarct zone is proportionally related to the reduction in systolic function measured by the radial transmural velocity gradient or by strain rate imaging. Measurement of both systolic and post-systolic deformation both at rest and during a graded dobutamine infusion may help to distinguish between transmural and non transmural infarcts. In conclusion, strain imaging has the ability to evaluate of regional myocardial function. Strain rate has not replaced conventional grey-scale imaging in the assessment of regional left ventricular function and the implement of these new indices in the routine clinical practice will need additional clinical and large-scale studies.

  19. Value of quantitative tissue velocity imaging in the detection of regional myocardial function in dogs with acute subendocardial ischemia.

    Science.gov (United States)

    Zhang, Qinyyang; Deng, Youbin; Liu, Yani; Yang, Haoyi; Liu, Bingbing; Shentu, Weihui; Li, Peng

    2008-12-01

    This study evaluated the application of quantitative tissue velocity imaging (QTVI) in assessing regional myocardial systolic and diastolic functions in dogs with acute subendocardial ischemia. Animal models of subendocardial ischemia were established by injecting microspheres (about 300 microm in diameter) into the proximal end of left circumflex coronary artery in 11 hybrid dogs through cannulation. Before and after embolization, two-dimensional echocardiography, QTVI and real-time myocardial contrast echocardiography (RT-MCE) via intravenous infusion of self-made microbubbles, were performed, respectively. The systolic segmental wall thickening and subendocardial myocardial longitudinal velocities of risk segments before and after embolization were compared by using paired t analysis. The regional myocardial video intensity versus contrast time could be fitted to an exponential function: y=A.(1-exp(-beta.t)), in which the product of A and beta provides a measure of myocardial blood flow. RT-MCE showed that subendocardial normalized A.beta was decreased markedly from 0.99+/-0.19 to 0.35+/-0.11 (Psubendocardial myocardium to subepicardial myocardium in these segments was significantly decreased from 1.10+/-0.10 to 0.31+/-0.07 (P0.05), the longitudinal peak systolic velocities (Vs) and early-diastolic peak velocities (Ve) recorded by QTVI were declined significantly (Psubendocardial velocity curves during isovolumic relaxation predominantly showed positive waves, whereas they mainly showed negative waves before the embolization. This study demonstrates that QTVI can more sensitively and accurately detect abnormal regional myocardial function and post-systolic systole caused by acute subendocardial ischemia.

  20. Hydroxysafflor yellow A alleviates myocardial ischemia/reperfusion in hyperlipidemic animals through the suppression of TLR4 signaling

    OpenAIRE

    Han, Dan; Wei, Jie; Zhang, Rui; Ma, Wenhuan; Shen, Chen; Feng, Yidong; Xia, Nian; Xu, Dan; Cai, Dongcheng; Li, Yunman; Fang, Weirong

    2016-01-01

    Hyperlipidemia aggravates myocardial ischemia/reperfusion (MI/R) injury through stimulating excessive inflammatory response. Therefore, blockade of inflammatory signal is a potential therapeutic management for MI/R complicated with hyperlipidemia. Hydroxysafflor yellow A (HSYA, a monomer extracted from Carthamus tinctorius L.), was studied in this article to address that the regulation of inflammatory signal would alleviate MI/R combined with hyperlipidemia injury. High-fat diet induced hyper...

  1. Cardioprotection of vitexin on myocardial ischemia/reperfusion injury in rat via regulating inflammatory cytokines and MAPK pathway.

    Science.gov (United States)

    Dong, Liu-Yi; Li, Sheng; Zhen, Yi-Lan; Wang, Ya-Nan; Shao, Xu; Luo, Zhi-Gang

    2013-01-01

    This study was conducted to demonstrate myocardial protective effects and possible underlying mechanisms of vitexin on myocardial ischemia/reperfusion (I/R) injury in rats. Occluding the anterior descending artery for 30 min and restoring blood perfusion for 60 min in rat established a model of myocardial I/R. The elevation of the ST segment of Electrocardiograph (ECG) was observed. The infarct size of the rat heart was assessed by triphenyltetrazolium chloride staining (TTC). LDH, CK, SOD activities and MDA content were determined. An immunohistochemical analysis was applied to measure the expression of myocardial NF-κBp65 and TNF-α. ERK/phospho-ERKand c-Jun/phospho-c-Jun protein expression was examined via Western Blot. Vitexin significantly reduced the elevation of the ST segment of ECG and myocardial infarct size. LDH and CK activities and MDA content were attenuated in serum, while SOD activity was markedly enhanced. Vitexin significantly attenuated I/R-induced increases of myocardial NF-κB and TNF-α. Moreover, Western Blot analysis presented that vitexin markedly enhanced the expression of phospho-ERK and weakened the expression of phospho-c-Jun compared to I/R group. The significant protective effect against myocardial ischemical/reperfusion injury in rat, which is exhibited by vitexin, may be related to its antioxidative and anti-inflammatory effects by regulating inflammatory cytokines and the MAPK pathway.

  2. Grade 3 ischemia on the admission electrocardiogram predicts rapid progression of necrosis over time and less myocardial salvage by primary angioplasty.

    Science.gov (United States)

    Billgren, Therese; Maynard, Charles; Christian, Timothy F; Rahman, Mohmmad A; Saeed, Mahammad; Hammill, Stephen C; Wagner, Galen S; Birnbaum, Yochai

    2005-07-01

    Among patients with ST-elevation acute myocardial infarction, those with terminal QRS distortion (grade 3 ischemia) have higher mortality and larger infarct size (IS) than patients without QRS distortion (grade 2 ischemia). We assessed the relation of baseline electrocardiographic ischemia grades to area at risk (AR) and myocardial salvage [100 (AR-IS)/AR] in 79 patients who underwent primary angioplasty for first ST-elevation acute myocardial infarction and had technetium Tc 99m sestamibi single-photon emission computed tomography before angioplasty (AR) and at predischarge (IS). Patients were classified as having grade 2 ischemia (ST elevation without terminal QRS distortion in any of the leads, n = 48), grade 2.5 ischemia (ST elevation with terminal QRS distortion in 1 lead, n = 16), or grade 3 ischemia (ST elevation with terminal QRS distortion in >2 adjacent leads, n = 15). Time to treatment was comparable among groups. AR was comparable among groups (38% +/- 20%, 33% +/- 23%, and 34% +/- 23%, respectively; P = .70). There were no differences among groups in residual myocardial perfusion (severity index 0.28 +/- 0.12, 0.29 +/- 0.16, and 0.30 +/- 0.15 in grades 2, 2.5, and 3 ischemia, respectively; P = .97). In contrast, there was a trend toward lower myocardial salvage (45% +/- 32%) in the grade 3 group than in the grade 2 (65% +/- 33%) and grade 2.5 (65% +/- 40%) groups ( P = .16). Salvage was dependent on time only in the grade 3 group. Spearman rank correlation coefficients between time to treatment and percentage salvage were 0.003 ( P = .99), -0.24 ( P = .38), and -0.63 ( P = .022) for grades 2, 2.5, and 3, respectively. Patients with grade 3 ischemia have rapid progression of necrosis over time and less myocardial salvage. This admission pattern is a predictor of myocardial salvage by primary angioplasty.

  3. Speckle tracking imaging improves in vivo assessment of EPO-induced myocardial salvage early after ischemia-reperfusion in rats.

    Science.gov (United States)

    Treguer, Frederic; Donal, Erwan; Tamareille, Sophie; Ghaboura, Nehmat; Derumeaux, Geneviève; Furber, Alain; Prunier, Fabrice

    2010-06-01

    A noninvasive assessment of infarct size and transmural extension of myocardial infarction (TEMI) is fundamental in experimental models of ischemia-reperfusion. Conventional echocardiography parameters are limited in this purpose. This study was designed to examine whether speckle tracking imaging can be used in a rat model of ischemia-reperfusion to accurately detect the reduction of infarct size and TEMI induced by erythropoietin (EPO) as early as 24 h after reperfusion. Rats were randomly assigned to one of three groups: myocardial infarction (MI)-control group, 45 min ischemia followed by 24 h of reperfusion; MI-EPO group, similar surgery with a single bolus of EPO administered at the onset of reperfusion; and sham-operated group. Short-axis two-dimensional echocardiography was performed after reperfusion. Global radial (GS(r)) and circumferential (GS(cir)) strains were compared with infarct size and TEMI assessed after triphenyltetrazolium chloride staining. As a result, ejection fraction, shortening fraction, GS(r), and GS(cir) significantly correlated to infarct size, whereas only GS(r) and GS(cir) significantly correlated to TEMI. EPO significantly decreased infarct size (30.8 + or - 3.5 vs. 56.2 + or - 5.7% in MI-control, P 0.75 24 h after reperfusion. In conclusion, these findings demonstrate the usefulness of speckle tracking imaging in the early evaluation of a cardioprotective strategy in a rat model of ischemia-reperfusion.

  4. Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy; Evaluation by exercise [sup 201]Tl SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Yoko; Sugihara, Hiroki; Ootsuki, Katsuichi (Kyoto Prefectural Univ. of Medicine (Japan)) (and others)

    1993-01-01

    Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) was evaluated by exercise stress myocardial [sup 201]Tl SPECT (EX-Tl). EX-Tl was performed before and after 8.8 weeks of oral verapamil (240 mg/day) in 12 patients with HCM who showed transient [sup 201]Tl perfusion defects under control conditions. [sup 201]Tl perfusion defect was visually scored and judged for 4 grades as normal (0), mild defect (1), moderate defect (2), and severe defect (3). Transient dilation index (TDI) was calculated as an index of subendocardial ischemia. Improvements of defect score were demonstrated in 10 patients after administration of verapamil. Two patients showed no change of defect score. Mean defect score decreased significantly from 5.50 to 3.03 (p<0.001). Although 11 of 12 patients showed abnormal TDI under control conditions, 10 of these revealed improvements of TDI and 7 of the 10 disclosed normal TDI after verapamil. Mean TDI decreased from 1.263 to 1.090 significantly (p<0.01). In conclusion, verapamil may improve myocardial ischemia in patients with HCM. (author).

  5. Novel curcumin analogue 14p protects against myocardial ischemia reperfusion injury through Nrf2-activating anti-oxidative activity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weixin [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wu, Mingchai [Department of Pharmacy, The Third Affiliated Hospital of Wenzhou Medical University, Wenzou, Zhejiang (China); Tang, Longguang; Pan, Yong; Liu, Zhiguo [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zeng, Chunlai [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Wang, Jingying [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wei, Tiemin, E-mail: lswtm@sina.com [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2015-01-15

    Background: Alleviating the oxidant stress associated with myocardial ischemia reperfusion has been demonstrated as a potential therapeutic approach to limit ischemia reperfusion (I/R)-induced cardiac damage. Curcumin, a natural compound with anti-oxidative activity, exerts beneficial effect against cardiac I/R injury, but poor chemical and metabolic stability. Previously, we have designed and synthesized a series of mono-carbonyl analogues of curcumin (MACs) with high stability. This study aims to find new anti-oxidant MACs and to demonstrate their effects and mechanisms against I/R-induced heart injury. Methods: H9c2 cells challenged with H{sub 2}O{sub 2} or TBHP were used for in vitro bio-screening and mechanistic studies. The MDA, H{sub 2}O{sub 2} and SOD levels in H9C2 cells were determined, and the cell viability was assessed by MTT assay. Myocardial I/R mouse models administrated with or without the compound were used for in vivo studies. Results: The in vitro cell-based screening showed that curcumin analogues 8d and 14p exhibited strong anti-oxidative effects. Pre-treatment of H9c2 cells with 14p activated Nrf2 signaling pathway, attenuated H{sub 2}O{sub 2}-increased MDA and SOD level, followed by the inhibition of TBHP-induced cell death and Bax/Bcl-2–caspase-3 pathway activation. Silencing Nrf2 significantly reversed the protective effects of 14p. In in vivo animal model of myocardial I/R, administration of low dose 14p (10 mg/kg) reduced infarct size and myocardial apoptosis to the same extent as the high dose curcumin (100 mg/kg). Conclusion: These data support the novel curcumin analogue 14p as a promising antioxidant to decrease oxidative stress and limit myocardial ischemia reperfusion injury via activating Nrf2. - Highlights: • Mono-carbonyl analogue of curcumin, 14p, exhibited better chemical stability. • Compound 14p inhibited TBHP-induced apoptosis through activating Nrf2 in vitro. • Compound 14p limited myocardial ischemia

  6. Effect of Escitalopram on Mental Stress-Induced Myocardial Ischemia: The Results of the REMIT Trial

    Science.gov (United States)

    Jiang, Wei; Velazquez, Eric J.; Kuchibhatla, Maragatha; Samad, Zainab; Boyle, Stephen H.; Kuhn, Cynthia; Becker, Richard C.; Ortel, Thomas L.; Williams, Redford B.; Rogers, Joseph G.; O’Connor, Christopher

    2015-01-01

    Importance Mental-stress-induced myocardial ischemia (MSIMI) is an intermediate surrogate endpoint representing the pathophysiological link between psychosocial risk factors and adverse outcomes of coronary heart disease (CHD). However, pharmacological interventions aimed at reducing MSIMI have not been well studied. Objective To examine the effects of 6 weeks of escitalopram treatment vs. placebo on MSIMI and other psychological stress-related biophysiological and emotional parameters. Design, Setting, and Participants The REMIT study is a randomized, double-blind, placebo-controlled trial of patients with clinically stable CHD and laboratory MSIMI. Enrollment occurred from 7/24/2007–8/24/2011 at a tertiary medical center. Interventions Eligible participants were randomized 1:1 to receive escitalopram (dose began at 5 mg with titration to 20 mg/day in 3 weeks) or placebo over 6 weeks. Main Outcome Measure Occurrence of MSIMI, defined as (1) development or worsening of regional wall motion abnormality; (2) left ventricular ejection fraction reduction ≥8%; and/or (3) horizontal or downsloping ST-segment depression ≥1mm in ≥2 leads lasting for ≥3 consecutive beats during ≥1 of 3 mental tasks. Results 127 participants were randomized to escitalopram (n=64) or placebo (n=63); 112 (96.1%) completed endpoint assessments (n=56 in each arm). At the end of 6 weeks, more patients taking escitalopram (34.2% [95% CI, 25.4 to 43.0]) had absence of MSIMI during the 3 mental stressors compared with patients taking placebo (17.5% [95% CI, 10.4 to 24.5]) based on unadjusted multiple imputation model for intention-to-treat analysis. A significant difference favoring escitalopram was observed (OR=2.62 [95% CI, 1.06 to 6.44]). Rates of exercise-induced ischemia were slightly lower at 6 weeks in the escitalopram group (45.8% [95% CI, 36.6 to 55.0]) than in patients receiving placebo (52.5% [95% CI, 43.3 to 61.7]), compared with baseline escitalopram (49.2% [95% CI, 39.9 to

  7. The cardioprotective effect of salidroside against myocardial ischemia reperfusion injury in rats by inhibiting apoptosis and inflammation.

    Science.gov (United States)

    Zhu, Lingpeng; Wei, Tingting; Gao, Jin; Chang, Xiayun; He, He; Luo, Fen; Zhou, Rui; Ma, Chunhua; Liu, Yu; Yan, Tianhua

    2015-11-01

    The main purpose of this study was to investigate effect of salidroside (Sal) on myocardial ischemia reperfusion injury in rats and the underlying mechanism. Myocardial ischemia reperfusion injury (MI/RI) model was treated with 30 min of left anterior descending (LAD) occlusion followed by 24 h of reperfusion. The male Sprague-Dawley rats were randomly divided into 7 groups: (1) Sham; (2) Sham + diltiazem (Dit, 10 mg/kg); (3) Sham + Sal (40 mg/kg); (4) I/R; (5) I/R + diltiazem (Dit, 10 mg/kg); (6) I/R + Sal (20 mg/kg); (7) I/R + Sal (40 mg/kg). Sal could ameliorate myocardial ischemia reperfusion injury as evidenced by Histopathological examination and triphenyl tetrazolium chloride (TTC) staining. Moreover, terminal deoxynucleotidyl transferase dUTP nickend labeling (TUNEL) assay demonstrated that Sal suppressed myocardial apoptosis, which may be related to up-regulation of Bcl-2/Bax ratio and inhibition of caspase-3, caspase-9 activation. Pretreatment with Sal affected serum biochemical parameters and cardiac dysfunction compared with I/R group. Sal also attenuated the pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in serum by inhibiting TLR4/NF-κB signaling pathway. Sal exerts strong favorable cardioprotective function on myocardial I/R injury which may relate to the down-regulation of the TLR4/NF-κB signaling pathway and the inhibition of cell apoptosis.

  8. Myocardial and Peripheral Ischemia Causes an Increase in Circulating Pregnancy-Associated Plasma Protein-A in Non-atherosclerotic, Non-heparinized Pigs.

    Science.gov (United States)

    Steffensen, Lasse Bach; Poulsen, Christian Bo; Shim, Jeong; Bek, Marie; Jacobsen, Kevin; Conover, Cheryl A; Bentzon, Jacob Fog; Oxvig, Claus

    2015-12-01

    The usefulness of circulating pregnancy-associated plasma protein-A (PAPP-A) as a biomarker for acute coronary syndrome (ACS) is widely debated. We used the pig as a model to assess PAPP-A dynamics in the setting of myocardial ischemia. Induction of myocardial ischemia by ligation of the left anterior descending (LAD) coronary artery caused a systemic rise in PAPP-A. However, the ischemic myocardium was excluded as the source of PAPP-A. Interestingly, induction of ischemia in peripheral tissues by ligation of the left femoral artery caused a systemic rise in PAPP-A originating from the left hind limb. This is the first study to demonstrate PAPP-A elevations in the absence of atherosclerosis or heparin during myocardial ischemia. Our findings thus add to the current discussion of the usefulness of PAPP-A as a biomarker for ACS.

  9. Dobutamine stress MRI. Part I. Safety and feasibility of dobutamine cardiovascular magnetic resonance in patients suspected of myocardial ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Kuijpers, Dirkjan [State University and Academic Hospital Groningen, Department of Radiology, Groningen (Netherlands); Bronovo Hospital, Department of Radiology and Cardiology, Bronovolaan 1, P.O. Box 96900, The Hague (Netherlands); Janssen, Caroline H.C.; Oudkerk, Matthijs [State University and Academic Hospital Groningen, Department of Radiology, Groningen (Netherlands); Dijkman, Paul R.M. van [Bronovo Hospital, Department of Radiology and Cardiology, Bronovolaan 1, P.O. Box 96900, The Hague (Netherlands)

    2004-10-01

    The aim of the study was to evaluate safety and feasibility of dobutamine cardiovascular magnetic resonance (CMR) in patients with proven or suspected coronary artery disease. Dobutamine CMR was evaluated retrospectively in 400 consecutive patients with suspicion of myocardial ischemia. Dobutamine was infused using an incremental protocol up to 40 {mu}g/kg body weight per minute. All anti-anginal medication was stopped 4 days before the CMR study and infusion time of dobutamine was 6 min per stage. Hemodynamic data, CMR findings and side effects were reported. Patients with contraindications to CMR (metallic implants and claustrophobia) were excluded from analysis. Dobutamine CMR was successfully performed in 355 (89%) patients. Forty-five (11%) patients could not be investigated adequately because of non-cardiac side effects in 29 (7%) and cardiac side effects in 16 (4%) patients. Hypotension (1.5%) and arrhythmias (1%) were the most frequent cardiac side effects. One patient developed a severe complication (ventricular fibrillation) at the end of the study. There were no myocardial infarctions or fatal complications of the stress test. The most frequent non-cardiac side effects were nausea, vomiting and claustrophobia. Age >70 years, prior myocardial infarction and rest wall motion abnormalities showed no significant differences with side effects (P>0.05). Dobutamine CMR is safe and feasible in patients with suspicion of myocardial ischemia. (orig.)

  10. Intake of hot water-extracted apple protects against myocardial injury by inhibiting apoptosis in an ischemia/reperfusion rat model.

    Science.gov (United States)

    Kim, Mi Young; Lim, Sun Ha; Lee, Jongwon

    2014-11-01

    Intakes of apple and its products are shown to reduce the risk of coronary heart disease by delaying occlusion of coronary arteries. In our previous study, we showed that apple pectin protected against myocardial injury by prohibiting apoptotic cascades in a rat model of ischemia/reperfusion. Thus, we hypothesized that water-extracted apple, into which apple pectin was released from the cell wall, might exhibit the same efficacy as apple pectin. To test this hypothesis, we fed rats either cold water- (400 mg kg(-1) d(-1)) or hot water-extracted apples (HWEA; 40, 100, and 400 mg kg(-1) d(-1)). Three days later, the rats were subjected to myocardial injuries by ligating the left anterior descending coronary artery (30 minutes), and subsequently, the heart (3 hours) reperfused by releasing the ligation. Only the rats that were supplemented with HWEA (400 mg kg(-1) d(-1)) showed significant reductions in infarct size, which was 28.5% smaller than that of the control group. This infarct size reduction could be partly attributed to the prevention of steps leading to apoptosis. These steps are manifested by a higher Bcl-2/Bax ratio, lower procaspase-3 conversion to caspase-3, and inhibition of DNA nick generation, which reflects the extent of apoptosis. The findings indicate that HWEA supplementation reduces myocardial injury by inhibiting apoptosis under ischemia/reperfusion conditions. In conclusion, this study suggests that apple intake, specifically boiled apple, might reduce the risk of coronary heart disease by inhibiting postocclusion steps, such as myocardial injury after artery occlusion, as well as preocclusion steps, such as atherosclerotic plaque formation. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Sphingosine 1-Phosphate Postconditioning Protects Against Myocardial Ischemia/reperfusion Injury in Rats via Mitochondrial Signaling and Akt-Gsk3β Phosphorylation.

    Science.gov (United States)

    Fang, Rui; Zhang, Lu-Lu; Zhang, Li-Zhi; Li, Wenchang; Li, Mengmeng; Wen, Ke

    2017-02-01

    Although preconditioning of sphingosine 1-phosphate (S1P) has been shown to protect myocytes from hypoxia reoxgenation injury in vitro, the role of S1P postconditioning on myocardial ischemia reperfusion injury (MIRI) in vivo and its related mechanism are unknown. The aim of this study was to investigate the protective role of sphingosine 1-phosphate (S1P) postconditioning in MIRI via its effects on mitochondrial signaling and Akt/Gsk3β phosphorylation. Rats were subjected to MIRI, consisting of 30 min of ischemia followed by 120 min of reperfusion, with S1P administered at the beginning of the reperfusion. Myocardial infarct size and apoptotic index were measured by triphenyltetrazolium (TTC) and terminal deoxynucleotide transferase dUTP nick-end labeling (TUNEL) assays, respectively. Akt and Gsk3β phosphorylation, caspase-3 cleavage, and cytochrome c translocation were assessed by western blot. Mitochondrial permeability transition pore (MPTP) opening and mitochondrial membrane potential (MMP, ΔΨ) were also examined to determine overall mitochondrial function. S1P postconditioning significantly decreased myocardial infarct size and apoptosis, as well as enhanced Akt and Gsk3β phosphorylation, attenuated caspase-3 cleavage and cytosolic cytochrome c translocation, and inhibited MPTP opening, which subsequently preserved Δψ. Electron microscopy also confirmed that S1P helped maintain myocardial mitochondria integrity. Moreover, the protective effects of S1P treatment were blocked by cotreatment with a PI3K inhibitor, LY294002. These results suggest that S1P postconditioning protects against MIRI by regulating mitochondrial signaling and Akt/Gsk3β phosphorylation. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  12. muView: A Visual Analysis System for Exploring Uncertainty in Myocardial Ischemia Simulations

    KAUST Repository

    Rosen, Paul

    2016-05-23

    In this paper we describe the Myocardial Uncertainty Viewer (muView or μView) system for exploring data stemming from the simulation of cardiac ischemia. The simulation uses a collection of conductivity values to understand how ischemic regions effect the undamaged anisotropic heart tissue. The data resulting from the simulation is multi-valued and volumetric, and thus, for every data point, we have a collection of samples describing cardiac electrical properties. μView combines a suite of visual analysis methods to explore the area surrounding the ischemic zone and identify how perturbations of variables change the propagation of their effects. In addition to presenting a collection of visualization techniques, which individually highlight different aspects of the data, the coordinated view system forms a cohesive environment for exploring the simulations. We also discuss the findings of our study, which are helping to steer further development of the simulation and strengthening our collaboration with the biomedical engineers attempting to understand the phenomenon.

  13. Synthesis and biological evaluation of cyclic analogs of L-carnitine as potential agents in the treatment of myocardial ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Woster, P.M.

    1987-01-01

    The purpose of this research was to synthesize a number of cyclic, rigid analogs of L-carnitine, having a variety of predetermined positional and stereochemical orientations, to be used as probes into the spatial and conformational requirements of the enzyme known as carnitine/acylcarnitine translocase. The ability of these analogs to serve as substrates for this enzyme was to be determined by assessing the degree to which they initiate efflux of {sup 14}C-L-carnitine from isolated heart mitochondria. Toward this end, synthesis of several such analogs was attempted, resulting in the isolation and characterization of 9 cyclic analogs of carnitine, 5 of which are previously unreported. Bioevaluation of these synthetic carnitine analogs was conducted in a previously described assay system. Rat heart mitochondria were isolated by differential centrifugation and prepared for the study by incubation with {sup 14}C-L-carnitine. Efflux of radiolabeled carnitine was then monitored in the presence of the compound being evaluated. This represents the first instance in which non-naturally occurring analogs of L-carnitine have been shown to undergo transport via this mitochondrial translocase, suggesting the possibility that cyclic carnitine analogs may find utility as agents in the treatment of myocardial ischemia.

  14. Troxerutin Protects Against Myocardial Ischemia/Reperfusion Injury Via Pi3k/Akt Pathway in Rats

    Directory of Open Access Journals (Sweden)

    Liliang Shu

    2017-12-01

    Full Text Available Background/Aims: Troxerutin, also known as vitamin P4, has been commonly used in the treatment of chronic venous insufficiency (CVI disease. However, its effect on in vivo myocardial ischemia/reperfusion (I/R injury, a model that closely mimics acute myocardial infarction in humans, is still unknown. Methods: The myocardial I/R injury rat model was created with troxerutin preconditioning. Myocardial infarct size was evaluated by the Evans blue-TTC method. Hemodynamic parameters, including the heart rate (HR, left ventricular end-diastolic pressure (LVEDP, left ventricular systolic pressure (LVSP, maximal rate of rise in blood pressure in the ventricular chamber (+dp/dt max, and maximal rate of decline in blood pressure in the ventricular chamber (-dp/dt max were monitored. Serum TNF-α and IL-10 were determined by ELISA kit. Cell apoptosis was detected by MTT method. Results: Troxerutin preconditioning significantly reduced myocardial infarct size, improved cardiac function, and decreased the levels of creatine kinase (CK, aspartate aminotransferase (AST and lactate dehydrogenase (LDH in the I/R injury rat model. The serum and mRNA levels of TNF-α and IL-10 as well as some apoptosis markers (Bax, Caspase 3 also decreased. Moreover, troxerutin pretreatment markedly increased the phosphorylation of Akt, and blocking PI3K activity by LY294002 abolished the protective effect of troxerutin on I/R injury. Conclusion: Troxerutin preconditioning protected against myocardial I/R injury via the PI3K/Akt pathway.

  15. Cardioprotective Effect of Aloe vera Biomacromolecules Conjugated with Selenium Trace Element on Myocardial Ischemia-Reperfusion Injury in Rats.

    Science.gov (United States)

    Yang, Yang; Yang, Ming; Ai, Fen; Huang, Congxin

    2017-06-01

    The present study was undertaken to evaluate the cardioprotection potential and underlying molecular mechanism afforded by a selenium (Se) polysaccharide (Se-AVP) from Aloe vera in the ischemia-reperfusion (I/R) model of rats in vivo. Myocardial I/R injury was induced by occluding the left anterior descending coronary artery (LAD) for 30 min followed by 2-h continuous reperfusion. Pretreatment with Se-AVP (100, 200, and 400 mg/kg) attenuated myocardial damage, as evidenced by reduction of the infarct sizes, increase in serum and myocardial endogenous antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT)), and decrease in the malondialdehyde (MDA) level in the rats suffering I/R injury. This cardioprotective activity afforded by Se-AVP is further supported by the decreased levels of cardiac marker enzymes creatine kinase (CK) and lactate dehydrogenase (LDH), as well as the rise of myocardial Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in I/R rats. Additionally, cardiomyocytic apoptosis was measured by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining and the result showed that the percent of TUNEL-positive cells in myocardium of Se-AVP-treated groups was lower than I/R rats. In conclusion, we clearly demonstrated that Se-AVP had a protective effect against myocardial I/R injury in rats by augmenting endogenous antioxidants and protecting rat hearts from oxidative stress-induced myocardial apoptosis.

  16. Captopril Pretreatment Produces an Additive Cardioprotection to Isoflurane Preconditioning in Attenuating Myocardial Ischemia Reperfusion Injury in Rabbits and in Humans

    Directory of Open Access Journals (Sweden)

    Yi Tian

    2015-01-01

    Full Text Available Background. Pretreatment with the angiotensin-converting inhibitor captopril or volatile anesthetic isoflurane has, respectively, been shown to attenuate myocardial ischemia reperfusion (MI/R injury in rodents and in patients. It is unknown whether or not captopril pretreatment and isoflurane preconditioning (Iso may additively or synergistically attenuate MI/R injury. Methods and Results. Patients selected for heart valve replacement surgery were randomly assigned to five groups: untreated control (Control, captopril pretreatment for 3 days (Cap3d, or single dose captopril (Cap1hr, 1 hour before surgery with or without Iso (Cap3d+Iso and Cap1hr+Iso. Rabbit MI/R model was induced by occluding coronary artery for 30 min followed by 2-hour reperfusion. Rabbits were randomized to receive sham operation (Sham, MI/R (I/R, captopril (Cap, 24 hours before MI/R, Iso, or the combination of captopril and Iso (Iso+Cap. In patients, Cap3d+Iso but not Cap1hr+Iso additively reduced postischemic myocardial injury and attenuated postischemic myocardial inflammation. In rabbits, Cap or Iso significantly reduced postischemic myocardial infarction. Iso+Cap additively reduced cellular injury that was associated with improved postischemic myocardial functional recovery and reduced myocardial apoptosis and attenuated oxidative stress. Conclusion. A joint use of 3-day captopril treatment and isoflurane preconditioning additively attenuated MI/R by reducing oxidative stress and inflammation.

  17. CPU0213, a novel endothelin type A and type B receptor antagonist, protects against myocardial ischemia/reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Z.Y. Wang

    2011-11-01

    Full Text Available The efficacy of endothelin receptor antagonists in protecting against myocardial ischemia/reperfusion (I/R injury is controversial, and the mechanisms remain unclear. The aim of this study was to investigate the effects of CPU0123, a novel endothelin type A and type B receptor antagonist, on myocardial I/R injury and to explore the mechanisms involved. Male Sprague-Dawley rats weighing 200-250 g were randomized to three groups (6-7 per group: group 1, Sham; group 2, I/R + vehicle. Rats were subjected to in vivo myocardial I/R injury by ligation of the left anterior descending coronary artery and 0.5% sodium carboxymethyl cellulose (1 mL/kg was injected intraperitoneally immediately prior to coronary occlusion. Group 3, I/R + CPU0213. Rats were subjected to identical surgical procedures and CPU0213 (30 mg/kg was injected intraperitoneally immediately prior to coronary occlusion. Infarct size, cardiac function and biochemical changes were measured. CPU0213 pretreatment reduced infarct size as a percentage of the ischemic area by 44.5% (I/R + vehicle: 61.3 ± 3.2 vs I/R + CPU0213: 34.0 ± 5.5%, P < 0.05 and improved ejection fraction by 17.2% (I/R + vehicle: 58.4 ± 2.8 vs I/R + CPU0213: 68.5 ± 2.2%, P < 0.05 compared to vehicle-treated animals. This protection was associated with inhibition of myocardial inflammation and oxidative stress. Moreover, reduction in Akt (protein kinase B and endothelial nitric oxide synthase (eNOS phosphorylation induced by myocardial I/R injury was limited by CPU0213 (P < 0.05. These data suggest that CPU0123, a non-selective antagonist, has protective effects against myocardial I/R injury in rats, which may be related to the Akt/eNOS pathway.

  18. Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II

    Directory of Open Access Journals (Sweden)

    Luz Ibarra-Lara

    2016-12-01

    Full Text Available Renin-angiotensin system (RAS activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II/Angiotensin II type 1 receptor (AT1 and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia. Control and MetS rats were assigned to the following groups: (a sham; (b vehicle-treated myocardial infarction (MI (MI-V; and (c fenofibrate-treated myocardial infarction (MI-F. Treatment with fenofibrate significantly reduced triglycerides, non-high density lipoprotein cholesterol (non-HDL-C, insulin levels and insulin resistance index (HOMA-IR in MetS animals. MetS and MI increased Ang II concentration and AT1 expression, favored myocardial oxidative stress (high levels of malondialdehyde, overexpression of nicotinamide adenine dinucleotide phosphate (NADPH oxidase 4 (NOX4, decreased total antioxidant capacity and diminished expression of superoxide dismutase (SOD1, SOD2 and catalase and inhibited expression of the insulin signaling cascade: phosphatidylinositol 3-kinase (PI3K/protein kinase B (PkB, also known as Akt/Glut-4/endothelial nitric oxide synthase (eNOS. In conclusion, fenofibrate treatment favors an antioxidant environment as a consequence of a reduction of the Ang II/AT1/NOX4 signaling pathway, reestablishing the cardiac insulin signaling pathway. This might optimize cardiac metabolism and improve the vasodilator function during myocardial ischemia.

  19. Gαi2- and Gαi3-Deficient Mice Display Opposite Severity of Myocardial Ischemia Reperfusion Injury

    Science.gov (United States)

    Köhler, David; Devanathan, Vasudharani; Bernardo de Oliveira Franz, Claudia; Eldh, Therese; Novakovic, Ana; Roth, Judith M.; Granja, Tiago; Birnbaumer, Lutz; Rosenberger, Peter; Beer-Hammer, Sandra; Nürnberg, Bernd

    2014-01-01

    G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart and therefore are common targets for cardiovascular therapeutics. The activated GPCRs transduce their signals via heterotrimeric G-proteins. The four major families of G-proteins identified so far are specified through their α-subunit: Gαi, Gαs, Gαq and G12/13. Gαi-proteins have been reported to protect hearts from ischemia reperfusion injury. However, determining the individual impact of Gαi2 or Gαi3 on myocardial ischemia injury has not been clarified yet. Here, we first investigated expression of Gαi2 and Gαi3 on transcriptional level by quantitative PCR and on protein level by immunoblot analysis as well as by immunofluorescence in cardiac tissues of wild-type, Gαi2-, and Gαi3-deficient mice. Gαi2 was expressed at higher levels than Gαi3 in murine hearts, and irrespective of the isoform being knocked out we observed an up regulation of the remaining Gαi-protein. Myocardial ischemia promptly regulated cardiac mRNA and with a slight delay protein levels of both Gαi2 and Gαi3, indicating important roles for both Gαi isoforms. Furthermore, ischemia reperfusion injury in Gαi2- and Gαi3-deficient mice exhibited opposite outcomes. Whereas the absence of Gαi2 significantly increased the infarct size in the heart, the absence of Gαi3 or the concomitant upregulation of Gαi2 dramatically reduced cardiac infarction. In conclusion, we demonstrate for the first time that the genetic ablation of Gαi proteins has protective or deleterious effects on cardiac ischemia reperfusion injury depending on the isoform being absent. PMID:24858945

  20. Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p.

    Directory of Open Access Journals (Sweden)

    Chen Bian

    Full Text Available Luteolin (LUT, a kind of flavonoid which is extracted from a variety of diets, has been reported to convey protective effects of various diseases. Recent researches have suggested that LUT can carry out cardioprotective effects during ischemia/reperfusion (I/R. However, there have no reports on whether LUT can exert protective effects against myocardial I/R injury through the actions of specific microRNAs (miRs. The purpose of this study was to determine which miRs and target genes LUT exerted such function through.Expression of various miRs in perfused rat hearts was detected using a gene chip. Target genes were predicted with TargetScan, MiRDB and MiRanda. Anoxia/reoxygenation was used to simulate I/R. Cells were transfected by miR-208b-3p mimic, inhibitor and small interfering RNA of Ets1 (avian erythroblastosis virus E26 (v ets oncogene homolog 1. MiR-208b-3p and Ets1 mRNA were quantified by real-time quantitative polymerase chain reaction. The percentage of apoptotic cells was detected by annexin V-fluorescein isothiocyanate/propidium iodide dyeing and flow cytometry. The protein expression levels of cleaved caspase-3, Bcl-2, Bax, and Ets1 were examined by western blot analysis. A luciferase reporter assay was used to verify the combination between miR-208b-3p and the 3'-untranslated region of Ets1.LUT pretreatment reduced miR-208b-3p expression in myocardial tissue, as compared to the I/R group. And LUT decreased miR-208b-3p expression and apoptosis caused by I/R. However, overexpression of miR-208b-3p further aggravated the changes caused by I/R and blocked all the effects of LUT. Knockdown of miR-208b-3p expression also attenuated apoptosis, while knockdown of Ets1 promoted apoptosis. Further, the luciferase reporter assay showed that miR-208b-3p could inhibit Ets1 expression.LUT pretreatment conveys anti-apoptotic effects after myocardial I/R injury by decreasing miR-208b-3p and increasing Ets1 expression levels.

  1. Remote Ischemic Postconditioning Protects against Myocardial Ischemia-Reperfusion Injury by Inhibition of the RAGE-HMGB1 Pathway

    Directory of Open Access Journals (Sweden)

    Xiangming Wang

    2018-01-01

    Full Text Available Background. The aim of the present study was to observe the effect of RAGE-HMGB1 signal pathway on remote ischemic postconditioning in mice with myocardial ischemia reperfusion injury. Methods. Mice model of MIRI was established and randomly divided into three groups: control group, ischemia reperfusion group, and remote ischemic postconditioning group. Infarction size was detected by Evans blue and TTC staining. Cardiac function was detected by echocardiography measurement. The protein levels of RAGE, HMGB1, P-AKT, and ERK1/2 were detected by Western blot 120 min following reperfusion. Results. RIPostC could decrease the infarct size and increase LVEF and FS compared with I/R group. Two hours after myocardial ischemia reperfusion, the levels of RAGE and HMGB1 were significantly decreased in RIPostC group compared with those in I/R group. The level of p-AKT was significantly higher in the RIPostC group than in the I/R group. LY294002 significantly attenuated RIPostC-increased levels of Akt phosphorylation. Conclusion. RIPostC may inhibit the expression of RAGE and HMGB1 and activate PI3K/Akt signaling pathway to extenuate ischemic reperfusion injury in mice. It could further suppress the oxidative stress, have antiapoptosis effect, and reduce inflammatory reaction, but this effect has certain timeliness.

  2. Autophagy is involved in the cardioprotection effect of remote limb ischemic postconditioning on myocardial ischemia/reperfusion injury in normal mice, but not diabetic mice.

    Directory of Open Access Journals (Sweden)

    Zhihua Han

    Full Text Available BACKGROUND: Recent animal study and clinical trial data suggested that remote limb ischemic postconditioning (RIPostC can invoke potent cardioprotection. However, during ischemia reperfusion injury (IR, the effect and mechanism of RIPostC on myocardium in subjects with or without diabetes mellitus (DM are poorly understood. Autophagy plays a crucial role in alleviating myocardial IR injury. The aim of this study was to determine the effect of RIPostC on mice myocardial IR injury model with or without DM, and investigate the role of autophagy in this process. METHODOLOGY AND RESULTS: Streptozocin (STZ induced DM mice model and myocardial IR model were established. Using a noninvasive technique, RIPostC was induced in normal mice (ND and DM mice by three cycles of ischemia (5 min and reperfusion (5 min in the left hindlimb. In ND group, RIPostC significantly reduced infarct size (32.6±3.0% in ND-RIPostC vs. 50.6±2.4% in ND-IR, p<0.05 and improved cardiac ejection fraction (49.70±3.46% in ND-RIPostC vs. 31.30±3.95% in ND-IR, p<0.05. However, in DM group, no RIPostC mediated cardioprotetion effect was observed. To analyze the role of autophagy, western blot and immunohistochemistry was performed. Our data showed that a decreased sequestosome 1 (SQSTM1/p62 level, an increased Beclin-1 level, and higher ratio of LC3-II/LC3-I were observed in ND RIPostC group, but not DM RIPostC group. CONCLUSIONS: The current study suggested that RIPostC exerts cardioprotection effect on IR in normal mice, but not DM mice, and this difference is via, at least in part, the up-regulation of autophagy.

  3. Detection of Myocardial Ischemia-Reperfusion Injury Using a Fluorescent Near-Infrared Zinc(II-Dipicolylamine Probe and 99mTc Glucarate

    Directory of Open Access Journals (Sweden)

    Leonie wyffels

    2012-05-01

    Full Text Available A fluorescent zinc 2,2′-dipicolylamine coordination complex PSVue®794 (probe 1 is known to selectively bind to phosphatidylserine exposed on the surface of apoptotic and necrotic cells. In this study, we investigated the cell death targeting properties of probe 1 in myocardial ischemia-reperfusion injury. A rat heart model of ischemia-reperfusion was used. Probe 1, control dye, or 99mTc glucarate was intravenously injected in rats subjected to 30-minute and 5-minute myocardial ischemia followed by 2-hour reperfusion. At 90 minutes or 20 hours postinjection, myocardial uptake was evaluated ex vivo by fluorescence imaging and autoradiography. Hematoxylin-eosin and cleaved caspase-3 staining was performed on myocardial sections to demonstrate the presence of ischemia-reperfusion injury and apoptosis. Selective accumulation of probe 1 could be detected in the area at risk up to 20 hours postinjection. Similar topography and extent of uptake of probe 1 and 99mTc glucarate were observed at 90 minutes postinjection. Histologic analysis demonstrated the presence of necrosis, but only a few apoptotic cells could be detected. Probe 1 selectively accumulates in myocardial ischemia-reperfusion injury and is a promising cell death imaging tool.

  4. Impact of coronary revascularization vs medical therapy on ischemia among stable patients with or suspected coronary artery disease undergoing serial myocardial perfusion scintigraphy.

    Science.gov (United States)

    Nudi, Francesco; Di Belardino, Natale; Versaci, Francesco; Pinto, Annamaria; Procaccini, Enrica; Neri, Giandomenico; Vetere, Maurizio; Frati, Giacomo; Peruzzi, Mariangela; Schillaci, Orazio; Gaspardone, Achille; Tomai, Fabrizio; Biondi-Zoccai, Giuseppe

    2017-10-01

    Randomized trials have challenged the role of revascularization in stable coronary artery disease. We aimed to appraise the impact of revascularization on ischemia in patients undergoing serial myocardial perfusion scintigraphy (MPS). We queried our institutional database for stable subjects undergoing serial MPS and appraised the impact of revascularization on changes in ischemia. A total of 3631 patients were included: 967 (27%) undergoing revascularization and 2664 (73%) receiving medical therapy only. Patients treated with revascularization had a significantly lower burden of myocardial ischemia at follow-up (odds ratio = 0.577 [95% confidence interval 0.483-0.689] vs medical therapy, P revascularization was associated with a follow-up prevalence of 80% for no, minimal, or mild ischemia and 20% for moderate or severe ischemia, vs 43% and 57% for medical therapy (P revascularization was associated with a significantly lower prevalence of moderate or severe ischemia at follow-up (respectively P Revascularization appears superior to medical therapy in reducing ischemic burden and normalizing myocardial perfusion among subjects with moderate or severe ischemia at baseline.

  5. Troxerutin Preconditioning and Ischemic Postconditioning Modulate Inflammatory Response after Myocardial Ischemia/Reperfusion Injury in Rat Model.

    Science.gov (United States)

    Badalzadeh, Reza; Baradaran, Behzad; Alihemmati, Alireza; Yousefi, Bahman; Abbaszadeh, Azam

    2017-02-01

    Protective effects of ischemic postconditioning in myocardial ischemia/reperfusion (I/R) injury have been ever demonstrated, but the exact mechanisms remain unclear. Because of their multiplex activities, using natural pharmaceuticals seems to be clinically interesting. The aim of present study was to investigate the effects of troxerutin preconditioning and ischemic postconditioning on inflammatory responses after myocardial I/R injury in a rat model. Twenty-four Wistar rats were divided into four groups as the control, troxerutin receiving (TXR), postconditioning receiving (PostC), and combined therapy (TXR + PostC). Rats' isolated hearts underwent 30-min LAD regional ischemia followed by 45-min reperfusion. Troxerutin was orally administered for a month before I/R. Ischemic PostC was applied by alternative three cycles of 30-s R/I at the onset of reperfusion. The coronary effluent and ischemic left ventricular samples were used to determine the activities of creatine kinase (CK), intercellular adhesion molecule-1 (ICAM-1), interlukin-1beta (IL-1β), tumor-necrosis factor (TNF-α), and also histopathological studies. Pretreatment of rats with troxerutin significantly reduced myocardial inflammatory cytokines TNF-α and IL-1β levels and ICAM-1 activity after I/R insult compared to those of control I/R hearts (P inflammatory mechanisms of both treatments were associated with their protective effects against myocardial damages causing from I/R injury. Pretreatment with troxerutin as well as postconditioning can induce cardioprotection through prevention of the cell-cell interaction and release of inflammatory mediators, minimizing I/R pathological changes in myocardial cells. These two treatments may share same mechanisms in their actions since they showed no significant additive effects.

  6. Shuangshen Ningxin Capsule, a Traditional Chinese Medicinal Preparation, Alleviates Myocardial Ischemia through Autophagy Regulation

    Directory of Open Access Journals (Sweden)

    Jun Wang

    2015-01-01

    Full Text Available Shuangshen Ningxin capsule (SSNX, a modern Chinese formula, has been used to treat cardiovascular diseases in Eastern Asia. Our study focuses on the autophagy regulation of SSNX against coronary artery injuries. Myocardial infarction model was established in Chinese miniswines (CMS by coronary artery balloon injury. SSNX was administered to the CMS for 8 weeks with 4 mg/kg or 16 mg/kg. Myocardial cells were incubated with 20% SSNX medicated serum for 2 hours. Assays were performed to detect the effects of SSNX on (i coronary artery diameter by angiography, (ii hemodynamics by noninvasive hemodynamic monitoring system, (iii plaque burden and plaque volume by intravenous ultrasound (iv coronary artery histology by H&E staining, (v autophagosome by transmission electron microscopy, (vi lactate dehydrogenase (LDH leakage, and (vii Beclin-1 and LC3-I/II expressions by Western blot. The results showed that CMS treated with SSNX exhibited the correction for the disturbed cardiac hemodynamics, increase of coronary artery diameter, reduction of high plaque burden and plaque volume, and decrease of LDH. The inhibitory effect of SSNX on CMS autophagy was demonstrated by the reduction of autophagosome and the downregulation of beclin-1 and LC3-I/II. SSNX may protect coronary artery and increase the stability of plaque through the suppression of myocardial cellular autophagy, which suggests the potentially therapeutic effect of SSNX on ischemic cardiovascular disease.

  7. Adenosine stress high-pitch 128-slice dual-source myocardial computed tomography perfusion for imaging of reversible myocardial ischemia: comparison with magnetic resonance imaging.

    Science.gov (United States)

    Feuchtner, Gudrun; Goetti, Robert; Plass, André; Wieser, Monika; Scheffel, Hans; Wyss, Christophe; Stolzmann, Paul; Donati, Olivio; Schnabl, Johannes; Falk, Volkmar; Alkadhi, Hatem; Leschka, Sebastian; Cury, Ricardo C

    2011-09-01

    Coronary computed tomography angiography (CTA) enables accurate anatomic evaluation of coronary artery stenosis but lacks information about hemodynamic significance. The aim of this study was to evaluate 128-slice myocardial CT perfusion (CTP) imaging with adenosine stress using a high-pitch mode, in comparison with cardiac MRI (CMR). Thirty-nine patients with intermediate to high coronary risk profile underwent adenosine stress 128-slice dual source CTP (128×0.6 mm, 0.28 seconds). Among those, 30 patients (64 ± 10 years, 6% women) also underwent adenosine stress CMR (1.5T). The 2-step CTP protocol consisted of (1) adenosine stress-CTP using a high-pitch factor (3.4) ECG-synchronized spiral mode and (2) rest-CTP/coronary-CTA using either high-pitch (heart rate 63 bpm). Results were compared with CMR and with invasive angiography in 25 patients. The performance of stress-CTP for detection of myocardial perfusion defects compared with CMR was sensitivity, 96%; specificity, 88%; positive predictive value (PPV), 93%; negative predictive value (NPV), 94% (per vessel); and sensitivity, 78%; specificity, 87%; PPV, 83%; NPV, 84% (per segment). The accuracy of stress-CTP for imaging of reversible ischemia compared with CMR was sensitivity, 95%; specificity, 96%; PPV, 95%; and NPV, 96% (per vessel). In 25 patients who underwent invasive angiography, the accuracy of CTA for detection of stenosis >70% was (per segment): sensitivity, 96%; specificity, 88%; PPV, 67%; and NPV, 98.9%. The accuracy improved from 84% to 95% after adding stress CTP to CTA. Radiation exposure of the entire stress/rest CT protocol was only 2.5 mSv. Adenosine-induced stress 128-slice dual-source high-pitch myocardial CTP allows for simultaneously assessment of reversible myocardial ischemia and coronary stenosis, with good diagnostic accuracy as compared with CMR and invasive angiography, at a very low radiation exposure.

  8. Acute Intravenous Infusion of Immunoglobulins Protects Against Myocardial Ischemia-Reperfusion Injury Through Inhibition of Caspase-3

    Directory of Open Access Journals (Sweden)

    Waleed Al-Herz

    2017-08-01

    Full Text Available Background/Aims: To investigate the cardioprotective effects of intravenous immunoglobulins (IVIG in rats subjected to regional myocardial ischemia reperfusion (I/R. Methods: Langendorff-perfused rat hearts were used in this study. Hearts subjected to regional ischemia served as a negative untreated control. The effects of IVIG pre- and post-ischemic treatment on left ventricular function, coronary vascular dynamics and contractility were assessed. IVIG were administered in either a low or high dose. The infarct size was determined using triphenyltetrazolium chloride and through biochemical assays using the measured creatine kinase and lactate dehydrogenase levels. Apoptosis was evaluated by the TUNEL assay, and the caspase-3 expression level was assessed by immunoblotting. The cytokine levels were measured by ELISA. Results: Low and high doses of immunoglobulins administered 2 hours before sacrifice, before the ischemic insult or at reperfusion resulted in a significant improvement in cardiac hemodynamics, coronary vascular dynamics and heart contractility. A significant decrease in the infarct size and cardiac enzymes was also evident compared to those in the control. IVIG administered as an infusion at reperfusion or pre-treatment resulted in a marked decrease in myocyte apoptosis, which was associated with decreased levels of caspase-3 expression in the supernatants of homogenized left ventricles. Infusion of IVIG both pre-ischemia and at reperfusion did not show the same protective effects. Conclusions: This study demonstrates a novel protection to the heart by low and high doses of IVIG given either pre- or post-ischemia.

  9. Initial and Secondary ST-T Alternans During Acute Myocardial Ischemia in the In-Situ Pig Heart.

    Science.gov (United States)

    Watanabe, Ichiro; Gettes, Leonard S

    2016-05-25

    The factors responsible for the ST-T wave alternans (STTA) and associated arrhythmias during acute ischemia have not been clarified.In acutely ischemic porcine myocardium, we recorded transmural unipolar and bipolar electrocardiograms and mid-myocardial extracellular K(+) ([K(+)]e) from the center of the ischemic zone during 8-minute episodes of ischemia. Two different STTAs occurred. The initial STTA, which occurred at 4 minutes 15 seconds ± 12 seconds of ischemia during sinus rhythm, was most prominent in the subendocardium, independent of [K(+)]e and activation block, and heart rate dependent. It occurred in 13/19 (68%) occlusions at heart rates ≤ 100 bpm and in 22/23 (96%) at > 100 bpm. The second STTA was more obvious and greatest in the subepicardium. It began in the later phase of ischemia and was also heart rate dependent (5/19 [26%] occlusions at heart rates ≤ 100 bpm and 10/23 [44%] at > 100 bpm). This STTA was consistently associated with 2:1 change in the bipolar electrogram morphology, possibly due to 2:1 conduction block. Ventricular fibrillation (VF) occurred only at > 100 bpm.The initial STTA may be independent of conduction abnormalities and represent primary repolarization alternans. The second STTA may be secondary to and indicative of 2:1 activation block or marked alternans of the action potential amplitude/duration. The associated VF most likely reflects the underlying conduction abnormality.

  10. SILENT MYOCARDIAL ISCHEMIA AND CARDIAC RHYTHM DISTURBANCES IN WOMEN WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    D. S. Novikova

    2014-07-01

    Full Text Available Objective: to assess the rate of silent myocardial ischemia (SMI and the pattern of cardiac rhythm disturbances in women with rheumatoidarthritis (RA, their association with traditional risk factors (TRF for cardiovascular diseases (CVD, with subclinical structural and functionalchanges in the heart and vessels, with the activity and severity of rheumatoid inflammation.Subjects and methods. Two hundred and ninety-one female patients aged less than 60 years with a valid diagnosis of RA and no clinicalsigns were examined. A control group consisted of 125 women without rheumatic diseases. In addition to the clinical manifestations, activity,and severity of RA, the authors assessed major TRFs for CVD, performed Holter ECG monitoring, common carotid artery duplex scanning, transthoracic echocardiographic study, and determined the levels of serum inflammatory markers.Results. The women with RA differ from the control group in the higher incidence of SMI, supraventricular arrhythmias (SVA and highgradepremature ventricular contractions (PVC. The patients with RA and SMI are characterized in terms of age-adjustment by higher disease activity (DAS28, systemic manifestations, cumulative larger-dose glucocorticoids (GC and a higher percentage of patients receiving disease-modifying anti-rheumatic drugs as compared with those with RA and no SMI with adjustment for age. High disease activity(DAS28, level of inflammatory markers, IgM rheumatoid arthritis seropositivity, and GC therapy are SVA-associated factors in women with RA; larger left ventricular end-diastolic dimension and serositis are factors associated with high-grade PVC.Conclusion. The RA women without clinical manifestations of CVD are recorded to have high rates of SMI, SVA, and high-grade PVC, which is primarily due to the activity and severity of rheumatoid inflammation.

  11. Silent Myocardial Ischemia (SMI and its Association with Microalbuminuria in Type 2 Diabetes Mellitus (DM

    Directory of Open Access Journals (Sweden)

    Shahana Zabeen

    2012-06-01

    Full Text Available Background: As silent myocardial ischemia (SMI is more common in diabetic population leading to the development of future coronary artery disease (CAD, so its early diagnosis is important. SMI can be diagnosed by conventional cardiac stress testing. Presence of SMI can also be suspected by microalbuminuria (MAU because recently it is claimed that MAU is one of the important predictor for cardiovascular disease. Objective: The study was designed to explore the association between SMI & MAU in type 2 DM. Methods: It was a cross sectional study carried out in the Department of Biochemistry, BSMMU during the period of July 2006 to June 2008. One hundred diagnosed type 2 DM patients were selected from out patient department of BIRDEM. Enrolled study subjects were advised to do ETT and then categorized as ETT +ve & ETT-ve on the basis of ETT findings. Urinary micro albumin was measured in all study subjects. Unpaired t test, , chi square test, odds ratio were used to see the level of significance Results: Among the 100 type 2 diabetic subjects of both sexes 50 (male -24, female- 26 were ETT +ve designated as type 2 DM with silent MI and rest 50 ( male- 25 , female-25 were ETT –ve designated as type 2 DM without silent MI. 21 patients (42% out of 50 type 2 DM with silent MI & 16 patients (32% out of 50 type 2 DM without silent MI found to have microalbuminuria. Calculated odds ratio was 1.5. Conclusion: Microalbuminuria is a possible risk factor for SMI in type 2 DM. Urinary micro albumin can be used particularly as a screening test for early detection of SMI.DOI: http://dx.doi.org/10.3329/bsmmuj.v5i1.11016 BSMMU J 2012; 5(1:42-45

  12. Rheb is a critical regulator of autophagy during myocardial ischemia: pathophysiological implications in obesity and metabolic syndrome.

    Science.gov (United States)

    Sciarretta, Sebastiano; Zhai, Peiyong; Shao, Dan; Maejima, Yasuhiro; Robbins, Jeffrey; Volpe, Massimo; Condorelli, Gianluigi; Sadoshima, Junichi

    2012-03-06

    Rheb is a GTP-binding protein that promotes cell survival and mediates the cellular response to energy deprivation (ED). The role of Rheb in the regulation of cell survival during ED has not been investigated in the heart. Rheb is inactivated during cardiomyocyte (CM) glucose deprivation (GD) in vitro, and during acute myocardial ischemia in vivo. Rheb inhibition causes mTORC1 inhibition, because forced activation of Rheb, through Rheb overexpression in vitro and through inducible cardiac-specific Rheb overexpression in vivo, restored mTORC1 activity. Restoration of mTORC1 activity reduced CM survival during GD and increased infarct size after ischemia, both of which were accompanied by inhibition of autophagy, whereas Rheb knockdown increased autophagy and CM survival. Rheb inhibits autophagy mostly through Atg7 depletion. Restoration of autophagy, through Atg7 reexpression and inhibition of mTORC1, increased cellular ATP content and reduced endoplasmic reticulum stress, thereby reducing CM death induced by Rheb activation. Mice with high-fat diet-induced obesity and metabolic syndrome (HFD mice) exhibited deregulated cardiac activation of Rheb and mTORC1, particularly during ischemia. HFD mice presented inhibition of cardiac autophagy and displayed increased ischemic injury. Pharmacological and genetic inhibition of mTORC1 restored autophagy and abrogated the increase in infarct size observed in HFD mice, but they failed to protect HFD mice in the presence of genetic disruption of autophagy. Inactivation of Rheb protects CMs during ED through activation of autophagy. Rheb and mTORC1 may represent therapeutic targets to reduce myocardial damage during ischemia, particularly in obese patients.

  13. Differential coronary microvascular function in patients with left ventricular dysfunction of unknown cause--implication for possible mechanism of myocardial ischemia in early stage of cardiomyopathy.

    Science.gov (United States)

    Chen, J W; Ting, C T; Chen, Y H; Wu, T C; Hsu, N W; Lin, S J; Chang, M S

    1999-06-01

    To evaluate whether or not coronary microvascular dysfunction is associated with exercise-induced myocardial ischemia in left ventricular dysfunction of unknown cause, both the treadmill exercise test (TET) and coronary hemodynamics were studied in 20 patients with impaired left ventricular ejection fraction (ventriculogram), normal cardiac size, normal coronary angiogram and no evidence of clinical heart failure. Ten subjects with atypical chest pain were studied as the control. Coronary hemodynamics were studied both at baseline and after dipyridamole infusion (0.56mg/kg, i.v. for 4'). There was no difference in age, gender, blood pressure, baseline great cardiac venous flow (GCVF) and coronary vascular resistance between ten patients with a positive TET and the other ten with a negative TET. At baseline, coronary sinus oxygen concentration was increased and myocardial oxygen consumption reduced in patients with a positive TET compared with those with negative a TET. After dipyridamole infusion, maximum GCVF (102+/-47 vs. 144+/-31 ml/min, P=0.027) and coronary flow reserve (2.31+/-0.49 vs. 3.00+/-0.61, P=0.012) were significantly reduced and minimum coronary vascular resistance was higher (1.00+/-0.42 vs. 0.63+/-0.12 mmHg/ml/min, P=0.016) in patients with a positive TET than in those with a negative TET. At follow-up, 40% of patients with a positive TET and 10% of those with a negative TET developed clinical heart failure with a dilated left ventricle during a period of 45 months. Thus, coronary microvascular function is heterogeneous in patients with left ventricular dysfunction of unknown cause. In some of them, coronary microvascular dysfunction could be related to the presence of exercise-induced myocardial ischemia, suggesting that similar pathophysiology underlies the early stage of dilated cardiomyopathy and syndrome X.

  14. QRS-ST-T triangulation with repolarization shortening as a precursor of sustained ventricular tachycardia during acute myocardial ischemia.

    Science.gov (United States)

    Batchvarov, Velislav N; Behr, Elijah R

    2015-04-01

    We present segments from a 24-hour 12-lead digital Holter recording in a 48-year-old man demonstrating transient ST elevations in the inferior leads that triggered sustained ventricular tachycardia/ventricular fibrillation (VT/VF) requiring cardioversion. The onset of VT was preceded by a gradual increase in the ST with marked QRS broadening that lacked distinction between the end of the QRS and the beginning of the ST (QRS-ST-T "triangulation"), and shortening of the QT interval not caused by an increased heart rate. This is a relatively rare documentation of the mechanisms immediately triggering sustained ventricular arrhythmias during acute myocardial ischemia obtained with 12-lead ECG.

  15. [Surgical Treatment of Left Main Trunk Coronary Artery Aneurysm with Asymptomatic Myocardial Ischemia;Report of a Case].

    Science.gov (United States)

    Okugi, Satoshi; Saito, Hiroyuki; Umeda, Etsuji; Takiguchi, Yoji

    2017-05-01

    Coronary artery aneurysm is rare, and there is no established protocol for surgical indication. On preoperative examination of orthopedic surgery, a 76-year-old male was found with asymptomatic myocardial ischemia. Radiological examinations revealed triple vessel disease and a coronary artery aneurysm, 10 mm in size, at the bifurcation of the left main trunk. Combined with quintuple coronary artery bypass grafting, surgical repair of the aneurysm was peformed under cardiopulmonary bypass on beating heart. Epicardial echocardiography was used to detect the site and the blood flow on the aneurysm. Postoperative course was uneventful. Epicardial echocardiography was useful for detecting the coronary artery aneurysm in the myocardium and the residual aneurysmal blood flow.

  16. Protective Effects of Shen-Yuan-Dan, a Traditional Chinese Medicine, against Myocardial Ischemia/Reperfusion Injury In Vivo and In Vitro

    Directory of Open Access Journals (Sweden)

    Hongxu Liu

    2013-01-01

    Full Text Available Objectives. The study was to investigate the effects and mechanisms of Shen-Yuan-Dan (SYD pharmacological postconditioning on myocardial ischemia/reperfusion (I/R injury. Methods. In the in vivo experiment, myocardial injury markers and histopathology staining were examined. In the in vitro experiment, cell viability and cell apoptosis were, respectively, detected by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assays and Hoechst 33342 fluorochrome staining. The protein expressions of Bcl-2 and Bax were determined by immunocytochemistry assay. Results. Both low and high doses of SYD protected myocardium against I/R injury in rat model by reducing lactic dehydrogenase (LDH and creatine kinase-MB (CK-MB activity and malondialdehyde (MDA content, increasing superoxide dismutase (SOD activity and attenuating histopathology injury. Meanwhile, in the in vitro experiment, SYD promoted cell viability and inhibited the cardiomyocyte apoptosis. The level of Bcl-2 protein was restored to the normal level by SYD pharmacological postconditioning. In contrast, the Bax protein level was markedly reduced by SYD pharmacological postconditioning. These effects of SYD were inhibited by LY294002. Conclusions. The results of this study suggested that SYD pharmacological postconditioning has protective effects against myocardial I/R injury in both in vivo and in vitro models, which are related to activating the phosphatidylinositol 3-kinase/Akt (PI3K/Akt pathway.

  17. Regional myocardial oxygen consumption estimated by carbon-11 acetate and positron emission tomography before and after repetitive ischemia

    DEFF Research Database (Denmark)

    Kofoed, K F; Hansen, P R; Holm, S

    2011-01-01

    Preserved myocardial oxygen consumption estimated by carbon 11-acetate and positron emission tomography (PET) in myocardial regions with chronic but reversibly depressed contractile function in patients with ischemic heart disease have been suggested to be caused by repeated short episodes of acute...

  18. Grade 3 ischemia on the admission electrocardiogram predicts failure of ST resolution and of adequate flow restoration after primary percutaneous coronary intervention for acute myocardial infarction.

    Science.gov (United States)

    Wolak, Arik; Yaroslavtsev, Sergei; Amit, Guy; Birnbaum, Yochai; Cafri, Carlos; Atar, Shaul; Gilutz, Harel; Ilia, Reuben; Zahger, Doron

    2007-03-01

    Failure of ST-segment resolution (STR) after primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction is associated with adverse outcome but currently cannot be predicted on admission. Our aim was to determine whether failure of STR can be predicted from clinical and electrocardiographic data available on admission and whether the adverse outcome associated with grade 3 ischemia (distortion of the terminal portion of the QRS complex) is mediated through impaired tissue reperfusion. We prospectively studied 100 consecutive patients who underwent PPCI for a first ST-elevation myocardial infarction. Multiple variables available on admission were analyzed as predictors of STR. Electrocardiograms and angiograms were analyzed by blinded investigators. Grade 2 ischemia was found in 71 patients (71%) and 29 (29%) had grade 3 ischemia. Complete STR was observed in 42 (59%) of 71 patients with grade 2 ischemia as compared to 8 (28%) of 29 patients with grade 3 ischemia (P = .004). In a multivariate model, grade 3 ischemia was the sole predictor of failure of STR (odds ratio [OR] 0.26, 95% CI 0.1-0.72) and the strongest predictor of failure to achieve TIMI grade 3 flow (OR 0.07, CI 0.02-0.3) and TIMI myocardial perfusion grade 3 (OR 0.09, CI 0.02-0.4) after the procedure. Grade 3 ischemia is a strong independent predictor available on admission of failure to achieve myocardial reperfusion after PPCI, as assessed both electrocardiographically and angiographically. This association may underlie the larger infarcts associated with grade 3 ischemia and may allow the identification upon admission of patients who require more aggressive management to improve reperfusion.

  19. Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion

    Science.gov (United States)

    Fauconnier, Jérémy; Meli, Albano C.; Thireau, Jérôme; Roberge, Stephanie; Shan, Jian; Sassi, Yassine; Reiken, Steven R.; Rauzier, Jean-Michel; Marchand, Alexandre; Chauvier, David; Cassan, Cécile; Crozier, Christine; Bideaux, Patrice; Lompré, Anne-Marie; Jacotot, Etienne; Marks, Andrew R.; Lacampagne, Alain

    2011-01-01

    Myocardial ischemic disease is the major cause of death worldwide. After myocardial infarction, reperfusion of infracted heart has been an important objective of strategies to improve outcomes. However, cardiac ischemia/reperfusion (I/R) is characterized by inflammation, arrhythmias, cardiomyocyte damage, and, at the cellular level, disturbance in Ca2+ and redox homeostasis. In this study, we sought to determine how acute inflammatory response contributes to reperfusion injury and Ca2+ homeostasis disturbance after acute ischemia. Using a rat model of I/R, we show that circulating levels of TNF-α and cardiac caspase-8 activity were increased within 6 h of reperfusion, leading to myocardial nitric oxide and mitochondrial ROS production. At 1 and 15 d after reperfusion, caspase-8 activation resulted in S-nitrosylation of the RyR2 and depletion of calstabin2 from the RyR2 complex, resulting in diastolic sarcoplasmic reticulum (SR) Ca2+ leak. Pharmacological inhibition of caspase-8 before reperfusion with Q-LETD-OPh or prevention of calstabin2 depletion from the RyR2 complex with the Ca2+ channel stabilizer S107 (“rycal”) inhibited the SR Ca2+ leak, reduced ventricular arrhythmias, infarct size, and left ventricular remodeling after 15 d of reperfusion. TNF-α–induced caspase-8 activation leads to leaky RyR2 channels that contribute to myocardial remodeling after I/R. Thus, early prevention of SR Ca2+ leak trough normalization of RyR2 function is cardioprotective. PMID:21788490

  20. Low-intensity pulsed ultrasound induces angiogenesis and ameliorates left ventricular dysfunction in a porcine model of chronic myocardial ischemia.

    Directory of Open Access Journals (Sweden)

    Kenichiro Hanawa

    Full Text Available Although a significant progress has been made in the management of ischemic heart disease (IHD, the number of severe IHD patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. In the present study, we aimed to develop low-intensity pulsed ultrasound (LIPUS therapy for the treatment of IHD.We first confirmed that in cultured human endothelial cells, LIPUS significantly up-regulated mRNA expression of vascular endothelial growth factor (VEGF with a peak at 32-cycle (P<0.05. Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF (n = 28. The heart was treated with either sham (n = 14 or LIPUS (32-cycle with 193 mW/cm2 for 20 min, n = 14 at 3 different short axis levels. Four weeks after the treatment, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05 without any adverse effects, whereas it remained unchanged in the sham group (46±5 to 47±6%, P = 0.33. Capillary density in the ischemic region was significantly increased in the LIPUS group compared with the control group (1084±175 vs. 858±151/mm2, P<0.05. Regional myocardial blood flow was also significantly improved in the LIPUS group (0.78±0.2 to 1.39±0.4 ml/min/g, P<0.05, but not in the control group (0.84±0.3 to 0.97±0.4 ml/min/g. Western blot analysis showed that VEGF, eNOS and bFGF were all significantly up-regulated only in the LIPUS group.These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD.

  1. Cardioprotective Effect of Licochalcone D against Myocardial Ischemia/Reperfusion Injury in Langendorff-Perfused Rat Hearts.

    Directory of Open Access Journals (Sweden)

    Xuan Yuan

    Full Text Available Flavonoids are important components of 'functional foods', with beneficial effects on cardiovascular function. The present study was designed to investigate whether licochalcone D (LD could be a cardioprotective agent in ischemia/reperfusion (I/R injury and to shed light on its possible mechanism. Compared with the I/R group, LD treatment enhanced myocardial function (increased LVDP, dp/dtmax, dp/dtmin, HR and CR and suppressed cardiac injury (decreased LDH, CK and myocardial infarct size. Moreover, LD treatment reversed the I/R-induced cleavage of caspase-3 and PARP, resulting in a significant decrease in proinflammatory factors and an increase in antioxidant capacity in I/R myocardial tissue. The mechanisms underlying the antiapoptosis, antiinflammation and antioxidant effects were related to the activation of the AKT pathway and to the blockage of the NF-κB/p65 and p38 MAPK pathways in the I/R-injured heart. Additionally, LD treatment markedly activated endothelial nitric oxide synthase (eNOS and reduced nitric oxide (NO production. The findings indicated that LD had real cardioprotective potential and provided support for the use of LD in myocardial I/R injury.

  2. Piperine modulates isoproterenol induced myocardial ischemia through antioxidant and anti-dyslipidemic effect in male Wistar rats.

    Science.gov (United States)

    Dhivya, Velumani; Priya, Lohanathan Bharathi; Chirayil, Hilda T; Sathiskumar, Swamiappan; Huang, Chih-Yang; Padma, Viswanadha Vijaya

    2017-03-01

    Myocardial infarction due to ischemia accounts for majority of deaths among cardiovascular disorders. Isoproterenol (ISO) induced myocardial infarction and the protection offered by piperine was investigated in the present report. Lipid profile analysis by determining the levels of cholesterol, phospholipids, triglycerides and lipoproteins in serum and heart tissues showed anti-dyslipidemic action of piperine against ISO induced myocardial injury by modulating the ISO induced altered lipid profiles, maintaining to near control values. ISO treatment increased TBARS levels, PCC, serum markers of heart, depleted antioxidant status (GSH, SOD, CAT, GPx and GST) in tissues and, total, protein- and non-protein-sulfhydryl levels in serum and heart tissues. Piperine pre-treatment decreased the levels of serum markers, lipid peroxidation and PCC with increased antioxidant status in the heart tissues of ISO administered rats. Increased levels of the glycoprotein components in serum and decreased levels in heart tissues upon ISO administration were restored to near normal levels by piperine pre-treatment. Our present reports also showed the modulatory effect of piperine on membrane bound ATPase's showing protection against ISO induced changes in membrane fluidity. The present study proved piperine as a potent therapeutic agent with its antioxidant and anti-dyslipidemic action against ISO induced myocardial infarction. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Mitochondrial DNA‑induced inflammatory damage contributes to myocardial ischemia reperfusion injury in rats: Cardioprotective role of epigallocatechin.

    Science.gov (United States)

    Qin, Chao-Yi; Zhang, Hong-Wei; Gu, Jun; Xu, Fei; Liang, Huai-Min; Fan, Kang-Jun; Shen, Jia-Yu; Xiao, Zheng-Hua; Zhang, Er-Yong; Hu, Jia

    2017-11-01

    Inflammation serves an important role in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. Fragments of endogenous damaged‑associated molecular patterns, recently identified as mitochondrial DNA (mtDNA), have been proven to be a potent pro‑inflammatory mediator. Epigallocatechin‑3‑gallate (EGCG) is able to regulate the expression levels of a series of inflammatory cytokines. However, the involvement of endogenous mtDNA in EGCG‑regulated inflammatory activities in the context of myocardial I/R injury remains to be elucidated. The present study was designed to investigate the role of mtDNA in EGCG‑mediated myocardial protection in a rat I/R model. Significant positive correlations between elevated plasma mtDNA copy numbers and the expression levels of tumor necrosis factor (TNF) and interleukins (IL)‑6 and ‑8 were observed in the myocardial tissue following an I/R injury (Pcardioprotective effects may be achieved by inhibiting the release of mtDNA from damaged mitochondria and that this protection was at least in part dependent on the PI3K/RAC‑α serine/threonine‑protein kinase associated signaling pathway.

  4. Diagnosis of Coronary Heart Diseases Using Gene Expression Profiling; Stable Coronary Artery Disease, Cardiac Ischemia with and without Myocardial Necrosis.

    Directory of Open Access Journals (Sweden)

    Nabila Kazmi

    Full Text Available Cardiovascular disease (including coronary artery disease and myocardial infarction is one of the leading causes of death in Europe, and is influenced by both environmental and genetic factors. With the recent advances in genomic tools and technologies there is potential to predict and diagnose heart disease using molecular data from analysis of blood cells. We analyzed gene expression data from blood samples taken from normal people (n = 21, non-significant coronary artery disease (n = 93, patients with unstable angina (n = 16, stable coronary artery disease (n = 14 and myocardial infarction (MI; n = 207. We used a feature selection approach to identify a set of gene expression variables which successfully differentiate different cardiovascular diseases. The initial features were discovered by fitting a linear model for each probe set across all arrays of normal individuals and patients with myocardial infarction. Three different feature optimisation algorithms were devised which identified two discriminating sets of genes, one using MI and normal controls (total genes = 6 and another one using MI and unstable angina patients (total genes = 7. In all our classification approaches we used a non-parametric k-nearest neighbour (KNN classification method (k = 3. The results proved the diagnostic robustness of the final feature sets in discriminating patients with myocardial infarction from healthy controls. Interestingly it also showed efficacy in discriminating myocardial infarction patients from patients with clinical symptoms of cardiac ischemia but no myocardial necrosis or stable coronary artery disease, despite the influence of batch effects and different microarray gene chips and platforms.

  5. Postoperative myocardial infarction documented by technetium pyrophosphate scan using single-photon emission computed tomography: Significance of intraoperative myocardial ischemia and hemodynamic control

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, D.C.; Chung, F.; Burns, R.J.; Houston, P.L.; Feindel, C.M. (Toronto Hospital, Ontario (Canada))

    1989-12-01

    The aim of this prospective study was to document postoperative myocardial infarction (PMI) by technetium pyrophosphate scan using single-photon emission computed tomography (TcPPi-SPECT) in 28 patients undergoing elective coronary bypass grafting (CABG). The relationships of intraoperative electrocardiographic myocardial ischemia, hemodynamic responses, and pharmacological requirements to this incidence of PMI were correlated. Radionuclide cardioangiography and TcPPi-SPECT were performed 24 h preoperatively and 48 h postoperatively. A standard high-dose fentanyl anesthetic protocol was used. Twenty-five percent of elective CABG patients were complicated with PMI, as documented by TcPPi-SPECT with an infarcted mass of 38.0 +/- 5.5 g. No significant difference in demographic, preoperative right and left ventricular function, number of coronary vessels grafted, or aortic cross-clamp time was observed between the PMI and non-PMI groups. The distribution of patients using preoperative beta-adrenergic blocking drugs or calcium channel blocking drugs was found to have no correlation with the outcome of PMI. As well, no significant differences in hemodynamic changes or pharmacological requirements were observed in the PMI and non-PMI groups during prebypass or postbypass periods, indicating careful intraoperative control of hemodynamic indices did not prevent the outcome of PMI in these patients. However, the incidence of prebypass ischemia was 39.3% and significantly correlated with the outcome of positive TcPPi-SPECT, denoting a 3.9-fold increased risk of developing PMI. Prebypass ischemic changes in leads II and V5 were shown to correlate with increased CPK-MB release (P less than 0.05) and tends to occur more frequently with lateral myocardial infarction.

  6. Effects of bisoprolol and isosorbide dinitrate on the circadian distribution of myocardial ischemia

    NARCIS (Netherlands)

    Portegies, MCM; Brouwer, J; Ven, LLMVD; Viersma, JW; Lie, KI

    1995-01-01

    The effects of bisoprolol 10 mg once daily, isosorbide dinitrate (ISDN) 20 mg three times daily, or a combination of these drugs on ischemia during exercise testing and on the occurrence and the circadian variation of ischemia during ambulatory monitoring were evaluated in 23 patients with stable

  7. Grade 3 ischemia on admission electrocardiogram and chest pain duration predict failure of ST-segment resolution after primary percutaneous coronary intervention for acute myocardial infarction.

    Science.gov (United States)

    McGehee, Jarrett T; Rangasetty, Umamahesh C; Atar, Shaul; Barbagelata, Nestor N; Uretsky, Barry F; Birnbaum, Yochai

    2007-01-01

    ST resolution (STR) is a surrogate marker of myocardial tissue reperfusion and a predictor of outcome after primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI). Terminal QRS distortion (grade 3 ischemia) has been shown to predict failure of STR after thrombolysis for STEMI, but the ability of grade 3 ischemia to predict STR with pPCI is unclear. We retrospectively analyzed 155 patients who underwent pPCI and compared grade 2 ischemia (ST elevation without terminal QRS distortion; n = 89) to grade 3 ischemia (n = 66) on admission for baseline characteristics, in-hospital course, and STR immediately after pPCI and at 18 to 24 hours. Patients with grade 3 ischemia were older (60 +/- 12 vs 56 +/- 11 years; P = .018), had more anterior STEMI (42% vs 17%; P = .0004), and were less often smokers (41% vs 90%; P = .004). The grade 3 ischemic group had significantly less complete STR (35% vs 75% [P grade 3 ischemia (OR, 0.181; 95% CI, 0.068-0.480; P Grade 3 ischemia on presentation of STEMI and duration of chest pain are strong independent predictors of failure to achieve complete STR after pPCI.

  8. Protective effects of Ping-Lv-Mixture (PLM), a medicinal formula on arrhythmias induced by myocardial ischemia-reperfusion.

    Science.gov (United States)

    An, Wei; Yang, Jing

    2006-11-03

    Ping-Lv-Mixture (PLM) is a Chinese medicinal formula. The present study aimed to determine the effects of PLM on myocardial ischemia-reperfusion (MI/R) induced arrhythmias in rats. Arrhythmia model was established by occlusion of the left arterial descending coronary artery and thereafter reperfusion. A lead II electrocardiogram was monitored throughout the experiment. The results showed that pretreatment of PLM to MI/R rats significantly reduced the incidence and duration of ventricular tachycardia and ventricular fibrillation. On induction of MI/R, the activities of creatine kinase and lactate dehydrogenase were increased in vehicle group. PLM (0.04-1.00 g/kg) administration prevented the increase of these enzymes. Moreover, a significant increase of myocardium superoxide dismutase and decrease of malondialdehyde contents were observed in rats of PLM groups. On the other hand, the expressions of platelet activating factor (PAF) receptor mRNA was down-regulated in a dose-dependent manner in the PLM-treated groups by RT-PCR. Thus, it can be concluded that pretreatment with PLM inhibited lipid peroxidation in rats through suppressing the expression of PAF receptor, which may contribute to its preventive effect on myocardial ischemia-reperfusion induced arrhythmias.

  9. Real-Time 12-Lead High-Frequency QRS Electrocardiography for Enhanced Detection of Myocardial Ischemia and Coronary Artery Disease

    Science.gov (United States)

    Schlegel, Todd T.; Kulecz, Walter B.; DePalma, Jude L.; Feiveson, Alan H.; Wilson, John S.; Rahman, M. Atiar; Bungo, Michael W.

    2004-01-01

    Several studies have shown that diminution of the high-frequency (HF; 150-250 Hz) components present within the central portion of the QRS complex of an electrocardiogram (ECG) is a more sensitive indicator for the presence of myocardial ischemia than are changes in the ST segments of the conventional low-frequency ECG. However, until now, no device has been capable of displaying, in real time on a beat-to-beat basis, changes in these HF QRS ECG components in a continuously monitored patient. Although several software programs have been designed to acquire the HF components over the entire QRS interval, such programs have involved laborious off-line calculations and postprocessing, limiting their clinical utility. We describe a personal computer-based ECG software program developed recently at the National Aeronautics and Space Administration (NASA) that acquires, analyzes, and displays HF QRS components in each of the 12 conventional ECG leads in real time. The system also updates these signals and their related derived parameters in real time on a beat-to-beat basis for any chosen monitoring period and simultaneously displays the diagnostic information from the conventional (low-frequency) 12-lead ECG. The real-time NASA HF QRS ECG software is being evaluated currently in multiple clinical settings in North America. We describe its potential usefulness in the diagnosis of myocardial ischemia and coronary artery disease.

  10. Transient ischemic dilation ratio (TID) correlates with HbA(1c) in patients with diabetes type 2 with proven myocardial ischemia according to exercise myocardial SPECT.

    Science.gov (United States)

    Adamikova, Alena; Bakala, Jiri; Bernatek, Jaromir; Rybka, Jaroslav; Svacina, Stepan

    2006-11-01

    Abnormal values of the transient ischemic dilation ratio (TID) according to an exercise myocardial SPECT are linked to severe coronary artery disease. The authors investigated the relationship between TID and the levels of VCAM, ICAM, E-selectin, microalbuminuria, intima-media thickness and HbA(1c) of diabetic subjects. We observed 38 subjects with diabetes type 2 (10 women, 28 men), of average age 56.08 +/- 8.24 years, with no past history of cardiovascular disease. All subjects were examined using an exercise myocardial SPECT. Transient ischemic dilation, summed stress score (SSS), summed rest score (SRS) and stress total severity score (STSS) were determined to quantify myocardial ischemia. The average IMT value was 1.05 +/- 0.31 mm. The TID value was 1.02 +/- 0.154, VCAM 795.24 +/- 163.25 mg/l, ICAM 516.55 +/- 164.07, E-selectin 63.82 +/- 38.89, HbA(1c) 7.09 +/- 1.68%, microalbuminuria 68.01 +/- 55.21 mg/l. When ascertaining the relation of TID to the other factors we used Pearson's correlation at the level of significance p TID and glycosylated hemoglobin HbA(1c) (p = 0.035); the other factors did not show any significant correlation. Diabetes and its long- term unsatisfactory compensation can be one of the factors which affect left ventricular transient ischemic dilation.

  11. Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

    Directory of Open Access Journals (Sweden)

    Arheden Håkan

    2010-09-01

    Full Text Available Abstract Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg, a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8 or saline (9 mg/ml, n = 8. Area at risk (AAR was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007. Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23. The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.

  12. Grade 3 ischemia on the admission electrocardiogram is associated with severe microvascular injury on cardiac magnetic resonance imaging after ST elevation myocardial infarction.

    Science.gov (United States)

    Weaver, James C; Rees, David; Prasan, Ananth M; Ramsay, David D; Binnekamp, Maurits F; McCrohon, Jane A

    2011-01-01

    Grade 3 ischemia during ST elevation myocardial infarction (STEMI) is defined as ST elevation with distortion of the terminal portion of the QRS on electrocardiogram (ECG). The aim of this study was to evaluate the effect of ischemic grade on cardiac magnetic resonance (CMR) imaging infarct characteristics such as infarct size, microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and myocardial salvage. Patients with STEMI treated with primary percutaneous coronary intervention had a 12-lead ECG on presentation for analysis of ischemic grade. Gadolinium-enhanced CMR imaging was performed within 7 days to assess infarct size, MVO, IMH, and myocardial salvage. Of the 37 patients enrolled in the study, grade 3 ischemia was present in 32%. Those with grade 3 ischemia had higher peak troponin I levels (P = .013), more MVO (P grade 3 ischemia, infarct size, and peak troponin I level were significantly associated with MVO and IMH. Grade 3 ischemia on the admission ECG during STEMI is closely associated with the development of severe microvascular damage on CMR imaging. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  13. Predictors and outcome of grade 3 ischemia in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

    NARCIS (Netherlands)

    Postma, S.; Heestermans, T.; Berg, J.W. Ten; Werkum, J.W. van; Suryapranata, H.; Birnbaum, Y.; Hamm, C.W.; Hof, A.W. van 't

    2011-01-01

    PURPOSE: Grade 3 ischemia (G3I: distortion of the terminal portion of the QRS complex) is a predictor of serious complications after acute myocardial infarction. However, less is known about which patients are more prone to present with G3I. METHODS: Patients who were enrolled in the Ongoing

  14. 77. High preoperative myocardial ischemia biomarkers as predictors of postoperative mortality after CABG surgery: Short and mid term outcome of tertiary center experience

    Directory of Open Access Journals (Sweden)

    Mohamed Abdulwahab Alassal

    2015-10-01

    Conclusion: Old age, multiple diseased vessels and low left ventricular ejection fraction in conjunction with high preoperative serum levels of myocardial ischemia biomarkers could predict PO mortality after CABG surgery. However, high preoperative troponin levels were significantly superior predictor for PO mortality than CK-MB.

  15. Maternal treatment with agonistic autoantibodies against type-1 angiotensin II receptor in late pregnancy increases apoptosis of myocardial cells and myocardial susceptibility to ischemia-reperfusion injury in offspring rats.

    Directory of Open Access Journals (Sweden)

    Zhu Jin

    Full Text Available Epidemiological studies have demonstrated that offspring born to mothers preeclampsia (PE are at increased risk for developing cardiovascular diseases after birth, but the underlying mechanism is unknown. Angiotensin II receptor type 1 autoantibody (AT1-AA, an agonist acting via activation of the AT1 receptor, is believed to be involved in the pathogenesis of both PE and fetal growth restriction. The aim of the present study was to confirm the hypothesis that prenatal AT1-AA exposure increases the heart susceptibility to ischemia/reperfusion injury (IRI in the offspring in an AT1-AA-induced animal model of PE, and determine whether or not the increase of maternal AT1-AA level is a factor contributing to sustained abnormalities of the heart structure during infancy. The hearts of 45-day-old offspring rats were studied using Langendorff preparation to determine the susceptibility of the heart to IRI. The results showed that the body weight of the maternal rats was not significantly different between the study and control groups, but the body weight of their offspring in AT1-AA group was decreased slightly at day 21 of gestational age, and at day 3 after birth. Although the heart weight index was not significantly affected at all ages examined, AT1-AA significantly increased the size of myocardial cells of the left ventricle (LV at the age of 45 days. AT1-AA gained access to fetal circulation via the placenta and induced apoptosis of fetal myocardial cells. AT1-AA also significantly delayed recovery from IRI and affected the LV function of 45-day-old offspring. This was associated with a significant increase in IRI-induced LV myocardial infarct size. These results suggest that AT1-AA induced abnormal apoptosis of fetal myocardial cells during the fetal period and increased the cardiac susceptibility to IRI in adult offspring.

  16. Maternal treatment with agonistic autoantibodies against type-1 angiotensin II receptor in late pregnancy increases apoptosis of myocardial cells and myocardial susceptibility to ischemia-reperfusion injury in offspring rats.

    Science.gov (United States)

    Jin, Zhu; Zhang, Wenhui; Yang, Hailiang; Wang, Xiaofang; Zheng, Yanqian; Zhang, Qiaoyan; Zhi, Jianming

    2013-01-01

    Epidemiological studies have demonstrated that offspring born to mothers preeclampsia (PE) are at increased risk for developing cardiovascular diseases after birth, but the underlying mechanism is unknown. Angiotensin II receptor type 1 autoantibody (AT1-AA), an agonist acting via activation of the AT1 receptor, is believed to be involved in the pathogenesis of both PE and fetal growth restriction. The aim of the present study was to confirm the hypothesis that prenatal AT1-AA exposure increases the heart susceptibility to ischemia/reperfusion injury (IRI) in the offspring in an AT1-AA-induced animal model of PE, and determine whether or not the increase of maternal AT1-AA level is a factor contributing to sustained abnormalities of the heart structure during infancy. The hearts of 45-day-old offspring rats were studied using Langendorff preparation to determine the susceptibility of the heart to IRI. The results showed that the body weight of the maternal rats was not significantly different between the study and control groups, but the body weight of their offspring in AT1-AA group was decreased slightly at day 21 of gestational age, and at day 3 after birth. Although the heart weight index was not significantly affected at all ages examined, AT1-AA significantly increased the size of myocardial cells of the left ventricle (LV) at the age of 45 days. AT1-AA gained access to fetal circulation via the placenta and induced apoptosis of fetal myocardial cells. AT1-AA also significantly delayed recovery from IRI and affected the LV function of 45-day-old offspring. This was associated with a significant increase in IRI-induced LV myocardial infarct size. These results suggest that AT1-AA induced abnormal apoptosis of fetal myocardial cells during the fetal period and increased the cardiac susceptibility to IRI in adult offspring.

  17. 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...

  18. Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation

    Science.gov (United States)

    Nakano, Yasuhiro; Matoba, Tetsuya; Tokutome, Masaki; Funamoto, Daiki; Katsuki, Shunsuke; Ikeda, Gentaro; Nagaoka, Kazuhiro; Ishikita, Ayako; Nakano, Kaku; Koga, Jun-Ichiro; Sunagawa, Kenji; Egashira, Kensuke

    2016-07-01

    Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction (AMI), in which the recruitment of inflammatory monocytes plays a causative role. Here we develop bioabsorbable poly-lactic/glycolic acid (PLGA) nanoparticles incorporating irbesartan, an angiotensin II type 1 receptor blocker with a peroxisome proliferator-activated receptor (PPAR)γ agonistic effect (irbesartan-NP). In a mouse model of IR injury, intravenous PLGA nanoparticles distribute to the IR myocardium and monocytes in the blood and in the IR heart. Single intravenous treatment at the time of reperfusion with irbesartan-NP (3.0 mg kg-1 irbesartan), but not with control nanoparticles or irbesartan solution (3.0 mg kg-1), inhibits the recruitment of inflammatory monocytes to the IR heart, and reduces the infarct size via PPARγ-dependent anti-inflammatory mechanisms, and ameliorates left ventricular remodeling 21 days after IR. Irbesartan-NP is a novel approach to treat myocardial IR injury in patients with AMI.

  19. Cardiac Per2 functions as novel link between fatty acid metabolism and myocardial inflammation during ischemia and reperfusion injury of the heart.

    Directory of Open Access Journals (Sweden)

    Stephanie Bonney

    Full Text Available Disruption of peripheral circadian rhyme pathways dominantly leads to metabolic disorders. Studies on circadian rhythm proteins in the heart indicated a role for Clock or Per2 in cardiac metabolism. In contrast to Clock(-/-, Per2(-/- mice have larger infarct sizes with deficient lactate production during myocardial ischemia. To test the hypothesis that cardiac Per2 represents an important regulator of cardiac metabolism during myocardial ischemia, we measured lactate during reperfusion in Per1(-/-, Per2(-/- or wildtype mice. As lactate measurements in whole blood indicated an exclusive role of Per2 in controlling lactate production during myocardial ischemia, we next performed gene array studies using various ischemia-reperfusion protocols comparing wildtype and Per2(-/- mice. Surprisingly, high-throughput gene array analysis revealed dominantly lipid metabolism as the differentially regulated pathway in wildtype mice when compared to Per2(-/-. In all ischemia-reperfusion protocols used, the enzyme enoyl-CoA hydratase, which is essential in fatty acid beta-oxidation, was regulated in wildtype animals only. Studies using nuclear magnet resonance imaging (NMRI confirmed altered fatty acid populations with higher mono-unsaturated fatty acid levels in hearts from Per2(-/- mice. Unexpectedly, studies on gene regulation during reperfusion revealed solely pro inflammatory genes as differentially regulated 'Per2-genes'. Subsequent studies on inflammatory markers showed increasing IL-6 or TNFα levels during reperfusion in Per2(-/- mice. In summary, these studies reveal an important role of cardiac Per2 for fatty acid metabolism and inflammation during myocardial ischemia and reperfusion, respectively.

  20. Troponin levels within the normal range and probability of inducible myocardial ischemia and coronary events in patients with acute chest pain.

    Science.gov (United States)

    Bouzas-Mosquera, Alberto; Peteiro, Jesús; Broullón, Francisco J; Constanso, Ignacio P; Rodríguez-Garrido, Jorge L; Martínez, Dolores; Yáñez, Juan C; Bescos, Hildegart; Álvarez-García, Nemesio; Vázquez-Rodríguez, José Manuel

    2016-03-01

    Patients with suspected acute coronary syndromes and negative cardiac troponin (cTn) levels are deemed at low risk. Our aim was to assess the effect of cTn levels on the frequency of inducible myocardial ischemia and subsequent coronary events in patients with acute chest pain and cTn levels within the normal range. We evaluated 4474 patients with suspected acute coronary syndromes, nondiagnostic electrocardiograms and serial cTnI levels below the diagnostic threshold for myocardial necrosis using a conventional or a sensitive cTnI assay. The end points were the probability of inducible myocardial ischemia and coronary events (i.e., coronary death, myocardial infarction or coronary revascularization within 3 months). The probability of inducible myocardial ischemia was significantly higher in patients with detectable peak cTnI levels (25%) than in those with undetectable concentrations (14.6%, pacute coronary syndromes and seemingly negative cTnI. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  1. Rosmarinic Acid Protects against Inflammation and Cardiomyocyte Apoptosis during Myocardial Ischemia/Reperfusion Injury by Activating Peroxisome Proliferator-Activated Receptor Gamma

    Directory of Open Access Journals (Sweden)

    Jichun Han

    2017-07-01

    Full Text Available The cardiac ischemia-reperfusion (I/R injury greatly influences the therapeutic effect and remains an urgent challenge in clinical therapy. Polypharmacology opens a new therapeutic opportunity to design drugs with a specific target for improving the efficacy. In this study, we first forecasted that Rosmarinic acid (RosA could be used for the treatment of cardiovascular disease using text mining, chemometric and chemogenomic methods. Consistent with the effect of the positive drug (pioglitazone, PIO, we subsequently validated that RosA pretreatment could restore the decreased cardiac hemodynamic parameters (LVDP, ± dp/dtmin, ± dp/dtmax and CF, decreased the infarct size and the cardiomyocyte apoptosis in a rat model of cardiac I/R injury. Furthermore, RosA pre-treatment inhibited the levels of inflammatory cytokines (IL-6, TNF-α and CRP, up-regulated PPARγ expression and down-regulated NF-κB expression in myocardial tissue isolated from the rat model of I/R-induced myocardial injury. In addition, the effects of RosA were reversed by co-treatment with PPAR-γ inhibitor GW9662 and T0070907, respectively. These data suggest that RosA attenuates cardiac injury through activating PPARγ and down-regulating NF-κB-mediated signaling pathway, which inhibiting inflammation and cardiomyocyte apoptosis in a rat model of cardiac I/R injury.

  2. Rosmarinic Acid Protects against Inflammation and Cardiomyocyte Apoptosis during Myocardial Ischemia/Reperfusion Injury by Activating Peroxisome Proliferator-Activated Receptor Gamma.

    Science.gov (United States)

    Han, Jichun; Wang, Dong; Ye, Lei; Li, Peng; Hao, Wenjin; Chen, Xiaoyu; Ma, Jun; Wang, Bo; Shang, Jing; Li, Defang; Zheng, Qiusheng

    2017-01-01

    The cardiac ischemia-reperfusion (I/R) injury greatly influences the therapeutic effect and remains an urgent challenge in clinical therapy. Polypharmacology opens a new therapeutic opportunity to design drugs with a specific target for improving the efficacy. In this study, we first forecasted that Rosmarinic acid (RosA) could be used for the treatment of cardiovascular disease using text mining, chemometric and chemogenomic methods. Consistent with the effect of the positive drug (pioglitazone, PIO), we subsequently validated that RosA pretreatment could restore the decreased cardiac hemodynamic parameters (LVDP, ± dp/dtmin, ± dp/dtmax and CF), decreased the infarct size and the cardiomyocyte apoptosis in a rat model of cardiac I/R injury. Furthermore, RosA pre-treatment inhibited the levels of inflammatory cytokines (IL-6, TNF-α and CRP), up-regulated PPARγ expression and down-regulated NF-κB expression in myocardial tissue isolated from the rat model of I/R-induced myocardial injury. In addition, the effects of RosA were reversed by co-treatment with PPAR-γ inhibitor GW9662 and T0070907, respectively. These data suggest that RosA attenuates cardiac injury through activating PPARγ and down-regulating NF-κB-mediated signaling pathway, which inhibiting inflammation and cardiomyocyte apoptosis in a rat model of cardiac I/R injury.

  3. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

    Science.gov (United States)

    Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

    2015-01-01

    Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1–7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1–7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation. PMID:26569234

  4. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

    Directory of Open Access Journals (Sweden)

    Guoxing Wang

    2015-11-01

    Full Text Available Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg group. Thirty min after drug infusion, ventricular fibrillation (8 min and cardiopulmonary resuscitation (up to 30 min was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II and Ang (1–7 levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE, ACE2, Ang II type 1 receptor (AT1R, and the Ang (1–7 receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS, cyclic guanosine monophosphate (cGMP and inducible nitric oxide synthase(iNOS. Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

  5. MicroRNA-103/107 Regulate Programmed Necrosis and Myocardial Ischemia/Reperfusion Injury Through Targeting FADD.

    Science.gov (United States)

    Wang, Jian-Xun; Zhang, Xiao-Jie; Li, Qian; Wang, Kun; Wang, Yin; Jiao, Jian-Qin; Feng, Chang; Teng, Sun; Zhou, Lu-Yu; Gong, Ying; Zhou, Zhi-Xia; Liu, Jia; Wang, Jian-Ling; Li, Pei-feng

    2015-07-31

    Necrosis is one of the main forms of cardiomyocyte death in heart disease. Recent studies have demonstrated that certain types of necrosis are regulated and programmed dependent on the activation of receptor-interacting serine/threonine-protein kinase (RIPK) 1 and 3 which may be negatively regulated by Fas-associated protein with death domain (FADD). In addition, microRNAs and long noncoding RNAs have been shown to play important roles in various biological processes recently. The purpose of this study was to test the hypothesis that microRNA-103/107 and H19 can participate in the regulation of RIPK1- and RIPK3-dependent necrosis in fetal cardiomyocyte-derived H9c2 cells and myocardial infarction through targeting FADD. Our results show that FADD participates in H2O2-induced necrosis by influencing the formation of RIPK1 and RIPK3 complexes in H9c2 cells. We further demonstrate that miR-103/107 target FADD directly. Knockdown of miR-103/107 antagonizes necrosis in the cellular model and also myocardial infarction in a mouse ischemia/reperfusion model. The miR-103/107-FADD pathway does not participate in tumor necrosis factor-α-induced necrosis. In exploring the molecular mechanism by which miR-103/107 are regulated, we show that long noncoding RNA H19 directly binds to miR-103/107 and regulates FADD expression and necrosis. Our results reveal a novel myocardial necrosis regulation model, which is composed of H19, miR-103/107, and FADD. Modulation of their levels may provide a new approach for preventing myocardial necrosis. © 2015 American Heart Association, Inc.

  6. Electrocardiologic and related methods of non-invasive detection and risk stratification in myocardial ischemia: state of the art and perspectives

    Directory of Open Access Journals (Sweden)

    Seeck, Andrea

    2010-01-01

    Full Text Available Background: Electrocardiographic methods still provide the bulk of cardiovascular diagnostics. Cardiac ischemia is associated with typical alterations in cardiac biosignals that have to be measured, analyzed by mathematical algorithms and allegorized for further clinical diagnostics. The fast growing fields of biomedical engineering and applied sciences are intensely focused on generating new approaches to cardiac biosignal analysis for diagnosis and risk stratification in myocardial ischemia. Objectives: To present and review the state of the art in and new approaches to electrocardiologic methods for non-invasive detection and risk stratification in coronary artery disease (CAD and myocardial ischemia; secondarily, to explore the future perspectives of these methods. Methods: In follow-up to the Expert Discussion at the 2008 Workshop on "Biosignal Analysis" of the German Society of Biomedical Engineering in Potsdam, Germany, we comprehensively searched the pertinent literature and databases and compiled the results into this review. Then, we categorized the state-of-the-art methods and selected new approaches based on their applications in detection and risk stratification of myocardial ischemia. Finally, we compared the pros and cons of the methods and explored their future potentials for cardiology. Results: Resting ECG, particularly suited for detecting ST-elevation myocardial infarctions, and exercise ECG, for the diagnosis of stable CAD, are state-of-the-art methods. New exercise-free methods for detecting stable CAD include cardiogoniometry (CGM; methods for detecting acute coronary syndrome without ST elevation are Body Surface Potential Mapping, functional imaging and CGM. Heart rate variability and blood pressure variability analyses, microvolt T-wave alternans and signal-averaged ECG mainly serve in detecting and stratifying the risk for lethal arrythmias in patients with myocardial ischemia or previous myocardial infarctions

  7. Effects of acidic reperfusion fluid on myocardial endoplasmic reticulum stress and apoptosis after ischemia/reperfusion in rabbits

    Directory of Open Access Journals (Sweden)

    Hai-yan YANG

    2011-01-01

    Full Text Available Objective To determine the effect of acidic reperfusion fluid in cardiopulmonary bypass(CPB on the myocardial endoplasmic reticulum stress(ERS and apoptosis after ischemia/reperfusion in rabbits.Methods Twenty-four adult New Zealand white rabbits of both sexes weighing 2.5~3.0 kg were randomly divided into 4 groups(6 each.Control group(C:CPB for 3 hours without aortic clamping;pH7.4 group and pH6.9 group:hearts were subjected to ischemia for 40min followed by 2 hours of reperfusion,and then perfused with Krebs-Henseleit bicarbonate buffer solution,respectively,at pH7.4 and pH6.9 in the first 2min of reperfusion;ischemic postconditioning group(I-postC:40min after aortic clamping,6 cycles of 10-second reperfusion/10-second occlusion were given in the first 2min of 2-hour reperfusion.Cardiac troponin I(cTnI concentration was determined with ELISA,apoptosis of myocardial cell was detected by TUNEL,the expressions of glucose-regulated protein 78(GRP78and calreticulin(CRT mRNA were detected by RT-PCR,and the expressions of caspase-12 and C/EBP homologous protein(CHOP were assayed by immunohistochemistry.Results Compared with the C group,the cTnI concentration,apoptotic rate,expressions of GRP78,CRT mRNA,caspase-12 and CHOP of the other groups increased significantly(P 0.05.Conclusion Acidic reperfusion may protect the heart against I/R injury,regulate ERS response,inhibit excessive ERS,and alleviate ERS-mediated apoptosis during I/R.

  8. The protective effect of trimetazidine on myocardial ischemia/reperfusion injury through activating AMPK and ERK signaling pathway.

    Science.gov (United States)

    Liu, Zhenling; Chen, Ji-Mei; Huang, Huanlei; Kuznicki, Michelle; Zheng, Shaoyi; Sun, Wanqing; Quan, Nanhu; Wang, Lin; Yang, Hui; Guo, Hui-Ming; Li, Ji; Zhuang, Jian; Zhu, Ping

    2016-03-01

    Trimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. AMP-activated protein kinase (AMPK) is an energy sensor that controls ATP supply from substrate metabolism and protects heart from energy stress. TMZ changes the cardiac AMP/ATP ratio by modulating fatty acid oxidation, thereby triggering AMPK signaling cascade that contributes to the protection of the heart from ischemia/reperfusion (I/R) injury. The mouse model of in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) was used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. TMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (pmyocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (pmetabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Therefore, both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration. Copyright © 2015. Published by Elsevier Inc.

  9. Dietary n-3 fatty acids promote arrhythmias during acute regional myocardial ischemia in isolated pig hearts

    NARCIS (Netherlands)

    Coronel, R.; Wilms-Schopman, F.J.; den Ruijter, H.M.; Belterman, C.N.; Schumacher, C.A.; Opthof, T.; Hovenier, R.; Lemmens, A.G.; Terpstra, A.H.; Katan, M.B.; Zock, P.

    2007-01-01

    Objective: Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the

  10. Berberine Attenuates Myocardial Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Inflammation Response: Role of Silent Information Regulator 1

    Directory of Open Access Journals (Sweden)

    Liming Yu

    2016-01-01

    Full Text Available Berberine (BBR exerts potential protective effect against myocardial ischemia/reperfusion (MI/R injury. Activation of silent information regulator 1 (SIRT1 signaling attenuates MI/R injury by reducing oxidative damage and inflammation response. This study investigated the antioxidative and anti-inflammatory effects of BBR treatment in MI/R condition and elucidated its potential mechanisms. Sprague-Dawley rats were treated with BBR in the absence or presence of the SIRT1 inhibitor sirtinol (Stnl and then subjected to MI/R injury. BBR conferred cardioprotective effects by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase levels, upregulating SIRT1, Bcl-2 expressions, and downregulating Bax and caspase-3 expressions. Stnl attenuated these effects by inhibiting SIRT1 signaling. BBR treatment also reduced myocardium superoxide generation, gp91phox expression, malondialdehyde (MDA level, and cardiac inflammatory markers and increased myocardium superoxide dismutase (SOD level. However, these effects were also inhibited by Stnl. Consistently, BBR conferred similar antioxidative and anti-inflammatory effects against simulated ischemia reperfusion injury in cultured H9C2 cardiomyocytes. SIRT1 siRNA administration also abolished these effects. In summary, our results demonstrate that BBR significantly improves post-MI/R cardiac function recovery and reduces infarct size against MI/R injury possibly due to its strong antioxidative and anti-inflammatory activity. Additionally, SIRT1 signaling plays a key role in this process.

  11. Diagnosis of myocardial infarction and ischemia in the setting of bundle branch block and cardiac pacing.

    Science.gov (United States)

    Herweg, B; Marcus, M B; Barold, S S

    2016-09-01

    The diagnosis of myocardial infarction (MI) in the presence of left bundle branch block (LBBB) or during ventricular pacing (VP) is challenging because of inherent changes in the sequence of ventricular depolarization and repolarization associated with both conditions. Although LBBB and right ventricular (RV) pacing may both produce abnormalities in the ECG, it is often possible to diagnose an acute MI (AMI) or an old MI based on selected morphologic changes. Primary ST-segment changes scoring 3 points or greater according to the Sgarbossa criteria are highly predictive of an AMI in patients with LBBB or RV pacing. The modified Sgarbossa criteria are useful for the diagnosis of AMI in patients with LBBB; however, these criteria have not yet been studied in the setting of RV pacing. Although changes of the QRS complex are not particularly sensitive for the diagnosis of an old MI in the setting of LBBB or RV pacing, the qR complex and Cabrera sign are highly specific for the presence of an old infarct. Diagnosing AMI in the setting of biventricular (BiV) pacing is challenging. To date there is minimal evidence suggesting that the traditional electrocardiographic criteria for diagnosis of AMI in bundle branch block may be applicable to patients with BiV pacing and positive QRS complexes on their ECG in lead V1. This report is a careful review of the electrocardiographic criteria facilitating the diagnosis of acute and remote MI in patients with LBBB and/or VP.

  12. Dynamics of Oxidative Stress Evoked by Myocardial Ischemia Reperfusion After Off-Pump Coronary Artery Bypass Grafting Elucidated by Bilirubin Oxidation.

    Science.gov (United States)

    Yamamoto, Masaki; Nishimori, Hideaki; Fukutomi, Takashi; Yamaguchi, Tokio; Orihashi, Kazumasa

    2017-10-25

    Revascularization therapy relieves myocardial ischemia, but can also result in ischemia-reperfusion injury caused by oxidative stress. However, the biokinetics of oxidative stress after myocardial ischemia-reperfusion are uncertain. This study aimed to evaluate the dynamics of oxidative stress after off-pump coronary artery bypass grafting (OPCAB) by measuring urinary biopyrrin levels. Biopyrrin is an oxidative metabolite of bilirubin thought to reflect oxidative stress, along with reactive nitrogen species (RNS).Methods and Results:The study included 18 patients who underwent OPCAB; patients were divided into effort angina pectoris (EAP; n=11) and unstable angina pectoris (UAP; n=7). Urinary biopyrrin and RNS levels were measured during the perioperative period (≤48 h after surgery). Biopyrrin levels transiently increased 4-12 h post-surgery (early phase), followed by a prolonged increase approximately 24-32 h post-surgery (late phase). The delayed increase in biopyrrin tended to be higher in patients with UAP, with a simultaneous increase in RNS. The patients in the UAP group had generally high pulmonary capillary wedge pressure (PCWP), although the cardiac index was within a normal range during the delay phase. The dynamics of biopyrrin levels revealed a biphasic pattern of oxidative stress after OPCAB. Delayed production of oxidative stress may be influenced by preoperative severity of myocardial ischemia and delayed RNS production.

  13. Increased myocardial vulnerability to ischemia-reperfusion injury in the presence of left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Mølgaard, Søren; Faricelli, Barbara; Salomonsson, Max

    2016-01-01

    .  Conclusion: Hearts from hypertensive (SHR-SP) rats with left ventricle hypertrophy appeared more vulnerable to ischemia-reperfusion injury, as supported by a more profound infarct development and an earlier loss of postconditioning by Exe-4. Mitochondrial complexes III and IV were identified among possible...... loci of this increased, hypertrophy-associated vulnerability....

  14. Short-Term Hesperidin Pretreatment Attenuates Rat Myocardial Ischemia/Reperfusion Injury by Inhibiting High Mobility Group Box 1 Protein Expression via the PI3K/Akt Pathway

    Directory of Open Access Journals (Sweden)

    Xuefei Li

    2016-10-01

    Full Text Available Background/Aims: Hesperidin pretreatment has been shown to protect against myocardial ischemia/reperfusion (I/R injury, but the underlying mechanism is poorly understood. This study aimed to investigate the cardioprotective effects of a 3-day hesperidin pretreatment on I/R injury and to further explore whether its mechanism of action was associated with the inhibition of high mobility group box 1 protein (HMGB1 expression via the PI3K/Akt pathway. Methods: In a fixed-dose study, hematoxylin and eosin staining and myocardial enzyme measurements were used to determine the optimal dose of hesperidin that elicited the best cardioprotective effects against I/R injury. Furthermore, rats were pretreated with 200 mg/kg hesperidin, and infarct size and the levels of myocardial enzymes, apoptosis, inflammatory and oxidative indices, and HMGB1 and p-Akt expression were measured. Results: Our results indicated that while different 3-day hesperidin pretreatment doses promoted histopathological changes and reduced myocardial enzymes induced by I/R the optimal dose was 200 mg/kg. Moreover, the 200 mg/kg hesperidin pretreatment not only significantly decreased the infarct size as well as myocardial enzyme levels but also inhibited myocardial apoptosis, the inflammatory response and oxidative stress. Additionally, hesperidin downregulated HMGB1 expression and upregulated p-Akt expression in the myocardium. LY294002, a specific PI3K inhibitor, partially reversed the decreased HMGB1 expression, increased p-Akt expression induced by hesperidin and abolished the anti-apoptotic, anti-inflammatory and anti-oxidative effects of hesperidin. Conclusion: These findings suggest that short-term pretreatment with hesperidin protects against myocardial I/R injury by suppressing myocardial apoptosis, the inflammatory response and oxidative stress via PI3K/Akt pathway activation and HMGB1 inhibition.

  15. Short-Term Hesperidin Pretreatment Attenuates Rat Myocardial Ischemia/Reperfusion Injury by Inhibiting High Mobility Group Box 1 Protein Expression via the PI3K/Akt Pathway.

    Science.gov (United States)

    Li, Xuefei; Hu, Xiaorong; Wang, Jichun; Xu, Weipan; Yi, Chunfeng; Ma, Ruisong; Jiang, Hong

    2016-01-01

    Hesperidin pretreatment has been shown to protect against myocardial ischemia/reperfusion (I/R) injury, but the underlying mechanism is poorly understood. This study aimed to investigate the cardioprotective effects of a 3-day hesperidin pretreatment on I/R injury and to further explore whether its mechanism of action was associated with the inhibition of high mobility group box 1 protein (HMGB1) expression via the PI3K/Akt pathway. In a fixed-dose study, hematoxylin and eosin staining and myocardial enzyme measurements were used to determine the optimal dose of hesperidin that elicited the best cardioprotective effects against I/R injury. Furthermore, rats were pretreated with 200 mg/kg hesperidin, and infarct size and the levels of myocardial enzymes, apoptosis, inflammatory and oxidative indices, and HMGB1 and p-Akt expression were measured. Our results indicated that while different 3-day hesperidin pretreatment doses promoted histopathological changes and reduced myocardial enzymes induced by I/R the optimal dose was 200 mg/kg. Moreover, the 200 mg/kg hesperidin pretreatment not only significantly decreased the infarct size as well as myocardial enzyme levels but also inhibited myocardial apoptosis, the inflammatory response and oxidative stress. Additionally, hesperidin downregulated HMGB1 expression and upregulated p-Akt expression in the myocardium. LY294002, a specific PI3K inhibitor, partially reversed the decreased HMGB1 expression, increased p-Akt expression induced by hesperidin and abolished the anti-apoptotic, anti-inflammatory and anti-oxidative effects of hesperidin. These findings suggest that short-term pretreatment with hesperidin protects against myocardial I/R injury by suppressing myocardial apoptosis, the inflammatory response and oxidative stress via PI3K/Akt pathway activation and HMGB1 inhibition. © 2016 The Author(s) Published by S. Karger AG, Basel.

  16. Impact of a regimented aminophylline administration protocol on the burden of regadenoson-induced ischemia detected by SPECT myocardial perfusion imaging.

    Science.gov (United States)

    Fughhi, Ibtihaj; Campagnoli, Tania; Ali, Amjad; Doukky, Rami

    2017-10-01

    In patients undergoing regadenoson SPECT myocardial perfusion imaging (MPI), it is unknown how soon and at which dose intravenous aminophylline can be administered to reverse regadenoson-related adverse effects without blunting stress-induced myocardial ischemia. We analyzed the pooled database of the ASSUAGE and ASSUAGE-CKD trials (n = 548). These were double-blinded, placebo-controlled, randomized clinical trials in which 75 mg of aminophylline or placebo was administered intravenously 90 seconds following 99m Tc-tetrofosmin injection. There were no statistically significant differences in summed difference score (SDS) burden (P = .87) and in the rates of myocardial ischemia (SDS ≥ 2) (P = .93) between the aminophylline (n = 274) and placebo (n = 274) groups. There was no interaction between aminophylline use and SDS as a determinant of the composite endpoint of cardiac death or MI (P = .32) or the composite endpoint of cardiac death, MI, or coronary revascularization (P = .92). In patients undergoing regadenoson-stress SPECT-MPI, the intravenous administration of 75 mg of aminophylline as early as 90 seconds after radioisotope injection does not seem to attenuate the burden of myocardial ischemia.

  17. Cardioprotective Effects of Genistin in Rat Myocardial Ischemia-Reperfusion Injury Studies by Regulation of P2X7/NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Meng Gu

    2016-01-01

    Full Text Available The present study aimed to assess the effects and mechanisms of genistin in the rat model of myocardial ischemia reperfusion injury. The rat hearts were exposed to the left anterior descending coronary artery (LAD ligation for 30 min followed by 1 h of reperfusion. In the rat of myocardial ischemia/reperfusion (MI/R, it was found that genistin pretreatment reduced myocardial infarct size, improved the heart rate, and decreased creatine kinase (CK and lactate dehydrogenase (LDH levels in coronary flow. This pretreatment also increased catalase (CAT, superoxide dismutase (SOD activities but decreased glutathione (GSH, malondialdehyde (MDA levels. Furthermore, we determined that genistin can ameliorate the impaired mitochondrial morphology and oxidation system; interleukin-6 (IL-6, interleukin-8 (IL-8, interleukin-10 (IL-10, and tumor necrosis factor-α (TNF-α levels were also recovered. Besides, related-proteins of nuclear factor kappa-B (NF-κB signal pathway activated by P2X7 were investigated to determine the molecular mechanism of genistin and their expressions were measured by western blot. These results presented here demonstrated that genistin enhanced the protective effect on the rats with myocardial ischemia reperfusion injury. Therefore, the cardioprotective effects of genistin may rely on its antioxidant and anti-inflammatory activities via suppression of P2X7/NF-κB pathways.

  18. Quercetin postconditioning attenuates myocardial ischemia/reperfusion injury in rats through the PI3K/Akt pathway

    Directory of Open Access Journals (Sweden)

    Y. Wang

    2013-09-01

    Full Text Available Quercetin (Que, a plant-derived flavonoid, has multiple benefical actions on the cardiovascular system. The current study investigated whether Que postconditioning has any protective effects on myocardial ischemia/reperfusion (I/R injury in vivo and its potential cardioprotective mechanisms. Male Sprague-Dawley rats were randomly allocated to 5 groups (20 animals/group: sham, I/R, Que postconditioning, Que+LY294002 [a phosphatidylinositol 3-kinase (PI3K/Akt signaling pathway inhibitor], and LY294002+I/R. I/R was produced by 30-min coronary occlusion followed by 2-h reperfusion. At the end of reperfusion, myocardial infarct size and biochemical changes were compared. Apoptosis was evaluated by both TUNEL staining and measurement of activated caspase-3 immunoreactivity. The phosphorylation of Akt and protein expression of Bcl-2 and Bax were determined by Western blotting. Que postconditioning significantly reduced infarct size and serum levels of creatine kinase and lactate dehydrogenase compared with the I/R group (all P<0.05. Apoptotic cardiomyocytes and caspase-3 immunoreactivity were also suppressed in the Que postconditioning group compared with the I/R group (both P<0.05. Akt phosphorylation and Bcl-2 expression increased after Que postconditioning, but Bax expression decreased. These effects were inhibited by LY294002. The data indicate that Que postconditioning can induce cardioprotection by activating the PI3K/Akt signaling pathway and modulating the expression of Bcl-2 and Bax proteins.

  19. Quercetin postconditioning attenuates myocardial ischemia/reperfusion injury in rats through the PI3K/Akt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Y.; Zhang, Z.Z.; Wu, Y.; Ke, J.J.; He, X.H.; Wang, Y.L. [Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan (China)

    2013-09-24

    Quercetin (Que), a plant-derived flavonoid, has multiple benefical actions on the cardiovascular system. The current study investigated whether Que postconditioning has any protective effects on myocardial ischemia/reperfusion (I/R) injury in vivo and its potential cardioprotective mechanisms. Male Sprague-Dawley rats were randomly allocated to 5 groups (20 animals/group): sham, I/R, Que postconditioning, Que+LY294002 [a phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway inhibitor], and LY294002+I/R. I/R was produced by 30-min coronary occlusion followed by 2-h reperfusion. At the end of reperfusion, myocardial infarct size and biochemical changes were compared. Apoptosis was evaluated by both TUNEL staining and measurement of activated caspase-3 immunoreactivity. The phosphorylation of Akt and protein expression of Bcl-2 and Bax were determined by Western blotting. Que postconditioning significantly reduced infarct size and serum levels of creatine kinase and lactate dehydrogenase compared with the I/R group (all P<0.05). Apoptotic cardiomyocytes and caspase-3 immunoreactivity were also suppressed in the Que postconditioning group compared with the I/R group (both P<0.05). Akt phosphorylation and Bcl-2 expression increased after Que postconditioning, but Bax expression decreased. These effects were inhibited by LY294002. The data indicate that Que postconditioning can induce cardioprotection by activating the PI3K/Akt signaling pathway and modulating the expression of Bcl-2 and Bax proteins.

  20. Heart-specific overexpression of the human short CLC-3 chloride channel isoform limits myocardial ischemia-induced ERP and QT prolongation.

    Science.gov (United States)

    Yu, Ying; Ye, Linda; Li, Yi-Gang; Burkin, Dean J; Duan, Dayue Darrel

    2016-07-01

    Ischemia causes myocardial infarction and arrhythmias. Up-regulation of cardiac CLC-3 chloride channels is important for ischemic preconditioning-induced second-window protection against myocardial infarction. But its consequences in ischemia-induced electrical remodeling are still unknown. The recently-characterized heart-specific overexpression of human short CLC-3 isoform (hsCLC-3(OE)) mice was used to study the effects of CLC-3 up-regulation on cardiac electrophysiology under ischemia/reperfusion conditions. In vivo surface electrocardiography (ECG) and intracardiac electrophysiology (ICEP) were used to compare the electrophysiological properties of age-matched wild-type (Clcn3(+/+)) and hsCLC-3(OE) mice under control and myocardial ischemia-reperfusion conditions. QT and QTc intervals of hsCLC-3(OE) mice were significantly shorter than those of Clcn3(+/+) mice under control, ischemia and reperfusion conditions. In the ICEP, ventricular effective refractory period (VERP) of hsCLC-3(OE) mice (26.7±1.7ms, n=6) was significantly shorter than that of Clcn3(+/+) mice (36.9±2.8ms, n=8, P<0.05). Under ischemia condition, both VERP (19.8±1.3ms) and atrial effective refractory period (AERP, 34.8±2.5ms) of hsCLC-3(OE) mice were significantly shorter than those of Clcn3(+/+) mice (35.2±3.0ms and 45.8±1.6ms, P<0.01, respectively). Wenckebach atrioventricular nodal block point (AVBP, 91.13±4.08ms) and 2:1 AVBP (71.3±3.8ms) of hsCLC-3(OE) mice were significantly shorter than those of Clcn3(+/+) mice (102.0±2.0ms and 84.1±2.8ms, P<0.05, respectively). However, no differences of ICEP parameters between hsCLC-3(OE) and Clcn3(+/+) mice were observed under reperfusion conditions. Heart-specific overexpression of hsCLC-3 limited the ischemia-induced QT and ERP prolongation and postponed the advancements of Wenckebach and 2:1 AVBP. CLC-3 up-regulation may serve as an important adaptive mechanism against myocardial ischemia. Copyright © 2016 Elsevier Ireland Ltd. All

  1. Schisandrin B Ameliorates Myocardial Ischemia/Reperfusion Injury Through Attenuation of Endoplasmic Reticulum Stress-Induced Apoptosis.

    Science.gov (United States)

    Zhang, Wei; Sun, Zhiqing; Meng, Fanhua

    2017-12-01

    Schisandrin B (Sch B), an active composition isolated from the fruit of Schisandra chinensis, has been proved to possess antiinflammatory, antioxidant and anti-endoplasmic reticulum (ER) stress effects in many rodent tissues. However, the exact mechanism of cardioprotective effect of Sch B still needs more study. Here, we detected the effects of Sch B on myocardial ischemia/reperfusion (I/R) injury rats. I/R injury model in this study was established by left anterior descending coronary artery ligation for 40 min followed by 1 h of reperfusion. Male healthy rats were randomly divided into five groups: the sham, I/R, Sch B (20 mg/kg) + I/R, and Sch B (40 mg/kg) + I/R, Sch B (80 mg/kg) + I/R, with 10 rats in each group. We showed that Sch B treatment significantly protected against myocardial I/R injury, as demonstrated by the decrease in the percentage of infarct formation assessed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining in representative heart tissue slices, comparing with the I/R control group. The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), and total superoxide dismutase (T-SOD) were tested. The ER stress-related proteins such as C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6), and (PKR)-like ER kinase (PERK) were further measured by western blot, and their messenger RNA levels were measured by real-time PCR. The apoptosis of heart tissue cells was also tested through the expressions of caspase-9, caspase-3, Bcl-2, and Bax proteins. Collectively, these results revealed that Sch B exerts protection role on myocardial I/R injury through decreasing oxidative reaction, suppressing ATF6 and PERK pathway, and attenuating ER stress-induced apoptosis.

  2. Grade 3 ischemia on admission and absence of prior beta-blockade predict failure of ST resolution following thrombolysis for anterior myocardial infarction.

    Science.gov (United States)

    Buber, Jonathan; Gilutz, Harel; Birnbaum, Yochai; Friger, Michael; Ilia, Reuben; Zahger, Doron

    2005-09-30

    ST segment resolution (STR) is a strong predictor of outcome following thrombolysis. If failure of STR could be predicted on admission, better selection of treatment may be possible. Among patients given reperfusion, those with terminal QRS distortion (grade 3 ischemia) have larger infarcts, but the mechanism underlying this association is unclear. Whether grade 3 ischemia on admission can predict STR is unknown. We studied 180 consecutive patients given thrombolysis for a first anterior acute myocardial infarction (AMI). Multiple variables available on admission were analyzed as predictors of STR at 1, 2, and 24 h and as predictors of the need for rescue percutaneous coronary intervention (PCI). Multivariate predictors of failure of STR were: for 1 h: extent of ST elevation (OR: 1.09 [1.01-1.18]); for 2 h: no previous use of beta-blockers (OR: 4.71 [1.56-13.98]) and grade 3 ischemia (OR: 6.77 [3.27-13.95]); for 24 h: previous use of aspirin (OR: 6.70 [1.31-34.01]) and grade 3 ischemia (OR: 29.44 [7.30-118.1]). Grade 3 ischemia had a strong positive predictive value for failure of STR at 1 and 2 h and was the strongest predictor of the need for rescue PCI. Grade 3 ischemia on admission is the strongest independent predictor of failure to achieve myocardial reperfusion after thrombolysis. This association may underlie the larger infarcts associated with grade 3 ischemia. Other predictors of reperfusion failure are the extent of ST segment elevation, prior use of aspirin and no prior use of beta-blockers.

  3. Detection of subendocardial ischemia in the left anterior descending coronary artery territory with real-time myocardial contrast echocardiography during dobutamine stress echocardiography.

    Science.gov (United States)

    Xie, Feng; Dodla, Saritha; O'Leary, Edward; Porter, Thomas R

    2008-05-01

    The purpose of this study was to test whether the transmural delineation of myocardial perfusion during dobutamine stress imaging with real-time myocardial contrast echocardiography (RTMCE) might permit visualization of dobutamine-induced subendocardial ischemia. Significant coronary artery disease can be present despite normal transmural wall thickening (WT) responses during dobutamine stress echocardiography (DSE). One potential reason is dobutamine-induced recruitment of epicardial WT in the presence of subendocardial ischemia. Myocardial perfusion and WT were examined with RTMCE during DSE with a continuous infusion of ultrasound contrast in 94 patients with normal resting WT. Fifty-five of the patients had a >50% diameter stenosis in the left anterior descending coronary artery (LAD). The WT was visually assessed by a blinded reviewer at 2 time periods: initially after a high mechanical index impulse before myocardial contrast replenishment (MCR), and again during MCR. Subendocardial %WT was measured during MCR, if a subendocardial perfusion defect was visually evident, whereas transmural WT was quantified on the pre-MCR images. Fifty patients (91%) with LAD stenoses exhibited a myocardial contrast defect at peak stress, with 45 defects being subendocardial. Transmural WT pre-MCR appeared normal in 35 of the 45 patients with subendocardial perfusion defects (78%). However, a subendocardial WT abnormality was apparent during MCR in 18 of these 35 patients, even though transmural WT was not different from the 17 patients with normal subendocardial WT (33 +/- 15% vs. 36 +/- 14%). Quantitative measurements of WT within the subendocardium were significantly less in the patients with visually evident subendocardial WT abnormalities, when compared with those who seemed to have normal WT during MCR (17 +/- 8% vs. 25 +/- 10%, p subendocardial ischemia even when transmural WT appears normal. Real-time myocardial contrast echocardiography should be the preferred

  4. 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, 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...... acute) to 4 (most acute)) identifies patients with substantial myocardial salvage potential regardless of patient reported symptom duration. However, due to the complexity of the score, it is not used in clinical practice. Therefore, we aimed to develop a reliable algorithm that automatically computes...

  5. Diurnal variation in myocardial ischemia/reperfusion tolerance; mediation by the circadian clock within the cardiomyocyte

    Science.gov (United States)

    Circadian rhythms in cardiovascular physiology (e.g. blood pressure and heart rate) and pathophysiology (e.g. myocardial infarction (MI)) exist. Humans exhibit a marked increase in MI frequency during the early hours of the morning. However, MIs occurring during the evening are more likely to result...

  6. Prognostic value of high sensitive C-reactive protein in subjects with silent myocardial ischemia

    DEFF Research Database (Denmark)

    Mouridsen, Mette; Intzilakis, Theodoros; Binici, Zeynep

    2012-01-01

    . High-sensitive CRP and 48-hour ambulatory ECG monitoring were performed. The primary endpoint was the combined endpoint of death and myocardial infarction. RESULTS: The median follow-up time was 76 months. Seventy-seven subjects (11.4%) had SMI. The combined endpoint occurred in 26% of the subjects...

  7. Dietary n-3 fatty acids promote arrhythmias during acute regional myocardial ischemia in isolated pig hearts

    NARCIS (Netherlands)

    Coronel, R.; Wilms-Schopman, F.J.G.; Ruijter, den H.M.; Belterman, C.N.; Schumacher, C.A.; Opthof, T.; Hovernier, R.; Lemmens, A.G.; Terpstra, A.H.M.; Katan, M.B.; Zock, P.L.

    2007-01-01

    Objective Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the electrophysiologic

  8. 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

    , 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...

  9. [The structure of myocardial nerve plexus of human auricle of the right atrium and its relation to myocardial ischemia, functional status of the heart, and age].

    Science.gov (United States)

    Burkauskiene, Ausra; Azelis, Vidmantas; Senikiene, Zibuokle; Linonis, Vitas; Ramanauskiene, Irina

    2008-01-01

    The aim of this study was to investigate and evaluate morphometrically the relationship between changes in the structure of myocardial nerve plexus of the right atrium auricle and myocardial ischemia, parameters reflecting functional status of the heart, and age. A total of 56 females and males aged 20-94 years were investigated. Ischemic heart disease group consisted of 39 persons (their mean age was 63.83+/-15.67 years). The control group comprised 17 persons (the mean age was 60.53+/-9.89 years). Control group consisted of deceased persons who according to the pathologic and anatomic examination were not diagnosed with cardiac pathology leading to heart lesions or overload. Ischemic heart disease group consisted of patients who underwent aorta-coronary artery bypass grafting surgery. In ischemic heart disease group, degree of coronary artery stenosis was evaluated as well as the major indicators reflecting the size of atria and formation of postinfarction scar. After examination, postinfarction scars were found in 18 (46.2%) persons; no scars were found in 21 (53.8%) persons. Neurohistochemical method and video microscopy were employed for the evaluation of quantitative changes in the structure of the myocardial nerve plexus. In ischemic heart disease group, the structures of nerve plexus occupied 5.0+/-1.0% of the area, perimeter was 10 488+/-2134 microm, and number of the structures was 2698+/-981; the same parameters in the control group were 6.0+/-1.4%, 13 008+/-443 microm, and 3469+/-1511, respectively. In persons with postinfarction scar, the number of nerve plexus structures was lower by 9.3%, area by 8.9%, perimeter by 9.7% on average as compared to ischemic heart disease group without a scar. Regression analysis did not reveal any statistically significant correlation between the degree of coronary artery stenosis and quantitative parameters of nerve plexus (P>0.05). Changes in quantitative parameters of nerve plexus were not related to compensatory

  10. Compression of the right coronary artery by an aortic pseudoaneurysm after infective endocarditis: an unusual case of myocardial ischemia

    Directory of Open Access Journals (Sweden)

    Lacalzada-Almeida J

    2017-12-01

    Full Text Available Juan Lacalzada-Almeida,1 Alejandro De la Rosa-Hernández,1 María Manuela Izquierdo-Gómez,1 Javier García-Niebla,2 Iván Hernández-Betancor,1 Juan Alfonso Bonilla-Arjona,3 Antonio Barragán-Acea,1 Ignacio Laynez-Cerdeña1 1Cardiology Department, Hospital Universitario de Canarias, Tenerife, 2Health services from the Health Area of El Hierro, Valle del Golfo Health Center, El Hierro, 3Radiology Department, Hospital Universitario de Canarias, Tenerife, Spain Abstract: A 61-year-old male with a prosthetic St Jude aortic valve size 24 presented with heart failure symptoms and minimal-effort angina. Eleven months earlier, the patient had undergone cardiac surgery because of an aortic root dilatation and bicuspid aortic valve with severe regurgitation secondary to infectious endocarditis by Coxiela burnetii and coronary artery disease in the left circumflex coronary artery. Then, a prosthesis valve and a saphenous bypass graft to the left circumflex coronary artery were placed. The patient was admitted to the Cardiology Department of Hospital Universitario de Canarias, Tenerife, Spain and a transthoracic echocardiography was performed that showed severe paraprosthetic aortic regurgitation and an aortic pseudoaneurysm. The 64-slice multidetector computed tomography confirmed the pseudoaneurysm, originating from the right sinus of Valsalva, with a compression of the native right coronary artery and a normal saphenous bypass graft. On the basis of these findings, we performed surgical treatment with a favorable postoperative evolution. In our case, results from complementary cardiac imaging techniques were crucial for patient management. The multidetector computed tomography allowed for a confident diagnosis of an unusual mechanism of coronary ischemia. Keywords: pseudoaneurysm, infective endocarditis, myocardial ischemia, aortic valve prosthesis

  11. Effectiveness of Panax ginseng on Acute Myocardial Ischemia Reperfusion Injury Was Abolished by Flutamide via Endogenous Testosterone-Mediated Akt Pathway

    Directory of Open Access Journals (Sweden)

    Luo Pei

    2013-01-01

    Full Text Available Mechanisms for Panax ginseng’s cardioprotective effect against ischemia reperfusion injury involve the estrogen-mediated pathway, but little is known about the role of androgen. A standardized Panax ginseng extract (RSE was orally given with or without flutamide in a left anterior descending coronary artery ligation rat model. Infarct size, CK and LDH activities were measured. Time-related changes of NO, PI3K/Akt/eNOS signaling, and testosterone concentration were also investigated. RSE (80 mg/kg significantly inhibited myocardial infarction and CK and LDH activities, while coadministration of flutamide abolished this effect of RSE. NO was increased by RSE and reached a peak after 15 min of ischemia; however, flutamide cotreatment suppressed this elevation. Western blot analysis showed that RSE significantly reversed the decreases of expression and activation of PI3K, Akt, and eNOS evoked by ischemia, whereas flutamide attenuated the effects of these protective mechanisms induced by RSE. RSE completely reversed the dropping of endogenous testosterone level induced by I/R injury. Flutamide plus RSE treatment not only abolished RSE’s effect but also produced a dramatic change on endogenous testosterone level after pretreatment and ischemia. Our results for the first time indicate that blocking androgen receptor abolishes the ability of Panax ginseng to protect the heart from myocardial I/R injury.

  12. Deleterious effect of hypothermia in myocardial protection against cold ischemia: a comparative study in isolated rat hearts.

    Science.gov (United States)

    Lima, M L; Fiorelli, A I; Vassallo, D V; Batista, P R; Simoes, F V; Fiorim, J; Stefanon, I; Pinheiro, B B; Stolf, N A G; Gomes, O M

    2012-10-01

    with the other solutions at both temperatures. The solutions investigated were not able to fully suppress the deleterious effects of ischemia and reperfusion of the heart. However, these results allow us to conclude that temperature and the cardioprotective solution are interdependent as far as myocardial protection. Although CEL solution is the best for in myocardial protection, more studies are needed to understand the interaction between temperature and perfusion solution used. This will lead to development of better and more efficient cardioprotective methods. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Cardiac function improved by sarcoplasmic reticulum Ca2+-ATPase overexpression in a heart failure model induced by chronic myocardial ischemia

    Directory of Open Access Journals (Sweden)

    Wei XIN

    2011-04-01

    Full Text Available Objective Chronic myocardial ischemia(CMI has become an important cause of heart failure(HF.The aim of present study was to examine the effects of Sarco-endoplasmic reticulum calcium ATPase(SERCA2a gene transfer in HF model in large animal induced by CMI.Methods HF was reproduced in minipigs by ligating the initial segment of proximal left anterior descending(LAD coronary artery with an ameroid constrictor to produce progressive vessel occlusion and ischemia.After confirmation of myocardial perfusion defect and cardiac function impairment by SPECT and echocardiography in the model,animals were divided into 4 groups: HF group;HF+enhanced green fluorescent protein(EGFP group;HF+SERCA2a group;and sham operation group as control.rAAV1-EGFP and rAAV1-SERCA2a(1×1012 vg for each animal were directly and intramyocardially injected to the animals of HF+EGFP and HF+SERCA2a groups.Sixty days after the gene transfer,the expression of SERCA2a at the protein level was examined by Western blotting and immunohistochemistry,the changes in cardiac function were determined by echocardiographic and hemodynamic analysis,and the changes in serum inflammatory and neuro-hormonal factors(including BNP,TNF-a,IL-6,ET-1 and Ang II were determined by radioimmunoassay.Results Sixty days after gene transfer,LVEF,Ev/Av and ±dp/dtmax increased significantly(P < 0.05,along with an increase of SERCA2a protein expression in the ischemic myocardium(PP < 0.05,accompanied by a significant decrease of inflammatory and neural-hormonal factors(PP < 0.05 in HF+SERCA2a group as compared with HF/HF+EGFP group.Conclusions Overexpression of SERCA2a may significantly improve the cardiac function of the ischemic myocardium of HF model induced by CMI and reverse the activation of neural-hormonal factors,implying that it has a potential therapeutic significance in CMI related heart failure.

  14. 2-methoxycinnamaldehyde from Cinnamomum cassia reduces rat myocardial ischemia and reperfusion injury in vivo due to HO-1 induction.

    Science.gov (United States)

    Hwa, Jeong Seok; Jin, Yong Chun; Lee, Young Soo; Ko, Young Shin; Kim, Young Min; Shi, Lian Yu; Kim, Hye Jung; Lee, Jae Heun; Ngoc, Tran Minh; Bae, Ki Hwan; Kim, Yeong Shik; Chang, Ki Churl

    2012-01-31

    Cinnamomum cassia Blume has been used as a traditional Chinese herbal medicine for alleviation of fever, inflammation, chronic bronchitis, and to improve blood circulation. We addressed whether 2-methoxycinnamaldehyde (2-MCA), one of active ingredients of Cinnamomum cassia, reduces vascular cell adhesion molecule-1 (VCAM-1) expression in tumor necrosis factor-alpha (TNF-α)-activated endothelial cells and protects ischemia/reperfusion (I/R)-injury due to heme oxygenase (HO)-1 induction. Adult male rats were subjected to 30 min of ischemia by occlusion of the left anterior descending coronary artery followed by 24h of reperfusion. Rats were randomized to receive vehicle or 2-MCA (i.v.) 10 min before reperfusion. Administration of 2-MCA significantly improved I/R-induced myocardial dysfunction by increasing the values of the first derivative (±dp/dt) of left ventricular pressure and decreased infarct size. In addition, 2-MCA reduced the expression of high mobility group box 1 (HMGB1), an activator of the inflammatory cascade when released into the extracellular space, and VCAM-1 in I/R myocardium along with increase of HO-1 induction. The reduced injury was accompanied by significantly reduction of neutrophils infiltration and increased SOD activity in ischemic tissues and reduced serum level of cardiac troponin I (cTnI). Furthermore, 2-MCA significantly increased HO-1 induction by translocation of Nrf-2 from cytosol to nucleus in endothelial cells. Inhibition of VCAM-1 expression by 2-MCA was reversed both by SnPPIX, a HO-1 inhibitor and siHO-1 RNA trasfection in TNF-α-activated cells. In addition, 2-MCA significantly inhibited NF-κB luciferase activity in TNF-α-activated endothelial cells. As expected, 2-MCA significantly inhibited monocyte (U937) adhesion to endothelial cells. We concluded that 2-MCA protects of myocardial I/R-injury due to antioxidant and anti-inflammatory action possibly by HO-1 induction which can be explained why Cinnamomum cassia has been

  15. Relationship Between Anemia and Mortality Outcomes in a National Acute Coronary Syndrome Cohort: Insights From the UK Myocardial Ischemia National Audit Project Registry.

    Science.gov (United States)

    Mamas, Mamas A; Kwok, Chun Shing; Kontopantelis, Evangelos; Fryer, Anthony A; Buchan, Iain; Bachmann, Max O; Zaman, M Justin; Myint, Phyo K

    2016-11-19

    We aim to determine the prevalence of anemia in acute coronary syndrome (ACS) patients and compare their clinical characteristics, management, and clinical outcomes to those without anemia in an unselected national ACS cohort. The Myocardial Ischemia National Audit Project (MINAP) registry collects data on all adults admitted to hospital trusts in England and Wales with diagnosis of an ACS. We conducted a retrospective cohort study by analyzing patients in this registry between January 2006 and December 2010 and followed them up until August 2011. Multiple logistic regressions were used to determine factors associated with anemia and the adjusted odds of 30-day mortality with 1 g/dL incremental hemoglobin increase and the 30-day and 1-year mortality for anemic compared to nonanemic groups. Analyses were adjusted for covariates. Our analysis of 422 855 patients with ACS showed that 27.7% of patients presenting with ACS are anemic and that these patients are older, have a greater prevalence of renal disease, peripheral vascular disease, diabetes mellitus, and previous acute myocardial infarction, and are less likely to receive evidence-based therapies shown to improve clinical outcomes. Finally, our analysis suggests that anemia is independently associated with 30-day (OR 1.28, 95% CI 1.22-1.35) and 1-year mortality (OR 1.31, 95% CI 1.27-1.35), and we observed a reverse J-shaped relationship between hemoglobin levels and mortality outcomes. The prevalence of anemia in a contemporary national ACS cohort is clinically significant. Patients with anemia are older and multimorbid and less likely to receive evidence-based therapies shown to improve clinical outcomes, with the presence of anemia independently associated with mortality outcomes. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  16. Cardioprotective effects of salidroside on myocardial ischemia-reperfusion injury in coronary artery occlusion-induced rats and Langendorff-perfused rat hearts.

    Science.gov (United States)

    Chang, Xiayun; Zhang, Kai; Zhou, Rui; Luo, Fen; Zhu, Lingpeng; Gao, Jin; He, He; Wei, Tingting; Yan, Tianhua; Ma, Chunhua

    2016-07-15

    The current study was designed to investigate the protective role of salisroside on rats through the study of energy metabolism homeostasis and inflammation both in ex vivo and in vivo. Energy metabolism homeostasis and inflammation injury were respectively assessed in global ischemia of isolated hearts and coronary artery ligated rats. Excessive release of cardiac enzymes and pro-inflammatory cytokines was inhibited by salidroside in coronary artery occlusion-induced rats. ST segment was also restored with the treatment of salidroside. Triphenyltetrazolium chloride staining (TTC) staining and pathological analysis showed that salidroside could significantly alleviate myocardial injury in vivo. Accumulated data in ex vivo indicated that salidroside improved heart function recovery, which was reflected by enhanced myocardial contractility and coronary flow in isolated hearts. The contents of ATP and glycogen both in ex vivo and in vivo were restored by salidroside compared with those in the model group. Besides, the expressions of p-AMPK, PPAR-α and PGC-1α in rats and isolated hearts subjected to salidroside were significantly elevated, while the levels of p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ were dramatically reduced by salidroside. The present study comprehensively elaborated the protective effects of salidroside on myocardial injury and demonstrated that AMPK/PGC-1α and AMPK/NF-κB signaling cascades were implicated in the myocardial ischemia-reperfusion injury (I/R) model. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. [Evaluation of long-term therapy influence with angiotensin converting enzyme inhibitor lisinopril on morphofunctional parameters of the left ventricle, peripheral artery endothelium disfunction and painless myocardial ischemia in premenopausal women with hypertension].

    Science.gov (United States)

    Khabibulina, M M

    2010-01-01

    Aim of the study was to assess influence of long-term therapy with angiotensin converting enzyme inhibitor lisinopril on morphofunctional parameters of the left ventricle (LV) and painless myocardial ischemia in 109 premenopausal women with stage II hypertension depending on functional state of peripheral artery endothelium. The results show that lisinopril therapy in premenopausal women with hypertension can stop or even cause regression of LV myocardial hypertrophy and produce favorable effect on LV remodeling mostly in women with concentric type of hypertrophy and/or without endothelial dysfunction, and has positive effect on frequency of painless myocardial ischemia events.

  18. Transient myocardial ischemia after abrupt withdrawal of antianginal therapy in chronic stable angina

    DEFF Research Database (Denmark)

    Egstrup, K

    1988-01-01

    = 22) as regards the occurrence of cardiac events and total ischemic activity detected by ambulatory monitoring. Reinstitution of medical therapy was required in 6 patients (4 in group 1 and 2 in group 2). Ambulatory monitoring was initiated for 36 hours on 3 occasions: before withdrawal, and again 2...... less than 0.05). These results indicate that a rebound increase in ischemic activity (mainly silent) occurs after abrupt withdrawal of beta-receptor blockade in patients with chronic stable angina. This increase in ischemic activity may be caused by increased myocardial oxygen demand....

  19. Myocardial ischemia in the absence of epicardial coronary artery disease in Friedreich's ataxia

    Directory of Open Access Journals (Sweden)

    Dickerson Jennifer A

    2008-04-01

    Full Text Available Abstract We present the first in vivo detection of microvascular abnormality in a patient with Friedreich's ataxia (FA without epicardial coronary artery disease using cardiac magnetic resonance (CMR. The patient had exertional chest pain and dyspnea prompting referral for cardiac evaluation. These symptoms were reproduced during intravenous adenosine infusion, and simultaneous first-pass perfusion imaging showed a significant subendocardial defect; both symptoms and perfusion deficit were absent at rest. Epicardial coronaries were free of disease by invasive angiography; together, these findings support the notion of impaired myocardial perfusion reserve in FA.

  20. Ischemic preconditioning produces more powerful anti-inflammatory and cardioprotective effects than limb remote ischemic postconditioning in rats with myocardial ischemia-reperfusion injury.

    Science.gov (United States)

    Zhang, Jia-qiang; Wang, Qiang; Xue, Fu-shan; Li, Rui-ping; Cheng, Yi; Cui, Xin-long; Liao, Xu; Meng, Fan-min

    2013-10-01

    Both ischemic preconditioning (IPC) and limb remote ischemic postconditioning (LRIPOC) have been shown to possess significantly different cardioprotective effects against the myocardial ischemia reperfusion injury (IRI), but no study has compared the anti-inflammatory effects of IPC and LRIPOC during myocardial IRI process. We hypothesized that IPC and LRIPOC would produce different anti-inflammatory effects in an in vivo rat model with myocardial IRI. Eighty rats were randomly allocated into four equal groups: sham group, IRI group, IPC group and LRIPOC group. In 10 rats randomly selected from each group, serum levels of TNF-α, HMGB1, ICAM1, IL-1, IL-6 and IL-10 were assessed, and infarct size was determined. In another 10 rats of each group, myocardial levels of TNF-α, HMGB1, ICAM1, IL-1, IL-6 and IL-10 in both ischemic and non-ischemic regions were measured. The infarct size was significantly lower in IPC and LRIPOC groups than in IRI group. The serum and myocardial levels of pro-inflammatory cytokines including TNF-α, HMGB1, ICAM1, IL-1 and IL-6 during reperfusion were significantly reduced in IPC and LRIPOC groups compared to IRI group. As compared to the IPC group, infarct size, serum level of TNF-α at 60 minutes of reperfusion, serum levels of HMGB1 and ICAM1 at 120 minutes of reperfusion, myocardial levels of TNF-α, ICAM1, IL-1 and IL-6 in the ischemic region, myocardial levels of ICAM1, IL-1 and IL-6 in the non-ischemic region were significantly increased in the LRIPOC group. In the rats with myocardial IRI, IPC produces more powerful inhibitory effects on local myocardial and systemic inflammatory responses than LRIPOC. This may be partly attributed to more potent cardioprotection produced by IPC.

  1. Electroacupuncture Improved the Function of Myocardial Ischemia Involved in the Hippocampus-Paraventricular Nucleus-Sympathetic Nerve Pathway

    Directory of Open Access Journals (Sweden)

    Shuai Cui

    2018-01-01

    Full Text Available We investigated the hippocampus-paraventricular nucleus- (PVN- sympathetic nerve pathway in electroacupuncture (EA at the heart meridian for the treatment of myocardial ischemia by observing PVN neuronal discharge, sympathetic nerve discharge, and hemodynamics parameters. Sprague Dawley (SD rats were equally divided into four groups: Sham, Model, Model + EA, and Model + EA + Lesion. The model rat was established by ligating the left anterior descending branch of the coronary artery. Changes in the sympathetic nerve discharge and hemodynamic parameters were observed. The Model + EA exhibited a significantly lower discharge frequency of PVN neurons compared with the Model. The Model + EA + Lesion had a significantly higher discharge frequency compared with the Model + EA. The total discharge frequency of PVN neurons and interneurons were positively correlated with the sympathetic nerve discharge. The total discharge frequency of PVN neurons was positively correlated with heart rate (HR and negatively correlated with mean arterial pressure (MAP and rate pressure product (RPP. The discharge frequency of interneurons was positively correlated with HR and negatively correlated with MAP and RPP. The hippocampus-PVN-sympathetic nerve pathway is involved in electroacupuncture at the heart meridian and interneurons are the key neurons in PVNs.

  2. GsMTx4-D is a cardioprotectant against myocardial infarction during ischemia and reperfusion.

    Science.gov (United States)

    Wang, Jinli; Ma, Yina; Sachs, Frederick; Li, Ji; Suchyna, Thomas M

    2016-09-01

    GsMTx4 is a selective inhibitor of cationic mechanosensitive ion channels (MSCs) and has helped establish the role of MSCs in cardiac physiology. Inhomogeneous local mechanical stresses due to hypercontracture and swelling during ischemic reperfusion injury (IRI) likely induce elevated MSC activity that can contribute to cation imbalance. The aim of this study was to determine if the D enantiomer of GsMTx4 can act as a cardioprotectant in a mouse IRI model. Ischemia and reperfusion involved ligating a coronary artery followed by release of the ligature. GsMTx4-D was tested by either acute intravenous injection during the ischemic event or by two day pretreatment by intraperitoneal injection, both methods achieving similar results. Based on pharmacokinetic studies, GsMTx4-D dosage was set to achieve expected plasma concentrations between 50 and 5000nM and heart tissue concentrations between 1 and 200nM by intravenous injection. Relative to vehicle injected animals, GsMTx4-D reduced infarct area by ~40% for acute and pretreated animals for both 20 and 45min ischemic challenges. Many indicators of cardiac output were indistinguishable from sham-treated control hearts after GsMTx4-D treatment showing improvement at both 4 and 48h post ischemia, and premature ventricular beats immediately following reperfusion were also significantly reduced. To determine if GsMTx4-D cardioprotection could act directly at the level of cardiomyocytes, we tested its effects in vitro on indicators of IRI damage like cation influx and activation of inflammatory kinases in isolated myocytes cultured under hypoxic conditions. Hypoxia challenged cardiomyocytes treated with 10μM GsMTx4-D showed improved contractility and near normal contraction-related Ca(2+) influx. GsMTx4-D inhibited indicators of ischemic damage such as the apoptotic signaling system JNK/c-Jun, but also inhibited the energy response signaling system Akt kinase. We conclude that GsMTx4-D is a potent cardioprotectant in vivo

  3. Myocardial capillary permeability for small hydrophilic indicators during normal physiological conditions and after ischemia and reperfusion

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup

    1991-01-01

    Myocardial capillary permeability for small hydrophilic solutes (51Cr-EDTA or 99mTc-DTPA) has been measured using intracoronary indicator bolus injection and external radioactivity registration (the single injection, residue detection method). The method is based on kinetic separation...... of the injected indicator molecules in an extracted and a transmitted fraction of molecules. In open chest dog hearts measurements performed during normal physiological conditions gave mean capillary extraction values of 43.5-47.5% and the corresponding calculated PdS values were 47.1 - 57.5 ml.(100g.min)-1. From...... these PdS values Pd values between 1.57.10(-5) and 1.92.10(-5) cm.s-1 were calculated, in accordance with values obtained by other methods. Similar data have been obtained in myocardium of patients undergoing coronary angiography. Oxygen derived free radicals seems to participate in reperfusion injury...

  4. Ticagrelor Attenuates Apoptosis of Lung and Myocardial Cells Induced by Abdominal Aorta Ischemia/Reperfusion.

    Science.gov (United States)

    Findik, Orhan; Kunt, Atike Tekeli; Yazir, Yusufhan; Yardimoğlu, Melda; Yilmaz, Seda Güleç; Aydin, Ufuk; Rençber, Selenay Furat; Baris, Ozgur; Balci, Canan; Isbir, Turgay

    2016-01-01

    This study aimed to analyze the effect of ticagrelor pretreatment on the prevention of lung and heart injury induced by abdominal aorta ischemia and reperfusion (I/R) and also to determine the effective dose. Thirty-five male Sprague-Dawley rats weighing 350-400 g were randomized into five groups. The animals received ticagrelor at doses of 7.5 mg/kg, 15 mg/kg and 25 mg/kg or normal saline 0.1 ml/kg orally via gastric gavage before the ischemic period. In the control and study groups, I/R injury was induced by clamping the aorta infrarenally for 2 hs, followed by 4 h of reperfusion. After sacrifice, hearts and lungs of the animals were extracted for both histopathological and biochemical analysis. There was a significant difference between the animals that received 7.5 mg/kg and 25 mg/kg and 15 mg/kg and 25 mg/kg dose of ticagrelor regarding tissue malondealdehyde (MDA), and glutathione reductase levels in both lung and heart Ticagrelor treatment at 25 mg/kg led to significant cardiac remodeling activity and normal lung architecture against I/R induced injury. The number of TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells in alveolar epithelium and myocytes were increased in the sections from saline (I/R) group rats, and decreased following 25 mg/kg ticagrelor treatment. Ticagrelor dose-dependently inhibits platelet aggregation, increases cyclooxygenase-2 and also inhibits cellular uptake of adenosine all resulting in attenuation of I/R injury. Ticagrelor at 25 mg/kg was determined as the dose effective against I/R-induced injury in lung and heart in Sprague-Dawley rats in the present study. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Kaempferide Protects against Myocardial Ischemia/Reperfusion Injury through Activation of the PI3K/Akt/GSK-3β Pathway

    Directory of Open Access Journals (Sweden)

    Dong Wang

    2017-01-01

    Full Text Available The aim of this study is to investigate both the efficacy and mechanism of action of kaempferide (Kae as a therapy for the treatment of cardiovascular disease. A rat model of myocardial ischemia/reperfusion (I/R injury was established by ligation of the left anterior descending coronary artery for 30 min followed by a 2 h perfusion. In our study, we show that Kae remarkably improved cardiac function, alleviated myocardial injury via a decrease in myocardial enzyme levels, and attenuated myocardial infarct size in a dose-dependent manner. In addition, preconditioning treatment with Kae was found to significantly decrease serum TNF-α, IL-6, C-reactive protein (CRP, MDA, and ROS levels, while it was found to increase serum levels of SOD. Nuclear factor erythroid 2-related factor 2 (Nrf2 and cleaved caspase-3 expression levels were observed to be downregulated, while phospho-Akt (p-Akt and phospho-glycogen synthase kinase-3β (p-GSK-3β expression levels were upregulated. However, cotreatment with LY294002 (a PI3K inhibitor or TDZD-8 (a GSK-3β inhibitor was found to abolish the above cardioprotective effects observed with the Kae treatment. The data presented in this study provides evidence that Kae attenuates I/R-induced myocardial injury through inhibition of the Nrf2 and cleaved caspase-3 signaling pathways via a PI3K/Akt/GSK 3β-dependent mechanism.

  6. Toward modeling of regional myocardial ischemia and infarction: generation of realistic coronary arterial tree for the heart model of the XCAT phantom

    Science.gov (United States)

    Fung, George S. K.; Segars, W. Paul; Veress, Alexander I.; Gullberg, Grant T.; Tsui, Benjamin M. W.

    2009-02-01

    A realistic 3D coronary arterial tree (CAT) has been developed for the heart model of the computer generated 3D XCAT phantom. The CAT allows generation of a realistic model of the location, size and shape of the associated regional ischemia or infarction for a given coronary arterial stenosis or occlusion. This in turn can be used in medical imaging applications. An iterative rule-based generation method that systematically utilized anatomic, morphometric and physiologic knowledge was used to construct a detailed realistic 3D model of the CAT in the XCAT phantom. The anatomic details of the myocardial surfaces and large coronary arterial vessel segments were first extracted from cardiac CT images of a normal patient with right coronary dominance. Morphometric information derived from porcine data from the literature, after being adjusted by scaling laws, provided statistically nominal diameters, lengths, and connectivity probabilities of the generated coronary arterial segments in modeling the CAT of an average human. The largest six orders of the CAT were generated based on the physiologic constraints defined in the coronary generation algorithms. When combined with the heart model of the XCAT phantom, the realistic CAT provides a unique simulation tool for the generation of realistic regional myocardial ischemia and infraction. Together with the existing heart model, the new CAT provides an important improvement over the current 3D XCAT phantom in providing a more realistic model of the normal heart and the potential to simulate myocardial diseases in evaluation of medical imaging instrumentation, image reconstruction, and data processing methods.

  7. Impaired subendocardial wall thickening and post-systolic shortening are signs of critical myocardial ischemia in patients with flow-limiting coronary stenosis.

    Science.gov (United States)

    Ishizu, Tomoko; Seo, Yoshihiro; Baba, Masako; Machino, Tomoko; Higuchi, Haruhiko; Shiotsuka, Junji; Noguchi, Yuichi; Aonuma, Kazutaka

    2011-01-01

    The early diagnosis of myocardial ischemia is still challenging. The aim of the present study was to determine whether subendocardial hypokinesis and post-systolic contraction could be early markers of myocardial ischemia. Thirty-one consecutive patients with flow-limiting severe coronary stenosis but without visually abnormal left ventricular wall motion underwent quantitative echocardiography. Myocardial strain was measured using layer-by-layer analysis in severely hypoperfused segments. Radial strain (RS) was measured in the subendocardial, subepicardial, and total wall (innerRS, outerRS, and totalRS, respectively). Circumferential strain (CS) was also measured as 3 separate layers: subendocardial, mid-layer, and subepicardial layers (innerCS, midCS, and outerCS, respectively). Post-systolic shortening (PSS) was defined as the peak strain after end systole, and post-systolic strain index (PSI) was calculated as PSS divided by end-systolic strain. TotalRS was similar between ischemic and normally perfused segments, but innerRS and inner/outer RS ratio were significantly smaller in the ischemic segments than in corresponding segments in healthy subjects. Receiver operating characteristic analysis identified an optimum cut-off for PSI of 0.6. The combined criteria of inner/outer RS ratio 0.6 achieved 95% specificity for the presence of flow-limiting stenosis. Combined assessment of both subendocardial contractile impairment and PSS is very useful in identifying a severely hypoperfused left ventricular wall even without visual wall motion abnormality.

  8. Use of the myocardial tomo-scintigraphy at rest synchronized to ECG in the diagnosis of myocardial ischemia; Interet de la tomoscintigraphie myocardique au repos synchronisee a l`ECG dans le diagnonstic de l`ischemie myocardique

    Energy Technology Data Exchange (ETDEWEB)

    Eder, V.; Tranquart, F.; Casset-Senon, D.; Pottier, J.M. [Service Medecine Nucleaire TROUSSEAU 37000 TOURS (France)

    1997-12-31

    We have developed a new algorithm called kinetic scintigraphy (KS) able to pursue the evolution of endocardial contour during a cardiac cycle based on tomographic cross sections obtained at different phases of cycle by means of colored inter-zones. Twenty patients beneficiary by an in-effort myocardial scintigraphy or subject to dipyridamole (SS) and suspected of ischemic cardiopathy were studied at rest by {sup 99m}Tc-MYOVIEW synchronized to the ECG. The KS reproduces the global and segmentary kinetic estimated by echography (E) or gamma-angiography (GAC). In 15 cases the KS showed additional anomalies, a hypokinesia (10 cases), a hypokinesia associated to a tardive kinesia (3 cases), and a tardive-kinesia (2 cases). For 13 patients the SS made evident an ischemia in the same territory. In 4 patients the KS shows no anomaly while the SS finds a myocardial ischemia. Ten patients were subject to a coronarography: 9 presented significant coronary stenoses. In 8 cases the KS and the SS showed an anomaly in a corresponding territory. In one case only the stress scintigraphy occurred positive. In conclusion, the KS reveals additional anomalies as compared with the anomalies of segmentary kinetic, thus unveiling an at-rest systolic hypoperfusion corresponding to a scintigraphic ischemia. This examination of at-rest perfusion allows a mixed study of both perfusion and contraction

  9. Interventional effects of pretreatment with total polyphenols extracted from Toona sinensis on the injury induced by myocardial ischemia-reperfusion in rats

    Directory of Open Access Journals (Sweden)

    Hong-yue LI

    2011-01-01

    Full Text Available Objective To investigate the interventional effects of pretreatment with total polyphenols extracted from Toona sinensis Roem on the injury induced by myocardial ischemia-reperfusion in rats.Methods Fifty SD rats were randomly divided into 5 groups:sham operation group,model group and 3 pretreatment groups in which the rats were treated with total polyphenols in 3 different doses.Rats in sham operation and model group were treated with 5 sodium carboxy methyl cellulose,and in 3 pretreatment groups the rats were treated with 50,100 and 200mg/kg of total polyphenols,respactively,by gavage for 7 days,and then the myocardial ischemia/reperfusion injury was induced by ligating the left coronary artery(LAD for 30min followed by a 120 min reperfusion in anesthetized rats.Rats in sham operation group were operated with placing the ligature but without ligating.ECGs were recorded before and 30 min after ligating LAD,and 30,60 and 90min after reperfusion.The levels of J point at different time were observed and compared.After reperfusion,the blood was collected from abdominal aorta to prepare serum samples.The activity of CK,the level of cTnI,TXB2 and 6-keto-PGF1α in serum were then determincd.Finally,the hearts of rats below the ligature were cut into 5 slices and stained with 1% TTC for 15 min,the extent of myocardial infarction was calculated.Results Compared with that in sham operation group,the J point of ECG elevated obviously in model group,the activity of serum CK and the contents of cTnI and TXB2 increased markedly,while the 6-keto-PGF1α level declined significantly(P < 0.05,and notable myocardial infarction was apparent.Compared with those in model group,the height of J point descended,the activity of CK and the level of cTnI and TXB2 in serum decreased,while the level of 6-keto-PGF1α increased,and the degree of myocardial infarction was alleviated in the 3 pretreatment groups.All the data were found to have statistically significant

  10. [Silent myocardial ischemia and exercise-induced arrhythmia detected by the exercise test in the total health promotion plan (THP)].

    Science.gov (United States)

    Iwane, M; Shibe, Y; Itoh, K; Kinoshita, F; Kanagawa, Y; Kobayashi, M; Mugitani, K; Ohta, M; Ohata, H; Yoshikawa, A; Ikuta, Z; Nakamura, Y; Mohara, O

    2001-03-01

    We investigated the prevalence and characteristics of ischemic heart disease especially silent myocardial ischemia (SMI) and arrhythmia in need of careful observation in the exercise stress tests in the Total Health Promotion Plan (THP), which was conducted between 1994-96 for the purpose of measuring cardiopulmonary function. All workers (n = 4,918, 4,426 males) aged 18-60 yr old in an occupational field were studied. Exercise tests with an ergometer were performed by the LOPS protocol, in which the maximal workload was set up as a presumed 70-80% maximal oxygen intake, or STEP (original multistage protocol). ECG changes were evaluated with a CC5 lead. Two hundred and fifteen people refused the study because of a common cold, lumbago and so on. Of 4,703 subjects, 17 with abnormal rest ECG and 19 with probable anginal pain were excluded from the exercise tests. Of 4,667 who underwent the exercise test, 37 (0.79%) had ischemic ECG change, and 155 (3.32%) had striking arrhythmia. These 228 subjects then did a treadmill exercise test with Bruce protocol. Twenty-two (0.47% of 4,703) showed positive ECG change, 9 (0.19%) of 22 had abnormal findings on a 201Tl scan. 8 (0.17%) were diagnosed as SMI (Cohn I), in which the prevalence of hypertension, hyperlipidemia, diabetes mellitus, smoker and positive familial history of ischemic heart disease was greater than that of all subjects. In a 15-30 month follow up, none has developed cardiac accidents. Exercise-induced arrhythmia was detected in 11 (0.23%) subjects. Four were non-sustained ventricular tachycardia without any organic disease, 4 were ventricular arrhythmia based on cardiomyopathy detected by echocardiography, 2 were atrial fibrillation and another was WPW syndrome. It is therefore likely that the ergometer exercise test in THP was effective in preventing sudden death caused by ischemic heart disease or striking arrhythmia.

  11. Comparative analysis of the performance of various crystalloid cardioplegic solutions on myocardial protection after prolonged cold ischemia.

    Science.gov (United States)

    Lima, M L; Fiorelli, A I; Gomes, O M; Pinheiro, B B; Da Silva, M A F; Porto, L A B J; Novaes, L; Stolf, N A G; Souza, D R

    2011-01-01

    The quality and effectiveness of myocardial protection are fundamental problems to expand the use of and consequently good outcomes of donated hearts for transplantation. The purpose of this investigation was to compare the cardioprotective effects of Krebs-Henseleit, Bretschneider-HTK, St Thomas, and Celsior solutions using a modified nonrecirculating Langendorff column model of isolated perfused rat heart during prolonged cold storage. After removal 36 rat hearts underwent isolated perfusion into a Langendorff apparatus using Krebs-Henseleit solution for a 15-minute period of recovery; we excluded organs that did not maintain an aortic pressure above 100 m Hg. Subsequently, we equally distributed the hearts into four groups according to the cardioprotection solution; group 1, Krebs-Henseleit (control); group II, Bretschneider-HTK; group III, St Thomas; and group IV, Celsior. Each heart received the specific cardioplegic solution at 10°C for 2-hour storage at 20°C, before a 15 minutes perfusion with Krebs-Henseleit solution for recovery and stabilization. After 60 additional minutes of perfusion, every 5 minutes we determined heart rate (HR), coronary flow (CF), left ventricular systolic pressure (LVSP), and positive and negative peak of the first derivative of left ventricular pressure (+dP/dt and -dP/dt, respectively). Comparative analysis by Turkey's test showed the following performances among the groups at 60 minutes of reperfusion: HR: II = IV > III > I; CF: II = IV > I = III; LVSP: IV > I = II = III; +dP/dt: IV > I = II = III; and -dP/dt: IV = II > I = II. Cardioprotective solutions generally used in clinical practice are not able to avoid hemodynamic alterations in hearts exposed to prolonged ischemia. Celsior solution showed better performance than Bretschneider-HTK, St Thomas, and Krebs-Henseleit. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Diallyl trisulfide ameliorates myocardial ischemia-reperfusion injury by reducing oxidative stress and endoplasmic reticulum stress-mediated apoptosis in type 1 diabetic rats: role of SIRT1 activation.

    Science.gov (United States)

    Yu, Liming; Li, Shu; Tang, Xinlong; Li, Zhi; Zhang, Jian; Xue, Xiaodong; Han, Jinsong; Liu, Yu; Zhang, Yuji; Zhang, Yong; Xu, Yinli; Yang, Yang; Wang, Huishan

    2017-07-01

    Diallyl trisulfide (DATS) protects against apoptosis during myocardial ischemia-reperfusion (MI/R) injury in diabetic state, although the underlying mechanisms remain poorly defined. Previously, we and others demonstrated that silent information regulator 1 (SIRT1) activation inhibited oxidative stress and endoplasmic reticulum (ER) stress during MI/R injury. We hypothesize that DATS reduces diabetic MI/R injury by activating SIRT1 signaling. Streptozotocin (STZ)-induced type 1 diabetic rats were subjected to MI/R surgery with or without perioperative administration of DATS (40 mg/kg). We found that DATS treatment markedly improved left ventricular systolic pressure and the first derivative of left ventricular pressure, reduced myocardial infarct size as well as serum creatine kinase and lactate dehydrogenase activities. Furthermore, the myocardial apoptosis was also suppressed by DATS as evidenced by reduced apoptotic index and cleaved caspase-3 expression. However, these effects were abolished by EX527 (the inhibitor of SIRT1 signaling, 5 mg/kg). We further found that DATS effectively upregulated SIRT1 expression and its nuclear distribution. Additionally, PERK/eIF2α/ATF4/CHOP-mediated ER stress-induced apoptosis was suppressed by DATS treatment. Moreover, DATS significantly activated Nrf-2/HO-1 antioxidant signaling pathway, thus reducing Nox-2/4 expressions. However, the ameliorative effects of DATS on oxidative stress and ER stress-mediated myocardial apoptosis were inhibited by EX527 administration. Taken together, these data suggest that perioperative DATS treatment effectively ameliorates MI/R injury in type 1 diabetic setting by enhancing cardiac SIRT1 signaling. SIRT1 activation not only upregulated Nrf-2/HO-1-mediated antioxidant signaling pathway but also suppressed PERK/eIF2α/ATF4/CHOP-mediated ER stress level, thus reducing myocardial apoptosis and eventually preserving cardiac function.

  13. 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 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 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.

  14. Non invasive evaluation of the coronary atherosclerosis illness in patients with silent ischemia: utility of the SPECT of myocardial perfusion. Electric, angiographic and image correlation; Valoracion no invasiva de la enfermedad ateroesclerosa coronaria en pacientes con isquemia silente: utilidad del SPECT de perfusion miocardica. Correlacion electrica, angiografica y de imagen

    Energy Technology Data Exchange (ETDEWEB)

    Puente B, A.; Roffe G, F.; Aceves C, J.; Gomez A, E. [Hospital Centro Medico Nacional 20 de Noviembre, ISSSTE, Mexico D.F. (Mexico)

    2005-07-01

    The objective of the work was to determine the utility of the SPECT (Single Photon Emission Computerized Tomography) of myocardial perfusion for the ischemia detection in asymptomatic patients with Coronary Atherosclerosis Illness. It was concluded that the SPECT of myocardial perfusion has a high sensitivity (97%) for the silent ischemia diagnosis.

  15. Interventional effects of pretreatment with total polyphenols extracted from Toona sinensis on the injury induced by myocardial ischemia-reperfusion in rats

    OpenAIRE

    Hong-yue LI; Chen, Chao

    2011-01-01

    Objective To investigate the interventional effects of pretreatment with total polyphenols extracted from Toona sinensis Roem on the injury induced by myocardial ischemia-reperfusion in rats.Methods Fifty SD rats were randomly divided into 5 groups:sham operation group,model group and 3 pretreatment groups in which the rats were treated with total polyphenols in 3 different doses.Rats in sham operation and model group were treated with 5 sodium carboxy methyl cellulose,and in 3 pretreatment g...

  16. Heme oxygenase-1 induction improves cardiac function following myocardial ischemia by reducing oxidative stress.

    Directory of Open Access Journals (Sweden)

    Yossi Issan

    Full Text Available Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1, a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation.In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP and tin protoporphyrin (SnPP prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured.HO-1 induction lowered release of lactate dehydrogenase (LDH and creatine phospho kinase (CK, decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS was lower than non-diabetic mice (35±1%vs.41±2, respectively p<0.05. CoPP-treated diabetic animals improved cardiac function (43±2% p<0.01, reduced CK, Troponin T levels and infarct size compared to non-treated diabetic mice (P<0.01, P<0.001, P<0.01 respectively. CoPP-enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the decrease in superoxide levels in cardiac tissues and plasma TNFα levels (p<0.05. The increased levels of HO-1 by CoPP treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the antiapoptotic process (p<0.05. CoPP significantly increased the expression levels of pAKT and pGSK3β (p<0.05 in cardiomyocytes and in diabetic mice with MI. SnPP abolished CoPP's cardioprotective effects.HO-1 induction plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in reducing post ischemic cardiac damage in the diabetic heart as proved by the increased levels of pAKT with

  17. Heme Oxygenase-1 Induction Improves Cardiac Function following Myocardial Ischemia by Reducing Oxidative Stress

    Science.gov (United States)

    Issan, Yossi; Kornowski, Ran; Aravot, Dan; Shainberg, Asher; Laniado-Schwartzman, Michal; Sodhi, Komal; Abraham, Nader G.; Hochhauser, Edith

    2014-01-01

    Background Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation. Methods In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured. Results HO-1 induction lowered release of lactate dehydrogenase (LDH) and creatine phospho kinase (CK), decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS) was lower than non-diabetic mice (35±1%vs.41±2, respectively p<0.05). CoPP-treated diabetic animals improved cardiac function (43±2% p<0.01), reduced CK, Troponin T levels and infarct size compared to non-treated diabetic mice (P<0.01, P<0.001, P<0.01 respectively). CoPP-enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the decrease in superoxide levels in cardiac tissues and plasma TNFα levels (p<0.05). The increased levels of HO-1 by CoPP treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the antiapoptotic process (p<0.05). CoPP significantly increased the expression levels of pAKT and pGSK3β (p<0.05) in cardiomyocytes and in diabetic mice with MI. SnPP abolished CoPP's cardioprotective effects. Conclusions HO-1 induction plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in reducing post ischemic cardiac damage in the diabetic heart as proved by

  18. Involvement of glycogen synthase kinase-3β in liver ischemic conditioning induced cardioprotection against myocardial ischemia and reperfusion injury in rats.

    Science.gov (United States)

    Yang, Shuai; Abbott, Geoffrey W; Gao, Wei Dong; Liu, Jin; Luo, Chaozhi; Hu, Zhaoyang

    2017-05-01

    Remote ischemic conditioning has been convincingly shown to render the myocardium resistant to a subsequent more severe sustained episode of ischemia. Compared with other organs, little is known regarding the effect of transient liver ischemic conditioning. We proposed the existence of cardioprotection induced by remote liver conditioning. Male Sprague-Dawley rats were divided into sham-operated control (no further hepatic intervention) and remote liver ischemic conditioning groups. For liver ischemic conditioning, three cycles of 5 min of liver ischemia-reperfusion stimuli were conducted before-(liver preconditioning), post-myocardial ischemia (liver postconditioning), or in combination of both (liver preconditioning + liver postconditioning). Rats were exposed to 45 min of left anterior descending coronary artery occlusion, followed by 3 h of reperfusion thereafter. ECG and hemodynamics were measured throughout the experiment. The coronary artery was reoccluded at the end of reperfusion for infarct size determination. Blood samples were taken for serum lactate dehydrogenase and creatine kinase-MB test. Heart tissues were taken for apoptosis measurements and Western blotting. Our data demonstrate that liver ischemic preconditioning, postconditioning, or a combination of both, offered strong cardioprotection, as evidenced by reduction in infarct size and cardiac tissue damage, recovery of cardiac function, and inhibition of apoptosis after ischemia-reperfusion. Moreover, liver ischemic conditioning increased cardiac (not hepatic) glycogen synthase kinase-3β (GSK-3β) phosphorylation. Accordingly, inhibition of GSK-3β mimicked the cardioprotective action of liver conditioning. These results demonstrate that remote liver ischemic conditioning protected the heart against ischemia and reperfusion injury via GSK-3β-dependent cell-survival signaling pathway.NEW & NOTEWORTHY Remote ischemic conditioning protects hearts against ischemia and reperfusion (I/R) injury

  19. 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

    Abstract: P5632 Global ischemia ECG pattern for diagnosis of acute left main occlusion: prevalence and associated mortality in patients with suspected acute myocardial infarction Authors: C. Stengaard1, J.T. Sorensen2, M.P. Andersen3, K. Thygesen1, J.F. Lassen2, K. Nikus4, G. Wagner5, C...... by automated analysis using the Marquette 12SL algorithm. Data of mortality and angiography were obtained from the Danish cause of death registry and the Western Denmark Heart Registry. Prevalence and diagnostic performance of GIP was calculated. Kaplan Meier plots were constructed and mortality compared using...... log rank statistics. Results: ECG's from 3402 patients qualified for analysis. 211 patients (6.2%) showed GIP pattern, 73 of these were diagnosed with myocardial infarction, of whom only 9 had an acute LM occlusion. This corresponds to a positive predictive value of GIP for identification of LM...

  20. Combined analysis of stress myocardial tomo-scintigraphies and coronaries angio scanners to identify the arteries responsible of ischemia;Analyse combinee des tomoscintigraphies myocardiques de stress et angioscanners coronaires pour identifier les arteres responsables de l'ischemie

    Energy Technology Data Exchange (ETDEWEB)

    Didot, N.; Djaballah, W.; Daragon, N.; Gillet, N.; Meneroux, B.; Netter, F.; Paris-Grandpierre, S.; Karcher, G.; Marie, P.Y. [CHU de Nancy-Brabois, Service de medecine nucleaire, 54 (France); Mandry, D. [CHU de Nancy-Brabois, Service de radiologie, 54 (France)

    2010-05-15

    The purpose of this study is to assess the contribution of an analysis by image fusion of myocardium tomo-scintigraphy and coronary angio scanner in the identification of coronary artery responsible for myocardial ischemia stress. As results, the identification in myocardium tomo-scintigraphy of the ischemic arterial trunk is rarely changed by a combined analysis with coronary angio scanner. Discrepancies between the two examinations are common, even after fusion, but especially for mild ischemia. (N.C.)

  1. A soluble receptor for advanced glycation end-products inhibits myocardial apoptosis induced by ischemia/reperfusion via the JAK2/STAT3 pathway.

    Science.gov (United States)

    Jiang, Xue; Guo, Cai-xia; Zeng, Xiang-jun; Li, Hui-hua; Chen, Bu-xing; Du, Feng-he

    2015-08-01

    sRAGE can protect cardiomyocytes from apoptosis induced by ischemia/reperfusion (I/R). However, the signaling mechanisms in cardioprotection by sRAGE are currently unknown. We investigated the cardioprotective effect and potential molecular mechanisms of sRAGE inhibition on apoptosis in the mouse myocardial I/R as an in vivo model and neonatal rat cardiomyocyte subjected to ischemic buffer as an in vitro model. Cardiac function and myocardial infarct size following by I/R were evaluated with echocardiography and Evans blue/2,3,5-triphenyltetrazolium chloride. Apoptosis was detected by TUNEL staining and caspase-3 activity. Expression of the apoptosis-related proteins p53, Bax, Bcl-2, JAK2/p-JAK2, STAT3/p-STAT3, AKT/p-AKT, ERK/p-ERK, STAT5A/p-STAT5A and STAT6/p-STAT6 were detected by western blot analysis in the presence and absence of the JAK2 inhibitor AG 490. sRAGE (100 µg/day) improved the heart function in mice with I/R: the left ventricular ejection fraction and fractional shortening were increased by 42 and 57%, respectively; the infarct size was decreased by 52%, the TUNEL-positive myocytes by 66%, and activity of caspase-3 by 24%, the protein expression of p53 and ratio of Bax to Bcl-2 by 29 and 88%, respectively; protein expression of the p-JAK2, p-STAT3 and p-AKT were increased by 92, 280 and 31%, respectively. sRAGE have no effect on protein expression of p-ERK1/2, p-STAT5A and p-STAT6 following by I/R. sRAGE (900 nmol/L) exhibited anti-apoptotic effects in cardiomyocytes by decreasing TUNEL-positive myocytes by 67% and caspase-3 activity by 20%, p53 protein level and the Bax/Bcl-2 ratio by 58 and 86%, respectively; increasing protein expression of the p-JAK2 and p-STAT3 by 26 and 156%, respectively, p-AKT protein level by 33%. The anti-apoptotic effects of sRAGE following I/R were blocked by JAK2 inhibitor AG 490. The effect of sRAGE reduction on TUNEL-positive myocytes and caspase-3 activity were abolished by PI3K inhibitor LY294002, but not ERK 1

  2. Development of solid lipid nanoparticles containing total flavonoid extract from Dracocephalum moldavica L. and their therapeutic effect against myocardial ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Tan, Mei-E; He, Cheng-Hui; Jiang, Wen; Zeng, Cheng; Yu, Ning; Huang, Wei; Gao, Zhong-Gao; Xing, Jian-Guo

    2017-01-01

    Total flavonoid extract from Dracocephalum moldavica L. (TFDM) contains effective components of D. moldavica L. that have myocardial protective function. However, the cardioprotection function of TFDM is undesirable due to its poor solubility. In order to improve the solubility and efficacy of TFDM, we developed TFDM-loaded solid lipid nanoparticles (TFDM-SLNs) and optimized the formulation of TFDM-SLNs using central composite design and response surface methodology. The physicochemical properties of TFDM-SLNs were characterized, and the pharmacodynamics was investigated using the myocardial ischemia-reperfusion injury model in rats. The nanoparticles of optimal formulation for TFDM-SLNs were spherical in shape with the average particle size of 104.83 nm and had a uniform size distribution with the polydispersity index value of 0.201. TFDM-SLNs also had a negative zeta potential of -28.7 mV to ensure the stability of the TFDM-SLNs emulsion system. The results of pharmacodynamics demonstrated that both TFDM and TFDM-SLN groups afforded myocardial protection, and the protective effect of TFDM-SLNs was significantly superior to that of TFDM alone, based on the infarct area, histopathological examination, cardiac enzyme levels and inflammatory factors in serum. Due to the optimal quality and the better myocardial protective effect, TFDM-SLNs are expected to become a safe and effective nanocarrier for the oral delivery of TFDM.

  3. Dose reduction assessment in dynamic CT myocardial perfusion imaging in a porcine balloon-induced-ischemia model

    Science.gov (United States)

    Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2014-03-01

    We investigated the use of an advanced hybrid iterative reconstruction (IR) technique (iDose4, Philips Health- care) for low dose dynamic myocardial CT perfusion (CTP) imaging. A porcine model was created to mimic coronary stenosis through partial occlusion of the left anterior descending (LAD) artery with a balloon catheter. The severity of LAD occlusion was adjusted with FFR measurements. Dynamic CT images were acquired at end-systole (45% R-R) using a multi-detector CT (MDCT) scanner. Various corrections were applied to the acquired scans to reduce motion and imaging artifacts. Absolute myocardial blood flow (MBF) was computed with a deconvolution-based approach using singular value decomposition (SVD). We compared a high and a low dose radiation protocol corresponding to two different tube-voltage/tube-current combinations (80kV p/100mAs and 120kV p/150mAs). The corresponding radiation doses for these protocols are 7.8mSv and 34.3mSV , respectively. The images were reconstructed using conventional FBP and three noise-reduction strengths of the IR method, iDose. Flow contrast-to-noise ratio, CNRf, as obtained from MBF maps, was used to quantitatively evaluate the effect of reconstruction on contrast between normal and ischemic myocardial tissue. Preliminary results showed that the use of iDose to reconstruct low dose images provide better or comparable CNRf to that of high dose images reconstructed with FBP, suggesting significant dose savings. CNRf was improved with the three used levels of iDose compared to FBP for both protocols. When using the entire 4D dynamic sequence for MBF computation, a 77% dose reduction was achieved, while considering only half the scans (i.e., every other heart cycle) allowed even further dose reduction while maintaining relatively higher CNRf.

  4. Revascularization compared to medical treatment in patients with silent vs. symptomatic residual ischemia after thrombolyzed myocardial infarction

    DEFF Research Database (Denmark)

    Madsen, Jan K; Nielsen, Torsten T; Grande, Peer

    2007-01-01

    . conservative treatment in patients with inducible ischemia after thrombolysis in AMI. METHODS AND RESULTS: One thousand and eight patients were randomized to invasive or conservative treatment, stratified by the type of ischemia: silent, i.e. ST depression during an exercise test prior to discharge in 56...

  5. Breathing Maneuvers as a Vasoactive Stimulus for Detecting Inducible Myocardial Ischemia - An Experimental Cardiovascular Magnetic Resonance Study.

    Directory of Open Access Journals (Sweden)

    Kady Fischer

    Full Text Available Breathing maneuvers can elicit a similar vascular response as vasodilatory agents like adenosine; yet, their potential diagnostic utility in the presence of coronary artery stenosis is unknown. The objective of the study is to investigate if breathing maneuvers can non-invasively detect inducible ischemia in an experimental animal model when the myocardium is imaged with oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR.In 11 anesthetised swine with experimentally induced significant stenosis (fractional flow reserve <0.75 of the left anterior descending coronary artery (LAD and 9 control animals, OS-CMR at 3T was performed during two different breathing maneuvers, a long breath-hold; and a combined maneuver of 60s of hyperventilation followed by a long breath-hold. The resulting change of myocardial oxygenation was compared to the invasive measurements of coronary blood flow, blood gases, and oxygen extraction. In control animals, all breathing maneuvers could significantly alter coronary blood flow as hyperventilation decreased coronary blood flow by 34±23%. A long breath-hold alone led to an increase of 97±88%, while the increase was 346±327% (p<0.001, when the long breath-hold was performed after hyperventilation. In stenosis animals, the coronary blood flow response was attenuated after both hyperventilation and the following breath-hold. This was matched by the observed oxygenation response as breath-holds following hyperventilation consistently yielded a significant difference in the signal of the MRI images between the perfusion territory of the stenosis LAD and remote myocardium. There was no difference between the coronary territories during the other breathing maneuvers or in the control group at any point.In an experimental animal model, the response to a combined breathing maneuver of hyperventilation with subsequent breath-holding is blunted in myocardium subject to significant coronary artery stenosis. This

  6. A comparative study of myocardial molecular phenotypes of two tfr2β null mice: role in ischemia/reperfusion.

    Science.gov (United States)

    Boero, Martina; Pagliaro, Pasquale; Tullio, Francesca; Pellegrino, Rosa M; Palmieri, Antonietta; Ferbo, Ludovica; Saglio, Giuseppe; De Gobbi, Marco; Penna, Claudia; Roetto, Antonella

    2015-01-01

    Transferrin receptor 2 (Tfr2) is an iron-modulator transcribed in two isoforms, Tfr2α and Tfr2β. The latter is expressed in the heart. We obtained two mouse models with silencing of Tfr2β: one with a normal systemic iron amount (SIA), i.e., Tfr2-KI, and the other, i.e., LCKO-KI, with high SIA due to hepatic Tfr2α silencing. We aimed to assess whether Tfr2β might play a role in myocardial injury and whether Tfr2β silencing might modify proteins of iron metabolism, antioxidant, apoptotic, and survival enzyme activities in the heart undergoing ischemia/reperfusion (I/R). Isolated hearts of wild-type (WT) and Tfr2-null mice were studied before or after an I/R protocol, and proteins/RNA analyzed by Western blot and/or quantitative PCR. Tfr2β increased in WT hearts subject to I/R, and both Tfr2β null mice hearts were protected against I/R injury (about 40% smaller infarct-size compared to WT hearts). RISK kinases (ERK1/2-AKT-PKCε) were found up-regulated after I/R in Tfr2-KI, whereas SAFE enzyme (Stat3) and GSK3β resulted phosphorylated during I/R in LCKO-KI hearts. While HO-1 and HIF-2a were high in both Tfr2β-null mice, Catalase, and proapoptotic factors were upregulated only in LCKO-KI. Finally, Tfr2-KI hearts presented an increased Ferritin-H and a decreased Ferroportin1, whereas LCKO-KI hearts displayed an upregulation of Ferritin-L chain and DMT1/Hamp-RNA. In conclusion, Tfr2β isoform is involved in cardiac iron metabolism and its silencing leads to a protected phenotype (antioxidants, RISK, and/or SAFE upregulation) against I/R challenging. Iron-dependent signals involved in cardioprotection seem to be positively affected by Tfr2β downregulation and subsequent Ferritins upregulation. © 2015 International Union of Biochemistry and Molecular Biology.

  7. A computational and functional study elicits the ameliorating effect of the Chinese herbal formula Huo Luo Xiao Ling Dan on experimental ischemia-induced myocardial injury in rats via inhibition of apoptosis

    Directory of Open Access Journals (Sweden)

    Han XD

    2015-02-01

    ADMET (absorption, distribution, metabolism, excretion and toxicity Predictor to have favorable pharmacokinetic and low hepatotoxicity profiles. The acute myocardial ischemia was established by surgical ligation of the left anterior descending coronary artery. The rats were divided into a sham operative group, a model group, a positive control group treated with 0.2 mg/kg isosorbide mononitrate, and groups treated with 2.7, 5.4, or 10.8 g/kg HLXLD. The results showed that administration of HLXLD increased mean arterial pressure, left ventricular systolic pressure, heart rate, and maximal rate of rise/descent of left ventricular pressure levels. Administration of HLXLD significantly ameliorated coronary artery ligation-induced tissue damage in the left ventricle, with restored arrangement of myocardial fibers and recovered myoplasm in rats. Furthermore, HLXLD markedly increased the expression level of Bcl-2 but decreased the level of cleaved caspase 3. Taken together, administration of HLXLD attenuated acute myocardial ischemia-induced damage in cardiomyocytes and inhibited apoptotic death of cardiomyocytes, thereby exerting a cardioprotective effect in rats with IHD. These findings suggest that HLXLD may represent a promising herbal formula for the treatment of cardiovascular disease by counteracting apoptotic cell death via multiple active compounds. More studies are warranted to fully elucidate the mechanisms of action, identify the therapeutic targets, and validate the efficacy and safety of HLXLD in the treatment of IHD. Keywords: Huo Luo Xiao Ling Dan, myocardial ischemia, coronary artery ligation, hemodynamics, apoptosis, molecular docking

  8. Metabonomic Strategy to the Evaluation of Chinese Medicine Compound Danshen Dripping Pills Interfering Myocardial Ischemia in Rats

    Directory of Open Access Journals (Sweden)

    Xue Xin

    2013-01-01

    Full Text Available Coronary heart disease (CHD is one of the highest mortality diseases in the world. Traditional Chinese medicine compound Danshen dripping pills (CDDPs have currently made a great achievement in treating CHD. However, the therapeutic mechanism of CDDP is often poorly interpreted. In this study, a GC-MS-based metabonomic study was conducted to assess the holistic efficacy of CDDP for myocardial infarction in male Sprague-Dawley rats, which were divided into the control group, the sham group, the model group, the control + CDDP group, and the model + CDDP, with CDDP at a dose of 107 mg/kg·d (equal to 1.8 mL/kg·d. The metabonomic findings demonstrated great differences of metabolic pattern among sham, model, and the model + CDDP in the orthogonal partial least squares discriminant analysis (OPLS-DA models, which coordinated well with the assessment of plasma biochemistry and histopathological assay. Differentially expressed metabolites suggested that energy metabolism, glycolysis, and lipid metabolism might be disrupted by myocardial infarction. Both the potential metabolic biomarkers and the biochemical histopathological indices were regulated effectively by CDDP.

  9. Does isolated myocardial bridge really interfere with coronary blood flow?

    Directory of Open Access Journals (Sweden)

    Eid M. Daoud

    2013-06-01

    Conclusions: Myocardial bridging must be considered especially in patients at low risk for coronary atherosclerosis but with angina like chest pain or established myocardial ischemia. We suggest that coronary blood flow is decreased in the patients with MB compared with the patients having normal coronary.

  10. Protection against myocardial ischemia-reperfusion injury at onset of type 2 diabetes in Zucker diabetic fatty rats is associated with altered glucose oxidation.

    Directory of Open Access Journals (Sweden)

    Jonas Agerlund Povlsen

    Full Text Available BACKGROUND: Inhibition of glucose oxidation during initial reperfusion confers protection against ischemia-reperfusion (IR injury in the heart. Mitochondrial metabolism is altered with progression of type 2 diabetes (T2DM. We hypothesized that the metabolic alterations present at onset of T2DM induce cardioprotection by metabolic shutdown during IR, and that chronic alterations seen in late T2DM cause increased IR injury. METHODS: Isolated perfused hearts from 6 (prediabetic, 12 (onset of T2DM and 24 (late T2DM weeks old male Zucker diabetic fatty rats (ZDF and their age-matched heterozygote controls were subjected to 40 min ischemia/120 min reperfusion. IR injury was assessed by TTC-staining. Myocardial glucose metabolism was evaluated by glucose tracer kinetics (glucose uptake-, glycolysis- and glucose oxidation rates, myocardial microdialysis (metabolomics and tissue glycogen measurements. RESULTS: T2DM altered the development in sensitivity towards IR injury compared to controls. At late diabetes ZDF hearts suffered increased damage, while injury was decreased at onset of T2DM. Coincident with cardioprotection, oxidation of exogenous glucose was decreased during the initial and normalized after 5 minutes of reperfusion. Metabolomic analysis of citric acid cycle intermediates demonstrated that cardioprotection was associated with a reversible shutdown of mitochondrial glucose metabolism during ischemia and early reperfusion at onset of but not at late type 2 diabetes. CONCLUSIONS: The metabolic alterations of type 2 diabetes are associated with protection against IR injury at onset but detrimental effects in late diabetes mellitus consistent with progressive dysfunction of glucose oxidation. These findings may explain the variable efficacy of cardioprotective interventions in individuals with type 2 diabetes.

  11. RNAi-Mediated Down-Regulation of CD47 Protects against Ischemia/Reperfusion-Induced Myocardial Damage via Activation of eNOS in a Rat Model

    Directory of Open Access Journals (Sweden)

    Hui-bo Wang

    2016-12-01

    Full Text Available Background/Aims: Oxidative stress is strongly implicated in the pathogenesis of myocardial damage caused by ischemia reperfusion (I/R. Previous studies have confirmed that cardiac CD47 drives left ventricular heart failure. However, the role for CD47 in myocardial I/R injury (MIRI has not previously been proposed. This study was designed to investigate whether down-regulation of CD47 using RNA interference (RNAi technology can relieve inhibition of nitric oxide signaling and attenuate myocardial damage in a rat model of I/R. Methods: Male Sprague-Dawley rats (n = 40 were randomly allocated to four groups and pre-treated either with saline (Sham and I/R groups, or adenovirus expressing either control (Ad-EGFP-N or CD47-targeting (Ad-EGFP-CD47 RNAi. After four days, the rat MIRI model was established by occluding the left anterior descending coronary artery for 30 min, followed by reperfusion for 3 h. Heart tissue was harvested and assessed by immunohistochemistry, western blot, and quantitative RT-PCR. Outcome measures included infarct size, myocardial enzyme (creatine kinase, creatine kinase-MB, and lactate dehydrogenase levels in serum, markers of oxidative stress, and morphological changes to the myocardium. Results: Delivery of Ad-EGFP-CD47 RNAi into the myocardium remarkably decreased CD47 expression levels. Down-regulation of CD47 was significantly associated with reduced infarct size and serum levels of myocardial enzymes, increased activity of endothelial nitric oxide synthase, increased levels of nitric oxide, and decreased levels of oxidative stress. Conclusion: These data indicate that down-regulation of CD47 exerts a protective effect against MIRI, which may be attributable to attenuation of oxidative stress via activation of the eNOS/NO signaling pathway.

  12. RNAi-Mediated Down-Regulation of CD47 Protects against Ischemia/Reperfusion-Induced Myocardial Damage via Activation of eNOS in a Rat Model.

    Science.gov (United States)

    Wang, Hui-Bo; Yang, Jun; Ding, Jia-Wang; Chen, Li-Hua; Li, Song; Liu, Xiao-Wen; Yang, Chao-Jun; Fan, Zhi-Xin; Yang, Jian

    2016-01-01

    Oxidative stress is strongly implicated in the pathogenesis of myocardial damage caused by ischemia reperfusion (I/R). Previous studies have confirmed that cardiac CD47 drives left ventricular heart failure. However, the role for CD47 in myocardial I/R injury (MIRI) has not previously been proposed. This study was designed to investigate whether down-regulation of CD47 using RNA interference (RNAi) technology can relieve inhibition of nitric oxide signaling and attenuate myocardial damage in a rat model of I/R. Male Sprague-Dawley rats (n = 40) were randomly allocated to four groups and pre-treated either with saline (Sham and I/R groups), or adenovirus expressing either control (Ad-EGFP-N) or CD47-targeting (Ad-EGFP-CD47) RNAi. After four days, the rat MIRI model was established by occluding the left anterior descending coronary artery for 30 min, followed by reperfusion for 3 h. Heart tissue was harvested and assessed by immunohistochemistry, western blot, and quantitative RT-PCR. Outcome measures included infarct size, myocardial enzyme (creatine kinase, creatine kinase-MB, and lactate dehydrogenase) levels in serum, markers of oxidative stress, and morphological changes to the myocardium. Delivery of Ad-EGFP-CD47 RNAi into the myocardium remarkably decreased CD47 expression levels. Down-regulation of CD47 was significantly associated with reduced infarct size and serum levels of myocardial enzymes, increased activity of endothelial nitric oxide synthase, increased levels of nitric oxide, and decreased levels of oxidative stress. These data indicate that down-regulation of CD47 exerts a protective effect against MIRI, which may be attributable to attenuation of oxidative stress via activation of the eNOS/NO signaling pathway. © 2016 The Author(s) Published by S. Karger AG, Basel.

  13. Selection of reference genes in different myocardial regions of an in vivo ischemia/reperfusion rat model for normalization of antioxidant gene expression

    Directory of Open Access Journals (Sweden)

    Vesentini Nicoletta

    2012-02-01

    Full Text Available Abstract Background Changes in cardiac gene expression due to myocardial injury are usually assessed in whole heart tissue. However, as the heart is a heterogeneous system, spatial and temporal heterogeneity is expected in gene expression. Results In an ischemia/reperfusion (I/R rat model we evaluated gene expression of mitochondrial and cytoplasmatic superoxide dismutase (MnSod, Cu-ZnSod and thioredoxin reductase (trxr1 upon short (4 h and long (72 h reperfusion times in the right ventricle (RV, and in the ischemic/reperfused (IRR and the remote region (RR of the left ventricle. Gene expression was assessed by Real-time reverse-transcription quantitative PCR (RT-qPCR. In order to select most stable reference genes suitable for normalization purposes, in each myocardial region we tested nine putative reference genes by geNorm analysis. The genes investigated were: Actin beta (actb, Glyceraldehyde-3-P-dehydrogenase (gapdh, Ribosomal protein L13A (rpl13a, Tyrosine 3-monooxygenase (ywhaz, Beta-glucuronidase (gusb, Hypoxanthine guanine Phosphoribosyltransferase 1 (hprt, TATA binding box protein (tbp, Hydroxymethylbilane synthase (hmbs, Polyadenylate-binding protein 1 (papbn1. According to our findings, most stable reference genes in the RV and RR were hmbs/hprt and hmbs/tbp/hprt respectively. In the IRR, six reference genes were recommended for normalization purposes; however, in view of experimental feasibility limitations, target gene expression could be normalized against the three most stable reference genes (ywhaz/pabp/hmbs without loss of sensitivity. In all cases MnSod and Cu-ZnSod expression decreased upon long reperfusion, the former in all myocardial regions and the latter in IRR alone. trxr1 expression did not vary. Conclusions This study provides a validation of reference genes in the RV and in the anterior and posterior wall of the LV of cardiac ischemia/reperfusion model and shows that gene expression should be assessed separately in

  14. Selection of reference genes in different myocardial regions of an in vivo ischemia/reperfusion rat model for normalization of antioxidant gene expression.

    Science.gov (United States)

    Vesentini, Nicoletta; Barsanti, Cristina; Martino, Alessandro; Kusmic, Claudia; Ripoli, Andrea; Rossi, AnnaMaria; L'Abbate, Antonio

    2012-02-29

    Changes in cardiac gene expression due to myocardial injury are usually assessed in whole heart tissue. However, as the heart is a heterogeneous system, spatial and temporal heterogeneity is expected in gene expression. In an ischemia/reperfusion (I/R) rat model we evaluated gene expression of mitochondrial and cytoplasmatic superoxide dismutase (MnSod, Cu-ZnSod) and thioredoxin reductase (trxr1) upon short (4 h) and long (72 h) reperfusion times in the right ventricle (RV), and in the ischemic/reperfused (IRR) and the remote region (RR) of the left ventricle. Gene expression was assessed by Real-time reverse-transcription quantitative PCR (RT-qPCR). In order to select most stable reference genes suitable for normalization purposes, in each myocardial region we tested nine putative reference genes by geNorm analysis. The genes investigated were: Actin beta (actb), Glyceraldehyde-3-P-dehydrogenase (gapdh), Ribosomal protein L13A (rpl13a), Tyrosine 3-monooxygenase (ywhaz), Beta-glucuronidase (gusb), Hypoxanthine guanine Phosphoribosyltransferase 1 (hprt), TATA binding box protein (tbp), Hydroxymethylbilane synthase (hmbs), Polyadenylate-binding protein 1 (papbn1). According to our findings, most stable reference genes in the RV and RR were hmbs/hprt and hmbs/tbp/hprt respectively. In the IRR, six reference genes were recommended for normalization purposes; however, in view of experimental feasibility limitations, target gene expression could be normalized against the three most stable reference genes (ywhaz/pabp/hmbs) without loss of sensitivity. In all cases MnSod and Cu-ZnSod expression decreased upon long reperfusion, the former in all myocardial regions and the latter in IRR alone. trxr1 expression did not vary. This study provides a validation of reference genes in the RV and in the anterior and posterior wall of the LV of cardiac ischemia/reperfusion model and shows that gene expression should be assessed separately in each region.

  15. Screening β1AR inhibitors by cell membrane chromatography and offline UPLC/MS method for protecting myocardial ischemia.

    Science.gov (United States)

    Yue, Yuan; Dou, Lili; Wang, Xin; Xue, Hui; Song, Yanhong; Li, Xiaoni

    2015-11-10

    A high expression β1AR/cell membrane chromatography (β1AR-CMC) and offline UPLC/MS method has been developed for screening active ingredients from Coptis chinensis. In this study, the fractions retained by CMC column were separated and identified by UPLC/MS system. Using metoprolol as a positive control drug, coptisine from C. chinensis was identified as the active component which could inhibit β1AR. Compared with the control group: coptisine could attenuate the infarct size and release malondialdehyde (MDA) while increasing superoxide dismutase (SOD) activity, suggesting a role in reducing myocardial injury. In vitro, coptisine could decrease apoptosis, showing their protective effects upon cardiomyocytes. This β1AR-CMC-offline-UPLC/MS method can be applied for screening active components acting on β1AR from traditional Chinese medicines. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Triggers of myocardial ischemia during daily life in patients with coronary artery disease: physical and mental activities, anger and smoking

    National Research Council Canada - National Science Library

    Gabbay, F H; Krantz, D S; Kop, W J; Hedges, S M; Klein, J; Gottdiener, J S; Rozanski, A

    1996-01-01

    This study assessed the potency of physical and mental activities and emotions (anger and anxiety) and smoking and other substance use as proximate triggers of ischemia in patients with coronary artery disease during daily life...

  17. Effect of Ischemia Duration and Door-to-Balloon Time on Myocardial Perfusion in ST-Segment Elevation Myocardial Infarction: An Analysis From HORIZONS-AMI Trial (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction).

    Science.gov (United States)

    Prasad, Abhiram; Gersh, Bernard J; Mehran, Roxana; Brodie, Bruce R; Brener, Sorin J; Dizon, José M; Lansky, Alexandra J; Witzenbichler, Bernhard; Kornowski, Ran; Guagliumi, Giulio; Dudek, Dariusz; Stone, Gregg W

    2015-12-28

    This study sought to investigate the effect of treatment delay on microvascular reperfusion in ST-segment elevation myocardial infarction (STEMI) patients from the large, multicenter, prospective HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial. Despite restoration of epicardial blood flow during primary percutaneous coronary intervention (PCI), one-third of patients do not obtain myocardial perfusion due to impairment in the microvascular circulation. We examined the effect of symptom onset-to-balloon time (SBT) and door-to-balloon time (DBT) on myocardial reperfusion during primary PCI in STEMI, utilizing resolution of ST-segment elevation (STR) and the myocardial blush grade (MBG). The primary analysis was the relationships between SBT ≤2, >2 to 4, and >4 h and DBT ≤1, >1 to 1.5, >1.5 to 2, and >2 h with MBG and STR. Clinical risk was assessed using a modified version of the Thrombolysis In Myocardial Infarction risk score for STEMI. In 2,056 patients, absent microvascular perfusion (MBG 0/1) and STR (STR <30%) after primary PCI was significantly more common in patients with longer SBT, in patients with both low and high clinical risk profiles. By multivariable analysis, SBT (p < 0.0001), anterior infarction (p < 0.0001), reference vessel diameter (p = 0.005), lesion minimum lumen diameter (p < 0.0001), hyperlipidemia (p = 0.03), and current smoking (p = 0.001) were independent predictors of MBG 0/1, whereas SBT (p = 0.007), anterior infarction (p < 0.0001), and history of renal insufficiency (p = 0.0002) were independent predictors of absent STR. DBT (p < 0.0001) was an independent predictor of MBG 0/1. MBG 0/1 and STR<30% identified patients with increased 3-year mortality. The present study suggests that delay in mechanical reperfusion therapy during STEMI is associated with greater injury to the microcirculation. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier

  18. Effects of the AT1 receptor blocker candesartan on myocardial ischemia/reperfusion in isolated rat hearts.

    Science.gov (United States)

    Songur, C Murat; Songur, Merve Ozenen; Kocabeyoglu, Sinan Sabit; Basgut, Bilgen

    2014-10-01

    We sought to investigate the effects of the angiotension II receptor blocker candesartan on ischemia-reperfusion injury using a cardioplegia arrested isolated rat heart model. Ischemia-reperfusion injury was induced in isolated rat hearts with 40 minutes of global ischemia followed by a 30-minute reperfusion protocol. Throughout the experiment, constant pressure perfusion was achieved using a Langendorff apparatus. Cardioplegic solution alone, and in combination with candesartan, was administered before ischemia and 20 minutes after ischemia. Post-ischemic recovery of contractile function, left ventricular developed pressure, left ventricular end-diastolic pressure and contraction and relaxation rates were evaluated. In the control group, left ventricular developed pressure, rate pressure product, contraction and relaxation rates and coronary flow significantly decreased but coronary resistance increased following reperfusion. With the administration of candesartan alone, parameters did not differ compared to controls. Contractile parameters improved in the group that received candesartan in combination with the cardioplegia compared to the group that received cardioplegia alone; however, the difference between these two groups was insignificant. In this study, the addition of candesartan to a cardioplegic arrest protocol routinely performed during cardiac surgery did not provide a significant advantage in protection against ischemia-reperfusion injury compared with the administration of cardioplegic solution alone.

  19. Involvement of adenosine and standardization of aqueous extract of garlic (Allium sativum Linn.) on cardioprotective and cardiodepressant properties in ischemic preconditioning and myocardial ischemia-reperfusion induced cardiac injury

    Science.gov (United States)

    Sharma, Ashish Kumar; Munajjam, Arshee; Vaishnav, Bhawna; Sharma, Richa; Sharma, Ashok; Kishore, Kunal; Sharma, Akash; Sharma, Divya; Kumari, Rita; Tiwari, Ashish; Singh, Santosh Kumar; Gaur, Samir; Jatav, Vijay Singh; Srinivasan, Barthu Parthi; Agarwal, Shyam Sunder

    2012-01-01

    The present study investigated the effect of garlic (Allium sativum Linn.) aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic preconditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the 0.05% dose was found to be the most effective. Higher doses (more than 0.05%) were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline (1,000 µmol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide. PMID:23554727

  20. 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.

    Science.gov (United States)

    Nagaoka, Kazuhiro; Matoba, Tetsuya; Mao, Yajing; Nakano, Yasuhiro; Ikeda, Gentaro; Egusa, Shizuka; Tokutome, Masaki; Nagahama, Ryoji; Nakano, Kaku; Sunagawa, Kenji; Egashira, Kensuke

    2015-01-01

    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.

  1. 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.

  2. Is residual ischemia related to a worsening of the prognosis of patients treated with beta-blockers after myocardial infarction?; L'ischemie residuelle est-elle de mauvais pronostic chez les patients traites par beta-bloquant apres un infarctus myocardique,

    Energy Technology Data Exchange (ETDEWEB)

    Mercenier, C.; Hassan, N.; Grentzinger, A. [Centre Hospitalier Universitaire, 54 - Nancy (France)] [and others

    1999-11-01

    It has been demonstrated that myocardial ischemia, documented by exercise myocardial tomo-scintigraphy (MTS), was related to a worsening of prognosis. Our study was aimed at determining whether this deleterious effect persists in patients treated by beta-blockers, which are strong anti-anginal medications having a proven beneficial effect on prognosis. We have retrospectively included 300 patients (58{+-}11 years) treated by beta-blockers after myocardial infarction and for whom exercise thallium-201 MST had been performed on medical treatment. A myocardial ischemia was observed using MST in 224 patients (74%) and was extended on at least 15 % of the left ventricle in 86 patients (29%). During a follow-up period of 2.5{+-}1.4 years, only 22 patients had a major cardiac event (12 infarctions, 10 cardiac deaths). On Cox analysis of the MST parameters, the patients prognosis was correlated to the extent of necrotic myocardial areas (p < 0.001) but not to exercise ischemia. The annual rates of major events were 2% in the absence of ischemia, 2% when ischemia had a low extent (< 15 % of LV) and 3.5 % only when ischemia had a higher extent. Therefore, residual ischemia, detected after myocardial infarction by exercise MST, does not appear to have a deleterious prognosis effect when the patients are treated by beta-blockers. This might at least partly be related to the protective effect of beta-blockers against fatal cardiac arrhythmias which may be induced by ischemia. (author)

  3. Head-to-head comparison of dipyridamole, dobutamine and pacing stress echocardiography for the detection of myocardial ischemia in an animal model of coronary artery stenosis

    Directory of Open Access Journals (Sweden)

    A. Schmidt

    2001-07-01

    Full Text Available To compare the sensitivity of dipyridamole, dobutamine and pacing stress echocardiography for the detection of myocardial ischemia we produced a physiologically significant stenosis in the left circumflex artery of 14 open-chest dogs (range: 50 to 89% reduction in luminal diameter. In each study, dobutamine (5 to 40 µg kg-1 min-1 in 3-min stages and pacing (20 bpm increments, each 2 min, up to 260 bpm were performed randomly, and then followed by dipyridamole (up to 0.84 mg/kg over 10 min. The positivity of stress echocardiography tests was quantitatively determined by a significant (P<0.05 reduction of or failure to increase absolute and percent systolic wall thickening in the stenotic artery supplied wall, as compared to the opposite wall (areas related to the left anterior descending artery. Systolic and diastolic frozen images were analyzed off-line by two blinded observers in the control and stress conditions. The results showed that 1 the sensitivity of dobutamine, dipyridamole and pacing stress tests was 57, 57 and 36%, respectively; 2 in animals with positive tests, the mean percent change of wall thickening in left ventricular ischemic segments was larger in the pacing (-19 ± 11% and dipyridamole (-18 ± 16% tests as compared to dobutamine (-9 ± 6% (P = 0.05, but a similar mean reduction of wall thickening was observed when this variable was normalized to a control left ventricular segment (area related to the left anterior descending artery (pacing: -16 ± 7%; dipyridamole: -25 ± 16%; dobutamine: -26 ± 10%; not significant, and 3 a significant correlation was observed between magnitude of coronary stenosis and left ventricular segmental dysfunction induced by ischemia in dogs submitted to positive stress tests. We conclude that the dobutamine and dipyridamole stress tests showed identical sensitivities for the detection of myocardial ischemia in this one-vessel disease animal model with a wide range of left circumflex artery

  4. Myocardial Ablation of G Protein-Coupled Receptor Kinase 2 (GRK2 Decreases Ischemia/Reperfusion Injury through an Anti-Intrinsic Apoptotic Pathway.

    Directory of Open Access Journals (Sweden)

    Qian Fan

    Full Text Available Studies from our lab have shown that decreasing myocardial G protein-coupled receptor kinase 2 (GRK2 activity and expression can prevent heart failure progression after myocardial infarction. Since GRK2 appears to also act as a pro-death kinase in myocytes, we investigated the effect of cardiomyocyte-specific GRK2 ablation on the acute response to cardiac ischemia/reperfusion (I/R injury. To do this we utilized two independent lines of GRK2 knockout (KO mice where the GRK2 gene was deleted in only cardiomyocytes either constitutively at birth or in an inducible manner that occurred in adult mice prior to I/R. These GRK2 KO mice and appropriate control mice were subjected to a sham procedure or 30 min of myocardial ischemia via coronary artery ligation followed by 24 hrs reperfusion. Echocardiography and hemodynamic measurements showed significantly improved post-I/R cardiac function in both GRK2 KO lines, which correlated with smaller infarct sizes in GRK2 KO mice compared to controls. Moreover, there was significantly less TUNEL positive myocytes, less caspase-3, and -9 but not caspase-8 activities in GRK2 KO mice compared to control mice after I/R injury. Of note, we found that lowering cardiac GRK2 expression was associated with significantly lower cytosolic cytochrome C levels in both lines of GRK2 KO mice after I/R compared to corresponding control animals. Mechanistically, the anti-apoptotic effects of lowering GRK2 expression were accompanied by increased levels of Bcl-2, Bcl-xl, and increased activation of Akt after I/R injury. These findings were reproduced in vitro in cultured cardiomyocytes and GRK2 mRNA silencing. Therefore, lowering GRK2 expression in cardiomyocytes limits I/R-induced injury and improves post-ischemia recovery by decreasing myocyte apoptosis at least partially via Akt/Bcl-2 mediated mitochondrial protection and implicates mitochondrial-dependent actions, solidifying GRK2 as a pro-death kinase in the heart.

  5. Thallium myocardial tomoscintigraphy: detection of ischemia during weaning from mechanical ventilation in patients with chronic obstructive pulmonary disease. Tomoscintigraphie myocardique au thallium: detection de l'ischemie provoquee par le sevrage de la ventilation assistee chez le bronchiteux chronique

    Energy Technology Data Exchange (ETDEWEB)

    Andre, L.; Valette, H.; Obama, S.; Archambaud, F.; Richard, C.; Teboul, J.L.; Hebert, J.L.; Auzepy, P.; Desgrez, A. (Hopital de Bicetre, 94 - Le Kremlin-Bicetre (FR))

    1990-01-01

    In order to evidence myocardial ischemia-leading to ventricular dysfunction-during weaning from mechanical ventilation in patients with chronic obstructive pulmonary disease, thallium myocardial tomography and gated blood pool studies were performed in 9 patients during mechanical ventilation and during weaning from mechanical ventilation. During the latter, results of gated blood pool studies showed a diffuse homogeneous left ventricular dysfunction. A fixed lower thallium uptake in the septum than in the lateral wall was found with the quantitative analysis of myocardial tomograms. Partial volume effect is likely the cause of this septal defect. The hypothesis of a diffuse ischemia cannot be excluded; but, without the absolute quantification of tomographic data, it cannot be proven.

  6. Toll-like receptor 4 mediates the inflammatory responses and matrix protein remodeling in remote non-ischemic myocardium in a mouse model of myocardial ischemia and reperfusion.

    Science.gov (United States)

    Zhai, Yufeng; Ao, Lihua; Cleveland, Joseph C; Zeng, Qingchun; Reece, T Brett; Fullerton, David A; Meng, Xianzhong

    2015-01-01

    The signaling mechanism that mediates inflammatory responses in remote non-ischemic myocardium following regional ischemia/reperfusion (I/R) remains incompletely understood. Myocardial Toll-like receptor 4 (TLR4) can be activated by multiple proteins released from injured cells and plays a role in myocardial inflammation and injury expansion. We tested the hypothesis that TLR4 occupies an important role in mediating the inflammatory responses and matrix protein remodeling in the remote non-ischemic myocardium following regional I/R injury. TLR4-defective (C3H/HeJ) and TLR4-competent (C3H/HeN) mice were subjected to coronary artery ligation (30 min) and reperfusion for 1, 3, 7 or 14 days. In TLR4-competent mice, levels of monocyte chemoattractant protein -1 (MCP-1), keratinocyte chemoattractant (KC), intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were elevated in the remote non-ischemic myocardium at day 1, 3, and 7 of reperfusion. Levels of collagen I, collagen IV, matrix metalloproteinase (MMP) 2 and MMP 9 were increased in the remote non-ischemic myocardium at day 7 and 14 of reperfusion. MMP 2 and MMP 9 activities were also increased. TLR4 deficiency resulted in a moderate reduction in myocardial infarct size. However, it markedly downgraded the changes in the levels of chemokines, adhesion molecules and matrix proteins in the remote non-ischemic myocardium. Further, left ventricular function at day 14 was significantly improved in TLR4-defective mice. In conclusion, TLR4 mediates the inflammatory responses and matrix protein remodeling in the remote non-ischemic myocardium following regional myocardial I/R injury and contributes to the mechanism of adverse cardiac remodeling.

  7. Release of Tissue-specific Proteins into Coronary Perfusate as a Model for Biomarker Discovery in Myocardial Ischemia/Reperfusion Injury

    DEFF Research Database (Denmark)

    Cordwell, Stuart; Edwards, Alistair; Liddy, Kiersten

    2012-01-01

    reperfusion post-15I. Proteins released during irreversible I/R (60I/60R) were profiled using gel-based (2-DE and one-dimensional gel electrophoresis coupled to liquid chromatography and tandem mass spectrometry; geLC–MS) and gel-free (LC–MS/MS) methods. A total of 192 tissue-specific proteins were identified......Diagnosis of acute coronary syndromes is based on protein biomarkers, such as the cardiac troponins (cTnI/cTnT) and creatine kinase (CK-MB) that are released into the circulation. Biomarker discovery is focused on identifying very low abundance tissue-derived analytes from within albumin......-rich plasma, in which the wide dynamic range of the native protein complement hinders classical proteomic investigations. We employed an ex vivo rabbit model of myocardial ischemia/reperfusion (I/R) injury using Langendorff buffer perfusion. Nonrecirculating perfusate was collected over a temporal profile...

  8. Two-Dimensional Speckle-Tracking during Dobutamine Stress Echocardiography in the Detection of Myocardial Ischemia in Patients with Suspected Coronary Artery Disease.

    Science.gov (United States)

    Uusitalo, Valtteri; Luotolahti, Matti; Pietilä, Mikko; Wendelin-Saarenhovi, Maria; Hartiala, Jaakko; Saraste, Markku; Knuuti, Juhani; Saraste, Antti

    2016-05-01

    Two-dimensional speckle-tracking applied to dobutamine stress echocardiography (DSE) may aid in the detection of coronary artery disease (CAD). The aim of this study was to determine the value of strain, strain rate, and postsystolic strain index (PSI) measured by speckle-tracking during DSE in the evaluation of the presence, extent, and severity of myocardial ischemia. Fifty patients 63 ± 7 years of age with intermediate probability of CAD were prospectively recruited. All patients underwent DSE, quantitative positron emission tomographic perfusion imaging, and invasive angiography. Regional peak systolic longitudinal strain, strain rate, and PSI were measured at rest, at a dobutamine dose of 20 μg/kg/min, at peak stress, and at early recovery (1 min after stress). Obstructive CAD was defined as >75% stenosis or 40% to 75% stenosis combined with either fractional flow reserve Strain analyses showed the highest reproducibility at rest, at a dobutamine dose of 20 μg/kg/min, and at early recovery. Increased PSI and reduced strain during early recovery were the strongest predictors of obstructive CAD and were associated with the extent, localization, and depth of myocardial ischemia by positron emission tomography. On vessel-based analysis, strain, PSI, and visual analysis of wall motion provided comparable diagnostic accuracy, whereas the combination of strain or PSI with visual analysis provided incremental value over visual analysis alone. Assessment of systolic or postsystolic strain by speckle-tracking echocardiography during early recovery after DSE can help in the detection of hemodynamically significant coronary stenosis compared with visual wall motion analysis alone. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  9. Differentiation of myocardial ischemia and infarction assessed by dynamic computed tomography perfusion imaging and comparison with cardiac magnetic resonance and single-photon emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Yuki; Kido, Teruhito; Kurata, Akira; Miyagawa, Masao; Mochizuki, Teruhito [Ehime University Graduate School of Medicine, Department of Radiology, Toon, Ehime (Japan); Uetani, Teruyoshi; Kono, Tamami; Ogimoto, Akiyoshi [Ehime University Graduate School of Medicine, Department of Cardiology, Pulmonology, Hypertension and Nephrology, Toon, Ehime (Japan); Soma, Tsutomu [FUJIFILM RI Pharma Co., Ltd., QMS Group, Quality Assurance Department, Tokyo (Japan); Graduate School of Medicine, University of Tokyo, Department of Radiology, Tokyo (Japan); Murase, Kenya [Osaka University Graduate School of Medicine, Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Osaka (Japan); Iwaki, Hirotaka [Ehime University Graduate School of Medicine, Center for Clinical Research Data and Biostatistics, Toon, Ehime (Japan)

    2016-11-15

    To evaluate the feasibility of myocardial blood flow (MBF) by computed tomography from dynamic CT perfusion (CTP) for detecting myocardial ischemia and infarction assessed by cardiac magnetic resonance (CMR) or single-photon emission computed tomography (SPECT). Fifty-three patients who underwent stress dynamic CTP and either SPECT (n = 25) or CMR (n = 28) were retrospectively selected. Normal and abnormal perfused myocardium (ischemia/infarction) were assessed by SPECT/CMR using 16-segment model. Sensitivity and specificity of CT-MBF (mL/g/min) for detecting the ischemic/infarction and severe infarction were assessed. The abnormal perfused myocardium and severe infarction were seen in SPECT (n = 90 and n = 19 of 400 segments) and CMR (n = 223 and n = 36 of 448 segments). For detecting the abnormal perfused myocardium, sensitivity and specificity were 80 % (95 %CI, 71-90) and 86 % (95 %CI, 76-91) in SPECT (cut-off MBF, 1.23), and 82 % (95 %CI, 76-88) and 87 % (95 %CI, 80-92) in CMR (cut-off MBF, 1.25). For detecting severe infarction, sensitivity and specificity were 95 % (95 %CI, 52-100) and 72 % (95 %CI, 53-91) in SPECT (cut-off MBF, 0.92), and 78 % (95 %CI, 67-97) and 80 % (95 %CI, 58-86) in CMR (cut-off MBF, 0.98), respectively. Dynamic CTP has a potential to detect abnormal perfused myocardium and severe infarction assessed by SPECT/CMR using comparable cut-off MBF. (orig.)

  10. Diallyl trisulfide exerts cardioprotection against myocardial ischemia-reperfusion injury in diabetic state, role of AMPK-mediated AKT/GSK-3β/HIF-1α activation.

    Science.gov (United States)

    Yu, Liming; Di, Wencheng; Dong, Xue; Li, Zhi; Xue, Xiaodong; Zhang, Jian; Wang, Qi; Xiao, Xiong; Han, Jinsong; Yang, Yang; Wang, Huishan

    2017-09-26

    Diallyl trisulfide (DATS), the major active ingredient in garlic, has been reported to confer cardioprotective effects. However, its effect on myocardial ischemia-reperfusion (MI/R) injury in diabetic state and the underlying mechanism are still unknown. We hypothesize that DATS reduces MI/R injury in diabetic state via AMPK-mediated AKT/GSK-3β/HIF-1α activation. Streptozotocin-induced diabetic rats received MI/R surgery with or without DATS (20mg/kg) treatment in the presence or absence of Compound C (Com.C, an AMPK inhibitor, 0.25mg/kg) or LY294002 (a PI3K inhibitor, 5mg/kg). We found that DATS significantly improved heart function and reduced myocardial apoptosis. Additionally, in cultured H9c2 cells, DATS (10μM) also attenuated simulated ischemia-reperfusion injury. We found that AMPK and AKT/GSK-3β/HIF-1α signaling were down-regulated under diabetic condition, while DATS markedly increased the phosphorylation of AMPK, ACC, AKT and GSK-3β as well as HIF-1α expression in MI/R-injured myocardium. However, these protective actions were all blunted by Com.C administration. Additionally, LY294002 abolished the stimulatory effect of DATS on AKT/GSK-3β/HIF-1α signaling without affecting AMPK signaling. While 2-methoxyestradiol (a HIF-1α inhibitor) reduced HIF-1α expression without affecting AKT/GSK-3β signaling. Taken together, these data showed that DATS protected against MI/R injury in diabetic state by attenuating cellular apoptosis via AMPK-mediated AKT/GSK-3β/HIF-1α signaling. Its cardioprotective effect deserves further study.

  11. Severe cardiac trauma or myocardial ischemia? Pitfalls of polytrauma treatment in patients with ST-elevation after blunt chest trauma

    Directory of Open Access Journals (Sweden)

    Orkun Özkurtul

    2015-09-01

    Conclusion: This case outlines the importance of understanding the key mechanism of injury and the importance of communication at each stage of healthcare transfer. A transesophageal echocardiography can help to identify injuries after myocardial contusion.

  12. Dexamethasone induces transcriptional activation of Bcl-xL gene and inhibits cardiac injury by myocardial ischemia.

    Science.gov (United States)

    Xu, Beibei; Strom, Joshua; Chen, Qin M

    2011-10-01

    Psychological or physical stress causes an elevation of glucocorticoids in the circulating system. Glucocorticoids regulate a variety of physiological functions, from energy metabolism and biochemical homeostasis to immune response. Synthetic steroids are among the most prescribed drugs for immune suppression and chemotherapy. While glucocorticoids are best known for inducing apoptosis in a number of cell types, we have found that corticosteroids at stress relevant levels protect cardiomyocytes from apoptosis. Current study addresses whether glucocorticoids inhibit cardiac injury in vivo. Adult male C57BL6 mice were administered with dexamethasone (20mg/kg, i.p.) or vehicle control 20 h prior to left anterior descending coronary artery occlusion surgery. Myocardial infarction was measured by triphenyl tetrazoliumchloride staining in tissue slices and by levels of cardiac Troponin (cTn I) in the blood. Treatment of dexamethasone markedly reduced infarct size (19.6 ± 4.3%, vs. 29.2 ± 4.9%, pdexamethasone induces the expression of Bcl-xL gene in the myocardium. With cardiomyocytes in culture, glucocorticoids increased transcription of Bcl-xL gene as evidenced by Bcl-xL mRNA increase and promoter activation. The glucocorticoid receptor antagonist mifepristone prevented dexamethasone from inducing cardiac protection or Bcl-xL expression. Our data suggest that activation of glucocorticoid receptor can prevent cardiac injury through transcriptional activation of Bcl-xL gene. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Olmesartan restores the protective effect of remote ischemic perconditioning against myocardial ischemia/reperfusion injury in spontaneously hypertensive rats.

    Science.gov (United States)

    Lu, Xin; Bi, Yan-Wen; Chen, Ke-Biao

    2015-07-01

    Remote ischemic perconditioning is the newest technique used to lessen ischemia/reperfusion injury. However, its effect in hypertensive animals has not been investigated. This study aimed to examine the effect of remote ischemic perconditioning in spontaneously hypertensive rats and determine whether chronic treatment with Olmesartan could influence the effect of remote ischemic perconditioning. Sixty rats were randomly divided into six groups: vehicle-sham, vehicle-ischemia/reperfusion injury, vehicle-remote ischemic perconditioning, olmesartan-sham, olmesartan-ischemia/reperfusion and olmesartan-remote ischemic perconditioning. The left ventricular mass index, creatine kinase concentration, infarct size, arrhythmia scores, HIF-1α mRNA expression, miR-21 expression and miR-210 expression were measured. Olmesartan significantly reduced the left ventricular mass index, decreased the creatine kinase concentration, limited the infarct size and reduced the arrhythmia score. The infarct size, creatine kinase concentration and arrhythmia score during reperfusion were similar for the vehicle-ischemia/reperfusion group and vehicle-remote ischemic perconditioning group. However, these values were significantly decreased in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. HIF-1α, miR-21 and miR-210 expression were markedly down-regulated in the Olmesartan-sham group compared to the vehicle-sham group and significantly up-regulated in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. The results indicate that (1) the protective effect of remote ischemic perconditioning is lost in vehicle-treated rats and that chronic treatment with Olmesartan restores the protective effect of remote ischemic perconditioning; (2) chronic treatment with Olmesartan down-regulates HIF-1α, miR-21 and miR-210 expression and reduces hypertrophy, thereby limiting

  14. The Athena trials: Autologous adipose-derived regenerative cells for refractory chronic myocardial ischemia with left ventricular dysfunction.

    Science.gov (United States)

    Henry, Timothy D; Pepine, Carl J; Lambert, Charles R; Traverse, Jay H; Schatz, Richard; Costa, Marco; Povsic, Thomas J; David Anderson, R; Willerson, James T; Kesten, Steven; Perin, Emerson C

    2017-02-01

    To assess safety and feasibility of autologous adipose-derived regenerative cells (ADRCs), for treatment of chronic ischemic cardiomyopathy patients. Preclinical and early clinical trials suggest ADRCs have excellent potential for ischemic conditions. The Athena program consisted of two parallel, prospective, randomized (2:1, active: placebo), double-blind trials assessing intramyocardial (IM) ADRC delivery [40-million, n = 28 (ATHENA) and 80-million (ATHENA II) cells, n = 3]). Patients with an EF ≥20% but ≤45%, multivessel coronary artery disease (CAD) not amenable to revascularization, inducible ischemia, and symptoms of either angina (CCS II-IV) or heart failure (NYHA Class II-III) on maximal medical therapy were enrolled. All patients underwent fat harvest procedure (≤450 mL adipose), on-site cell processing (Celution® System, Cytori Therapeutics), electromechanical mapping, and IM delivery of ADRCs or placebo. Enrollment was terminated prematurely due to non-ADRC-related adverse events and subsequent prolonged enrollment time. Thirty-one patients (17-ADRCs, 14-placebo) mean age 65 ± 8 years, baseline LVEF(%) 31.1 ± 8.7 (ADRC), 31.8 ± 7.7 (placebo) were enrolled. Change in V0 2 max favored ADRCs (+45.4 ± 222 vs. -9.5 ± 137 mL/min) but there was no difference in left ventricular function or volumes. At 12-months, heart failure hospitalizations occurred in 2/17 (11.7%) [ADRC] and 3/14 (21.4%) [placebo]. Differences in NYHA and CCS classes favored ADRCs at 12-months with significant improvement in MLHFQ (-21.6 + 13.9 vs. -5.5 + 23.8, P = 0.038). A small volume fat harvest, automated local processing, and IM delivery of autologous ADRCs is feasible with suggestion of benefit in "no option" CAD patients. Although the sample size is limited, the findings support feasibility and scalability for treatment of ischemic cardiomyopathy with ADRCs. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Isquemia miocárdica silente en diabéticos tipo 2 Silent myocardial ischemia in type 2 diabetes patients

    Directory of Open Access Journals (Sweden)

    Yordanka Piña Rivera

    2012-08-01

    con los niveles patológicos de colesterol y el mal control glucémico.Objectives: to determine the frequency of silent myocardial infarction in type 2 diabetes patients and its relation with the metabolic control. Methods: a cross-sectional descriptive study of 79 asymptomatic patients suffering type 2 diabetes mellitus and without a history of ischemic cardiopathy, blood hypertension or smoking. These patients were seen at the endocrinology service of "Dr Carlos J. Finlay" from February 2009 to February 2011. They underwent Doppler tissue imaging echocardiography and their levels of glycemia on fasting, pospandrial glycemia, glycated haemoglobin, cholesterol and triglycerides were determined. The analyzed clinical variables lfor the silent myocardial ischemia were age, sex, time of evolution of diabetes and body mass index. Frequency distributions and percentage estimations were used for the qualitative variables whereas the Chi square test served to establish relationships among variables. Results: the average age of the patients was 54 years, 69.1 % were males and 31.9 % females. The Doppler tissue imaging echocardiography showed signs of myocardial ischemia in 20 % of these patients, and 75 % had pathological levels of total cholesterol with statistically significant relation (p=0.01 and their relative risk of developing myocardial ischemia was 4.4 times higher than the rest of patients with normal cholesterol. The values of glycemia on fasting, pospandrial glycemia and glycated haemoglobin were significantly higher than in the ischemic group. The patients having significantly higher values of glycemia on fasting exhibited a risk of myocardial ischemia that was 10.5 times higher than that of the patients with adequate values for this variable. Likewise, the risk of getting sick was 12 times higher in those cases with high values of pospandrial glycemia. Conclusions: silent myocardial ischemia is frequent in type 2 diabetes mellitus patients and is associated with

  16. Incremental Value of Subtended Myocardial Mass for Identifying FFR-Verified Ischemia Using Quantitative CT Angiography: Comparison With Quantitative Coronary Angiography and CT-FFR.

    Science.gov (United States)

    Yang, Dong Hyun; Kang, Soo-Jin; Koo, Hyun Jung; Kweon, Jihoon; Kang, Joon-Won; Lim, Tae-Hwan; Jung, Joonho; Kim, Namkug; Lee, June-Goo; Han, Seungbong; Ahn, Jung-Min; Park, Duk-Woo; Lee, Seung-Whan; Lee, Cheol Whan; Park, Seong-Wook; Park, Seung-Jung; Mintz, Gary S; Kim, Young-Hak

    2018-01-12

    This study examined the incremental value of subtended myocardial mass (Vsub) as assessed by coronary computed tomography angiography (CTA) for identifying lesion-specific ischemia verified by invasive fractional flow reserve (FFR) in quantitative coronary CTA. FFR is determined not only by coronary stenosis severity, but also by Vsub. One-step evaluation of combined Vsub and coronary lesion morphology may improve the accuracy of coronary CTA for identifying ischemia-producing lesions. A total of 246 intermediate coronary artery lesions (30% to 80% diameter stenosis) in 220 patients (mean age 61.7 years, 168 men) interrogated by FFR were retrospectively studied. Coronary CTA data were used to assess the Vsub by coronary artery stenosis, minimal lumen area (MLA), percentage of aggregated plaque volume (%APV), positive remodeling, and low-attenuation plaque. The ability of Vsub/MLA2 to discriminate lesions with FFR ≤0.80 was examined. Diagnostic performance, odds ratios, and category-less net reclassification improvements of coronary CTA parameters for FFR-verified (≤0.80) ischemia were evaluated. On-site computed tomography (CT) derived-FFR (CT-FFR) and quantitative coronary angiography (QCA) data were also compared. Of 246 lesions, 84 (34.1%) showed an FFR ≤0.80. Vsub was independently associated with an FFR ≤0.80 (odds ratio: 1.04/1 cm3; p = 0.032) and showed incremental value over MLA. Vsub/MLA2 >4.16 was the best single parameter for discriminating an FFR ≤0.80 with 83.3% sensitivity and 67.9% specificity. The area under the curve (AUC) of Vsub/MLA2 >4.16 (0.80 [95% confidence interval: 0.75 to 0.85]) was better than that of MLA (change in [Δ]AUC: 0.069; p MLA2 >4.16 assessed by coronary CTA shows better diagnostic performance for the detection of ischemia-producing lesions than CT-derived MLA alone or %APV and QCA parameters and was comparable to that of on-site CT-FFR. Copyright © 2018 American College of Cardiology Foundation. Published by

  17. Exercise treadmill testing using a modified exercise protocol in women with suspected myocardial ischemia: findings from the National Heart, Lung and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

    Science.gov (United States)

    Lewis, Jannet F; McGorray, Susan; Lin, Lang; Pepine, Carl J; Chaitman, Bernard; Doyle, Mark; Edmundowicz, Daniel; Sharaf, Barry L; Merz, C Noel Bairey

    2005-03-01

    Exercise testing, a major diagnostic modality in individuals with suspected coronary artery disease (CAD), has in general demonstrated less overall diagnostic accuracy in women compared to men. As part of the WISE, a modified protocol was examined with the intention of improving reliability of exercise testing. Criteria for entry in the WISE study include clinically indicated coronary angiography. Exercise testing was performed using a protocol modified to be more appropriate for women. The study population consisted of 96 women, mean age of 55.8 y (range 34-77), who completed exercise treadmill test (ETT). Most (78%) were postmenopausal; 96% had >or =2 risk factors for CAD. By core laboratory angiography, 29/96 women had stenosis > or =50% in at least one coronary artery. Of these 29 women, 9 had abnormal ETT, yielding overall sensitivity of 31%. The remaining 20 women had normal (12/29, 41%) or nondiagnostic (8/29, 28%) studies. Among the 67 women with minimal or no coronary stenosis, 35 had no ischemic ST-segment changes during ETT, yielding overall specificity of 52%. Analysis with exclusion of women with nondiagnostic studies yielded sensitivity and specificity of 43% and 66%, respectively. The presence of coronary artery stenosis and inability to perform ETT, but not results of testing, predicted the outcomes of myocardial infarction, heart failure, and death. Exercise treadmill test appears to be of limited diagnostic value in women with suspected myocardial ischemia referred for coronary angiography. Sensitivity and specificity remain poor even with modified exercise protocol and core laboratory angiographic analysis. These findings merit consideration in view of current guidelines that recommend exercise testing in women with suspected CAD.

  18. Exenatide reduces final infarct size in patients with ST-segment-elevation myocardial infarction and short-duration of ischemia

    DEFF Research Database (Denmark)

    Lønborg, Jacob Thomsen; Kelbæk, Henning Skov; Vejlstrup, Niels Grove

    2012-01-01

    Exenatide has been demonstrated to be cardioprotective as an adjunct to primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction (STEMI). The aim of the post hoc analysis study was to evaluate the effect of exenatide in relation to system delay, defined...

  19. Variable effects of anti-diabetic drugs in animal models of myocardial ischemia and remodeling : A translational perspective for the cardiologist

    NARCIS (Netherlands)

    Yin, Meimei; Westenbrink, B. Daan; Meissner, Maxi; van Gilst, Wiek H.; de Boer, Rudolf A.

    2013-01-01

    Diabetes and heart failure are very prevalent, and affect each other's incidence and severity. Novel therapies to reduce post-myocardial infarction (MI) remodeling that progresses into heart failure are urgently needed, especially in diabetic patients. Clinical studies have suggested that some oral

  20. Subendocardial ischemia in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Kawasaki, Tatsuya; Sugihara, Hiroki

    2014-02-01

    Hypertrophic cardiomyopathy (HCM) patients often develop subendocardial ischemia in the left ventricle without atherosclerotic coronary stenosis. Myocardial ischemia plays an important role in the pathophysiology of HCM, but diagnostic techniques for the detection of subendocardial ischemia have not been widely available. We developed specific techniques to quantify subendocardial ischemia on stress scintigraphy, and have compared the results with various clinical features in patients with HCM. This article reviews our understanding of subendocardial ischemia in HCM based on more than 20 years of experience. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  1. Long non-coding RNA MALAT1 functions as a mediator in cardioprotective effects of fentanyl in myocardial ischemia-reperfusion injury.

    Science.gov (United States)

    Zhao, Zhi-Hui; Hao, Wei; Meng, Qing-Tao; Du, Xiao-Bing; Lei, Shao-Qing; Xia, Zhong-Yuan

    2017-01-01

    Long non-coding (lncRNA) MALAT1 can be increased by hypoxia or ischemic limbs. Also, downregulation of MALAT1 contributes to reduction of cardiomyocyte apoptosis. However, the functional involvement of MALAT1 in myocardial ischemia-reperfusion (I/R) injury has not been defined. This study investigated the functional involvement of lncRNA-MALAT1 in cardioprotective effects of fentanyl. HL-1, a cardiac muscle cell line from the AT-1 mouse atrial cardiomyocyte tumor lineage was pre-treated with fentanyl and generated cell model of hypoxia-reoxygenation (H/R). Relative expression of MALAT1, miR-145, and Bnip3 mRNA in cells was determined by quantitative real-time PCR. Cardiomyocyte H/R injury was indicated by lactate dehydrogenase (LDH) release and cell apoptosis. The results showed that fentanyl abrogates expression of responsive gene for H/R and induces downregulation of MALAT1 and Bnip3 and upregulation of miR-145. We found that miR-145/Bnip3 pathway was negatively regulated by MALAT1 in H/R-HL-1 cell with or without fentanyl treatment. Moreover, both MALAT1 overexpression and miR-145 knockdown reverse cardioprotective effects of fentanyl, as indicated by increase in LDH release and cell apoptosis. The reversal effect of MALAT1 for fentanyl is confirmed in cardiac ischemia/reperfusion (I/R) mice. In summary, lncRNA-MALAT1 is sensitive to H/R injury and abrogates cardioprotective effects of Fentanyl by negatively regulating miR-145/Bnip3 pathway. © 2016 International Federation for Cell Biology.

  2. Ambient fine particulate matter exposure and myocardial ischemia in the Environmental Epidemiology of Arrhythmogenesis in the Women's Health Initiative (EEAWHI) study.

    Science.gov (United States)

    Zhang, Zhu-Ming; Whitsel, Eric A; Quibrera, P Miguel; Smith, Richard L; Liao, Duanping; Anderson, Garnet L; Prineas, Ronald J

    2009-05-01

    Ambient particulate matter (PM) air pollution is associated with coronary heart disease, but the pathways underlying the association remain to be elucidated. We studied the association between PM and ischemia among 57,908 Women's Health Initiative clinical trial participants from 1999-2003. We used the Minnesota Code criteria to identify ST-segment and T-wave abnormalities, and estimated T amplitude (microvolt) from resting, standard 12-lead electrocardiogram (ECG). We used U.S. Environmental Protection Agency's monitor data to estimate concentrations of PM or = 120 msec. Overall, 6% of the remaining 55,529 women (52-90 years of age; 83% non-Hispanic white) had ST abnormalities and 16% had T abnormalities. Lead-specific T amplitude was normally distributed (range of means from -14 to 349 microV). PM(2.5) (mean +/- SD) averaged over lag(0-2) was 14 +/- 7 microg/m(3). In logistic and linear regression models adjusted for demographic, clinical, temporal, and climatic factors, a 10-microg/m(3) increase in lag(0-2) PM(2.5) was associated with a 4% [95% confidence interval (CI), -3%, to 10%] increase in the odds of ST abnormality and a 5% (95% CI, 0% to 9%) increase in the odds of T abnormality. We observed corresponding decreases in T amplitude in all exam sites and leads except lead V1, reaching a minimum of -2 microV (95% CI, -5 to 0 microV) in lead V3. Short-term PM(2.5) exposure is associated with ECG evidence of myocardial ischemia among postmenopausal women. The principal manifestations include subclinical but potentially arrhythmogenic ST-T abnormalities and decreases in T amplitude.

  3. Regional myocardial oxygen consumption estimated by carbon-11 acetate and positron emission tomography before and after repetitive ischemia

    DEFF Research Database (Denmark)

    Kofoed, K F; Hansen, P R; Holm, S

    2000-01-01

    alternating with 5 minutes of reperfusion. Before and after repetitive coronary occlusions, oxygen 15 water/oxygen 15 carbon monoxide (blood flow), and 11C-acetate (oxygen consumption) PET imaging were performed. Left ventricular regional systolic wall thickening was measured with sonomicrometry. Forty......-five minutes after the ischemic episodes, systolic ventricular wall thickening was decreased by 90%, whereas myocardial blood flow was reduced by 21% compared with baseline values (P

  4. PlGF repairs myocardial ischemia through mechanisms of angiogenesis, cardioprotection and recruitment of myo-angiogenic competent marrow progenitors.

    Directory of Open Access Journals (Sweden)

    Hiroto Iwasaki

    Full Text Available Despite preclinical success in regenerating and revascularizing the infarcted heart using angiogenic growth factors or bone marrow (BM cells, recent clinical trials have revealed less benefit from these therapies than expected.We explored the therapeutic potential of myocardial gene therapy of placental growth factor (PlGF, a VEGF-related angiogenic growth factor, with progenitor-mobilizing activity.Myocardial PlGF gene therapy improves cardiac performance after myocardial infarction, by inducing cardiac repair and reparative myoangiogenesis, via upregulation of paracrine anti-apoptotic and angiogenic factors. In addition, PlGF therapy stimulated Sca-1(+/Lin(- (SL BM progenitor proliferation, enhanced their mobilization into peripheral blood, and promoted their recruitment into the peri-infarct borders. Moreover, PlGF enhanced endothelial progenitor colony formation of BM-derived SL cells, and induced a phenotypic switch of BM-SL cells, recruited in the infarct, to the endothelial, smooth muscle and cardiomyocyte lineage.Such pleiotropic effects of PlGF on cardiac repair and regeneration offer novel opportunities in the treatment of ischemic heart disease.

  5. A new combination of sitagliptin and furosemide protects against remote myocardial injury induced by renal ischemia/reperfusion in rats.

    Science.gov (United States)

    Youssef, Mahmoud I; Mahmoud, Amr A A; Abdelghany, Rasha H

    2015-07-01

    Acute kidney injury (AKI) is associated with high mortality resulting from extra-renal organ damage, particularly the heart. The present study aimed to investigate the protective effect of sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, against renal and remote cardiac damage induced by ischemia/reperfusion (IR), a leading cause of AKI. In this attempt, we compared the effects of sitagliptin to furosemide, a loop diuretic. Furosemide is commonly used clinically in AKI however, there is a lack of evidence regarding its beneficial effects in AKI. In addition, the combined administration of both drugs was also investigated. Ischemia was induced in anesthetized male Wistar rats by occluding both renal pedicles for 30min followed by reperfusion for 24h. Sitagliptin (5mg kg(-1)), furosemide (245mg kg(-1)) or their combination were administered orally at 5h post-IR and 2h before euthanasia. Administration of sitagliptin or furosemide ameliorated renal and cardiac deterioration induced by renal IR. This was manifested as significant reduction of serum creatinine, urea, cystatin c, creatine kinase-MB, cardiac troponin-I and lactate dehydrogenase (Pfurosemide alone. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Cardioprotection of CAPE-oNO2 against myocardial ischemia/reperfusion induced ROS generation via regulating the SIRT1/eNOS/NF-κB pathway in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Dejuan Li

    2018-05-01

    Full Text Available Caffeic acid phenethyl ester (CAPE could ameliorate myocardial ischemia/reperfusion injury (MIRI by various mechanisms, but there hadn’t been any reports on that CAPE could regulate silent information regulator 1 (SIRT1 and endothelial nitric oxide synthase (eNOS to exert cardioprotective effect. The present study aimed to investigate the cardioprotective potential of caffeic acid o-nitro phenethyl ester (CAPE-oNO2 on MIRI and the possible mechanism based on the positive control of CAPE. The SD rats were subjected to left coronary artery ischemia /reperfusion (IR and the H9c2 cell cultured in hypoxia/reoxygenation (HR to induce the MIRI model. Prior to the procedure, vehicle, CAPE or CAPE-oNO2 were treated in the absence or presence of a SIRT1 inhibitor nicotinamide (NAM and an eNOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME. In vivo, CAPE and CAPE-oNO2 conferred a cardioprotective effect as shown by reduced myocardial infarct size, cardiac marker enzymes and structural abnormalities. From immunohistochemical and sirius red staining, above two compounds ameliorated the TNF-α release and collagen deposition of IR rat hearts. They could agitate SIRT1 and eNOS expression, and consequently enhance NO release and suppress NF-κB signaling, to reduce the malondialdehyde content and cell necrosis. In vitro, they could inhibit HR-induced H9c2 cell apoptosis and ROS generation by activating SIRT1/eNOS pathway and inhabiting NF-κB expression. Emphatically, CAPE-oNO2 presented the stronger cardioprotection than CAPE both in vivo and in vitro. However, NAM and L-NAME eliminated the CAPE-oNO2-mediated cardioprotection by restraining SIRT1 and eNOS expression, respectively. It suggested that CAPE-oNO2 ameliorated MIRI by suppressing the oxidative stress, inflammatory response, fibrosis and necrocytosis via the SIRT1/eNOS/NF-κB pathway.

  7. Myocardial Protective Effects of L-Carnitine on Ischemia-Reperfusion Injury in Patients With Rheumatic Valvular Heart Disease Undergoing Cardiac Surgery.

    Science.gov (United States)

    Li, Ming; Xue, Li; Sun, Haifeng; Xu, Suochun

    2016-12-01

    The authors used L-carnitine as an ingredient in cardioplegic solution during valve replacement surgery to investigate the protective effect of L-carnitine on myocardial ischemia-reperfusion injury (MIRI) and its possible mechanism. Prospective, randomized study. A tertiary-care hospital. The study comprised 90 patients undergoing valve replacement under cardiopulmonary bypass. Patients were divided randomly into 3 groups. L-carnitine was added to the crystalloid cardioplegic solution for experimental group 1 (3 g/L) and experimental group 2 (6 g/L), whereas no L-carnitine was used in the control group. The remainder of the treatment was identical for all 3 groups. Serum was collected from each patient 1 hour before the surgery and at 2, 6, 24, and 72 hours after unclamping the aorta, and tissue samples were obtained before cardiac arrest and after unclamping the aorta. The postoperative levels of serum aspartate aminotransferase, creatine kinase, creatine kinase-MB isozyme, and lactic acid dehydrogenase and the apoptotic index were all lower in the 2 experimental groups than those in the control group. In addition, each of the aforementioned serum enzyme levels and the apoptotic index in all 3 groups significantly increased after unclamping the aorta compared with baseline levels taken before surgery. Bcl-2 expression was higher and Bax was lower in the 2 experimental groups compared with those of the control group after unclamping the aorta. However, there was no significant difference in all the postoperative indices between the 2 experimental groups. L-carnitine may reduce cardiopulmonary bypass-induced myocardial apoptosis through modulating the expressions of Bcl-2 and Bax, resulting in a protective effect from MIRI. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Transient myocardial ischemia during daily life in rest and exertional angina pectoris and comparison of effectiveness of metoprolol versus nifedipine

    DEFF Research Database (Denmark)

    Ardissino, D; Savonitto, S; Egstrup, K

    1991-01-01

    to the questionnaire, the proportion of effort-induced anginal episodes ranged from 1 to 99%. The ischemic threshold during exercise testing ranged from 110 x 10(2) to 350 x 10(2) mm Hg x beats/min. At least 1 episode of ST-segment depression was observed in 29 of the 65 patients during Holter monitoring. Ischemic......The clinical characteristics of 65 patients with mixed angina were classified by means of (1) a questionnaire investigating the proportion of symptoms occurring at rest and on effort, (2) an exercise stress test, (3) 24-hour ambulatory Holter monitoring, and (4) coronary arteriography. According...... episodes during Holter monitoring were more frequent (p less than 0.05) in patients reporting greater than or equal to 50% of anginal attacks on effort, with moderate to severe limitation of exercise capacity and with multivessel coronary artery disease. The effect on ambulatory ischemia of a 6-week...

  9. Correlation of serum visfatin level with chest pain scoring as an indication of myocardial ischemia in chronic kidney disease patients

    Directory of Open Access Journals (Sweden)

    Mohamed F Almaghraby

    2014-01-01

    Conclusion It could be concluded that patients with CKD are at an actual risk of developing CP secondary to myocardial ischemic attack, presenting either as typical or as atypical anginal pain. Elevated serum visfatin levels may be the cornerstone for the relationship between CKD and coronary heart disease. Serum visfatin levels in range of 12.4-16.4 ng/ml could predict the possibility of developing an anginal attack in patients with atypical anginal CP, with high sensitivity and specificity for diagnosis.

  10. Chronic intermittent fasting improves the survival following large myocardial ischemia by activation of BDNF/VEGF/PI3K signaling pathway.

    Science.gov (United States)

    Katare, Rajesh G; Kakinuma, Yoshihiko; Arikawa, Mikihiko; Yamasaki, Fumiyasu; Sato, Takayuki

    2009-03-01

    Chronic heart failure (CHF) is the major cause of death in the developed countries. Calorie restriction is known to improve the recovery in these patients; however, the exact mechanism behind this protective effect is unknown. Here we demonstrate the activation of cell survival PI3kinase/Akt and VEGF pathway as the mechanism behind the protection induced by intermittent fasting in a rat model of established chronic myocardial ischemia (MI). Chronic MI was induced in rats by occlusion of the left coronary artery. Two weeks later, the rats were randomly assigned to a normal feeding group (MI-NF) and an alternate-day feeding group (MI-IF). After 6 weeks of observation, we evaluated the effect of intermittent fasting on cellular and ventricular remodeling and long-term survival after CHF. Compared with the normally fed group, intermittent fasting markedly improved the survival of rats with CHF (88.5% versus 23% survival, Pfasted hearts. Immunohistochemical studies confirmed increased capillary density (Pfasting also upregulated the expression of other anti-apoptotic factors such as Akt and Bcl-2 and reduced the TUNEL positive apoptotic nuclei in the border zone. Chronic intermittent fasting markedly improves the long-term survival after CHF by activation through its pro-angiogenic, anti-apoptotic and anti-remodeling effects.

  11. SPECT imaging of myocardial infarction using {sup 99m}Tc-labeled C2A domain of synaptotagmin I in a porcine ischemia-reperfusion model

    Energy Technology Data Exchange (ETDEWEB)

    Fang Wei [Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037 (China); Wang Feng [Nuclear Medicine Department, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006 (China); Ji Shundong [Jiangsu Institute of Hematology, 1st Hospital of Suzhou University, Suzhou 215006 (China); Zhu Xiaoguang [Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226 (United States); Meier, Heidi T. [Clinical Veterinarian and Radiology Research, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin, WI 53295 (United States); Hellman, Robert S. [Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226 (United States); Brindle, Kevin M. [MRC Laboratory of Molecular Biology, Cambridge CB2 2QH (United Kingdom); Davletov, Bazbek [Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA (United Kingdom); Zhao Ming [Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226 (United States)], E-mail: mzhao@mcw.edu

    2007-11-15

    Introduction: The C2A domain of synaptotagmin I recognizes necrotic and apoptotic cells by binding to exposed anionic phospholipids. The goal is to explore the potential imaging utility of {sup 99m}Tc-labeled C2A in the detection of acute cardiac cell death in a porcine model that resembles human cardiovascular physiology. Methods: Ischemia (20-25 min) was induced in pigs (M/F, 20-25 kg) using balloon angioplasty. {sup 99m}Tc-C2A-GST (n=7) or {sup 99m}Tc-BSA (n=2) was injected intravenously 1-2 h after reperfusion. Noninfarct animals were injected with {sup 99m}Tc-C2A-GST (n=4). SPECT images were acquired at 3 and 6 h postinjection. Cardiac tissues were analyzed to confirm the presence of cell death. Results: Focal uptake was detected in five out of seven subjects at 3 h and in all infarct subjects at 6 h postinjection but not in infarct animals injected with {sup 99m}Tc-BSA or in noninfarct animals with {sup 99m}Tc-C2A-GST. Gamma counting of infarct versus normal myocardium yielded a 10.2{+-}5.7-fold elevation in absolute radioactivity, with histologically confirmed infarction. Conclusions: We present data on imaging myocardial cell death in the acute phase of infarction in pigs. C2A holds promise and warrants further development as an infarct-avid molecular probe.

  12. The effect of lesion size and tissue remodeling on ST deviation in partial-thickness ischemia

    NARCIS (Netherlands)

    Potse, Mark; Coronel, Ruben; Falcao, Stéphanie; LeBlanc, A.-Robert; Vinet, Alain

    2007-01-01

    BACKGROUND: Myocardial ischemia causes ST segment elevation or depression in electrocardiograms and epicardial leads. ST depression in epicardium overlying the ischemic zone indicates that the ischemia is nontransmural. However, nontransmural ischemia does not always cause ST depression. Especially

  13. Diagnostic advantage of stress computed tomography myocardial perfusion over single-photon emission computed tomography for the assessment of myocardial ischemia.

    Science.gov (United States)

    Ueki, Yasushi; Izawa, Atsushi; Kashiwagi, Daisuke; Nishiyama, Shigeki; Aso, Shinichi; Suzuki, Chihiro; Sakurai, Shumpei; Oguchi, Kazuhiro; Yazaki, Yoshikazu; Ikeda, Uichi; Kuwahara, Koichiro

    2017-08-01

    This study compared adenosine stress computed tomography myocardial perfusion (CTP) with single-photon emission computed tomography (SPECT) in the diagnosis of functionally significant coronary artery stenosis using fractional flow reserve (FFR) as reference standard. We included a total of 93 coronary arteries from 31 patients in whom at least one vessel with ≥50% stenosis was detected with computed tomography coronary angiography. All patients underwent both SPECT and adenosine stress CTP, followed by invasive coronary angiography (ICA) and FFR. Diagnostic accuracy between CTP and SPECT was compared according to positive findings of either ≥99% stenosis on ICA or FFR ≤0.8. Among 78 vessels eligible for the quantitative analyses, significant coronary artery disease (CAD) was diagnosed in 22 vessels of 19 patients. Comparison of CTP vs. SPECT for sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy in detecting significant CAD were 59% vs. 18%, 96% vs. 93%, 87% vs. 50%, 86% vs. 74%, and 86% vs. 72%, respectively. CTP demonstrated a significant diagnostic advantage over SPECT in the identification of significant CAD, especially in terms of sensitivity and PPV. Adenosine stress CTP is useful for the noninvasive diagnosis of functionally significant CAD. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  14. Electrocardiography as a Tool for Validating Myocardial Ischemia–Reperfusion Procedures in Mice

    Science.gov (United States)

    Preda, Mihai B; Burlacu, Alexandrina

    2010-01-01

    This paper evaluates the modifications induced by ischemia and ischemia–reperfusion in mice after permanent or transient, respectively, ligation of the left coronary artery and establishes a correlation among the extent of ischemia, electrocardiograph features, and infarct size. The left coronary artery was ligated 1 mm distal from the tip of the left auricle. Histologic analysis revealed that 30-min ischemia (n = 9) led to infarction involving 9.7% ± 0.5% of the left ventricle, whereas 1-h ischemia (n = 9) resulted in transmural infarction of 16.1% ± 4.6% of the left ventricle. In contrast, 24-h ischemia (n = 8) and permanent ischemia (n = 8) induced similarly sized infarcts (33% ± 2% and 31.8% ± 0.7%, respectively), suggesting ineffective reperfusion after 24-h ischemia. Electrocardiography revealed that ligation of the left coronary artery led to ST height elevation (204 compared with 14 μV) and QTc prolongation (136 compared with 76 ms). Both parameters rapidly normalized on reperfusion, demonstrating that electrocardiography was important for validating correct ligation and reperfusion. In addition, electrocardiography predicted the severity of the myocardial damage induced by ischemia. Our results show that electrocardiographic changes present after 30-min ischemia were reversed on reperfusion; however, prolonged ischemia induced pathologic electrocardiographic patterns that remained even after reperfusion. The mouse model of myocardial ischemia–reperfusion can be improved by using electrocardiography to validate ligation and reperfusion during surgery and to predict the severity of infarction. PMID:21262130

  15. Impact of electrical defibrillation on infarct size and no-reflow in pigs subjected to myocardial ischemia-reperfusion without and with ischemic conditioning.

    Science.gov (United States)

    Skyschally, Andreas; Amanakis, Georgios; Neuhäuser, Markus; Kleinbongard, Petra; Heusch, Gerd

    2017-11-01

    Ventricular fibrillation (VF) occurs frequently during myocardial ischemia-reperfusion (I/R) and must then be terminated by electrical defibrillation. We have investigated the impact of VF/defibrillation on infarct size (IS) or area of no reflow (NR) without and with ischemic conditioning interventions. Anesthetized pigs were subjected to 60/180 min of coronary occlusion/reperfusion. VF, as identified from the ECG, was terminated by intrathoracic defibrillation. The area at risk (AAR), IS, and NR were determined by staining techniques (patent blue, triphenyltetrazolium chloride, and thioflavin-S). Four experimental protocols were analyzed: I/R ( n = 49), I/R with ischemic preconditioning (IPC; n = 22), I/R with ischemic postconditioning (POCO; n = 22), or I/R with remote IPC (RIPC; n = 34). The incidence of VF was not different between I/R (44%), IPC (45%), POCO (50%), and RIPC (33%). IS was reduced by IPC (23 ± 12% of AAR), POCO (31 ± 16%), and RIPC (22 ± 13%, all P defibrillation, IS was 50% larger than in pigs without defibrillation but independent of the number of defibrillations. Analysis of covariance confirmed the established determinants of IS, i.e., AAR, residual blood flow during ischemia (RMBFi), and a conditioning protocol, and revealed VF/defibrillation as a novel covariate. VF/defibrillation in turn was associated with larger AAR and lower RMBFi. Lack of dose-response relation between IS and the number of defibrillations excluded direct electrical injury as the cause of increased IS. Obviously, AAR size and RMBFi account for both IS and the incidence of VF. IS and NR are mechanistically distinct phenomena. NEW & NOTEWORTHY Ventricular fibrillation/defibrillation is associated with increased infarct size. Electrical injury is unlikely the cause of such association, since there is no dose-response relation between infarct size and number of defibrillations. Ventricular fibrillation, in turn, is associated with a larger area at risk and

  16. Preoxygenated hemoglobin-based oxygen carrier HBOC-201 annihilates myocardial ischemia during brief coronary artery occlusion in pigs.

    Science.gov (United States)

    Te Lintel Hekkert, Maaike; Dubé, Gregory P; Regar, Evelyn; de Boer, Martine; Vranckx, Pascal; van der Giessen, Wim J; Serruys, Patrick W; Duncker, Dirk J

    2010-03-01

    Because of their ability to perfuse remote regions and deliver oxygen, hemoglobin-based oxygen carriers (HBOCs) may be considered in the treatment of several ischemic conditions such as acute coronary syndromes or high-risk percutaneous intervention. Here we studied the effects of intracoronary infusion of ex vivo preoxygenated HBOC-201 during brief total coronary artery occlusion (CAOs) on myocardial oxygenation and left ventricular (LV) function in a large animal model and investigated the influence of HBOC-201 temperature and infusion rate on these effects. Thirteen open-chest anesthetized swine were instrumented for measurement of global and regional LV function and metabolism. CAOs were induced by inflating an intracoronary balloon catheter; preoxygenated HBOC-201 (12 g/dL) was infused distally through the central lumen of the balloon catheter. Animals underwent consecutive 3-min CAOs interspersed by 30 min of reperfusion, accompanied by different HBOC-201 infusion rates (0, 15, 23, 30, 40, and 50 ml/min) and/or two infusion temperatures (18 degrees C or 37 degrees C) in random order. CAO elicited immediate loss of systolic shortening (SS) in the ischemic region (19 +/- 1% at baseline vs. -3 +/- 2% at end of CAO), resulting in decreases in maximum rate of rise in LV pressure (15 +/- 5%) and stroke volume (12 +/- 4%; all P < 0.05). Balloon deflation resulted in marked coronary reactive hyperemia (to 472 +/- 74% of baseline), increases in coronary venous concentrations of adenosine + inosine (to 218 +/- 26% of baseline; both P < 0.05) and rapid restoration of SS toward baseline. HBOC-201 ameliorated the CAO-induced changes in SS, stroke volume, reactive hyperemia, and coronary venous adenosine + inosine. The effects were temperature and flow dependent with full preservation of SS at 50 ml/min HBOC-201 of 37 degrees C. In conclusion, intracoronary preoxygenated HBOC-201 preserved myocardial oxygenation and LV function in swine during CAO in a dose- and

  17. [Explore molecular mechanism of Chinese herbs with promoting blood circulation and resolving phlegm effects on myocardial ischemia reperfusion injury based on correlation between microRNA and mtDNA].

    Science.gov (United States)

    Lin, Fei; Chen, Heng-Wen; Shi, Zhuo-Lin; Zhao, Guo-An; Sun, Ye-Xi

    2017-03-01

    A large number of basic and clinical studies have shown that the Chinese herbs with promoting blood circulation and resolving phlegm effects could prevent and treat myocardial ischemia-reperfusion injury(MIRI) by regulating lipid metabolism. But its mechanism is not yet clear. The studies show that mitochondrial DNA (mtDNA), microRNAs and lipid metabolism participate in the whole process of MIRI and affect the prognosis. mtDNA mutation is the primary factor to cause myocardial ischemia and reperfusion myocardial cell damage. microRNAs aggravate or reduce MIRI injury by down-regulating or up-regulating related genes expression, while miR-33, as a key regulator of cholesterol transport, regulates lipid metabolism through CROT, PGC-1α, AMPK and other genes located in the mitochondria. There are less studies on correlation between miR-33 and mtDNA, microRNAs. Therefore, further studies on the correlation between miR-33 and mtDNA, microRNAs, as well as the discussions on whether the traditional Chinese medicine (TCM) with promoting blood circulation and resolving phlegm effects could target miR-33 to regulate lipid metabolism and inducemt DNA mutations or deletions, would have important significance for the prevention and treatment of MIRI. Copyright© by the Chinese Pharmaceutical Association.

  18. Adenosine triphosphate stress dual-source computed tomography to identify myocardial ischemia: comparison with invasive coronary angiography.

    Science.gov (United States)

    Kido, Teruhito; Watanabe, Kouki; Saeki, Hideyuki; Shigemi, Susumu; Matsuda, Takeshi; Yamamoto, Masaya; Kurata, Akira; Kanza, Rene Epunza; Itoh, Toshihide; Mochizuki, Teruhito

    2014-01-01

    The purpose of this study was to investigate the utility incremental diagnostic value of combined assessment with coronary CT angiography (CCTA) and myocardial CT perfusion imaging (CTP) using dual-energy technology with an Adenosine Triphosphate (ATP) load technique. Twenty-one patients underwent ATP-provocation dual-energy CT and CAG. We compared the diagnostic accuracy with CAG, for ischemic region due coronary stenosis by CCTA alone and CCTA combined with CTP (Combined CCTA/CTP). All of 21 patients CTP images could be evaluated, however 8 CCTA images could not be evaluated by calcification and motion artifact, so assessability was 61.9% (13/21) for CCTA alone, and 100% for Combined CCTA/CTP. With CAG results as a comparison, the sensitivity, specificity, positive predictive value, and negative predictive value were, respectively, 83.3% (20/24), 74.4% (29/39), 66.7% (20/30), and 87.8% (29/33) for CCTA alone, and 66.7% (16/24), 92.3% (36/39), 84.2% (16/19), and 81.8% (36/44) for combined CCTA/CTP. The diagnostic accuracy of the two methods were 77.8% (49/63) and 82.5% (52/63). Dual-energy CT may be a useful modality for perfusion assessment and correlated well with the severity of stenosis on CAG. This technique may even be of use in cases of severe calcification in the coronary artery wall.

  19. Endothelial dysfunction, carotid artery plaque burden, and conventional exercise-induced myocardial ischemia as predictors of coronary artery disease prognosis

    Directory of Open Access Journals (Sweden)

    Ishihara Masayuki

    2008-12-01

    Full Text Available Abstract Background While both flow-mediated vasodilation (FMD in the brachial artery (BA, which measures endothelium-dependent vasodilatation, and intima-media thickness (IMT in the carotid artery are correlated with the prognosis of coronary artery disease (CAD, it is not clear which modality is a better predictor of CAD. Furthermore, it has not been fully determined whether either of these modalities is superior to conventional ST-segment depression on exercise stress electrocardiogram (ECG as a predictor. Thus, the goal of the present study was to compare the predictive value of FMD, IMT, and stress ECG for CAD prognosis. Methods and Results A total of 103 consecutive patients (62 ± 9 years old, 79 men with clinically suspected CAD had FMD and nitroglycerin-induced dilation (NTG-D in the BA, carotid artery IMT measurement using high-resolution ultrasound, and exercise treadmill testing. The 73 CAD patients and 30 normal coronary patients were followed for 50 ± 15 months. Fifteen patients had coronary events during this period (1 cardiac death, 2 non-fatal myocardial infarctions, 3 acute heart failures, and 9 unstable anginas. On Kaplan-Meier analysis, only FMD and stress ECG were significant predictors for cardiac events. Conclusion Brachial endothelial function as reflected by FMD and conventional exercise stress testing has comparable prognostic value, whereas carotid artery plaque burden appears to be less powerful for predicting future cardiac events.

  20. Diagnostic Accuracy of a New Cardiac Electrical Biomarker for Detection of Electrocardiogram Changes Suggestive of Acute Myocardial Ischemic Injury

    Science.gov (United States)

    Schreck, David M; Fishberg, Robert D

    2014-01-01

    Objective A new cardiac “electrical” biomarker (CEB) for detection of 12-lead electrocardiogram (ECG) changes indicative of acute myocardial ischemic injury has been identified. Objective was to test CEB diagnostic accuracy. Methods This is a blinded, observational retrospective case-control, noninferiority study. A total of 508 ECGs obtained from archived digital databases were interpreted by cardiologist and emergency physician (EP) blinded reference standards for presence of acute myocardial ischemic injury. CEB was constructed from three ECG cardiac monitoring leads using nonlinear modeling. Comparative active controls included ST voltage changes (J-point, ST area under curve) and a computerized ECG interpretive algorithm (ECGI). Training set of 141 ECGs identified CEB cutoffs by receiver-operating-characteristic (ROC) analysis. Test set of 367 ECGs was analyzed for validation. Poor-quality ECGs were excluded. Sensitivity, specificity, and negative and positive predictive values were calculated with 95% confidence intervals. Adjudication was performed by consensus. Results CEB demonstrated noninferiority to all active controls by hypothesis testing. CEB adjudication demonstrated 85.3–94.4% sensitivity, 92.5–93.0% specificity, 93.8–98.6% negative predictive value, and 74.6–83.5% positive predictive value. CEB was superior against all active controls in EP analysis, and against ST area under curve and ECGI by cardiologist. Conclusion CEB detects acute myocardial ischemic injury with high diagnostic accuracy. CEB is instantly constructed from three ECG leads on the cardiac monitor and displayed instantly allowing immediate cost-effective identification of patients with acute ischemic injury during cardiac rhythm monitoring. PMID:24118724

  1. Saffron (Crocus sativus) intake provides nutritional preconditioning against myocardial ischemia-reperfusion injury in Wild Type and ApoE(-/-) mice: Involvement of Nrf2 activation.

    Science.gov (United States)

    Efentakis, P; Rizakou, A; Christodoulou, E; Chatzianastasiou, A; López, M G; León, R; Balafas, E; Kadoglou, N P E; Tseti, I; Skaltsa, H; Kostomitsopoulos, N; Iliodromitis, E K; Valsami, G; Andreadou, I

    2017-10-01

    Saffron is an antioxidant herbal derivative; however, its efficacy as a nutritional cardioprotective agent has not been fully elucidated. We investigated the cardioprotective properties of a standardized saffron aqueous extract (SFE) against ischemia/reperfusion (I/R) injury in Wild-Type (WT) and ApoE(-/-) mice and the underlying molecular mechanisms. WT and ApoE(-/-) mice were subjected to 30 min I and 2 h R, with the following per os interventions for 4 weeks: 1) WT Control Group, receiving Water for Injection (WFI); 2) WT Crocus Group, receiving SFE at a dose of 60 mg/kg/day; 3) WT Crocus + Wort group, receiving SFE as described above and wortmannin at a dose of 60 μg/kg bolus 15 min before R; 4) ApoE(-/-) Control Group, receiving WFI; 5) ApoE(-/-) Crocus Group, receiving SFE at a dose of 60 mg/kg/day and 6) ApoE(-/-) Crocus + Wort: receiving SFE as described above and wortmannin at a dose of 60 μg/kg bolus, 15 min before R. Ischemic area/area at risk (I/R%) ratio was measured. Blood samples and ischemic myocardial tissue were collected at the 10th min of reperfusion for assessment of troponin I, malondialdehyde (MDA), nitrotyrosine (NT), p-eNOS, eNOS, p-Akt, Akt, p-p42/p-p44, p-GSK3β, GSK3β, IL-6, Nrf2, HO-1 and MnSOD expression. The effect of SFE on Nrf2 expression was also evaluated in vitro. SFE reduced infarct size in WT (16.15 ± 3.7% vs 41.57 ± 2.48%, ***p < 0.001) and in ApoE(-/-) mice (16.14 ± 1.47% vs 45.57 ± 1.73%, ***p < 0.001). The administration of wortmannin resulted in partial inhibition of the infarct size limitation efficacy of SFE (in both WT and Apo-E(-/-) mice). Mice receiving SFE showed increased levels of eNOS, p-Akt, p-ERK1/2, p-44/p-42 and p-GSK3β-Ser9 and reduced expression of IL-6 and iNOS; furthermore, SFE reduced the levels of MDA and NT. SFE induced Nrf2 expression and its downstream targets, HO-1 and MnSOD in the myocardium of the treated animals, and induced Nrf2 expression in vitro in a dose

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Time of symptom onset and value of myocardial blush and infarct size on prognosis in patients with ST-elevation myocardial infarction

    NARCIS (Netherlands)

    Wieringa, Wouter G; Lexis, Chris P H; Mahmoud, Karim D; Ottervanger, Jan Paul; Burgerhof, Johannes G M; Pundziute, Gabija; van 't Hof, Arnoud W J; van Gilst, Wiek H; Lipsic, Erik

    In patients with ST-segment elevation myocardial infarction (STEMI), the time of onset of ischemia has been associated with myocardial infarction (MI) size. Myocardial blush grade (MBG) reflects myocardial response to ischemia/reperfusion injury, which may differ according to time of the day. The

  4. Myocardial perfusion imaging study of CO(2)-induced panic attack.

    Science.gov (United States)

    Soares-Filho, Gastão L F; Machado, Sergio; Arias-Carrión, Oscar; Santulli, Gaetano; Mesquita, Claudio T; Cosci, Fiammetta; Silva, Adriana C; Nardi, Antonio E

    2014-01-15

    Chest pain is often seen alongside with panic attacks. Moreover, panic disorder has been suggested as a risk factor for cardiovascular disease and even a trigger for acute coronary syndrome. Patients with coronary artery disease may have myocardial ischemia in response to mental stress, in which panic attack is a strong component, by an increase in coronary vasomotor tone or sympathetic hyperactivity setting off an increase in myocardial oxygen consumption. Indeed, coronary artery spasm was presumed to be present in cases of cardiac ischemia linked to panic disorder. These findings correlating panic disorder with coronary artery disease lead us to raise questions about the favorable prognosis of chest pain in panic attack. To investigate whether myocardial ischemia is the genesis of chest pain in panic attacks, we developed a myocardial perfusion study through research by myocardial scintigraphy in patients with panic attacks induced in the laboratory by inhalation of 35% carbon dioxide. In conclusion, from the data obtained, some hypotheses are discussed from the viewpoint of endothelial dysfunction and microvascular disease present in mental stress response. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Regulation of heat shock proteins 27 and 70, p-Akt/p-eNOS and MAPKs by Naringin Dampens myocardial injury and dysfunction in vivo after ischemia/reperfusion.

    Directory of Open Access Journals (Sweden)

    Neha Rani

    Full Text Available Naringin has antioxidant properties that could improve redox-sensitive myocardial ischemia reperfusion (IR injury. This study was designed to investigate whether naringin restores the myocardial damage and dysfunction in vivo after IR and the mechanisms underlying its cardioprotective effects. Naringin (20-80 mg/kg/day, p.o. or saline were administered to rats for 14 days and the myocardial IR injury was induced on 15(th day by occluding the left anterior descending coronary artery for 45 min and subsequent reperfusion for 60 min. Post-IR rats exhibited pronounced cardiac dysfunction as evidenced by significantly decreased mean arterial pressure, heart rate, +LVdP/dt max (inotropic state, -LVdP/dt max (lusitropic state and increased left ventricular end diastolic pressure as compared to sham group, which was improved by naringin. Further, on histopathological and ultrastructural assessments myocardium and myocytes appeared more normal in structure and the infarct size was reduced significantly in naringin 40 and 80 mg/kg/day group. This amelioration of post-IR-associated cardiac injury by naringin was accompanied by increased nitric oxide (NO bioavailability, decreased NO inactivation to nitrotyrosine, amplified protein expressions of Hsp27, Hsp70, β-catenin and increased p-eNOS/eNOS, p-Akt/Akt, and p-ERK/ERK ratio. In addition, IR-induced TNF-α/IKK-β/NF-κB upregulation and JNK phosphorylation were significantly attenuated by naringin. Moreover, western blotting and immunohistochemistry analysis of apoptotic signaling pathway further established naringin cardioprotective potential as it upregulated Bcl-2 expression and downregulated Bax and Caspase-3 expression with reduced TUNEL positivity. Naringin also normalized the cardiac injury markers (lactate dehydrogenase and creatine kinase-MB, endogenous antioxidant activities (superoxide dismutase, reduced glutathione and glutathione peroxidase and lipid peroxidation levels. Thus, naringin

  6. Apoptosis and Histopathology of the Heart after Renal Ischemia-Reperfusion in Male Rat Running title: Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Alireza Alihemmati

    2018-01-01

    Full Text Available ABSTRACT Ischemia-reperfusion injury was seen in strokes, myocardial infarctions, acute kidney injury, mesenteric ischemia, liver and systemic shock. Renal ischemia-reperfusion is more importance in the setting of kidney transplantation that affects distant organs. In this study forty Male Albino Wistar rats (200-250g were randomly divided in four group (n=10 including control, sham operation group, nephrectomy and IRI group. All rats anesthetized with intraperitoneal injection of ketamine (50 mg/kg and xylazine (10 mg/kg and maintained the core body temperature at approximately 37°C. For inducing IRI group, it was performed right nephrectomy, and in continuing, the left kidney pedicle occluded to 45 min via nontraumatic microvascular clamp for making ischemia that followed 24 hours reperfusion. TUNEL assay was used to detect the cardiac apoptotic cells. Hematoxylin-Eosin staining and periodic acid-Schiff (PAS procedure was used to histopathological assessment and glycogen accumulation respectively. There was more heart damage at 24 h reperfusion in IRI group. Renal IRI group showed myocardial degeneration, necrosis and increasing connective tissue in myofibril. There were apparent hypertrophy and swelling of myofibril, fragmentation and vacuolization of sarcoplasm. In addition, it was shown elevated apoptotic cell at 24 hours reperfusion in renal IRI group than sham group. There were increases of glycogen accumulation in cardimyocyte of renal IRI group. Our findings suggest that renal IRI-induced cardiac damage, accompanied by an accumulation of glycogen granules, induced apoptosis and histological changes in cardiomyocytes.

  7. Chronic type-I diabetes could not impede the anti-inflammatory and anti-apoptotic effects of combined postconditioning with ischemia and cyclosporine A in myocardial reperfusion injury.

    Science.gov (United States)

    Badalzadeh, Reza; Azimi, Ako; Alihemmati, Alireza; Yousefi, Bahman

    2017-02-01

    It has been shown that diabetes modifies the myocardial responses to ischemia/reperfusion (I/R) and to cardioprotective agents. In this study, we aimed to investigate the effects of combined treatment with ischemic postconditioning (IPostC) and cyclosporine A (CsA) on inflammation and apoptosis of the diabetic myocardium injured by I/R. Eight weeks after induction of diabetes in Wistar rats, hearts were mounted on a Langendorff apparatus and were subsequently subjected to a 30-min regional ischemia followed by 45-min reperfusion. IPostC was induced at the onset of reperfusion, by 3 cycles of 30-s reperfusion/ischemia (R/I). The concentration of creatine kinase (CK), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were determined; the levels of total and phosphorylated glycogen synthase kinase 3 beta (p-GSK3β) and B-cell lymphoma 2 (Bcl-2) were quantified by western blotting, and the rate of apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. Administration of either IPostC or CsA alone in nondiabetic animals significantly reduced CK, TNF-α, IL-1β, and IL-6 concentrations, increased the p-GSK3β and Bcl-2, and decreased the level of apoptosis (P < 0.05) but had no effect on diabetic hearts. However, in diabetic animals, after administration of CsA, the cardioprotective effects of IPostC in increasing the p-GSK3β and Bcl-2 and decreasing apoptosis and inflammation were restored in comparison with nonpostconditioned diabetic hearts. IPostC or CsA failed to affect apoptosis and inflammation and failed to protect the diabetic myocardium against I/R injury. However, combined administration of IPostC and CsA at reperfusion can protect the diabetic myocardium by decreasing the inflammatory response and apoptosis.

  8. Adaptation to chronic continuous hypoxia potentiates Akt/HK2 anti-apoptotic pathway during brief myocardial ischemia/reperfusion insult

    Czech Academy of Sciences Publication Activity Database

    Kolář, D.; Grešíková, M.; Wasková-Arnoštová, P.; Elsnicová, B.; Kohutová, J.; Horníková, D.; Vebr, P.; Neckář, Jan; Blahová, T.; Kašparová, D.; Novotný, J.; Kolář, František; Nováková, O.; Žurmanová, J.M.

    2017-01-01

    Roč. 432, 1-2 (2017), s. 99-108 ISSN 0300-8177 R&D Projects: GA ČR(CZ) GA13-10267S Institutional support: RVO:67985823 Keywords : heart * hypoxia * ischemia/reperfusion * hexokinase * protein kinase B/Akt * mitochondria Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.669, year: 2016

  9. Preservation of global cardiac function in the rabbit following protracted ischemia/reperfusion using monophosphoryl lipid A (MLA).

    Science.gov (United States)

    Zhao, L; Kirsch, C C; Hagen, S R; Elliott, G T

    1996-01-01

    Monophosphoryl lipid A (MLA), a derivative of the minimal substructure of lipopolysaccharide (lipid A) possesses immunomodulatory activity of the parent lipid A yet enjoys reduced toxicity. It has previously been reported that pretreatment with MLA reduces myocardial infarct size and stunning in dogs following ischemia and reperfusion. The aim of this study was to evaluate the ability of monophosphoryl lipid A (MLA) to preserve global cardiac function and peripheral hemodynamics in a rabbit model of prolonged regional ischemia (90 min), and reperfusion (6 h). An evaluation of potential mechanisms by which MLA may preserve cardiac function was also undertaken. Single dose pretreatment with MLA (35 micrograms/kg i.v.) 24 h prior to ischemia resulted in significant improvement in left ventricular developed pressure, dP/dt, rate-pressure product and mean arterial pressure during reperfusion (P MLA pretreatment did not reduce infarct size (54.5 +/- 11.4% in control v 63.3 +/- 8.3% in MLA, P = N.S.), evaluation of myocardial adenylate and adenosine catabolite pools at the end of ischemia indicated a preservation of ATP and ADP and a decreased production of downstream adenosine catabolites including inosine, xanthine and uric acid. Adenosine kinase, but not 5'-nucleotidase (5'-NTase) or adenosine deaminase activity determined following reperfusion was 76% and 60% higher (P MLA pretreated rabbits compared with controls. Although there was a trend toward lower tissue myeloperoxidase activity in post-ischemic myocardium from treated rabbits, the results were not significantly different from control animals. These results suggest that a 24-h pretreatment with MLA, without further treatment during ischemia or reperfusion was associated with: (1) preservation of global myocardial function during reperfusion; (2) preservation of myocardial high energy adenylates and reduced formation of adenosine catabolites during ischemia; (3) elevated myocardial adenosine kinase activity

  10. A Translational Study of a New Therapeutic Approach for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model.

    Science.gov (United States)

    Ichimura, Kenzo; Matoba, Tetsuya; Nakano, Kaku; Tokutome, Masaki; Honda, Katsuya; Koga, Jun-Ichiro; Egashira, Kensuke

    2016-01-01

    There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction, for which interventional reperfusion therapy is hampered by ischemia-reperfusion (IR) injury. We recently reported that bioabsorbable poly(lactic acid/glycolic acid) (PLGA) nanoparticle-mediated treatment with pitavastatin (pitavastatin-NP) exerts a cardioprotective effect in a rat IR injury model by activating the PI3K-Akt pathway and inhibiting inflammation. To obtain preclinical proof-of-concept evidence, in this study, we examined the effect of pitavastatin-NP on myocardial IR injury in conscious and anesthetized pig models. Eighty-four Bama mini-pigs were surgically implanted with a pneumatic cuff occluder at the left circumflex coronary artery (LCx) and telemetry transmitters to continuously monitor electrocardiogram as well as to monitor arterial blood pressure and heart rate. The LCx was occluded for 60 minutes, followed by 24 hours of reperfusion under conscious conditions. Intravenous administration of pitavastatin-NP containing ≥ 8 mg/body of pitavastatin 5 minutes before reperfusion significantly reduced infarct size; by contrast, pitavastatin alone (8 mg/body) showed no therapeutic effects. Pitavastatin-NP produced anti-apoptotic effects on cultured cardiomyocytes in vitro. Cardiac magnetic resonance imaging performed 4 weeks after IR injury revealed that pitavastatin-NP reduced the extent of left ventricle remodeling. Importantly, pitavastatin-NP exerted no significant effects on blood pressure, heart rate, or serum biochemistry. Exploratory examinations in anesthetized pigs showed pharmacokinetic analysis and the effects of pitavastatin-NP on no-reflow phenomenon. NP-mediated delivery of pitavastatin to IR-injured myocardium exerts cardioprotective effects on IR injury without apparent adverse side effects in a preclinical conscious pig model. Thus, pitavastatin-NP represents a novel therapeutic modality for IR injury in acute myocardial

  11. Evaluation of myocardial abnormalities in patients with collagen diseases by thallium-201 myocardial scintigram

    Energy Technology Data Exchange (ETDEWEB)

    Yamano, Shigeru (Nara Medical Univ., Kashihara (Japan))

    1992-08-01

    This study was performed to evaluate myocardial lesions in patients with collagen diseases by rest and exercise thallium-201 myocardial scintigraphies. A total of 76 patients without ischemic ECG changes, consisting of 27 cases of systemic lupus erythematosus (SLE), 17 cases of polymyositis or dermatomyositis (PM[center dot]DM), 11 cases of progressive systemic sclerosis (PSS), and 21 cases of Sjoegren's syndrome (SjS), were enrolled in this study. Reversible exercise-induced defects suggesting myocardial ischemia were noted in 12 cases of SLE, 5 cases of PM[center dot]DM, 3 cases of PSS, and 3 cases of SjS. Of the 23 patients who had exercise-induced defects, 9 patients showed normal coronary angiograms by cardiac catheterization. Fixed hypoperfusion areas were observed in 5 cases of SLE, 6 cases of PM[center dot]DM, 4 cases of PSS and 3 cases of SjS. Rest thallium-201 myocardial scintigraphy disclosed hypoperfusion areas, which were not induced by exercise, in 1 case of SLE, 4 cases of PM[center dot]DM, 1 case of PSS and 5 cases of SjS. Endomyocardial biopsy was performed on 20 patients. Myocardial lesions in PM[center dot]DM and PSS were more severe and wide spread than in SLE. Ejection fraction and fractional shortening evaluated by echocardiography had no significant differences between each disease group and the healthy control group. These findings suggest that patients with collagen diseases show the presence of abnormalities of coronary circulation at the level of the intramyocardial vasculature in the stage before impairment of cardiac function, myocardial fibrosis and functional abnormalities of the cell membrane level that were not dependent on myocardial ischemia. (author).

  12. Clinical Characteristics and Outcomes of Patients with Myocardial Infarction, Myocardial Injury, and Nonelevated Troponins

    DEFF Research Database (Denmark)

    Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S

    2015-01-01

    was diagnosed in cases of a cardiac troponin I increase or decrease pattern with at least 1 value >30 ng/L (99th percentile) together with myocardial ischemia. Myocardial injury was defined as cardiac troponin I values >30 ng/L, but without signs or symptoms indicating overt cardiac ischemia. Patients with peak...... troponin value is encountered in the absence of obvious myocardial ischemia, a careful search for other clinical conditions is crucial. METHODS: In 2010 to 2011, we prospectively studied hospitalized patients who had cardiac troponin I measured on clinical indication. An acute myocardial infarction...

  13. Non-invasive imaging in detecting myocardial viability: Myocardial function versus perfusion

    Directory of Open Access Journals (Sweden)

    Iqbal A. Elfigih

    2014-12-01

    Full Text Available Coronary artery disease (CAD is the most prevalent and single most common cause of morbidity and mortality [1] with the resulting left ventricular (LV dysfunction an important complication. The distinction between viable and non-viable myocardium in patients with LV dysfunction is a clinically important issue among possible candidates for myocardial revascularization. Several available non-invasive techniques are used to detect and assess ischemia and myocardial viability. These techniques include echocardiography, radionuclide images, cardiac magnetic resonance imaging and recently myocardial computed tomography perfusion imaging. This review aims to distinguish between the available non-invasive imaging techniques in detecting signs of functional and perfusion viability and identify those which have the most clinical relevance in detecting myocardial viability in patients with CAD and chronic ischemic LV dysfunction. The most current available studies showed that both myocardial perfusion and function based on non-invasive imaging have high sensitivity with however wide range of specificity for detecting myocardial viability. Both perfusion and function imaging modalities provide complementary information about myocardial viability and no optimum single imaging technique exists that can provide very accurate diagnostic and prognostic viability assessment. The weight of the body of evidence suggested that non-invasive imaging can help in guiding therapeutic decision making in patients with LV dysfunction.

  14. Water-soluble acacetin prodrug confers significant cardioprotection against ischemia/reperfusion injury.

    Science.gov (United States)

    Liu, Hui; Yang, Lei; Wu, Hui-Jun; Chen, Kui-Hao; Lin, Feng; Li, Gang; Sun, Hai-Ying; Xiao, Guo-Sheng; Wang, Yan; Li, Gui-Rong

    2016-11-07

    The morbidity and mortality of patients with ischemic cardiomyopathy resulted from ischemia/reperfusion injury are very high. The present study investigates whether our previously synthesized water-soluble phosphate prodrug of acacetin was cardioprotective against ischemia/reperfusion injury in an in vivo rat model. We found that intravenous administration of acacetin prodrug (10 mg/kg) decreased the ventricular arrhythmia score and duration, reduced ventricular fibrillation and infarct size, and improved the impaired heart function induced by myocardial ischemia/reperfusion injury in anesthetized rats. The cardioprotective effects were further confirmed with the parent compound acacetin in an ex vivo rat regional ischemia/reperfusion heart model. Molecular mechanism analysis revealed that acacetin prevented the ischemia/reperfusion-induced reduction of the anti-oxidative proteins SOD-2 and thioredoxin, suppressed the release of inflammation cytokines TLR4, IL-6 and TNFα, and decreased myocyte apoptosis induced by ischemia/reperfusion. Our results demonstrate the novel evidence that acacetin prodrug confer significant in vivo cardioprotective effect against ischemia/reperfusion injury by preventing the reduction of endogenous anti-oxidants and the release of inflammatory cytokines, thereby inhibiting cardiomyocytes apoptosis, which suggests that the water-soluble acacetin prodrug is likely useful in the future as a new drug candidate for treating patients with acute coronary syndrome.

  15. Experimental Approaches to Acute Myocardial Infarction

    NARCIS (Netherlands)

    D.B. Uitterdijk (André)

    2015-01-01

    markdownabstractAbstract This thesis is dedicated to i) novel methods and optimization studies to improve the diagnosis of myocardial ischemia and myocardial infarction as well as fundamental studies that precede novel therapies for myocardial infarction. In part ii) 2 novel, adjunctive therapies

  16. Mesenteric ischemia.

    Science.gov (United States)

    Bobadilla, Joseph L

    2013-08-01

    This article reviews the presentation, diagnosis, evaluation, and treatment of the various forms of mesenteric ischemia, including acute and chronic ischemia. In addition, nonocclusive mesenteric ischemia and median arcuate ligament compressive syndrome are covered. The goals are to provide a structured and evidence-based framework for the evaluation and management of patients with these intestinal ischemia syndromes. Special attention is given to avoiding typical pitfalls in the diagnostic and treatment pathways. Operative techniques are also briefly discussed, including an evidence-based review of newer endovascular techniques. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. The relationship between ischemia-induced left ventricular dysfunction, coronary flow reserve, and coronary steal on regadenoson stress-gated 82Rb PET myocardial perfusion imaging

    Science.gov (United States)

    Van Tosh, Andrew; Votaw, John R.; Reichek, Nathaniel; Palestro, Christopher J.; Nichols, Kenneth J.

    2014-01-01

    values ≤1.0, consistent with coronary steal, in the LVD group than in the non-LVD group (39% vs 12%, P = .001). Conclusions LVD developed in 16% of patients undergoing 82Rb PET myocardial perfusion imaging, and was associated with multivessel coronary artery disease. There was a significant relationship between LVD and coronary blood flow during stress, with LVD corresponding to a low CFR. Territorial CFR ≤1.0 was more common in patients with LVD than those without, suggesting that coronary steal is an important pathophysiologic mechanism contributing to pharmacologic stress-induced LVD. PMID:24092270

  18. Myocardic extended ischemia after scombroid syndrome

    Directory of Open Access Journals (Sweden)

    Maria Serena Bassoni

    2006-08-01

    Full Text Available We describe a case of a healthy woman, presenting to the emergency department because of sudden onset of diffuse pruriginous erythema, profound arterial hypotension and anginal chest pain, just after consuing a meal with cooked fresh tuna fish. She developed progressive ECG signs of myocardial ischemia suggesting subendocardial infarction and increased serum level of troponin I. After vigourous fluid resuscitation with iv fluids and treatment with anti-hystamine drugs, corticosteroids, beta-blockers and calcium-channell blockers she progressively recovered. A clinical diagnosis of sgombroid syndrome was established: it is a syndrome which may follow the ingestion of some spoiled fish, characterized by urticara, headhache, gastrointestinal upset and rarely bronchospasm, shock, coronary ischemia and arrythmias. A sample of the consumed fish could be analysed, finding a very high level of hystamine concentration, conferming the diagnosis of sgombroid syndrome. A coronary angiography was performed and confermed the patient had a normal coronary tree, devoid of atherosclerotic lesions. Her anginal symptoms and ECG signs were probably due to functional ischemia determined by hystamine mediated vasoconstriction and hypotension. This not so rare but not well known syndrome is further discussed and addressed to the emergency physicians’ attention, because of its importance in the differential diagnoses of suspected food allergies

  19. 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

  20. Neonatal myocardial infarction: case report and review of the literature.

    Science.gov (United States)

    Farooqi, Kanwal M; Sutton, Nicole; Weinstein, Samuel; Menegus, Mark; Spindola-Franco, Hugo; Pass, Robert H

    2012-01-01

    Myocardial infarction in a neonate is rare. We describe the case of a full-term male who presented with respiratory distress. A chest radiograph demonstrated cardiomegaly. An electrocardiogram revealed ST segment changes suggestive of ischemia. Cardiac enzymes were elevated and an echocardiogram revealed a regional wall motion abnormality. Cardiac catheterization was performed demonstrating occlusion of the ramus intermedius branch of the left main coronary artery. The patient decompensated, requiring extracorporeal membrane oxygenation (ECMO). The infant was able to be decannulated from ECMO support in 5 days and was ultimately discharged on hospital day 25. We review this case as well as the literature on neonatal myocardial infarction. © 2012 Wiley Periodicals, Inc.

  1. Effect of verapamil on ischemia and ventricular arrhythmias after an acute myocardial infarction: prognostic implications. The Danish Verapamil Infarction Trial II Study Group

    DEFF Research Database (Denmark)

    Vaage-Nilsen, M; Rasmussen, Verner; Hansen, J F

    1991-01-01

    This article is a review of presented subsets of the Danish Verapamil Infarction Trial II (DAVIT II) regarding the effect of verapamil on postinfarction ischemia, ventricular arrhythmias, and heart rate (HR), and the prognostic implications of these findings. Patients underwent Holter monitoring......: In the placebo group the prevalence and incidence of many ventricular ectopic beats (VEBs), i.e., more than 10 VEBs/h, increased significantly during the first years after infarction; this was not the case in the verapamil patients group. The mean HR was significantly reduced by verapamil treatment after 1 month...

  2. NOGA-guided analysis of regional myocardial perfusion abnormalities treated with intramyocardial injections of plasmid encoding vascular endothelial growth factor A-165 in patients with chronic myocardial ischemia: subanalysis of the EUROINJECT-ONE multicenter double-blind randomized study

    DEFF Research Database (Denmark)

    Gyongyosi, Mariann; Khorsand, Aliasghar; Zamini, Sholeh

    2005-01-01

    BACKGROUND: The aim of this substudy of the EUROINJECT-ONE double-blind randomized trial was to analyze changes in myocardial perfusion in NOGA-defined regions with intramyocardial injections of plasmid encoding plasmid human (ph)VEGF-A(165) using an elaborated transformation algorithm. METHODS A...

  3. miR-28 promotes cardiac ischemia by targeting mitochondrial aldehyde dehydrogenase 2 (ALDH2) in mus musculus cardiac myocytes.

    Science.gov (United States)

    Li, S-P; Liu, B; Song, B; Wang, C-X; Zhou, Y-C

    2015-01-01

    Aldehyde dehydrogenase 2 (ALDH2) is a crucial enzyme involved in protecting the heart from ischemic. MicroRNAs (miRNAs) are involved in gene down-regulation. However, this mechanism is unclear. The aim of this study was to investigate the role of miR-28 in the regulation of ALDH2 and to explore the mechanism of miR-28 in musculus of myocardial ischemia. To evaluate the role of miR-28, we assessed cellular apoptosis. In addition, the regulation of ALDH2 by miR-199b was evaluated by Western blotting and luciferase assay. MiR-28 was up-regulated, while ALDH2 expression decreased in a time-dependent manner under normoxic conditions. The miR-28-transfected cells showed a significant decrease in the cellular apoptosis. Compared with the negative control 1 precursor molecules, miR-28 over-expression caused about 55% increase in myocardial apoptosis under hypoxic conditions, and miR-28 silencing by anti-miR-28 attenuated a 41% decreasing in apoptosis. MiR-28 and pGL3-ALDH2 vector-transfected cells showed that ALDH2 protein expression was suppressed and luciferase activity was reduced. These findings suggest that miR-28 promotes myocardial ischemia through the inhibition of ALDH2 expression in mus. miRNAs is as a probable index in identification of myocardial ischemia after acute myocardial infarction.

  4. Dipyridamole, cold pressor test, and demonstration of endothelial dysfunction: a PET study of myocardial perfusion in diabetes

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Meyer, Christian; Nielsen, Flemming S

    2003-01-01

    Much evidence suggests endothelial dysfunction to be present in non-insulin-dependent diabetes mellitus (NIDDM) and to be important for the development of myocardial ischemia. Endothelial function in the coronary vessels may be studied in various ways. We compared the effect of cold pressor testing...

  5. Evaluation of ischemia and myocardial viability in patients with coronary artery disease (CAD) with iodine-123-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP)

    Energy Technology Data Exchange (ETDEWEB)

    Kropp, J.; Joergens, M.; Glaenzer, K.P.; Luederitz, B.; Biersack, H.J. [Bonn Univ. (Germany); Knapp, F.F. Jr. [Oak Ridge National Lab., TN (United States)

    1993-10-01

    Twenty patients with coronary artery disease (CAD) controlled by coronary arteriography (CA) and biplane left ventricular cineventriculography (LVCV) were investigated with the 15- (p[I-123]iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) fatty acid analogue. During maximal symptom limited exercise 5 mCi (200 MBq) of BMIPP were injected followed by two SPECT studies within three hours. After another 30 min, with the patient at rest a third SPECT was performed after reinjection of 3 mCi (100 MBq) BMIPP. Visual inspection of the short and long axis slices and quantitative comparison of the short axis slices of the tomograms were performed to grade BMIPP uptake and refill and detect turnover abnormalities. These were addressed either as scar or as ischemia and compared to CA and a graded score of regional wall motion by LVCV which provided values for sensitivity (SE) and specificity (SP) to detect CAD. Fifteen infarctions had corresponded clinical, angiographic and scintigraphic findings in 93%.

  6. Intestinal Ischemia

    Science.gov (United States)

    ... weight loss Intestinal ischemia Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  7. Hepatic ischemia

    Science.gov (United States)

    ... MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Hepatic ischemia URL of this page: //medlineplus.gov/ency/ ...

  8. The myocardial ischemia evaluated by real-time contrast echocardiography may predict the response to cardiac resynchronization therapy: a large animal study.

    Directory of Open Access Journals (Sweden)

    Yongle Chen

    Full Text Available Evidence-based criteria for applying cardiac resynchronization therapy (CRT in patients with ischemic cardiomyopathy are still scarce. The aim of the present study was to evaluate the predictive value of real-time myocardial contrast echocardiography (RT-MCE in a preclinical canine model of ischemic cardiomyopathy who received CRT. Ischemic cardiomyopathy was produced by ligating the first diagonal branch in 20 beagles. Dogs were subsequently divided into two groups that were either treated with bi-ventricular pacing (CRT group or left untreated (control group. RT-MCE was performed at baseline, before CRT, and 4 weeks after CRT. Two-dimensional speckle tracking imaging was used to evaluate the standard deviation of circumferential (Cir12SD, radial (R12SD, and longitudinal (L12SD strains of left ventricular segments at basal as well as middle levels. Four weeks later, the Cir12SD, R12SD, and myocardial blood flow (MBF of the treated group were significantly improved compared to their non-CRT counterparts. Furthermore, MBF values measured before CRT were significantly higher in responders than in non-responders to bi-ventricular pacing. Meanwhile, no significant differences were observed between the responder and non-responder groups in terms of Cir12SD, R12SD, and L12SD. A high degree of correlation was found between MBF values before CRT and LVEF after CRT. When MBF value>24.9 dB/s was defined as a cut-off point before CRT, the sensitivity and specificity of RT-MCE in predicting the response to CRT were 83.3% and 100%, respectively. Besides, MBF values increased significantly in the CRT group compared with the control group after 4 weeks of pacing (49.8±15.5 dB/s vs. 28.5±4.6 dB/s, p<0.05. Therefore, we considered that myocardial perfusion may be superior to standard metrics of LV synchrony in selecting appropriate candidates for CRT. In addition, CRT can improve myocardial perfusion in addition to cardiac synchrony, especially in the setting

  9. Cardiac magnetic resonance myocardial perfusion reserve index is reduced in women with coronary microvascular dysfunction. A National Heart, Lung, and Blood Institute-sponsored study from the Women's Ischemia Syndrome Evaluation.

    Science.gov (United States)

    Thomson, Louise E J; Wei, Janet; Agarwal, Megha; Haft-Baradaran, Afsaneh; Shufelt, Chrisandra; Mehta, Puja K; Gill, Edward B; Johnson, B Delia; Kenkre, Tanya; Handberg, Eileen M; Li, Debiao; Sharif, Behzad; Berman, Daniel S; Petersen, John W; Pepine, Carl J; Bairey Merz, C Noel

    2015-04-01

    Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD), diagnosed by invasive coronary reactivity testing (CRT). Although traditional noninvasive stress imaging is often normal in CMD, cardiac MRI may be able to detect CMD in this population. Vasodilator stress cardiac MRI was performed in 118 women with suspected CMD who had undergone CRT and 21 asymptomatic reference subjects. Semi-quantitative evaluation of the first-pass perfusion images was completed to determine myocardial perfusion reserve index (MPRI). The relationship between CRT findings and MPRI was examined by Pearson correlations, logistic regression, and sensitivity/specificity. Symptomatic women had lower mean pharmacological stress MPRI compared with reference subjects (1.71±0.43 versus 2.23±0.37; P<0.0001). Lower MPRI was predictive of ≥1 abnormal CRT variables (odds ratio =0.78 [0.70, 0.88], P<0.0001, c-statistic 0.78 [0.68, 0.88]). An MPRI threshold of 1.84 predicted CRT abnormality with sensitivity 73% and specificity 74%. Noninvasive cardiac MRI MPRI can detect CMD defined by invasive CRT. Further work is aimed to optimize the noninvasive identification and management of CMD patients. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00832702. © 2015 American Heart Association, Inc.

  10. Metabolomics Study of Resina Draconis on Myocardial Ischemia Rats Using Ultraperformance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry Combined with Pattern Recognition Methods and Metabolic Pathway Analysis.

    Science.gov (United States)

    Qi, Yunpeng; Gu, Haiwei; Song, Yunlong; Dong, Xin; Liu, Aijun; Lou, Ziyang; Fan, Guorong; Chai, Yifeng

    2013-01-01

    Resina draconis (bright red resin isolated from Dracaena cochinchinensis, RD) has been clinically used for treatment of myocardial ischemia (MI) for many years. However, the mechanisms of its pharmacological action on MI are still poorly understood. This study aimed to characterize the plasma metabolic profiles of MI and investigate the mechanisms of RD on MI using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics combined with pattern recognition methods and metabolic pathway analysis. Twenty metabolite markers characterizing metabolic profile of MI were revealed, which were mainly involved in aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, vascular smooth muscle contraction, sphingolipid metabolism, and so forth. After RD treatment, however, levels of seven MI metabolite markers, including phytosphingosine, sphinganine, acetylcarnitine, cGMP, cAMP, L-tyrosine, and L-valine, were turned over, indicating that RD is likely to alleviate MI through regulating the disturbed vascular smooth muscle contraction, sphingolipid metabolism, phenylalanine metabolism, and BCAA metabolism. To our best knowledge, this is the first comprehensive study to investigate the mechanisms of RD for treating MI, from a metabolomics point of view. Our findings are very valuable to gain a better understanding of MI metabolic profiles and provide novel insights for exploring the mechanisms of RD on MI.

  11. Metabolomics Study of Resina Draconis on Myocardial Ischemia Rats Using Ultraperformance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry Combined with Pattern Recognition Methods and Metabolic Pathway Analysis

    Directory of Open Access Journals (Sweden)

    Yunpeng Qi

    2013-01-01

    Full Text Available Resina draconis (bright red resin isolated from Dracaena cochinchinensis, RD has been clinically used for treatment of myocardial ischemia (MI for many years. However, the mechanisms of its pharmacological action on MI are still poorly understood. This study aimed to characterize the plasma metabolic profiles of MI and investigate the mechanisms of RD on MI using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics combined with pattern recognition methods and metabolic pathway analysis. Twenty metabolite markers characterizing metabolic profile of MI were revealed, which were mainly involved in aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, vascular smooth muscle contraction, sphingolipid metabolism, and so forth. After RD treatment, however, levels of seven MI metabolite markers, including phytosphingosine, sphinganine, acetylcarnitine, cGMP, cAMP, L-tyrosine, and L-valine, were turned over, indicating that RD is likely to alleviate MI through regulating the disturbed vascular smooth muscle contraction, sphingolipid metabolism, phenylalanine metabolism, and BCAA metabolism. To our best knowledge, this is the first comprehensive study to investigate the mechanisms of RD for treating MI, from a metabolomics point of view. Our findings are very valuable to gain a better understanding of MI metabolic profiles and provide novel insights for exploring the mechanisms of RD on MI.

  12. Mesenteric Ischemia

    OpenAIRE

    Toohey, Shannon

    2016-01-01

    Mesenteric ischemia is classified as either acute or chronic. The former is a life-threatening emergency in which a sudden reduction in intestinal blood flow may ultimately result in bowel infarction. The most common causes are arterial embolism, arterial thrombosis, nonocclusive mesenteric ischemia, and mesenteric venous thrombosis. A high index of suspicion, early diagnosis and rapid intervention are necessary so that normal mesenteric perfusion is restored before fatal bowel infarction can...

  13. Brachial artery constriction during brachial artery reactivity testing predicts major adverse clinical outcomes in women with suspected myocardial ischemia: results from the NHLBI-sponsored women's ischemia Syndrome Evaluation (WISE Study.

    Directory of Open Access Journals (Sweden)

    Tara L Sedlak

    Full Text Available Limited brachial artery (BA flow-mediated dilation during brachial artery reactivity testing (BART has been linked to increased cardiovascular risk. We report on the phenomenon of BA constriction (BAC following hyperemia.To determine whether BAC predicts adverse CV outcomes and/or mortality in the women's ischemic Syndrome Evaluation Study (WISE. Further, as a secondary objective we sought to determine the risk factors associated with BAC.We performed BART on 377 women with chest pain referred for coronary angiography and followed for a median of 9.5 years. Forearm ischemia was induced with 4 minutes occlusion by a cuff placed distal to the BA and inflated to 40mm Hg > systolic pressure. BAC was defined as >4.8% artery constriction following release of the cuff. The main outcome was major adverse events (MACE including all-cause mortality, non-fatal MI, non-fatal stroke, or hospitalization for heart failure.BA diameter change ranged from -20.6% to +44.9%, and 41 (11% women experienced BAC. Obstructive CAD and traditional CAD risk factors were not predictive of BAC. Overall, 39% of women with BAC experienced MACE vs. 22% without BAC (p=0.004. In multivariate Cox proportional hazards regression, BAC was a significant independent predictor of MACE (p=0.018 when adjusting for obstructive CAD and traditional risk factors.BAC predicts almost double the risk for major adverse events compared to patients without BAC. This risk was not accounted for by CAD or traditional risk factors. The novel risk marker of BAC requires further investigation in women.

  14. The protective effects of polyphenols from jujube peel (Ziziphus Jujube Mill) on isoproterenol-induced myocardial ischemia and aluminum-induced oxidative damage in rats.

    Science.gov (United States)

    Cheng, Dai; Zhu, Chunqiu; Cao, Jiankang; Jiang, Weibo

    2012-05-01

    This study was aimed to evaluate the preventive effect of the polyphenols from Chinese jujube peel (Ziziphus jujube Mill. cv. Dongzao) against myocardial injury (MI) induced by isoproterenol (ISO) and biotoxicity of aluminum in rats. The free phenols from jujube peel (JPFP) and the bond phenols from jujube peel (JPBP) were administered to rats by gastric gavage. The results showed that prior administration of JPFP or JPBP remarkably inhibited increases in levels of malondialdehyde (MDA) and activities of Ca(2+)-ATPase and Mg(2+)-ATPase, reductions in activities of superoxide dismutase (SOD), glutathione peroxidase, creatine kinase, lactate dehydrogenase and Na(+)/K(+)-ATPase in the rats induced by ISO. The abnormal changes in morphology of heart muscle and in electrocardiograph induced by ISO treatment were also significantly prevented by the JPFP or JPBP. Treatment with aluminum chloride could cause a significant oxidative damage, including a significant increase in MDA level and decreases in glutathione-S- transferase and SOD activities in brain of the rats, the study showed that gavage with JPFP or JPBP could remarkably alleviate the toxic responses of the rats to aluminum chloride. In summary, our study showed that jujube phenolics can prevent ISO-induced myocardial injury and reduce aluminum toxicity in rats. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Radiological Evaluation of Bowel Ischemia

    Science.gov (United States)

    Dhatt, Harpreet S.; Behr, Spencer C; Miracle, Aaron; Wang, Zhen Jane; Yeh, Benjamin M.

    2015-01-01

    Intestinal ischemia, which refers to insufficient blood flow to the bowel, is a potentially catastrophic entity that may require emergent intervention or surgery in the acute setting. Although the clinical signs and symptoms of intestinal ischemia are nonspecific, CT findings can be highly suggestive in the correct clinical setting. In this chapter we review the CT diagnosis of arterial, venous, and non-occlusive intestinal ischemia. We discuss the vascular anatomy, pathophysiology of intestinal ischemia, CT techniques for optimal imaging, key and ancillary radiological findings, and differential diagnosis. In the setting of an acute abdomen, rapid evaluation is necessary to identify intraabdominal processes that require emergent surgical intervention (1). While a wide-range of intraabdominal diseases may be present from trauma to inflammation, one of the most feared disorders is mesenteric ischemia, also known as intestinal ischemia, which refers to insufficient blood flow to the bowel (2). Initial imaging evaluation for intestinal ischemia is typically obtained with CT. Close attention to technique and search for key radiologic features with relation to the CT technique is required. Accurate diagnosis depends on understanding the vascular anatomy, epidemiology, and pathophysiology of various forms of mesenteric ischemia and their corresponding radiological findings on MDCT. At imaging, not only is inspection of the bowel itself important, but evaluation of the mesenteric fat, vasculature, and surrounding peritoneal cavity also helps improves accuracy in the diagnosis of bowel ischemia. PMID:26526436

  16. Imaging myocardial metabolism and ischemic memory.

    Science.gov (United States)

    Taegtmeyer, Heinrich; Dilsizian, Vasken

    2008-08-01

    The advent of myocardial metabolic imaging more than 30 years ago ushered in a paradigm shift in the clinical management of patients with ischemic and nonischemic heart disease. A classic example is the so-called metabolic memory of altered glucose and fatty acid metabolism in regions of myocardial ischemia and reperfusion. At the cellular level, metabolic memory is driven by changes in the activities and expression of a host of metabolic enzymes, including reactivation of the fetal gene program. The future of metabolic imaging will require a more-refined understanding of the pathways of metabolic adaptation and maladaptation of the heart. Recent evidence suggests that metabolic signals alter metabolic fluxes and give rise to specific metabolic patterns that, in turn, lead to changes in translational and/or transcriptional activities in the cardiac myocyte. In other words, metabolism provides a link between environmental stimuli and a host of intracellular signaling pathways. This concept has not yet been fully explored in vivo, although metabolic adaptation represents the earliest response to myocardial ischemia and left ventricular remodeling.

  17. Acute myocardial infarction during regadenoson myocardial perfusion imaging.

    Science.gov (United States)

    Shah, Sachil; Parra, David; Rosenstein, Robert S

    2013-06-01

    Pharmacologic stress testing uses vasodilators to provide objective evidence of myocardial ischemia. Adenosine and dipyridamole are nonselective adenosine receptor agonists that have been associated with myocardial infarction (MI) during intravenous infusion. Mechanisms postulated for this effect include coronary steal, transmural steal, global hypotension, and direct vasoconstriction. Regadenoson, a direct A2A agonist, was approved for use in stress testing in 2008. We describe a 68-year-old man who presented to our institution with typical angina, relieved by nitroglycerin. He did not have electrocardiogram (ECG) changes suggestive of myocardial pathology, and laboratory testing did not reveal a significant rise in troponin-I levels. To further assess the etiology of his symptoms, he underwent a pharmacologic stress test with regadenoson followed by technetium 99 m sestamibi. Six minutes after regadenoson infusion, the patient developed severe retrosternal chest pain accompanied by ST elevations on ECG. Sublingual nitroglycerin was administered that resolved both the pain and ECG changes. The patient subsequently underwent urgent coronary angiography and was found to have a 95% critical stenosis involving the left anterior descending artery. We conclude this case represents a MI secondary to coronary steal phenomenon induced by regadenoson infusion. Clinicians should be aware this adverse effect can occur despite the improved side-effect profile of regadenoson. Continuous monitoring of vital signs and the ECG with regular assessment of symptoms is imperative to identify this rare but potentially devastating adverse event. © 2013 Pharmacotherapy Publications, Inc.

  18. [Prognostic significance of post-infarction "silent" ischemia].

    Science.gov (United States)

    Chikavashvili, D I; Blokhin, A B; Rado, Iu; Iliasov, A A; Ruda, M Ia

    1991-06-01

    To study the predictive value of silent ischemia, a total of 132 patients with first transmural myocardial infarction were examined, 69 had anterior and 63 had inferior myocardial infarction. On days 8-12 of onset of the disease, all the patients underwent loading two-dimensional echocardiography along with transesophageal pacing, as well as polyposition coronary angiography. According to the echocardiographic findings, 3 groups of patients were identified: 1) 34 (25.8%) with painful ischemia; 2) 37 (28.0%) with silent ischemia; 3) 61 (46.2%) with a negative test. Ischemic alterations were more frequently seen in inferior (73%) than in anterior (36.2%) myocardial infarction. The patients with painful ischemia showed a lower threshold of ischemia occurrence, more severe and prolonged ST segment depression, and greater extent of an asynergic area than did the patients with silent ischemia. A 1-5-year (mean 2.4) follow-up revealed that in terms of the risk for postinfarction angina, recurrent myocardial infarction and fatal outcomes, patients with silent ischemia represent an intermediate group between those with painful ischemia and those who have a negative load test.

  19. Efficacy of 15-(123I)-p-iodophenyl pentadecanoic acid (IPPA) in assessing myocardial metabolism in a model of reversible global ischemia.

    Science.gov (United States)

    Hudon, M P; Lyster, D M; Jamieson, E W; Qayumi, K A; Kiess, M C; Rosado, L J; Autor, A P; Sartori, C; Dougan, H; van den Broek, J

    1988-01-01

    In a canine model of reversible global ischemia, the residual quantity of 123I was assessed following a bolus injection of 15-p-(123I)-iodophenyl pentadecanoic acid (123I-IPPA). This technique was used to assess changes in free fatty acid metabolism following the utilization of three cardioplegic formulations. Cardioplegic arrest was initiated with Tyers' iso-osmolar (IO) solution (Group A); IO + superoxide dismutase (SOD) (Group B) and IO + allopurinol (Group C). Pre and post operative scanning were completed with 2-5 mCi 123I-IPPA. Clearance was assessed by IPPA time activity curve analysis generating t1/2 (half lives in min) for the early and late phases of the curve. The assessment between groups demonstrated that the elimination of 123I-IPPA products (early phase) was faster from the lateral wall in groups B and C versus group A (14 +/- 12 min, 13 +/- 9 min and 24 +/- 10 min, respectively). The elimination of IPPA (late phase) was also faster from the lateral wall in groups B and C when compared to group A (240 +/- 270 min, 132 +/- 85 min and 416 +/- 238 min). Examining the changes between control and postoperative values for each area of the left ventricle within each group demonstrated no significant changes for groups B and C. Group A, however, demonstrated significantly increased t1/2 values for the lateral wall (early and late phases) and the apical wall (late phase).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Evaluation of ischemia and myocardial viability in patients with coronary artery disease (CAD) with iodine-123 labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP)

    Energy Technology Data Exchange (ETDEWEB)

    Kropp, Joachim; Joergens, Matthias; Glaenzer, K.P.; Luederitz, Berndt; Biersack, H.J. [Bonn Univ. (Germany); Knapp, F.F. Jr.

    1993-12-01

    Twenty patients with coronary artery disease (CAD) controlled by coronary arteriography (CA) and biplane left ventricular cineventriculography (LVCV) were investigated with the 15-(p-[I-123]iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) fatty acid analogue. During maximal symptom limited exercise 5 mCi (200 MBq) of BMIPP were injected followed by two SPECT studies within three hours. After another 30 min, with the patient at rest a third SPECT was performed after reinjection of 3 mCi (100 MBq) BMIPP. Visual inspection of the short and long axis slices and quantitative comparison of the short axis slices of the tomograms were performed to grade BMIPP uptake and refill and detect turnover abnormalities. There were addressed either as scar or as ischemia and compared to CA and a graded score of regional wall motion by LVCV which provided values for sensitivity (SE) and specificity (SP) to detect CAD. By visual inspection, SE and SP values were 71% and 94%, respectively. SE could be improved by quantification to 86%. Fifteen infarctions had correspondent clinical, angiographic and scintigraphic findings in 93%. Our results of this study demonstrate that BMIPP scintigraphy is able to diagnose CAD and viability of the myocardium with great reliability. Furthermore, BMIPP seems to have advantages compared to the straight chain IPPA analogue because of its longer retention. (author).

  1. Evaluation of myocardial abnormalities in collagen diseases by thallium-201 myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yamano, Shigeru; Kagoshima, Tadashi; Sugihara, Kiyotaka (Nara Medical Univ., Kashihara (Japan)) (and others)

    1993-12-01

    This study was performed to evaluate myocardial abnormalities in patients with collagen diseases by exercise and rest thallium-201 myocardial scintigrams. A total of 65 patients without ischemic ECG changes, consisting of 18 with systemic lupus erythematosus (SLE), 18 with polymyositis (PM), 8 with progressive systemic sclerosis (PSS), and 21 with Sjoegren's syndrome (SjS), was enrolled in this study. Reversible exercise-induced defects scintigraphically suggesting myocardial ischemia were noted in 8 cases of SLE, 4 cases of PM, 4 cases of PSS, and 3 cases of SjS. Nineteen patients had exercise-induced defects and underwent cardiac catheterization, 8 of whom had normal coronary angiograms. Fixed hypoperfusion areas were observed in one case of SLE, 6 cases of PM and 3 cases of SjS. Rest thallium-201 myocardial scintigram disclosed hypoperfusion areas which were not induced by exercise in 2 cases of SLE, 3 cases of PM, one case of PSS and 5 cases of SjS. Echocardiogram showed no significant differences in ejection fraction and % fractional shortening between the disease groups and healthy control group. These findings suggest that patients with collagen diseases have abnormalities of coronary circulation at the level of the intramural vasculature before cardiac function impairment, myocardial fibrosis and functional abnormalities at the cell membrane. (author).

  2. Liraglutide-induced reduction of myocardial ischemiareperfusion ...

    African Journals Online (AJOL)

    Purpose: To investigate the protective effect of liraglutide on myocardial ischemia reperfusion (I/R) injury and its molecular mechanism. Methods: Ischemia reperfusion model male Sprague-Dawley (SD) rats were randomly divided into negative control group, I/R group (saline), liraglutide group (liraglutide) and PD group ...

  3. Pharmacologic myocardial preconditioning with monophosphoryl lipid A (MLA) reduces infarct size and stunning in dogs and rabbits.

    Science.gov (United States)

    Elliott, G T

    1996-09-30

    As the mechanism of ischemic preconditioning unfolds, various strategies for inducing pharmacologic preconditioning become apparent. Adenosine receptor agonists, KATP channel activators, and endothelial-neutrophil adhesion antagonists have enjoyed cardioprotective activity against ischemia/reperfusion injury in at least some preclinical models. Monophosphoryl lipid A (MLA), a structural derivative of the pharmacophore of endotoxin, enjoys an improved therapeutic index in relation to the parent biological product. MLA has found clinical application as a vaccine adjuvant and protects from sepsis and septic shock in the preclinical setting. In animal models of myocardial ischemia/reperfusion injury, pretreatment 12-24 hours prior to ischemia with a single IV bolus injection of MLA limits infarct size 50 to 75 percent in standard canine and rabbit models at doses of 10-35 micrograms/kg. Regional myocardial stunning following multiple 5-minute ischemic episodes as assessed by segment shortening is reduced in dogs pretreated 24 but not 1 hour prior to ischemia. Global cardiac function, as evaluated by pressure-volume constructs generated in dogs being weaned from cardiopulmonary bypass, recovers more quickly in animals pretreated with MLA. Cardiac protection in various models is associated with preservation of ATP during ischemia, induction of 5' nucleotidase and enhancement of calcium reuptake by SR during reperfusion. Limitation of infarct size by MLA in dogs and rabbits can be reversed by the administration of glibenclamide just prior to ischemia, suggesting a role for KATP channel opening during the first minutes of sustained ischemia. A clinical formulation of MLA (MPL-C) is currently undergoing clinical investigation in the Phase II setting in coronary artery bypass surgical patients. MLA may represent a novel means of inducing pharmacologic preconditioning, with potential for clinical application as a pretreatment before planned myocardial ischemia.

  4. Myocardial protection conferred by electromagnetic fields.

    Science.gov (United States)

    DiCarlo, A L; Farrell, J M; Litovitz, T A

    1999-02-16

    It has been reported that electromagnetic (EM) fields induce stress proteins in vitro. These proteins have been shown to be important in recovery from ischemia/reperfusion. It was, therefore, hypothesized that EM fields could activate stress responses in vivo and protect myocardial tissue during anoxia. Chick embryos were exposed to 4-, 6-, 8-, and 10- microT and 60-Hz EM fields for 20 minutes followed by a 1-hour rest period before placement in an anoxic chamber. Embryos were reoxygenated when survival of controls dropped to 500 EM field-exposed embryos) indicated that EM field protection was extremely significant (Pmyocardium from anoxia damage. These results suggest that EM field exposures may be a useful, noninvasive means of minimizing myocardial damage during surgery, transplantation, or heart attack in humans.

  5. Nanoparticle-Mediated Delivery of Mitochondrial Division Inhibitor 1 to the Myocardium Protects the Heart From Ischemia-Reperfusion Injury Through Inhibition of Mitochondria Outer Membrane Permeabilization: A New Therapeutic Modality for Acute Myocardial Infarction.

    Science.gov (United States)

    Ishikita, Ayako; Matoba, Tetsuya; Ikeda, Gentaro; Koga, Jun-Ichiro; Mao, Yajing; Nakano, Kaku; Takeuchi, Osamu; Sadoshima, Junichi; Egashira, Kensuke

    2016-07-22

    Mitochondria-mediated cell death plays a critical role in myocardial ischemia-reperfusion (IR) injury. We hypothesized that nanoparticle-mediated drug delivery of mitochondrial division inhibitor 1 (Mdivi1) protects hearts from IR injury through inhibition of mitochondria outer membrane permeabilization (MOMP), which causes mitochondrial-mediated cell death. We formulated poly (lactic-co-glycolic acid) nanoparticles containing Mdivi1 (Mdivi1-NP). We recently demonstrated that these nanoparticles could be successfully delivered to the cytosol and mitochondria of cardiomyocytes under H2O2-induced oxidative stress that mimicked IR injury. Pretreatment with Mdivi1-NP ameliorated H2O2-induced cell death in rat neonatal cardiomyocytes more potently than Mdivi1 alone, as indicated by a lower estimated half-maximal effective concentration and greater maximal effect on cell survival. Mdivi1-NP treatment of Langendorff-perfused mouse hearts through the coronary arteries at the time of reperfusion reduced infarct size after IR injury more effectively than Mdivi1 alone. Mdivi1-NP treatment also inhibited Drp1-mediated Bax translocation to the mitochondria and subsequent cytochrome c leakage into the cytosol, namely, MOMP, in mouse IR hearts. MOMP inhibition was also observed in cyclophilin D knockout (CypD-KO) mice, which lack the mitochondrial permeability transition pore (MPTP) opening. Intravenous Mdivi1-NP treatment in vivo at the time of reperfusion reduced IR injury in wild-type and CypD-KO mice, but not Bax-KO mice. Mdivi1-NP treatment reduced IR injury through inhibition of MOMP, even in the absence of a CypD/MPTP opening. Thus, nanoparticle-mediated drug delivery of Mdivi1 may be a novel treatment strategy for IR injury. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  6. Epidemiology and genetics of ventricular fibrillation during acute myocardial infarction

    DEFF Research Database (Denmark)

    Glinge, Charlotte; Sattler, Stefan; Jabbari, Reza

    2016-01-01

    of a family member is a risk factor for SCD and VF during acute myocardial infarction (MI), independent of traditional risk factors including family history of MI, suggesting a genetic component in the susceptibility to VF. To prevent SCD and VF due to MI, we need a better understanding of the genetic...... infarction, myocardial ischemia", "coronary artery disease", and "genetics". This review describes the epidemiology and evidence for genetic susceptibility to VF due to MI....... several genetic variants, both common and rare variants, have been associated to either VF or SCD. For this review, we searched PubMed for potentially relevant articles, using the following MeSH-terms: "sudden cardiac death", "ventricular fibrillation", "out-of-hospital cardiac arrest", "myocardial...

  7. NOGA-guided analysis of regional myocardial perfusion abnormalities treated with intramyocardial injections of plasmid encoding vascular endothelial growth factor A-165 in patients with chronic myocardial ischemia: subanalysis of the EUROINJECT-ONE multicenter double-blind randomized study.

    Science.gov (United States)

    Gyöngyösi, Mariann; Khorsand, Aliasghar; Zamini, Sholeh; Sperker, Wolfgang; Strehblow, Christoph; Kastrup, Jens; Jorgensen, Eric; Hesse, Birger; Tägil, Kristina; Bøtker, Hans Erik; Ruzyllo, Witold; Teresiñska, Anna; Dudek, Dariusz; Hubalewska, Alicja; Rück, Andreas; Nielsen, Søren Steen; Graf, Senta; Mundigler, Gerald; Novak, Jacek; Sochor, Heinz; Maurer, Gerald; Glogar, Dietmar; Sylven, Christer

    2005-08-30

    The aim of this substudy of the EUROINJECT-ONE double-blind randomized trial was to analyze changes in myocardial perfusion in NOGA-defined regions with intramyocardial injections of plasmid encoding plasmid human (ph)VEGF-A(165) using an elaborated transformation algorithm. After randomization, 80 no-option patients received either active, phVEGF-A165 (n=40), or placebo plasmid (n=40) percutaneously via NOGA-Myostar injections. The injected area (region of interest, ROI) was delineated as a best polygon by connecting of the injection points marked on NOGA polar maps. The ROI was projected onto the baseline and follow-up rest and stress polar maps of the 99m-Tc-sestamibi/tetrofosmin single-photon emission computed tomography scintigraphy calculating the extent and severity (expressed as the mean normalized tracer uptake) of the ROI automatically. The extents of the ROI were similar in the VEGF and placebo groups (19.4+/-4.2% versus 21.5+/-5.4% of entire myocardium). No differences were found between VEGF and placebo groups at baseline with regard to the perfusion defect severity (rest: 69+/-11.7% versus 68.7+/-13.3%; stress: 63+/-13.3% versus 62.6+/-13.6%; and reversibility: 6.0+/-7.7% versus 6.7+/-9.0%). At follow-up, a trend toward improvement in perfusion defect severity at stress was observed in VEGF group as compared with placebo (68.5+/-11.9% versus 62.5+/-13.5%, P=0.072) without reaching normal values. The reversibility of the ROI decreased significantly at follow-up in VEGF group as compared with the placebo group (1.2+/-9.0% versus 7.1+/-9.0%, P=0.016). Twenty-one patients in VEGF and 8 patients in placebo group (Por =5% increase in the normalized tracer uptake of the ROI. Projection of the NOGA-guided injection area onto the single-photon emission computed tomography polar maps permits quantitative evaluation of myocardial perfusion in regions treated with angiogenic substances. Injections of phVEGF A165 plasmid improve, but do not normalize, the stress

  8. Acute CD47 Blockade During Ischemic Myocardial Reperfusion Enhances Phagocytosis-Associated Cardiac Repair

    Directory of Open Access Journals (Sweden)

    Shuang Zhang, BS

    2017-08-01

    Full Text Available Our data suggest that, after a myocardial infarction, integrin-associated protein CD47 on cardiac myocytes is elevated. In culture, increased CD47 on the surface of dying cardiomyocytes impairs phagocytic removal by immune cell macrophages. After myocardial ischemia and reperfusion, acute CD47 inhibition with blocking antibodies enhanced dead myocyte clearance by cardiac phagocytes and also improved the resolution of cardiac inflammation, reduced infarct size, and preserved cardiac contractile function. Early targeting of CD47 in the myocardium after reperfusion may be a new strategy to enhance wound repair in the ischemic heart.

  9. Relationship of oxidized phospholipids and biomarkers of oxidized low-density lipoprotein with cardiovascular risk factors, inflammatory biomarkers, and effect of statin therapy in patients with acute coronary syndromes: Results from the MIRACL (Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering) trial.

    Science.gov (United States)

    Fraley, Alexander E; Schwartz, Gregory G; Olsson, Anders G; Kinlay, Scott; Szarek, Michael; Rifai, Nader; Libby, Peter; Ganz, Peter; Witztum, Joseph L; Tsimikas, Sotirios

    2009-06-09

    This study sought to define the relationship between oxidative biomarkers, cardiovascular disease (CVD) risk factors, and inflammatory and thrombosis biomarkers. Elevated levels of oxidized phospholipids (OxPL) on apolipoprotein B particles (apoB) represent a novel biomarker of CVD. Previous studies suggest that an increase in OxPL/apoB reflects a positive response to statins and a low-fat diet. This study measured OxPL/apoB, lipoprotein (a) [Lp(a)], and oxidized low-density lipoprotein (OxLDL) biomarkers, consisting of immunoglobulin (Ig)G and IgM autoantibodies to malondialdehyde (MDA)-low-density lipoprotein (LDL) and IgG and IgM apoB-100 immune complexes (IC/apoB), at baseline and after 16 weeks of treatment with atorvastatin 80 mg/day or placebo in 2,342 patients with acute coronary syndromes (ACS) enrolled in the MIRACL (Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering) trial. At baseline, potentially atheroprotective IgM autoantibodies and IgM IC/apoB were lower in male patients, diabetic patients, and patients >65 years of age. Patients with an LDL level greater than the median (122 mg/dl) had higher levels of OxPL/apoB, Lp(a), and OxLDL biomarkers compared with those who had an LDL level less than the median. Atorvastatin resulted in significantly larger changes in all biomarkers in female patients, patients age LDL cholesterol risk factors and were largely independent of inflammatory biomarkers. Atorvastatin uniformly increased OxPL/apoB levels in all subgroups studied. Future studies are warranted to assess whether the increase in OxPL/apoB levels reflects the benefit of effective therapeutic interventions and prediction of new CVD events.

  10. Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents

    Directory of Open Access Journals (Sweden)

    Bryce A. Small

    2015-01-01

    Full Text Available Opioids reduce injury from myocardial ischemia-reperfusion in humans. In experimental models, this mechanism involves GSK3β inhibition. HSP90 regulates mitochondrial protein import, with GSK3β inhibition increasing HSP90 mitochondrial content. Therefore, we determined whether morphine-induced cardioprotection is mediated by HSP90 and if the protective effect is downstream of GSK3β inhibition. Male Sprague-Dawley rats, aged 8–10 weeks, were subjected to an in vivo myocardial ischemia-reperfusion injury protocol involving 30 minutes of ischemia followed by 2 hours of reperfusion. Hemodynamics were continually monitored and myocardial infarct size determined. Rats received morphine (0.3 mg/kg, the GSK3β inhibitor, SB216763 (0.6 mg/kg, or saline, 10 minutes prior to ischemia. Some rats received selective HSP90 inhibitors, radicicol (0.3 mg/kg, or deoxyspergualin (DSG, 0.6 mg/kg alone or 5 minutes prior to morphine or SB216763. Morphine reduced myocardial infarct size when compared to control (42 ± 2% versus 60 ± 1%. This protection was abolished by prior treatment of radicicol or DSG (59 ± 1%, 56 ± 2%. GSK3β inhibition also reduced myocardial infarct size (41 ± 2% with HSP90 inhibition by radicicol or DSG partially inhibiting SB216763-induced infarct size reduction (54 ± 3%, 47 ± 1%, resp.. These data suggest that opioid-induced cardioprotection is mediated by HSP90. Part of this protection afforded by HSP90 is downstream of GSK3β, potentially via the HSP-TOM mitochondrial import pathway.

  11. Improved myocardial perfusion after transmyocardial laser revascularization in a patient with microvascular coronary artery disease

    Directory of Open Access Journals (Sweden)

    Peyman Mesbah Oskui

    2014-03-01

    Full Text Available We report the case of a 59-year-old woman who presented with symptoms of angina that was refractory to medical management. Although her cardiac catheterization revealed microvascular coronary artery disease, her symptoms were refractory to optimal medical management that included ranolazine. After undergoing transmyocardial revascularization, her myocardial ischemia completely resolved and her symptoms dramatically improved. This case suggests that combination of ranolazine and transmyocardial revascularization can be applied to patients with microvascular coronary artery disease.

  12. Simulated urban carbon monoxide air pollution exacerbates rat heart ischemia-reperfusion injury.

    Science.gov (United States)

    Meyer, G; André, L; Tanguy, S; Boissiere, J; Farah, C; Lopez-Lauri, F; Gayrard, S; Richard, S; Boucher, F; Cazorla, O; Obert, P; Reboul, C

    2010-05-01

    Myocardial damages due to ischemia-reperfusion (I/R) are recognized to be the result of a complex interplay between genetic and environmental factors. Epidemiological studies suggested that, among environmental factors, carbon monoxide (CO) urban pollution can be linked to cardiac diseases and mortality. The aim of this work was to evaluate the impact of exposure to CO pollution on cardiac sensitivity to I/R. Regional myocardial I/R was performed on isolated perfused hearts from rats exposed for 4 wk to air enriched with CO (30-100 ppm). Functional variables, reperfusion ventricular arrhythmias (VA) and cellular damages (infarct size, lactate dehydrogenase release) were assessed. Sarcomere length shortening and Ca(2+) handling were evaluated in intact isolated cardiomyocytes during a cellular anoxia-reoxygenation protocol. The major results show that prolonged CO exposure worsens myocardial I/R injuries, resulting in increased severity of postischemic VA, impaired recovery of myocardial function, and increased infarct size (60 +/- 5 vs. 33 +/- 2% of ischemic zone). The aggravating effects of CO exposure on I/R could be explained by a reduced myocardial enzymatic antioxidant status (superoxide dismutase -45%; glutathione peroxidase -49%) associated with impaired intracellular Ca(2+) handling. In conclusion, our results are consistent with the idea that chronic CO pollution dramatically increases the severity of myocardial I/R injuries.

  13. Myocardial imaging. Coxsackie myocarditis

    Energy Technology Data Exchange (ETDEWEB)

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-09-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

  14. Qual o erro da angiografia na definição de isquemia miocárdica durante intervenções coronarianas percutâneas? What is the angiography error when defining myocardial ischemia during percutaneous coronary interventions?

    Directory of Open Access Journals (Sweden)

    Fernando Mendes Sant'Anna

    2008-09-01

    Full Text Available FUNDAMENTO: A angiografia vem sendo utilizada como padrão de referência para definição de doença arterial coronariana (DAC, embora suas limitações sejam conhecidas. O valor da medida do fluxo fracionado de reserva do miocárdio (FFR na avaliação da DAC está bem estabelecido. OBJETIVO: O objetivo deste estudo é avaliar a acurácia da angiografia em definir as lesões isquêmicas e sua correlação com o FFR. MÉTODOS: Duzentos e cinqüenta pacientes foram incluídos no estudo (471 vasos. Todas as estenoses > 50% pela estimativa visual da angiografia (EVA foram avaliadas medindo-se o FFR. Se o FFR 0,75 a lesão não foi tratada. As lesões foram divididas em moderadas (BACKGROUND: The angiography has been used as a reference standard to define coronary artery disease (CAD, although its limitations are well-known. The significance of the myocardial fractional flow reserve (FFR in the assessment of CAD is well established. OBJECTIVE: The aim of this study was to evaluate the accuracy of angiography when defining ischemic lesions and its correlation with FFR. METHODS: Two hundred and fifty consecutive patients (471 arteries were included in this study. All stenoses > 50% at the angiography visual estimate (AVE were assessed by FFR measurements. When FFR was 0.75, no interventional treatment was carried out. Offline quantitative coronary angiography (QCA was performed in all stenoses, which were divided in intermediate (< 70% - 327 and severe (125. The correlation coefficients between the diameter of the stenosis (%DS and FFR and the accuracy of VA of the angiography when assessing ischemia were determined. RESULTS: FFR could be obtained in 452 lesions (96%. Mean %DS and FFR were 56 ± 8% and 0.74 and 76 ± 6% and 0.48 for moderate and severe stenoses, respectively. Concordance between QCA and FFR was poor, especially in intermediate stenoses (Spearman's rho = - 0.33, p<0.0001. Visual assessment resulted in an accuracy of 57% and 96% in

  15. Flow-mediated lipoprotein retention; Pregnancy-associated plasma protein-A inhibition in atherosclerosis and its release during myocardial ischemia

    DEFF Research Database (Denmark)

    Steffensen, Lasse Bach

    , which states that retention of lipoproteins is the key initiating event of atherosclerosis development. Pregnancy-associated plasma protein-A (PAPP-A) regulates the insulin-like growth factor (IGF) system by proteolytic cleavage of a subset of IGF-binding proteins. Studies in mice have established PAPP-A...... as a pro-atherogenic molecule and suggested PAPP-A inhibition as a therapeutic strategy in the treatment of atherosclerosis. Stanniocalcin 2 (STC-2) was recently discovered to be an endogenous inhibitor of PAPP-A, but has not previously been implicated in vascular disease. In Study II, the interaction...... between PAPP-A and STC-2 as a local regulatory mechanism in the artery wall is substantiated, and the first proof-of-principle for PAPP-A inhibition as a treatment for atherosclerosis is provided. PAPP-A has been demonstrated to be elevated in the circulation of patients of acute coronary syndrome (ACS...

  16. Risk stratification after myocardial infarction. Clinical overview

    Energy Technology Data Exchange (ETDEWEB)

    O' Rourke, R.A. (Department of Medicine, University of Texas Health Science Center, San Antonio (United States))

    1991-09-01

    Many patients with an acute myocardial infarction can be stratified into subgroups that are at high risk for morbidity and mortality on the basis of clinical characteristics that indicate recurrent myocardial ischemia, persistent left ventricular dysfunction, and/or recurrent cardiac arrhythmias. In patients with uncomplicated myocardial infarction the assessment of symptoms, physical findings, and ECG changes during predischarge exercise testing often identifies patients at increased risk for further cardiac events. Because of the suboptimum sensitivity and specificity of the exercise ECG for detecting myocardial ischemia, myocardial perfusion imaging with 201Tl and/or assessment of global and segmental ventricular function by two-dimensional echocardiography or radionuclide cineangiography during or immediately after exercise are often added to the predischarge risk stratification.

  17. Exercise Training Protects Against Acute Myocardial Infarction via Improving Myocardial Energy Metabolism and Mitochondrial Biogenesis

    OpenAIRE

    Lichan Tao; Yihua Bei; Shenghui Lin; Haifeng Zhang; Yanli Zhou; Jingfa Jiang; Ping Chen; Shutong Shen; Junjie Xiao; Xinli Li

    2015-01-01

    Background/Aims: Acute myocardial infarction (AMI) represents a major cause of morbidity and mortality worldwide. Exercise has been proved to reduce myocardial ischemia-reperfusion (I/R) injury However it remains unclear whether, and (if so) how, exercise could protect against AMI. Methods: Mice were trained using a 3-week swimming protocol, and then subjected to left coronary artery (LCA) ligation, and finally sacrificed 24 h after AMI. Myocardial infarct size was examined with triphenyltetr...

  18. Endoscopic retrograde cholangiopancreatography causes reduced myocardial blood flow

    DEFF Research Database (Denmark)

    Christensen, M; Hendel, H W; Rasmussen, V

    2002-01-01

    BACKGROUND AND STUDY AIMS: Previous studies have shown that up to 50% of healthy patients may develop ST-segment changes during upper gastrointestinal endoscopy. The aim of the study was to evaluate myocardial blood flow in patients during endoscopic retrograde cholangiopancreatography (ERCP...... with either of the two methods, while two patients developed signs of ischemia during ERCP with both the Holter tape recording and on myocardial scintigraphy (P = 0.02). CONCLUSIONS: Patients undergoing ERCP may develop true myocardial ischemia with reduced myocardial blood flow. Although this is a small...

  19. Recovery of the cardiac frequency to the minute post effort as early indicator of myocardial ischemia; Recuperacion de la frecuencia cardiaca al minuto postesfuerzo como indicador temprano de isquemia miocardica

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez M, L. [Centro Medico Nacional 20 de Noviembre, Mexico D.F. (Mexico)

    2007-07-01

    The objective of the work was to evaluate the recovery cardiac frequency like ischemia indicator, due to the immediate reactivity of the parasympathetic nervous system in the post-effort. It is obtained as conclusion that a slow descent of the cardiac frequency to the first minute of the post-effort is a predictor ischemia index when correlating it with the risk evaluated by cardiac SPECT with a high specificity; being this a marker of simple calculating in the daily practice. (Author)

  20. Protecting the heart from ischemia/reperfusion injury: an update on remote ischemic preconditioning and postconditioning.

    Science.gov (United States)

    Donato, Martín; Evelson, Pablo; Gelpi, Ricardo J

    2017-11-01

    The most effective strategy for reducing acute myocardial ischemic injury is timely and effective reperfusion. However, myocardial reperfusion can induce further cardiomyocyte death (reperfusion injury). Interventions that protect the heart from ischemia/reperfusion injury, reducing infarct size, can involve remote ischemic preconditioning and postconditioning. These interventions have a promising potential clinical application, and have been the focus of recent research. In this review, we provide an update of remote ischemic preconditioning and postconditioning mechanisms. Remote ischemic preconditioning cardioprotection can occur via a humoral pathway and/or a neural pathway. These two pathways have been described as mechanistically different, but it has been suggested that they could be interdependent. However, remote ischemic postconditioning mainly involves the humoral pathway. In this review, we will discuss the different pathways and mechanisms involved in remote ischemic preconditioning and postconditioning. Remote ischemic preconditioning and postconditioning is possible to perform in a clinical setting by intermittent ischemia of an upper or lower limb. Furthermore, clinical trials using this procedure in the context of predictable ischemia-reperfusion have produced promising results, and other studies to define the potential clinical use of these strategies are ongoing.

  1. Long-term effects of invasive treatment in patients with a post-thrombolytic Q-wave myocardial infarction

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Madsen, Jan K; Grande, Peer

    2010-01-01

    The aim of the present study was to assess the effect of a deferred invasive treatment strategy on long-term outcome in patients with a post-thrombolytic Q-wave myocardial infarction and inducible myocardial ischemia.......The aim of the present study was to assess the effect of a deferred invasive treatment strategy on long-term outcome in patients with a post-thrombolytic Q-wave myocardial infarction and inducible myocardial ischemia....

  2. Myocardial ischemia in hypertensive Nigerians | Ukoh | Nigerian ...

    African Journals Online (AJOL)

    No Abstract. Nigerian Medical Practitioner Vol. 52 (1) 2007: pp. 8-11. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Article Metrics. Metrics Loading ... Metrics powered by PLOS ALM · http://dx.doi.org/10.4314/nmp.v52i1.28882 · AJOL African Journals Online. HOW TO ...

  3. Long-term effects of invasive treatment in patients with a post-thrombolytic Q-wave myocardial infarction

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Madsen, Jan Kyst; Grande, Peer

    2010-01-01

    Abstract Objectives. The aim of the present study was to assess the effect of a deferred invasive treatment strategy on long-term outcome in patients with a post-thrombolytic Q-wave myocardial infarction and inducible myocardial ischemia. Design. Patients (N=751) with post-thrombolytic Q......-wave myocardial infarction and inducible ischemia (angina pectoris or silent myocardial ischemia) were randomized to a deferred invasive treatment (balloon angioplasty or coronary bypass surgery) or medical treatment. Vital status and non-fatal cardiac events defined as hospitalization caused by acute cardiac...... and improved survival among the patients with post-infarction angina pectoris and not among the patients with silent myocardial ischemia. Conclusions. A deferred invasive treatment strategy improves survival compared to medical treatment in patients with inducible myocardial ischemia after a post...

  4. Regular Alcohol Consumption Mimics Cardiac Preconditioning by Protecting against Ischemia-Reperfusion Injury

    Science.gov (United States)

    Miyamae, Masami; Diamond, Ivan; Weiner, Michael W.; Camacho, S. Albert; Figueredo, Vincent M.

    1997-04-01

    Epidemiologic studies indicate that long-term alcohol consumption decreases the incidence of coronary disease and may improve outcome after myocardial infarction. Attenuation of ischemia-reperfusion injury after myocardial infarction improves survival. This study investigates the possibility that alcohol consumption can improve survival after myocardial infarction by reducing ischemia-reperfusion injury. Hearts were isolated from guinea pigs after drinking ethanol for 3-12 weeks and subjected to global ischemia and reperfusion. Hearts from animals drinking ethanol showed improved functional recovery and decreased myocyte damage when compared with controls. Adenosine A1 receptor blockade abolished the protection provided by ethanol consumption. These findings indicate that long-term alcohol consumption reduces myocardial ischemia-reperfusion injury and that adenosine A1 receptors are required for this protective effect of ethanol. This cardioprotective effect of long-term alcohol consumption mimics preconditioning and may, in part, account for the beneficial effect of moderate drinking on cardiac health.

  5. BNP was Associated with Ischemic Myocardial Scintigraphy and Death in Patients at Chest Pain Unit

    Energy Technology Data Exchange (ETDEWEB)

    Azevedo, Jader Cunha de, E-mail: jadercazevedo@gmail.com [Universidade Federal Fluminense, Niterói, Rio de Janeiro, RJ (Brazil); Hospital Pró-Cardíaco, Rio de Janeiro, RJ (Brazil); Centro Universitário de Volta Redonda, Rio de Janeiro, RJ (Brazil); Reis, Bruno Cezario Costa; Barreto, Nathalia Monerat P.B. [Centro Universitário de Volta Redonda, Rio de Janeiro, RJ (Brazil); F, Diogenes S. Junior; Prezotti, Lais S. [Universidade Federal Fluminense, Niterói, Rio de Janeiro, RJ (Brazil); Procaci, Victor Rebelo; Octaviano, Vivian Werneck [Centro Universitário de Volta Redonda, Rio de Janeiro, RJ (Brazil); Volschan, Andre [Hospital Pró-Cardíaco, Rio de Janeiro, RJ (Brazil); Mesquita, Evandro Tinoco; Mesquita, Claudio Tinoco [Universidade Federal Fluminense, Niterói, Rio de Janeiro, RJ (Brazil); Hospital Pró-Cardíaco, Rio de Janeiro, RJ (Brazil)

    2015-01-15

    Recent studies have suggested that B-type Natriuretic Peptide (BNP) is an important predictor of ischemia and death in patients with suspected acute coronary syndrome. Increased levels of BNP are seen after episodes of myocardial ischemia and may be related to future adverse events. To determine the prognostic value of BNP for major cardiac events and to evaluate its association with ischemic myocardial perfusion scintigraphy (MPS). This study included retrospectively 125 patients admitted to the chest pain unit between 2002 and 2006, who had their BNP levels measured on admission and underwent CPM for risk stratification. BNP values were compared with the results of the MPS. The chi-square test was used for qualitative variables and the Student t test, for quantitative variables. Survival curves were adjusted using the Kaplan-Meier method and analyzed by using Cox regression. The significance level was 5%. The mean age was 63.9 ± 13.8 years, and the male sex represented 51.2% of the sample. Ischemia was found in 44% of the MPS. The mean BNP level was higher in patients with ischemia compared to patients with non-ischemic MPS (188.3 ± 208.7 versus 131.8 ± 88.6; p = 0.003). A BNP level greater than 80 pg/mL was the strongest predictor of ischemia on MPS (sensitivity = 60%, specificity = 70%, accuracy = 66%, PPV = 61%, NPV = 70%), and could predict medium-term mortality (RR = 7.29, 95% CI: 0.90-58.6; p = 0.045) independently of the presence of ischemia. BNP levels are associated with ischemic MPS findings and adverse prognosis in patients presenting with acute chest pain to the emergency room, thus, providing important prognostic information for an unfavorable clinical outcome.

  6. Ionic and metabolic imbalance as potential factors of ischemia reperfusion injury.

    Science.gov (United States)

    El Banani, H; Bernard, M; Cozzone, P; James, F; Feuvray, D

    1998-09-03

    This study examined the influence of metabolic substrates on the effects of trimetazidine on functional and metabolic aspects of the ischemic reperfused heart. Isovolumic rat hearts were submitted to a 30-minute period of global mild ischemia (coronary flow decreased by an average of 70%) and then reperfused at constant preischemic coronary flow rate. Either glucose (11 mM) or glucose and palmitic acid (0.1 mM) were used as metabolic substrates. Trimetazidine (6 x 10(-7)M) markedly reduced the increase in diastolic pressure that occurred on reperfusion after the ischemic episode, whatever the exogenous substrate used. However, in those hearts that received fatty acid, the postischemic increase in diastolic pressure was abolished. Ischemia-induced increase in acyl carnitine levels-determined as indicators of fatty acid utilization by myocardial cells-was significantly decreased by trimetazidine in those hearts receiving fatty acid. Also, similar effects to those of trimetazidine on the postischemic increase in diastolic pressure and on tissue levels of acyl carnitine were obtained in the presence of dichloroacetate. Moreover, the presence of trimetazidine was associated with a reduction in the intracellular pH decrease during ischemia in those hearts receiving fatty acid. Combined with previous studies, these results suggest that an improved metabolic balance by trimetazidine may well consequently decrease the ionic imbalance after a transient period of ischemia.

  7. Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury.

    Science.gov (United States)

    Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

    2015-01-01

    Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury.

  8. Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury

    Science.gov (United States)

    Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

    2015-01-01

    Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury. PMID:26103523

  9. Functional significance of myocardial perfusion defects induced by dipyridamole using thallium-201 single-photon emission computed tomography and two-dimensional echocardiography

    Energy Technology Data Exchange (ETDEWEB)

    Jain, A.; Suarez, J.; Mahmarian, J.J.; Zoghbi, W.A.; Quinones, M.A.; Verani, M.S. (Baylor College of Medicine, Houston, TX (USA))

    1990-10-01

    The mechanisms responsible for inhomogeneous myocardial blood flow after oral administration of a large dose (300 mg) of dipyridamole were assessed in 27 patients with serial thallium-201 single-photon emission computed tomography (SPECT) and simultaneous 2-dimensional echocardiograms. Myocardial tomographic images were obtained 50 minutes and 3 to 4 hours after administration of dipyridamole. Two-dimensional echocardiograms were recorded at baseline and then every 15 minutes for 60 minutes. Dipyridamole caused only a mild reduction in blood pressure (from 129 +/- 18 to 126 +/- 16 mm Hg) and a mild increase in heart rate (from 69 +/- 15 to 73 +/- 4 beats/min). Sixteen patients had perfusion defects after dipyridamole by SPECT, which underwent partial or total filling-in. Fourteen of these patients (87.5%) had either a new abnormality or further deterioration of a preexisting wall motion abnormality by 2-dimensional echocardiography, and thus were considered to have developed transient ischemia during dipyridamole administration. Ten of 11 patients (91%) with normal perfusion or fixed defects by SPECT had no further deterioration in wall motion after oral dipyridamole, and were thus considered to have no evidence of myocardial ischemia. In conclusion, most patients with transient thallium-201 defects after dipyridamole develop transient worsening of resting wall motion by 2-dimensional echocardiography, suggestive of true myocardial ischemia. Because myocardial oxygen demand, as indicated by the heart rate-blood pressure product, did not change significantly, the mechanism of myocardial ischemia in these patients is likely to be diminished regional blood flow related to a subendocardial steal induced by dipyridamole.

  10. Myocardial Scintigraphy in the Evaluation of Cardiac Events in Patients without Typical Symptoms

    Energy Technology Data Exchange (ETDEWEB)

    Smanio, Paola Emanuela Poggio, E-mail: pgmsmanio@gmail.com; Silva, Juliana Horie; Holtz, João Vitor; Ueda, Leandro; Abreu, Marilia; Marques, Carlindo; Machado, Leonardo [Instituto Dante Pazzanese de Cardiologia, São Paulo, SP - Brazil Mailing (Brazil)

    2015-08-15

    Cardiovascular disease is a leading cause of death in the world and in Brazil. Myocardial scintigraphy is an important noninvasive method for detecting ischemia in symptomatic patients, but its use in asymptomatic ones or those with atypical symptoms is yet to be defined. To verify the presence of major cardiac events in asymptomatic patients or those with atypical symptoms (atypical chest pain or dyspnea) that underwent myocardial scintigraphy (MS), over a period of 8 years. Secondary objectives were to identify cardiac risk factors associated with myocardial scintigraphy abnormalities and possible predictors for major cardiac events in this group. This was a retrospective, observational study using the medical records of 892 patients that underwent myocardial scintigraphy between 2005 and 2011 and who were followed until 2013 for assessment of major cardiac events and risk factors associated with myocardial scintigraphy abnormalities. Statistical analysis was performed by Fisher’s exact test, logistic regression and Kaplan-Meyer survival curves, with statistical significance being set at p ≤ 0.05. Of the total sample, 52.1% were men, 86.9% were hypertensive, 72.4% had hyperlipidemia, 33.6% were diabetic, and 12.2% were smokers; 44.5% had known coronary artery disease; and 70% had high Framingham score, 21.8% had moderate and 8% had low risk. Of the myocardial scintigraphies, 58.6% were normal, 26.1% suggestive of fibrosis and 15.3% suggestive of ischemia. At evolution, 13 patients (1.5%) had non-fatal myocardial infarction and six individuals (0.7%) died. The group with normal myocardial scintigraphy showed longer period of time free of major cardiac events, non-fatal myocardial infarction (p = 0.036) and death. Fibrosis in the myocardial scintigraphy determined a 2.4-fold increased risk of non-fatal myocardial infarction and five-fold higher risk of death (odds ratio: 2.4 and 5.7, respectively; p = 0.043). The occurrence of major cardiac events in 8 years

  11. Myocardial Scintigraphy in the Evaluation of Cardiac Events in Patients without Typical Symptoms

    Directory of Open Access Journals (Sweden)

    Paola Emanuela Poggio Smanio

    2015-01-01

    Full Text Available Background: Cardiovascular disease is a leading cause of death in the world and in Brazil. Myocardial scintigraphy is an important noninvasive method for detecting ischemia in symptomatic patients, but its use in asymptomatic ones or those with atypical symptoms is yet to be defined. Objective: To verify the presence of major cardiac events in asymptomatic patients or those with atypical symptoms (atypical chest pain or dyspnea that underwent myocardial scintigraphy (MS, over a period of 8 years. Secondary objectives were to identify cardiac risk factors associated with myocardial scintigraphy abnormalities and possible predictors for major cardiac events in this group. Methods: This was a retrospective, observational study using the medical records of 892 patients that underwent myocardial scintigraphy between 2005 and 2011 and who were followed until 2013 for assessment of major cardiac events and risk factors associated with myocardial scintigraphy abnormalities. Statistical analysis was performed by Fisher’s exact test, logistic regression and Kaplan-Meyer survival curves, with statistical significance being set at p ≤ 0.05. Results: Of the total sample, 52.1% were men, 86.9% were hypertensive, 72.4% had hyperlipidemia, 33.6% were diabetic, and 12.2% were smokers; 44.5% had known coronary artery disease; and 70% had high Framingham score, 21.8% had moderate and 8% had low risk. Of the myocardial scintigraphies, 58.6% were normal, 26.1% suggestive of fibrosis and 15.3% suggestive of ischemia. At evolution, 13 patients (1.5% had non-fatal myocardial infarction and six individuals (0.7% died. The group with normal myocardial scintigraphy showed longer period of time free of major cardiac events, non-fatal myocardial infarction (p = 0.036 and death. Fibrosis in the myocardial scintigraphy determined a 2.4-fold increased risk of non-fatal myocardial infarction and five-fold higher risk of death (odds ratio: 2.4 and 5.7, respectively; p = 0

  12. Myocardial perfusion abnormalities in asymptomatic patients with systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Hosenpud, J.D.; Montanaro, A.; Hart, M.V.; Haines, J.E.; Specht, H.D.; Bennett, R.M.; Kloster, F.E.

    1984-08-01

    Accelerated coronary artery disease and myocardial infarction in young patients with systemic lupus erythematosus is well documented; however, the prevalence of coronary involvement is unknown. Accordingly, 26 patients with systemic lupus were selected irrespective of previous cardiac history to undergo exercise thallium-201 cardiac scintigraphy. Segmental perfusion abnormalities were present in 10 of the 26 studies (38.5 percent). Five patients had reversible defects suggesting ischemia, four patients had persistent defects consistent with scar, and one patient had both reversible and persistent defects in two areas. There was no correlation between positive thallium results and duration of disease, amount of corticosteroid treatment, major organ system involvement or age. Only a history of pericarditis appeared to be associated with positive thallium-201 results (p less than 0.05). It is concluded that segmental myocardial perfusion abnormalities are common in patients with systemic lupus erythematosus. Whether this reflects large-vessel coronary disease or small-vessel abnormalities remains to be determined.

  13. The Role of Peroxisome Proliferator-Activated Receptor γ in Mediating Cardioprotection Against Ischemia/Reperfusion Injury.

    Science.gov (United States)

    Zhong, Chong-Bin; Chen, Xi; Zhou, Xu-Yue; Wang, Xian-Bao

    2017-01-01

    Myocardial infarction (MI) is a serious cardiovascular disease resulting in high rates of morbidity and mortality. Although advances have been made in restoring myocardial perfusion in ischemic areas, decreases in cardiomyocyte death and infarct size are still limited, attributing to myocardial ischemia/reperfusion (I/R) injury. It is necessary to develop therapies to restrict myocardial I/R injury and protect cardiomyocytes against further damage after MI. Many studies have suggested that peroxisome proliferator-activated receptor γ (PPARγ), a ligand-inducible nuclear receptor that predominantly regulates glucose and lipid metabolism, is a promising therapeutic target for ameliorating myocardial I/R injury. Thus, this review focuses on the role of PPARγ in cardioprotection during myocardial I/R. The cardioprotective effects of PPARγ, including attenuating oxidative stress, inhibiting inflammatory responses, improving glucose and lipid metabolism, and antagonizing apoptosis, are described. Additionally, the underlying mechanisms of cardioprotective effects of PPARγ, such as regulating the expression of target genes, influencing other transcription factors, and modulating kinase signaling pathways, are further discussed.

  14. Myocardial perfusion scintigraphy in the detection of silent ischemia in asymptomatic diabetic patients Cintilografia de perfusão miocárdica na detecção da isquemia silenciosa em pacientes diabéticos assintomáticos

    Directory of Open Access Journals (Sweden)

    Gláucia Celeste Rossatto Oki

    2013-02-01

    Full Text Available OBJECTIVE: This study was aimed to evaluate myocardial perfusion in asymptomatic patients with type 1 (DM1 and type 2 diabetes mellitus (DM2 without previous diagnoses of coronary artery disease (CAD or cerebral infarction. MATERIALS AND METHODS: Fifty-nine consecutive asymptomatic patients (16 DM1, 43 DM2 underwent myocardial perfusion scintigraphy with 99mTc-sestamibi (MPS. They were evaluated for body mass index, metabolic control of DM, type of therapy, systemic arterial hypertension, dyslipidemia, nephropathy, retinopathy, peripheral neuropathy, smoking, and familial history of CAD. RESULTS: MPS was abnormal in 15 patients (25.4%: 12 (20.3% with perfusion abnormalities, and 3 with isolated left ventricular dysfunction. The strongest predictors for abnormal myocardial perfusion were: age 60 years and above (p = 0.017; odds ratio [OR] = 6.0, peripheral neuropathy (p = 0.028; OR = 6.1, nephropathy (p = 0.031; OR = 5.6, and stress ECG positive for ischemia (p = 0.049; OR = 4.08. CONCLUSION: Silent myocardial ischemia occurs in more than one in five asymptomatic diabetic patients. The strongest predictors of ischemia in this study were: patient age, peripheral neuropathy, nephropathy, retinopathy and a stress ECG positive for ischemia.OBJETIVO: Este estudo teve por finalidade avaliar a perfusão miocárdica de pacientes com diabetes mellitus tipo 1 (DM1 e tipo 2 (DM2 assintomáticos, sem diagnóstico prévio de doença arterial coronariana (DAC ou acidente vascular cerebral. MATERIAIS E MÉTODOS: Cinquenta e nove pacientes consecutivos (16 DM1, 43 DM2 foram submetidos a cintilografia de perfusão miocárdica com sestamibi-99mTc (CPM. Foram avaliados quanto ao índice de massa corpórea, controle metabólico do diabetes, dislipidemia, terapia para o diabetes, hipertensão arterial sistêmica, nefropatia, retinopatia, neuropatia periférica, tabagismo e história familiar de DAC. RESULTADOS: CPM foi anormal em 25,4%: 12 (20,3% com alterações de

  15. Quantification of the total Na,K-ATPase concentration in atria and ventricles from mammalian species by measuring 3H-ouabain binding to intact myocardial samples. Stability to short term ischemia reperfusion

    DEFF Research Database (Denmark)

    Schmidt, Thomas A; Svendsen, J H; Haunsø, S

    1990-01-01

    Na,K-ATPase concentration was measured by vanadate facilitated 3H-ouabain binding to intact samples taken from various parts of porcine and canine myocardium. In porcine and canine heart 3H-ouabain binding site concentration in ventricles was 1.4-2.5 times larger than in atria. Evaluation of 3H-o...... were found to be stable for 20 min of ischemia, followed by 1 h of reperfusion, supporting the concept that myocyte injury induced by short term ischemia may be reversible and that reperfusion may result in normalization....

  16. PET detection of viable tissue in myocardial segments with persistent defects at T1-201 SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Brunken, R.C.; Kottou, S.; Nienaber, C.A.; Schwaiger, M.; Ratib, O.M.; Phelps, M.E.; Schelbert, H.R.

    1989-07-01

    To assess myocardial glucose metabolism and perfusion in 142 myocardial segments with defects seen at thallium-201 single photon emission computed tomography (SPECT), 27 studies with positron emission tomography (PET) utilizing nitrogen-13 ammonia and fluorine-18 deoxyglucose were performed in 26 patients. Myocardial infarction was defined on the basis of concordant reductions in segmental perfusion and glucose utilization; myocardial ischemia, on the basis of preservation of glucose utilization (metabolic viability) in segments with hypoperfusion at rest. Of the 142 segments analyzed, 101 had fixed defects, 31 had partially reversible defects, and ten had completely reversible defects. Preserved glucose utilization was identified in 47 (46.5%) of the segments with fixed defects and 20 (64.5%) of the segments with partially reversible defects. Of the ten segments with completely reversible defects, five (50%) were normal, and five (50%) exhibited ischemia at PET. Visual improvement in a persistent thallium defect at delayed imaging was not associated with residual glucose metabolic activity. Thus, PET can be used to detect glucose metabolic activity in a significant proportion of myocardial segments with fixed or partially redistributing defects seen at thallium SPECT, which suggests that the extent of tissue viability in patients with ischemic heart disease is underestimated at thallium scintigraphy.

  17. Mesenteric artery ischemia

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001156.htm Mesenteric artery ischemia To use the sharing features on this page, ... be removed. Outlook (Prognosis) The outlook for chronic mesenteric ischemia is good after a successful surgery. However, it ...

  18. Critical Limb Ischemia (CLI)

    Science.gov (United States)

    ... and; in the intestines it is known as mesenteric ischemia and can cause severe abdominal pain. What are ... you may be sent for coronary angiography. For mesenteric ischemia, imaging of the three vessels supplying the intestines ...

  19. Acute Mesenteric Ischemia

    Science.gov (United States)

    ... of Celiac Disease Additional Content Medical News Acute Mesenteric Ischemia By Parswa Ansari, MD, Assistant Professor and Program ... Abdominal Abscesses Abdominal Wall Hernias Inguinal Hernia Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of ...

  20. Intestinal ischemia and infarction

    Science.gov (United States)

    ... ency/article/001151.htm Small intestinal ischemia and infarction To use the sharing features on this page, please enable JavaScript. Intestinal ischemia and infarction occurs when there is a narrowing or blockage ...

  1. Hybrid CCTA/SPECT myocardial perfusion imaging findings in patients with anomalous origin of coronary arteries from the opposite sinus and suspected concomitant coronary artery disease.

    Science.gov (United States)

    Gräni, Christoph; Benz, Dominik C; Schmied, Christian; Vontobel, Jan; Mikulicic, Fran; Possner, Mathias; Clerc, Olivier F; Stehli, Julia; Fuchs, Tobias A; Pazhenkottil, Aju P; Gaemperli, Oliver; Buechel, Ronny R; Kaufmann, Philipp A

    2017-02-01

    Anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS) are associated with adverse cardiac events. Discrimination between ACAOS and coronary artery disease (CAD)-related perfusion defects may be difficult. The aim of the present study was to investigate the value of hybrid coronary computed tomography angiography (CCTA)/SPECT-MPI in patients with ACAOS and possible concomitant CAD. We retrospectively identified 46 patients (mean age 56 ± 12 years) with ACAOS revealed by CCTA who underwent additional SPECT-MPI. ACAOS with an interarterial course were classified as malignant, whereas all other variants were considered benign. CCTA/SPECT-MPI hybrid imaging findings (ischemia or scar) were analyzed according to the territory subtended by an anomalous vessel or a stenotic coronary artery. Twenty-six (57%) patients presented with malignant ACAOS. Myocardial ischemia or scar was found only in patients who had concomitant obstructive CAD in the vessel matching the perfusion defect as evidenced by hybrid CCTA/SPECT imaging. Hybrid CCTA/SPECT-MPI represents a valuable non-invasive tool to discriminate the impact of ACAOS from concomitant CAD on myocardial ischemia. Our results suggest that in a middle-aged population myocardial ischemia due to ACAOS per se may be exceedingly rare and is more likely attributable to concomitant CAD.

  2. Heart dysfunction and fibrosis in rat treated with myocardial ...

    African Journals Online (AJOL)

    use

    2011-11-16

    Nov 16, 2011 ... damage and death associated with myocardial cells. (Thygesen et al., 2007). Even if other heart tissue ... good material for regenerative medicine and cell therapy research in MI and reperfusion. Thus, the aim of .... improve the condition of myocardial ischemia, stem cell therapy research, and regenerative ...

  3. Heart dysfunction and fibrosis in rat treated with myocardial ...

    African Journals Online (AJOL)

    use

    2011-11-16

    Nov 16, 2011 ... study was to establish the rat model animal and to compare the heart dysfunction and fibrosis with SD ..... Figure 4. The myocardial fibrosis formation after myocardial ischemia and reperfusion surgery. Pictures on the left were hematoxylin and eosin (H and E) staining results, pictures on the right were ...

  4. The eNOS enhancer AVE 9488: a novel cardioprotectant against ischemia reperfusion injury.

    Science.gov (United States)

    Frantz, S; Adamek, A; Fraccarollo, D; Tillmanns, J; Widder, J D; Dienesch, C; Schäfer, A; Podolskaya, A; Held, M; Ruetten, H; Ertl, G; Bauersachs, J

    2009-11-01

    Nitric oxide (NO) is an important regulator of vascular and myocardial function. Cardiac ischemia/reperfusion injury is reduced in mice overexpressing endothelial NO synthase (eNOS) suggesting cardioprotection by eNOS. Novel pharmacological substances, so called eNOS enhancers, upregulate eNOS expression and thereby increase NO production. We tested the effects of the eNOS enhancer AVE 9488 on cardiac ischemia/reperfusion injury in vivo in mice. After treatment with the eNOS enhancer AVE 9488 (30 mg/kg/day) or placebo for one week mice underwent 30 min of coronary artery ligation and 24 h of reperfusion in vivo. Ischemia-reperfusion damage was significantly reduced in mice treated with the eNOS enhancer when compared to placebo treated mice (infarct/area at risk 65.4 +/- 4.1 vs. 36.9 +/- 4.0%, placebo vs. eNOS enhancer, P = 0.0002). The protective effect was blunted in eNOS knockout mice treated with the eNOS enhancer (infarct/area at risk 64.1 +/- 6.2%, eNOS knockout + eNOS enhancer vs. WT + eNOS enhancer, P = ns). Reactive oxygen species were significantly reduced in mice treated with the eNOS enhancer as indicated by significantly lower malondialdehyde-thiobarbituric acid levels (placebo vs. eNOS enhancer, 3.2 +/- 0.5 vs. 0.8 +/- 0.07 micromol/l, P = 0.0003). Thus pharmacological interventions addressed to increase eNOS-derived NO production constitute a promising therapeutic approach to prevent myocardial ischemia/reperfusion injury.

  5. Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene.

    Science.gov (United States)

    Melo, Luis G; Agrawal, Reitu; Zhang, Lunan; Rezvani, Mojgan; Mangi, Abeel A; Ehsan, Afshin; Griese, Daniel P; Dell'Acqua, Giorgio; Mann, Michael J; Oyama, Junichi; Yet, Shaw-Fang; Layne, Matthew D; Perrella, Mark A; Dzau, Victor J

    2002-02-05

    Ischemia and oxidative stress are the leading mechanisms for tissue injury. An ideal strategy for preventive/protective therapy would be to develop an approach that could confer long-term transgene expression and, consequently, tissue protection from repeated ischemia/reperfusion injury with a single administration of a therapeutic gene. In the present study, we used recombinant adeno-associated virus (rAAV) as a vector for direct delivery of the cytoprotective gene heme oxygenase-1 (HO-1) into the rat myocardium, with the purpose of evaluating this strategy as a therapeutic approach for long-term protection from ischemia-induced myocardial injury. Human HO-1 gene (hHO-1) was delivered to normal rat hearts by intramyocardial injection. AAV-mediated transfer of the hHO-1 gene 8 weeks before acute coronary artery ligation and release led to a dramatic reduction (>75%) in left ventricular myocardial infarction. The reduction in infarct size was accompanied by decreases in myocardial lipid peroxidation and in proapoptotic Bax and proinflammatory interleukin-1beta protein abundance, concomitant with an increase in antiapoptotic Bcl-2 protein level. This suggested that the transgene exerts its cardioprotective effects in part by reducing oxidative stress and associated inflammation and apoptotic cell death. This study documents the beneficial therapeutic effect of rAAV-mediated transfer, before myocardial injury, of a cytoprotective gene that confers long-term myocardial protection from ischemia/reperfusion injury. Our data suggest that this novel "pre-event" gene transfer approach may provide sustained tissue protection from future repeated episodes of injury and may be beneficial as preventive therapy for patients with or at risk of developing coronary ischemic events.

  6. Severe myocardial injury and extracorporeal membrane oxygenation following perinatal asphyxia

    Directory of Open Access Journals (Sweden)

    P. Benson Ham

    2015-05-01

    Full Text Available Perinatal asphyxia is a common cause of morbidity and mortality in the newborn and is associated with myocardial injury in a significant proportion of cases. Biomarkers, echocardiography, and rhythm disturbances are sensitive indicators of myocardial ischemia and may predict mortality. We present a case of severe myocardial dysfunction immediately after delivery managed with extracorporeal membrane oxygenation (ECMO and discuss the role of cardiac biomarkers, echocardiography, electrocardiography, and ECMO in the asphyxiated newborn.

  7. [Nonocclusive acute mesenteric ischemia].

    Science.gov (United States)

    Vasile, I; Meşină, C; Paşalega, M; Calotă, F; Vâlcea, I D

    2008-01-01

    The authors present one case of acute mesenteric ischemia appeared to the patient 70 years old, with HTA and coronary heart disease with heart arrhythmia treated with angiotensin-converting-enzyme inhibitor, anti arrhythmia agents and antithrombin therapy (trombostop). Acute mesenteric ischemia is not an isolated clinical entity, but a complex of diseases, including acute mesenteric arterial embolus and thrombus, mesenteric venous thrombus and nonocclusive mesenteric ischemia. These diseases have common clinical features caused by impaired blood perfusion of the intestine, bacterial translocation and systemic inflammatory response syndrome. Reperfusion injury is another important feature of nonocclusive mesenteric ischemia. We discuss about the nonocclusive mesenteric ischemia is the most lethal form of acute mesenteric ischemia because of the poor understanding of its pathophysiology and its nonspecific symptoms, which often delay its diagnosis. Although acute mesenteric ischemia is still lethal and in-hospital mortality rates have remained high over the last few decades, accumulated knowledge on this condition is expected to improve its prognosis.

  8. Effects of endogenous cardioprotective mechanisms on ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    Marcin Kunecki

    2017-01-01

    Full Text Available Ischemic heart disease have been remarked as a leading cause of morbidity and mortality in adults. Early restoration of cardiac perfusion is necessary to restore perfusion of ischemic heart muscle. Effective revascularization reduce mortality by limiting myocardial necrosis at the acute phase of the cardiac infarction. However, reperfusion may induce a cascade of pathophysiological reactions causing the increase of the infarct area of the myocardium This phenomenon known as ischemia-reperfusion injury is responsible for up to 50% of the final infarct size. Sequences of brief episodes of nonlethal ischemia and reperfusion applied before (preconditioning — IPC or after (postconditioning — POC the coronary occlusion are well documented to reduce the ischemiareperfusion injury. These phenomena improve cardiac function by mobilizing the molecular and cellular mechanisms limiting reperfusion injury. The mechanisms underlying IPC or POC are still not clarified, but strong experimental evidence suggests that opioids may be the part of the endogenous cardioprotective response to I/R injury. Stimulation of opioid receptors activates related to POC mechanisms affecting protection to the ischemic myocardium, while the use of non-selective opioid receptor antagonist - naloxone reduces this effect. There is no consensus that the subtype of opioid receptor is responsible for the protection of the human heart muscle.Morphine may reduce cardiac preload by peripheral vasodilatation. Numerous studies show a direct cardioprotective effect of the opioid pathway in ischemic conditions. Opioids act via membrane receptors: μ, δ, κ. The predominant subtype in the human cardiac cells are μ- and δ – opioid receptors. It has been hypothetized that opioid receptor activation exerts cardioprotection in human heart muscle pathway what may give insight into the explanation of the protective mechanisms in the acute myocardial infarction.

  9. Myocardial bridging as a cause of acute myocardial infarction: a case report

    Directory of Open Access Journals (Sweden)

    Emiroglu Yunus

    2002-09-01

    Full Text Available Abstract Background Systolic compression of a coronary artery by overlying myocardial tissue is termed myocardial bridging. Myocardial bridging usually has a benign prognosis, but some cases resulting in myocardial ischemia, infarction and sudden cardiac death have been reported. We are reporting a case of myocardial bridging which was complicated with acute myocardial infarction associated with inappropriate blood donation. Case presentation A 33 year-old-man was admitted to our emergency with acute anteroseptal myocardial infarction after a blood donation. The electrocardiography showed sinus rhythm and was consistent with an acute anteroseptal myocardial infarction. We decided to perform primary percutanous intervention (PCI. Myocardial bridging was observed in the mid segment of the left anterior descending coronary artery on coronary angiogram. PCI was canceled and medical follow up was decided. Blood transfusion was made because he had a deep anemia. A normal hemaglobin level and clinical reperfusion was achieved after ten hours by blood transfusion. At the one year follow up visit, our patient was healthy and had no cardiac complaints. Conclusions Myocardial bridging may cause acute myocardial infarction in various clinical conditions. Although the condition in this case caused profound anemia related acute myocardial infarction, its treatment and management was unusual.

  10. Niacin ameliorates kidney warm ischemia and reperfusion injury-induced ventricular dysfunction and oxidative s