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Sample records for reperfused rat heart

  1. Cardioprotective effects of morphine on rat heart suffering from ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    师恩祎; 江晓菁; 白菡; 谷天祥; 常业恬; 王俊科

    2003-01-01

    Objective To investigate the cardioprotective effects of morphine on ischemic reperfused rat heart in vitro and its mechanism.Methods The isolated rat heart was perfused in a Langendorff apparatus. Infarct myocardium was determined by TTC. Coronary flow (CF), heart rate (HR), left ventricular pressure (LVP), the first derivative of ventricular pressure (LVP/dtmax) and infarct size after ischemia and reperfusion in rat heart given 0.3 μmol/L morphine were observed. The effects of naloxone and glibenclamide on the cardioprotection of morphine were also measured.Results After ischemia and reperfusion, CF, HR, LVP and LVP/dtmax of isolated rat hearts decreased significantly (P0.05). The cardioprotective effects of morphine were abolished by naloxone or glibenclamide completely.Conclusions Morphine can reduce ischemia-reperfusion injuries in isolated rat heart. The cardioprotective effects of morphine are mediated by a local opioid receptor-KATP channel linked mechanism in rat hearts.

  2. Enhanced phosphodiesteratic breakdown and turnover of phosphoinositides during reperfusion of ischemic rat heart.

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    Otani, H; Prasad, M R; Engelman, R M; Otani, H; Cordis, G A; Das, D K

    1988-11-01

    In this study, we examined phosphoinositide metabolism during ischemia and reperfusion using an isolated and perfused rat heart. When myocardial phosphoinositides were prelabeled with [3H]inositol, reperfusion after 30 minutes of normothermic global ischemia resulted in significant accumulations of radiolabeled inositol phosphate, inositol bisphosphate, and inositol trisphosphate. Isotopic incorporation of [3H]inositol into phosphatidylinositol, phosphatidylinositol-4-phosphate, and phosphatidylinositol-4,5-bisphosphate was increased significantly in the heart reperfused with [3H]inositol after 30 minutes of ischemia compared with that perfused with [3H]inositol after 30 minutes of nonischemic perfusion. However, isotopic incorporation of [3H]glycerol into diacylglycerol, phosphatidic acid, and all of the three phosphoinositides was diminished in the reperfused hearts. Reperfusion of the ischemic heart prelabeled with [14C]arachidonic acid resulted in significant increases in [14C]diacylglycerol and [14C]phosphatidic acid. The enhanced accumulations of [3H]inositol phosphates during reperfusion were not affected by treatment with prazosin plus atropine or indomethacin, but were inhibited by hypoxic reperfusion, reperfusion with Ca2+-free buffer, or by mepacrine. These results suggest that myocardial reperfusion stimulates phosphodiesteratic breakdown and turnover of phosphoinositides, and increased Ca2+ influx caused by reperfusion may be involved in the mechanism of stimulation of phosphatidylinositol-specific phospholipase C activity in the rat heart.

  3. Cardioprotective properties of citicoline against hyperthyroidism-induced reperfusion damage in rat hearts.

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    Hernández-Esquivel, Luz; Pavón, Natalia; Buelna-Chontal, Mabel; González-Pacheco, Héctor; Belmont, Javier; Chávez, Edmundo

    2015-06-01

    Hyperthyroidism represents an increased risk factor for cardiovascular morbidity, especially when the heart is subjected to an ischemia/reperfusion process. The aim of this study was to explore the possible protective effect of the nucleotide citicoline on the susceptibility of hyperthyroid rat hearts to undergo reperfusion-induced damage, which is associated with mitochondrial dysfunction. Hence, we analyzed the protective effect of citicoline on the electrical behavior and on the mitochondrial function in rat hearts. Hyperthyroidism was established after a daily i.p. injection of triiodothyronine (at 2 mg/kg of body weight) during 5 days. Thereafter, citicoline was administered i.p. (at 125 mg/kg of body weight) for 5 days. In hyperthyroid rat hearts, citicoline protected against reperfusion-induced ventricular arrhythmias. Moreover, citicoline maintained the accumulation of mitochondrial Ca(2+), allowing mitochondria to reach a high transmembrane electric gradient that protected against the release of cytochrome c. It also preserved the activity of the enzyme aconitase that inhibited the release of cytokines. The protection also included the inhibition of oxidative stress-induced mDNA disruption. We conclude that citicoline protects against the reperfusion damage that is found in the hyperthyroid myocardium. This effect might be due to its inhibitory action on the permeability transition in mitochondria.

  4. Effects of Lipoteichoic Acid induced Delayed Preconditioning on Ischemia-reperfusion Injury in Isolated Rat Hearts

    Institute of Scientific and Technical Information of China (English)

    马世玉; 向继洲; 吴基良; 胡本容

    2003-01-01

    To explore the potential of lipoteichoic acid (LTA) induced cardioprotection against is-chemia-reperfusion (I/R) injury in isolated rat hearts and whether endogenous nitric oxide (NO)participates-in the protection, the rats were pretreated with LTA (1 mg/kg, i. p. ) 24 h before theexperiment, and the isolated hearts were subjected to 30 min no-flow normothermic global ischemiaand 60 min reperfusion after a 20-min stabilization period by the langendorff method. Cardiac func-tions were evaluated at the end of stabilization, and at 30 min, 60 min of reperfusion. The amountsof MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase(LDH) and total NO oxidationproducts in the coronary effluent were measured spectrophotometrically at the end of reperfusion. Itwas revealed that pretreatment with LTA could significantly improve the recovery of cardiac func-tion, reduce the release of CK-MB and LDH, and increase the concentrations of NO in coronary ef-fluent. The protective effects were abrogated by pretreatment of the rats with L-NAME. It wasconcluded that LTA could induce the delayed cardioprotection against I/R injury, and endogenousNO may be involved in the mechanisms.

  5. Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats

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    Noritomo Fujisaki

    2016-01-01

    Full Text Available Because inhaled carbon monoxide (CO provides potent anti-inflammatory and antioxidant effects against ischemia reperfusion injury, we hypothesized that treatment of organ donors with inhaled CO would decrease graft injury after heart transplantation. Hearts were heterotopically transplanted into syngeneic Lewis rats after 8 hours of cold preservation in University of Wisconsin solution. Donor rats were exposed to CO at a concentration of 250 parts per million for 24 hours via a gas-exposure chamber. Severity of myocardial injury was determined by total serum creatine phosphokinase and troponin I levels at three hours after reperfusion. In addition, Affymetrix gene array analysis of mRNA transcripts was performed on the heart graft tissue prior to implantation. Recipients of grafts from CO-exposed donors had lower levels of serum troponin I and creatine phosphokinase; less upregulation of mRNA for interleukin-6, intercellular adhesion molecule-1, and tumor necrosis factor-α; and fewer infiltrating cells. Although donor pretreatment with CO altered the expression of 49 genes expressly represented on the array, we could not obtain meaningful data to explain the mechanisms by which CO potentiated the protective effects.Pretreatment with CO gas before organ procurement effectively protected cardiac grafts from ischemia reperfusion-induced injury in a rat heterotopic cardiac transplant model. A clinical report review indicated that CO-poisoned organ donors may be comparable to non-poisoned donors.

  6. Cardioprotective effect of aqueous extract of Chichorium intybus on ischemia-reperfusion injury in isolated rat heart.

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    Sadeghi, Najmeh; Dianat, Mahin; Badavi, Mohammad; Malekzadeh, Ahad

    2015-01-01

    Several studies have shown that Chichorium intybus (C. intybus) which possesses flavonoid compounds has an effective role in treatment of cardiovascular diseases. Contractile dysfunction mostly occurs after acute myocardial infarction, cardiac bypass surgery, heart transplantation and coronary angioplasty. The aim of the present study was to investigate the effect of aqueous extract of C. intybus on ischemia- reperfusion injury in isolated rat heart. The animals were divided into four groups (Sham, Control, 1 mg/ml and 3 mg/ml of extract) of 8 rats. The aorta was cannulated, and then the heart was mounted on a Langendorff apparatus. Next, a balloon was inserted into the left ventricle (LV) and peak positive value of time derivate of LV pressure (+dp/dt), coronary flow (CF), and left ventricular systolic pressure (LVSP) in pre-ischemia and reperfusion period were calculated by a Power Lab system. All groups underwent a 30-minute global ischemia followed by a 60-minute reperfusion. The results showed that heart rate (HR), coronary flow, and left ventricular developed pressure (LVDP) and rate of pressure product (RPP) significantly decreased in the control group during reperfusion, while these values in the groups receiving the extract (3mg/ml) improved significantly during reperfusion (p<0.001). It seems that flavonoid compounds of aqueous extract of C. intybus reduce ischemia - reperfusion injuries, suggesting its protective effect on heart function after ischemia.

  7. Continuous inhibition of poly(ADP-ribose) polymerase does not reduce reperfusion injury in isolated rat heart.

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    Nishizawa, Kenya; Yanagida, Shigeki; Yamagishi, Tadashi; Takayama, Eiichi; Bessho, Motoaki; Kusuhara, Masatoshi; Adachi, Takeshi; Ohsuzu, Fumitaka

    2013-07-01

    Poly(ADP-ribose) polymerase (PARP), an enzyme that is important to the regulation of nuclear function, is activated by DNA strand breakage. In massive DNA damage, PARP is overactivated, exhausting nicotinamide adenine dinucleotide and leading to cell death. Recent studies have succeeded in reducing cellular damage in ischemia/reperfusion by inhibiting PARP. However, PARP plays an important part in the DNA repair system, and its inhibition may be hazardous in certain situations. We compared the short-time inhibition of PARP against continuous inhibition during ischemia/reperfusion using isolated rat hearts. The hearts were reperfused after 21 minutes of ischemia with a bolus injection of 3-aminobenzamide (3-AB) (10 mg/kg) followed by continuous 3-AB infusion (50 μM) for the whole reperfusion period or for the first 6 minutes or without 3-AB. At the end of reperfusion, contractile function, high-energy phosphate content, nicotinamide adenine dinucleotide content, and infarcted area were significantly preserved in the 3-AB 6-minute group. In the 3-AB continuous group, these advantages were not apparent. At the end of reperfusion, PARP cleavage had significantly proceeded in the 3-AB continuous group, indicating initiation of the apoptotic cascade. Thus, continuous PARP inhibition by 3-AB does not reduce reperfusion injury in the isolated rat heart, which may be because of acceleration of apoptosis.

  8. Sevoflurane postconditioning protects isolated rat hearts against ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    YAO Yun-tai; FANG Neng-xin; SHI Chun-xia; LI Li-huan

    2010-01-01

    Background Studies suggested that anesthetics administered upon the early reperfusion or "anesthetic postconditioning" could protect post-ischemic hearts against myocardial ischemia reperfusion injury (MIRI).However, the mechanism responsible for such protection was not well-elucidated.We investigated the cardioprotection induced by sevoflurane postconditioning (SpostC) in rat hearts in vitro, and the respective role of phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase 1 and 2 (ERK 1/2), mitochondrial KATP channels (mitoKATP) and mitochondrial permeability transition pore (mPTP), by selectively inhibiting PI3K, ERK 1/2, mitoKATP, with LY294002 (LY), PD98059 (PD), 5-hydroxydecanoate (5-HD) and by directly opening of mPTP with atractyloside (ATR), respectively.Methods Isolated rat hearts were randomly assigned to one of the 12 groups (n=15):Time control (continuous perfusion), ISCH (30 minutes of ischemia followed by 60 minutes of reperfusion alone), SpostC (3% sevoflurane postconditioning was administered during the first 15 minutes of reperfusion after 30 minutes of ischemia), ISCH+LY,ISCH+PD, ISCH+ATR, ISCH+5-HD and ISCH+ dimethyl sulfoxide (DMSO) groups (LY, PD, ATR, 5-HD and DMSO (the vehicle) was administered respectively during the first 15 minutes of reperfusion following test ischemia), SpostC+LY, SpostC+PD, SpostC+ATR and SpostC+5-HD groups (LY, PD, ATR and 5-HD was coadministered with 3% sevoflurane, respectively).Hemodynamics was compared within and between groups.Infarction size was determined at the end of experiments using triphenyltetrazolium chloride (TTC) staining.Lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) released from necrotic myocardium, were compared among TC, ISCH and SpostC groups.To investigate the relationships between RISK and mPTP implicated in SpostC, NAD+ content in myocardium, a marker of mPTP opening, was compared among some experimental groups (TC, ISCH, ISCH

  9. Administration of aqueous extract of Desmodium gangeticum (L) root protects rat heart against ischemic reperfusion injury induced oxidative stress.

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    Kurian, Gino A; Paddikkala, Jose

    2009-02-01

    Myocardial reperfusion is believed to be associated with free radical injury. The present study evaluates the effect of aqueous extract of D. gangeticum (DG) on lipid peroxides and antioxidants in ischemic reperfused (IR) Wistar albino male rats. Significant elevation in lipid peroxide products (thiobarbituric acid reactive substances) and decreased activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) were observed in the rat hearts during ischemia reperfusion phase. Pre treatment of rats with aqueous extract of DG orally for 30 days showed significantly improved preservation of antioxidant enzymes and subsequent reduction in lipid peroxidation. But 2,3,5 triphenyl tetrazolium chloride (TTC) stained rat heart did not show much significant antioxidant enzyme activities and lipid peroxidation. On the other hand, TTC unstained rat heart showed significant improvement in the antioxidant activities indicating cardio protective effect of aqueous extract of DG in myocardium affected by ischemia reperfusion insult. The administration of DG to normal rats did not have any significant effect on any of the parameter studied. These results indicate that DG improves the antioxidant capacity of heart and attenuate the degree of lipid peroxidation after IR.

  10. Effects of preconditioning on reperfusion arrhythmias, myocardial functions, formation of free radicals, and ion shifts in isolated ischemic/reperfused rat hearts.

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    Tosaki, A; Cordis, G A; Szerdahelyi, P; Engelman, R M; Das, D K

    1994-03-01

    The effects of preconditioning on development of reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT), free radical formation, and ion shifts, particularly those of Na, K, Ca, and Mg, were studied in isolated rat heart. Hearts were randomly divided into four groups: group I, aerobically perfused time-matched controls with no preconditioning or ischemia; group II, hearts subjected to 30-min global ischemia followed by 30-min reperfusion; group III, hearts subjected to one cycle of preconditioning, consisting of 5-min global ischemia plus 10-min reperfusion, followed by 30-min global ischemia plus 30-min reperfusion; and group IV, hearts subjected to four cycles of preconditioning (5-min ischemia plus 10-min reperfusion) followed by 30-min ischemia plus 30-min reperfusion. The incidences of VF and VT were reduced from their nonpreconditioned ischemic values of 100 and 100% in group II to 83 and 92% in group III and to 33% (p < 0.05) and 41% (p < 0.05) in group IV, respectively. Maximum malondialdehyde formation, as an indirect marker of free radicals, was observed after 30-min ischemia followed by 10-min reperfusion (0.72 +/- 0.1 nmol/ml) in the nonpreconditioned ischemic group (protocol II). One and four cycles of preconditioning reduced formation of malondialdehyde from the nonpreconditioned ischemic value of 0.72 +/- 0.1 to 0.35 +/- 0.02 and 0.26 +/- 0.02 nmol/ml (p < 0.05), respectively. The same trend was observed when free radical formation was directly detected by salicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. The Effects of Prenatal Protein Restriction on β-Adrenergic Signalling of the Adult Rat Heart during Ischaemia Reperfusion

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    Kevin J. P. Ryan

    2012-01-01

    Full Text Available A maternal low-protein diet (MLP fed during pregnancy leads to hypertension in adult rat offspring. Hypertension is a major risk factor for ischaemic heart disease. This study examined the capacity of hearts from MLP-exposed offspring to recover from myocardial ischaemia-reperfusion (IR and related this to cardiac expression of β-adrenergic receptors (β-AR and their associated G proteins. Pregnant rats were fed control (CON or MLP diets (n=12 each group throughout pregnancy. When aged 6 months, hearts from offspring underwent Langendorff cannulation to assess contractile function during baseline perfusion, 30 min ischemia and 60 min reperfusion. CON male hearts demonstrated impaired recovery in left ventricular pressure (LVP and dP/dtmax (P<0.01 during reperfusion when compared to MLP male hearts. Maternal diet had no effect on female hearts to recover from IR. MLP males exhibited greater membrane expression of β2-AR following reperfusion and urinary excretion of noradrenaline and dopamine was lower in MLP and CON female rats versus CON males. In conclusion, the improved cardiac recovery in MLP male offspring following IR was attributed to greater membrane expression of β2-AR and reduced noradrenaline and dopamine levels. In contrast, females exhibiting both decreased membrane expression of β2-AR and catecholamine levels were protected from IR injury.

  12. Acidic infusion in early reperfusion affects the activity of antioxidant enzymes in postischemic isolated rat heart.

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    Penna, Claudia; Perrelli, Maria-Giulia; Tullio, Francesca; Angotti, Carmelina; Pagliaro, Pasquale

    2013-07-01

    Acidic perfusion (AP) performed at the onset of reperfusion (i.e., acid postconditioning) is cardioprotective. We investigated the effect of AP on postischemic cardiac function and on the activity of endogenous superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase. The role of exogenous CAT or SOD on AP cardioprotection was also investigated. Phosphorylation of redox-sensitive survival kinases (protein kinase C [PKC] ε and extracellular signal-regulated kinase [ERK] 1/2) was also checked. Isolated rat hearts underwent ischemia and reperfusion (I/R) for 30 and 120 min, respectively. AP was obtained by lowering [HCO3(-)] in the perfusion buffer. Infarct size and left ventricular pressure were measured. Protocols include I/R only, I/R plus acidic perfusion in early reperfusion (I/R + AP), and I/R plus AP and CAT (I/R + AP + CAT) or SOD (I/R + AP + SOD). I/R + SOD and I/R + CAT additional hearts served as controls. AP and/or antioxidants were given in the initial 3 min of reperfusion. Enzyme activities were studied in postischemic phase (seventh minute of reperfusion) in I/R or I/R + AP and Sham (buffer-perfused) hearts. AP with (I/R + AP + CAT or I/R + AP + SOD) or without (I/R + AP) antioxidant enzymes resulted in a larger reduction of infarct size compared with I/R, I/R + SOD, or I/R + CAT. Compared with I/R, the postischemic systolic and diastolic recoveries of the cardiac function were markedly improved by the addition of AP and a lesser extent by AP + SOD or AP + CAT. AP increased the postischemic activity of CAT and lowered that of SOD and glutathione peroxidase compared with I/R only. Also, the phosphorylation and activity of ERK1/2 and PKCε were increased by AP. Acid postconditioning affects the activity of endogenous antioxidant enzymes, activates ERK1/2-PKCε pathways, and protects against myocardial I/R injury. The combination of AP and exogenous SOD or CAT still provides cardioprotection. It is likely that intracellular (not

  13. Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts

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    Guberski Dennis

    2008-10-01

    Full Text Available Abstract We investigated the role of polyol pathway enzymes aldose reductase (AR and sorbitol dehydrogenase (SDH in mediating injury due to ischemia-reperfusion (IR in Type 2 diabetic BBZ rat hearts. Specifically, we investigated, (a changes in glucose flux via cardiac AR and SDH as a function of diabetes duration, (b ischemic injury and function after IR, (c the effect of inhibition of AR or SDH on ischemic injury and function. Hearts isolated from BBZ rats, after 12 weeks or 48 weeks diabetes duration, and their non-diabetic littermates, were subjected to IR protocol. Myocardial function, substrate flux via AR and SDH, and tissue lactate:pyruvate (L/P ratio (a measure of cytosolic NADH/NAD+, and lactate dehydrogenase (LDH release (a marker of IR injury were measured. Zopolrestat, and CP-470,711 were used to inhibit AR and SDH, respectively. Myocardial sorbitol and fructose content, and associated changes in L/P ratios were significantly higher in BBZ rats compared to non-diabetics, and increased with disease duration. Induction of IR resulted in increased ischemic injury, reduced ATP levels, increases in L/P ratio, and poor cardiac function in BBZ rat hearts, while inhibition of AR or SDH attenuated these changes and protected hearts from IR injury. These data indicate that AR and SDH are key modulators of myocardial IR injury in BBZ rat hearts and that inhibition of polyol pathway could in principle be used as a therapeutic adjunct for protection of ischemic myocardium in Type 2 diabetic patients.

  14. Severe Calorie Restriction Reduces Cardiometabolic Risk Factors and Protects Rat Hearts from Ischemia/Reperfusion Injury

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    Melo, Dirceu S.; Costa-Pereira, Liliane V.; Santos, Carina S.; Mendes, Bruno F.; Costa, Karine B.; Santos, Cynthia Fernandes F.; Rocha-Vieira, Etel; Magalhães, Flávio C.; Esteves, Elizabethe A.; Ferreira, Anderson J.; Guatimosim, Sílvia; Dias-Peixoto, Marco F.

    2016-01-01

    Background and Aims: Recent studies have proposed that if a severe caloric restriction (SCR) is initiated at the earliest period of postnatal life, it can lead to beneficial cardiac adaptations later on. We investigated the effects of SCR in Wistar rats from birth to adult age on risk factors for cardiac diseases (CD), as well as cardiac function, redox status, and HSP72 content in response to ischemia/reperfusion (I/R) injury. Methods and Results: From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Food intake was assessed daily and body weight were assessed weekly. In the last week of the SCR protocol, systolic blood pressure and heart rate were measured and the double product index was calculated. Also, oral glucose and intraperitoneal insulin tolerance tests were performed. Thereafter, rats were decapitated, visceral fat was weighed, and blood and hearts were harvested for biochemical, functional, tissue redox status, and western blot analyzes. Compared to AL, CR50 rats had reduced the main risk factors for CD. Moreover, the FR50 rats showed increased cardiac function both at baseline conditions (45% > AL rats) and during the post-ischemic period (60% > AL rats) which may be explained by a decreased cardiac oxidative stress and increased HSP72 content. Conclusion: SCR from birth to adult age reduced risk factors for CD, increased basal cardiac function and protected hearts from the I/R, possibly by a mechanism involving ROS. PMID:27092082

  15. MCT1 and MCT4 Expression During Myocardial Ischemic-Reperfusion Injury in the Isolated Rat Heart

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    Yi Zhu

    2013-09-01

    Full Text Available Background/Aims: Myocardium ischemia-reperfusion (I/R injury can be caused by imbalances in cellular metabolism. Lactate, transported by monocarboxylate transporters (MCTs, has been implicated as a mechanism in this process. The present study was designed to investigate the expression and functional role of MCTs in rat hearts during ischemia and reperfusion. Methods: Langendorff-perfused rat hearts were subjected to 20 minutes stabilization, 30 minutes of global ischemia and 60 minutes reperfusion. Hearts were collected serially for detecting expression changes in MCT1, MCT4 during myocardial I/R injury and lactate concentration was measured. Post-ischemic left ventricular function and infract size were determined at end-point, followed by the pretreatment of D-lactate, a competitive inhibitor of MCTs. Results: MCT4 was significantly increased following global ischemia and MCT1 expression was increased during the early stages of reperfusion in isolated rat hearts, while the expression of the ancillary protein CD147 was increased during I/R injury. We determined increases in AMPK phosphorylation status, which was significantly elevated following ischemia and early reperfusion. Blocking monocarboxylate transport by competitive inhibition with D-lactate caused decreased left ventricular performance and increased infarct size. Conclusion: Increased MCT4 expression facilitates lactate extrusion during the ischemic period, while increased MCT1 may facilitate lactate transport into and out of cells simultaneously during early reperfusion, with increases in AMPK phosphorylation status during the myocardial I/R period. Lactate transport by MCTs has a profound protective effect during myocardial ischemia reperfusion injury.

  16. Cardioprotective effect of aqueous extract of Chichorium intybus L. on ischemia-reperfusion injury in isolated rat heart

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    Najmeh Sadeghi

    2015-10-01

    Full Text Available Objective: Several studies have shown that Chichorium intybus L. (C. intybus which possesses flavonoid compounds has an effective role in treatment of cardiovascular diseases. Contractile dysfunction mostly occurs after acute myocardial infarction, cardiac bypass surgery, heart transplantation and coronary angioplasty. The aim of the present study was to investigate the effect of aqueous extract of C. intybus on ischemia- reperfusion injury in isolated rat heart. Materials and Methods: The animals were divided into four groups (Sham, Control, 1 mg/ml and 3 mg/ml of extract of 8 rats. The aorta was cannulated, and then the heart was mounted on a Langendorff apparatus. Next, a balloon was inserted into the left ventricle (LV and peak positive value of time derivate of LV pressure (+dp/dt, coronary flow (CF, and left ventricular systolic pressure (LVSP in pre-ischemia and reperfusion period were calculated by a Power Lab system. All groups underwent a 30-minute global ischemia followed by a 60-minute reperfusion. Results: The results showed that heart rate (HR, coronary flow, and left ventricular developed pressure (LVDP and rate of pressure product (RPP significantly decreased in the control group during reperfusion, while these values in the groups receiving the extract (3mg/ml improved significantly during reperfusion (p

  17. Ozone protects rat heart against ischemia-reperfusion injury: A role for oxidative preconditioning in attenuating mitochondrial injury.

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    Meng, Weixin; Xu, Ying; Li, Dandan; Zhu, Erjun; Deng, Li; Liu, Zonghong; Zhang, Guowei; Liu, Hongyu

    2017-04-01

    Ischemia-reperfusion injury (IRI) is a major cause of cardiac dysfunction during cardiovascular surgery, heart transplantation and cardiopulmonary bypass procedures. The purpose of the present study was to explore, firstly, whether ozone induces oxidative preconditioning by activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and, secondly, whether ozone oxidative preconditioning (OzoneOP) can protect the heart against IRI by attenuating mitochondrial damage. Rats were subjected to 30min of cardiac ischemia followed by 2h of reperfusion, with or without prior OzoneOP (100μg/kg/day) for 5 days. Antioxidant capacity, myocardial apoptosis and mitochondrial damage were evaluated and compared at the end of reperfusion. OzoneOP was found to increase antioxidant capacity and to protect the myocardium against IRI by attenuating mitochondrial damage and myocardial apoptosis. The study suggests a potential role for OzoneOP in protecting the heart against IRI during cardiovascular surgery, cardiopulmonary bypass procedures or transplantation.

  18. Propofol improves cardiac functional recovery after ischemia-reperfusion by upregulating nitric oxide synthase activity in the isolated rat hearts

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    SUN Hai-yan; XUE Fu-shan; XU Ya-chao; LI Cheng-wen; XIONG Jun; LIAO Xu; ZHANG Yan-ming

    2009-01-01

    Background There are few studies to assess whether propofol attenuates myocardial ischemia-reperfusion injury via a mechanism related to nitric oxide (NO) route, so we designed this randomized blinded experiment to observe the changes of NO contents, nitric oxide synthase (NOS) activity, NOS contents in the myocardium, and cardiac function in ischemic reperfused isolated rat hearts, and to assess the relation between myocardial NO system and cardioprotection of propofol.Methods The hearts of 30 Sprague-Dawley male rats were removed, mounted on a Langendorff apparatus, and randomly assigned to one of three groups (n=10 each group) to be treated with the following treatments in a blinded manner: Group 1, control group, after perfusion with pure Krebs Henseleit bicarbonate (K-HBB) buffer solution for 15 minutes, hearts were subjected to 20 minutes global ischemia followed by 60 minutes reperfusion with pure K-HBB buffer; Group 2, after perfusion with K-HBB buffer solution containing propofol (10 μg/ml) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution; Group 3, after perfusion with K-HBB buffer solution containing propofol (10 μg/ml) and L-NAME (100 μmol/L) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution. The cardiac function was continuously monitored throughout the experiment.The coronary flow was also measured. An ISO-NO electrode was placed into the right atrium close to the coronary sinus to continuously measure NO concentration in the coronary effluent. The tissue samples from apex of hearts in Groups 1 and 2 were obtained to measure the NOS activity by spectrophotometry and the NOS contents by immunohistochemistry, respectively.Results The cardiac function was significantly inhibited after ischemia and then gradually improved with reperfusion in all three groups. As compared with Group 1

  19. Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

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    Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak; Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd

    2016-10-01

    The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes ( n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

  20. Hemidesmus indicus and Hibiscus rosa-sinensis Affect Ischemia Reperfusion Injury in Isolated Rat Hearts

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    Vinoth Kumar Megraj Khandelwal

    2011-01-01

    Full Text Available Hemidesmus indicus (L. R. Br. (HI and Hibiscus rosa-sinensis L. (HRS are widely used traditional medicine. We investigated cardioprotective effects of these plants applied for 15 min at concentrations of 90, 180, and 360 μg/mL in Langendorff-perfused rat hearts prior to 25-min global ischemia/120-min reperfusion (I/R. Functional recovery (left ventricular developed pressure—LVDP, and rate of development of pressure, reperfusion arrhythmias, and infarct size (TTC staining served as the endpoints. A transient increase in LVDP (32%–75% occurred at all concentrations of HI, while coronary flow (CF was significantly increased after HI 180 and 360. Only a moderate increase in LVDP (21% and 55% and a tendency to increase CF was observed at HRS 180 and 360. HI and HRS at 180 and 360 significantly improved postischemic recovery of LVDP. Both the drugs dose-dependently reduced the numbers of ectopic beats and duration of ventricular tachycardia. The size of infarction was significantly decreased by HI 360, while HRS significantly reduced the infarct size at all concentrations in a dose-dependent manner. Thus, it can be concluded that HI might cause vasodilation, positive inotropic effect, and cardioprotection, while HRS might cause these effects at higher concentrations. However, further study is needed to elucidate the exact mechanism of their actions.

  1. Cardioprotection by polysaccharide sulfate against ischemia/reperfusion injury in isolated rat hearts

    Institute of Scientific and Technical Information of China (English)

    Ying YANG; Shen-jiang HU; Liang LI; Guo-ping CHEN

    2009-01-01

    Aim: Polysaccharide sulfate (PSS) is a new type of heparinoid synthesized with alginic acid as the basic material and then by chemical introduction of effective groups. Although PSS is successfully applied in ischemic cardio-cerebrovascular dis-ease, its effect on cardiac function after ischemia/reperfusion (I/R) injury has previously not been investigated. The aim of the present study was to investigate whether PSS can protect the heart from I/R injury and the underlying mechanism of protection. Methods: Isolated rat hearts were perfused (Langendorff) and subjected to 20 min global ischemia followed by 60 min rep-effusion with Kreb's Henseleit solution or PSS (0.3-100 mg/L). Myocardial contractile function was continuously recorded. Creatine kinase (CK) and lactate dehydrogenase (LDH) leakage were measured. Tumor necrosis factor-α (TNF-α) expres-sion in cardiomyocytes was investigated. Western blot analysis for extracellular regulated kinases (ERKs), c-jun amino-terminal kinase (INKs) and p38 mitogen-activated protein kinase (MAPK) activity was performed. Results: After I/R, cardiac contractility decreased, CK and LDH levels increased in the coronary effluent, and TNF-α expression increased in cardiomyocytes. PSS administration at concentrations of 1-30 mg/L improved cardiac contractility, reduced CK and LDH release and inhibited TNF-α production. Phosphorylated-p38MAPK (p-p38MAPK) and p-p54/p46-JNK increased in I/R rat hearts but diminished in PSS (1-30 mg/L) treated hearts. P-p44/p42-ERK levels were unchanged. In contrast, high concentrations of PSS (100 mg/L) had adverse effects that caused a worsening of heart function. Conclusion: PSS has dose-dependent cardioprotective effects on the rat heart after I/R injury. The beneficial effects may be mediated through normalization of the activity of p38 MAPK and JNK pathways as well as controlling the level of TNF-α expression.

  2. Early reperfusion hemodynamics predict recovery in rat hearts: a potential approach towards evaluating cardiac grafts from non-heart-beating donors.

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    Monika Dornbierer

    Full Text Available AIMS: Cardiac grafts from non-heartbeating donors (NHBDs could significantly increase organ availability and reduce waiting-list mortality. Reluctance to exploit hearts from NHBDs arises from obligatory delays in procurement leading to periods of warm ischemia and possible subsequent contractile dysfunction. Means for early prediction of graft suitability prior to transplantation are thus required for development of heart transplantation programs with NHBDs. METHODS AND RESULTS: Hearts (n = 31 isolated from male Wistar rats were perfused with modified Krebs-Henseleit buffer aerobically for 20 min, followed by global, no-flow ischemia (32°C for 30, 50, 55 or 60 min. Reperfusion was unloaded for 20 min, and then loaded, in working-mode, for 40 min. Left ventricular (LV pressure was monitored using a micro-tip pressure catheter introduced via the mitral valve. Several hemodynamic parameters measured during early, unloaded reperfusion correlated significantly with LV work after 60 min reperfusion (p<0.001. Coronary flow and the production of lactate and lactate dehydrogenase (LDH also correlated significantly with outcomes after 60 min reperfusion (p<0.05. Based on early reperfusion hemodynamic measures, a composite, weighted predictive parameter, incorporating heart rate (HR, developed pressure (DP and end-diastolic pressure, was generated and evaluated against the HR-DP product after 60 min of reperfusion. Effective discriminating ability for this novel parameter was observed for four HR*DP cut-off values, particularly for ≥20 *10(3 mmHg*beats*min(-1 (p<0.01. CONCLUSION: Upon reperfusion of a NHBD heart, early evaluation, at the time of organ procurement, of cardiac hemodynamic parameters, as well as easily accessible markers of metabolism and necrosis seem to accurately predict subsequent contractile recovery and could thus potentially be of use in guiding the decision of accepting the ischemic heart for transplantation.

  3. Early Reperfusion Hemodynamics Predict Recovery in Rat Hearts: A Potential Approach towards Evaluating Cardiac Grafts from Non-Heart-Beating Donors

    Science.gov (United States)

    Dornbierer, Monika; Stadelmann, Mathieu; Sourdon, Joevin; Gahl, Brigitta; Cook, Stéphane; Carrel, Thierry P.; Tevaearai, Hendrik T.; Longnus, Sarah L.

    2012-01-01

    Aims Cardiac grafts from non-heartbeating donors (NHBDs) could significantly increase organ availability and reduce waiting-list mortality. Reluctance to exploit hearts from NHBDs arises from obligatory delays in procurement leading to periods of warm ischemia and possible subsequent contractile dysfunction. Means for early prediction of graft suitability prior to transplantation are thus required for development of heart transplantation programs with NHBDs. Methods and Results Hearts (n = 31) isolated from male Wistar rats were perfused with modified Krebs-Henseleit buffer aerobically for 20 min, followed by global, no-flow ischemia (32°C) for 30, 50, 55 or 60 min. Reperfusion was unloaded for 20 min, and then loaded, in working-mode, for 40 min. Left ventricular (LV) pressure was monitored using a micro-tip pressure catheter introduced via the mitral valve. Several hemodynamic parameters measured during early, unloaded reperfusion correlated significantly with LV work after 60 min reperfusion (p<0.001). Coronary flow and the production of lactate and lactate dehydrogenase (LDH) also correlated significantly with outcomes after 60 min reperfusion (p<0.05). Based on early reperfusion hemodynamic measures, a composite, weighted predictive parameter, incorporating heart rate (HR), developed pressure (DP) and end-diastolic pressure, was generated and evaluated against the HR-DP product after 60 min of reperfusion. Effective discriminating ability for this novel parameter was observed for four HR*DP cut-off values, particularly for ≥20 *103 mmHg*beats*min−1 (p<0.01). Conclusion Upon reperfusion of a NHBD heart, early evaluation, at the time of organ procurement, of cardiac hemodynamic parameters, as well as easily accessible markers of metabolism and necrosis seem to accurately predict subsequent contractile recovery and could thus potentially be of use in guiding the decision of accepting the ischemic heart for transplantation. PMID:22928009

  4. Gene transfer of heat-shock protein 20 protects against ischemia/reperfusion injury in rat hearts

    Institute of Scientific and Technical Information of China (English)

    Yan-hui ZHU; Tie-min MA; Xian WANG

    2005-01-01

    Aim: To explore whether overexpression of HSP20 in the myocardium could protect against ischemia/reperfusion injury in rats. Methods: Rat hearts were injected with vector, recombinant adenovirus encoding green fluorescent protein (Ad. GFP) or recombinant adenovirus encoding wild-type HSP20 (Ad. HSP20) in the left ventricle. Four days later, hearts were removed and expression of HSP20was measured in the left ventricle. Subsets of animals in the vector-, Ad. GFP-, and Ad. HSP20-treated groups were subjected to 20-min ischemia and 120-min reperfusion. Myocardial injury was evaluated by infarct size and level of serum cardiac troponin T and creatine phosphokinase. Apoptosis of cardiomyocytes was determined by TUNEL staining. Cardiac function was evaluated by hemodynamic indexes. Results: Infarct size and serum cardiac troponin T and creatine phosphokinase levels were significantly reduced in Ad. HSP20-treated hearts compared with vector- and Ad. GFP-treated hearts. The ratio of TUNEL-positive cardiomyocytes to total number of cardiomyocytes in the Ad. HSP20 group was significantly reduced as compared with the vector and Ad. GFP groups. Left ventricular end systolic pressure, and maximal rate of pressure increase (+dp/dtmax)and decrease (-dp/dtmin) values were increased significantly, while left ventricular end diastolic pressure was decreased significantly in Ad.HSP20-treated hearts compared with vector- and Ad. GFP-treated hearts. Conclusion: These data indicate that the cardioprotective effects of HSP20 may contribute to the reduction of myocardial necrosis and apoptosis in ischemia/reperfusion injury in rats.

  5. Protective Effects of Elaeagnus angustifolia Leaf Extract against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart

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    Binsheng Wang

    2014-01-01

    Full Text Available The purpose of this study is to clarify the cardioprotective property of the aqueous extract of Elaeagnus angustifolia L. leaf (EA against myocardial ischemia/reperfusion injury in isolated rat heart. The myocardial ischemia/reperfusion (I/R injury model of isolated rat heart was set up by the use of improved Langendorff retrograde perfusion technology. Compared with the ischemia/reperfusion (I/R group, the aqueous extract of Elaeagnus angustifolia L. leaf (0.5 mg/mL, 1.0 mg/mL pretreatment markedly improved the coronary flow (CF and raised left ventricular developed pressure (LVDP and maximum rise/down velocity (±dp/dtmax. The infarct size of the EA-treated hearts was smaller than that of I/R group. After treatment with EA, the superoxide dismutase (SOD activity increased; malondialdehyde (MDA and protein carbonyl content reduced more obviously (P<0.01 than that of I/R injury myocardial tissue. Conclusion. Results from the present study showed that the aqueous extract of Elaeagnus angustifolia L. leaf has obvious protective effects on myocardial I/R injury, which may be related to the improvement of myocardial oxidative stress states.

  6. Insulin Preconditioning Elevates p-Akt and Cardiac Contractility after Reperfusion in the Isolated Ischemic Rat Heart

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    Tamaki Sato

    2014-01-01

    Full Text Available Insulin induces cardioprotection partly via an antiapoptotic effect. However, the optimal timing of insulin administration for the best quality cardioprotection remains unclear. We tested the hypothesis that insulin administered prior to ischemia provides better cardioprotection than insulin administration after ischemia. Isolated rat hearts were prepared using Langendorff method and divided into three groups. The Pre-Ins group (Pre-Ins received 0.5 U/L insulin prior to 15 min no-flow ischemia for 20 min followed by 20 min of reperfusion. The Post-Ins group (Post-Ins received 0.5 U/L insulin during the reperfusion period only. The control group (Control was perfused with KH buffer throughout. The maximum of left ventricular derivative of pressure development (dP/dt(max was recorded continuously. Measurements of TNF-α and p-Akt in each time point were assayed by ELISA. After reperfusion, dP/dt(max in Pre-Ins was elevated, compared with Post-Ins at 10 minutes after reperfusion and Control at all-time points. TNF-α levels at 5 minutes after reperfusion in the Pre-Ins were lower than the others. After 5 minutes of reperfusion, p-Akt was elevated in Pre-Ins compared with the other groups. Insulin administration prior to ischemia provides better cardioprotection than insulin administration only at reperfusion. TNF-α suppression is possibly mediated via p-Akt leading to a reduction in contractile myocardial dysfunction.

  7. Oral delivery of insulin withDesmodium gangeticum root aqueous extract protects rat hearts against ischemia reperfusion injury in streptozotocin induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Gino A Kurian; Jose Paddikkala

    2010-01-01

    Objective:To evaluate the effect of insulin administered via oral route with the help of aqueous extract ofDesmodium gangeticum (DG) root in rendering cardio protection against ischemia reperfusion injury in diabetic rats.Methods: Diabetes mellitus was induced in rats by theβ-cell toxin, streptozotocin (STZ, 60 mg/kg). Isolated rat (IR) heart was used to investigate the effect of insulin mixed DG pretreatment on ischemia reperfusion injury. Mitochondrial respiratory enzymes and microsomal enzymes were used to assess the metabolic recovery of myocardium. Cardiac marker enzymes were used to find the functional recovery, which were compared with that of the STZ treated IR rats.Results: Compared with IR control group, rat treated with insulin mixed DG showed a significant functional and metabolic recovery of myocardium from the insult of ischemia reperfusion. Even though orally administered insulin mixed DG displayed a slow but prolonged hypoglycemic effect, the cardio protection it provided was more significant than when it was given intra peritoneal. Furthermore the above result indicates that insulin mixed DG can overcome the barriers in the gastrointestinal tract and be absorbed.Conclusions: The above results indicate the efficacy of insulin mixed DG in protecting the heart from ischemia reperfusion induced injury in diabetic rats. Furthermore the study gives additional information that herbal extracts can be used to transport insulin across the membrane and found to be a feasible approach for developing the oral delivery of insulin, as well as other peptide drugs.

  8. [Cardioprotective effect of heme oxygenase-1 induction by hemin on the isolated rat heart during ischemia--reperfusion].

    Science.gov (United States)

    Kukoba, T V; Moĭbenko, O O; Kotsioruba, A V

    2003-01-01

    The aim of the study was to determine the role of both an inducible isoform of heme oxygenase (HO-1) and products of heme catabolism (carbon monoxide (CO), cardiac bilirubin and Fe2+) in protecting myocardium against post-ischemic myocardial dysfunction. Rat hearts were isolated and perfused according to the Langendorff technique to evaluate the recovery of myocardial function after total ischemia (20 min) and reperfusion (40 min) and production of reactive oxygen forms at a reperfusion phase. Ischemia/reperfusion caused impairment in myocardial function: left ventricular developing pressure (LVDP) was shown to be decreased, while end-diastolic pressure (EDP) and both coronary perfusion pressure and coronary resistance increased. Free oxygen radicals were generated at the reperfusion phase which led to injuries to cardiomyocytes and creatine kinase efflux into perfusate. We have found that upregulation of HO-1 by preliminary (24 h before ischemia) injections of 25 mg/kg hemin (i.p.) resulted in improving the myocardial function due to increasing the enzyme activity and forming the cardial bilirubine, while generation of reactive oxygen forms was inhibited, as well as the contents of creatine kinase reduced. As a result, impairment in cardiomyocytes diminished, and coronary vessels dilated to improve the functional parametres of the heart work.

  9. Control of the cardiac consequences of myocardial ischemia and reperfusion by L-propionylcarnitine: age-response and dose-response studies in the rat heart.

    Science.gov (United States)

    Riva, E; Leopaldi, D

    1993-10-01

    We assessed the protective effects of L-propionylcarnitine, a liposoluble analogue of carnitine, in the isolated heart from rats of different ages subjected to global ischemia and reperfusion. Hearts from neonatal (3- to 7-d-old), immature (2- to 3-wk-old), and adult rats were retrogradely perfused with a modified Krebs bicarbonate buffer and subjected to ischemia and reperfusion. L-Pro-pionylcarnitine was given either before ischemia and throughout reperfusion (protocol 1) or during reperfusion only (protocol 2). Coronary flow, heart rate, left ventricular developed pressure, and left ventricular end-diastolic pressure were measured throughout the perfusion period. Ventricular arrhythmias and creatine kinase leakage were measured at the time of reperfusion. Postischemic recovery of coronary flow and left ventricular developed pressure were age dependent and were not affected by L-propionylcarnitine, but recovery of heart rate was decreased in neonatal and immature hearts by 10(-4) M and 10(-5) M (p Propionylcarnitine always reduced creatine kinase leakage in the adult (p propionylcarnitine. However, in the adult rat hearts, L-propionylcarnitine given before ischemia and throughout reperfusion was protective by reducing creatine kinase leakage.

  10. [PHARMACOLOGICAL CARDIOPROTECTION DURING REPERFUSION OF ISOLATED HEART].

    Science.gov (United States)

    Grigor'ev, E V; Toropova, Ya G; Plotnikov, G P; Krutitskiy, S S; Shukevich, D L; Salmin, V V; Golovkin, A S

    2015-01-01

    To study the contractile function, the degree of damage and regional myocardial metabolism in the isolated rat heart model subjected to cardioplegic stop and reperfusion under the protection of levosimendan. The study was performed on isolated rat hearts Wistar (group using "Custodiol" vs group using "Custodiol" + "Levosimendan". We assessed the extent of myocardial damage (in terms of markers of myocardial necrosis), the contractile function of the myocardium (coronary flow, heart rate, left ventricular pressure), the dynamics of redox processes during reperfusion with a parallel study of histology of the myocardium. We found a presence of cardioprotective effect of levosimendan in respect of the isolated heart in the reperfusion period of cardioplegic ischemia. The effect related to reducing the emission of reperfusion enzyme markers of myocardial damage, reducing the severity of pathological changes in the myocardium and reducing the intensity of free radical reactions in the myocardium. Cardioprotection with levosimendan reduces the severity of free radical attack the isolated heart, reduces the severity of damage to cardiomyocytes and preserves the contractile activity of the myocardium during reperfusion due to the effect of postconditioning.

  11. Effects of Acetyl-L-Carnitine on Cardiac Arrhythmias and Infarct Size in Ischemic-Reperfused Isolated Rat Heart

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    Moslem Najafi

    2010-01-01

    Full Text Available This study aimed to examine whether acetyl-L-carnitine (ALC was able to reduce cardiac arrhythmias and infarct size in the ischemic-reperfused isolated rat heart.Materials and MethodsThe isolated hearts were mounted on a Langendorff apparatus then perfused by a modified Krebs-Henseleit solution during 30 min regional ischemia and 120 min reperfusion (control or by enriched Krebs solution with 0.375, 0.75, 1.5 and 3 mM of ALC (treatment groups. The ECGs were recorded and analyzed to determine cardiac arrhythmias. The infarct size was determined by using a computerized planimetry package.ResultsDuring ischemia, all used concentrations of ALC decreased number and duration of ventricular tachycardia (VT, total number of ventricular ectopic beats (VEBs (P<0.01, incidence of total ventricular fibrillation (VF and the time spent for reversible VF (P<0.05. At the reperfusion phase, duration of VT, incidence of total VF and reversible VF were significantly lowered by ALC (P<0.05. In addition, infarct size significantly was decreased in all treated groups. In the control group, the infarct size was 23±3.1%, however, ALC (0.375, 0.75 and 3 mM reduced it to 8.7±2.3, 5.3±1.4, and 8±2.9%, respectively (P<0.01. ConclusionConsidering the results, it may be concluded that ALC has protective effects against cardiac ischemia-reperfusion (I/R injuries by reduction of infarct size and arrhythmias in isolated rat heart. Among the potential cardioprotective mechanisms for ALC, increase in glucose oxidation and resulting reduced lactate production, reduction of toxic fatty acid metabolites and removing free radicals from the myocytes are more relevant.

  12. Effects of Chronic Oral Administration of Natural Honey on Ischemia/Reperfusion-induced Arrhythmias in Isolated Rat Heart

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    Moslem Najafi

    2011-01-01

    Full Text Available Objective(sIn this study, effects of chronic administration of oral natural honey against ischemia/reperfusion (I/R-induced cardiac arrhythmias were investigated in isolated rat heart. Materials and MethodsMale Wistar rats were divided into four groups (n= 10-14 rats in each group and fed with natural honey (1%, 2% and 4% dissolved in the drinking water for 45 days except for the control group. After anesthesia, the rats’ hearts were isolated quickly, mounted on a Langendorff apparatus and perfused with a modified Krebs-Henseleit solution during stabilization, 30 min regional ischemia followed by 30 min reperfusion. The ECGs were recorded throughout the experiments to analyze cardiac arrhythmias based on the Lambeth conventions. ResultsIn the ischemic phase, honey (1% significantly reduced (P<0.05 the number and duration of ventricular tachycardia (VT. Honey (1% and 2% also significantly decreased number of ventricular ectopic beats (VEBs. In addition, incidence and duration of reversible ventricular fibrillation (Rev VF were lowered by honey 2% (P<0.05. During reperfusion time, VT incidence was 73% in the control group, however natural honey (1% decreased it to 22% (P<0.05. Honey also produced significant reduction in the incidences of total VF, Rev VF, duration and number of VT. ConclusionFor the first time, the results of present study demonstrated protective effects of chronic oral honey administration against I/R-induced arrhythmias in isolated rat heart. Antioxidant activity, the existence of energy sources such as glucose and fructose and improvement of some hemodynamic functions might be responsible for these effects.

  13. Glycyrrhizin protects rat heart against ischemia-reperfusion injury through blockade of HMGB1-dependent phospho-JNK/Bax pathway

    Institute of Scientific and Technical Information of China (English)

    Chang-lin ZHAI; Mei-qi ZHANG; Yun ZHANG; Hong-xia XU; Jing-min WANG; Gui-peng AN; Yuan-yuan WANG; Li LI

    2012-01-01

    Aim: Glycyrrhizin (GL) has been found to inhibit extracellular HMGB1 cytokine's activity,and protect spinal cord,liver and brain against I/R-induced injury in experimental animals.The purpose of this study was to investigate the protective effect of GL in rat myocardial I/R-induced injury and to elucidate the underlying mechanisms.Methods: Male adult Sprague-Dawley rats underwent a 30-min left coronary artery occlusion followed by a 24-h reperfusion.The rats were treated with glycyrrhizin or glycyrrhizin plus recombinant HMGB1 after 30 min of ischemia and before reperfusion.Serum HMGB1,TNF-α and IL-6 levels,and hemodynamic parameters were measured at the onset and different time points of reperfusion.At the end of the experiment,the heart was excised,and the infarct size and histological changes were examined.The levels of Bcl2,Bax and cytochrome c,as well as phospho-ERK1/2,phospho-JNK and phospho-P38 in the heart tissue were evaluated using Western blot analysis,and myocardial caspase-3 activity was measured colorimetrically using BD pharmingen caspase 3 assay kit.Results: Intravenous administration of GL (10 mg/kg) significantly reduced the infarct size,but did not change the hemodynamic parameters at different time points during reperfusion.GL significantly decreased the levels of serum HMGB1,TNF-α and IL-6.GL changed the distribution of Bax and cytochrome c expression between the mitochondrial and cytosolic fractions in the heart tissue,resulting in inhibition of myocardial apoptosis.Moreover,expression of phospho-JNK,but not ERK1/2 and P38 was decreased by GL in the heart tissue.All of the effects produced by GL treatment were reversed by co-administration with the recombinant HMGB1 (100 μg).Intravenous administration of SP600125,a selective phospho-JNK inhibitor (0.5 mg/kg),attenuated HMGB1-dependent Bax translocation and the subsequent apoptosis.Conclusion: These results demonstrate that GL alleviates rat myocardial I/R-induced injury via directly

  14. [Effect of different concentrations liposomal emoxipine on coronary flow, contractive and pump function of the isolated rat heart after normotermic ischema and further reperfusion].

    Science.gov (United States)

    Toropova, Ia G; Mukhamadiiarov, R A; Golovkin, A S

    2013-07-01

    In the experiments on the isolated perfused rat heart we studied the effects of liposomes containing different concentrations (0.25 and 0.1 mg/ml) of emoxipine on coronary flow, contractive and pump function of the isolated heart, which was effected by total normothermical ischemia and reperfusion. The parameters of the contractile activity of hearts, coronary flow and pump function of the hearts were assessed. It was detected that the introduction of the liposomal emoxipine during ischemia provides a protective effect against ischemic and reperfusion myocardial damage and smaller concentration of the emoxipin (0.1 mg/ml) in composition with the liposomes promote the best recovery of contractile activity and the pumping function of the ischemic heart in the period of the reperfusion.

  15. Activation of Akt and cardioprotection against reperfusion injury are maximal with only five minutes of sevoflurane postconditioning in isolated rat hearts

    Institute of Scientific and Technical Information of China (English)

    Yuan-yuan YAO; Man-hua ZHU; Feng-jiang ZHANG; Chuan-yun WEN; Lei-lei MA; Wen-na WANG; Can-can WANG

    2013-01-01

    It had been proved that administration of sevoflurane for the first two minutes of reperfusion effectively protects the heart against reperfusion injury in rats in vivo.Our aim was to investigate the duration of effective sevoflurane administration and its underlying mechanism in isolated rat hearts exposed to global ischemia/reperfusion (I/R) injury.Adult male Sprague-Dawley rats were randomly divided into six groups (n=12):a sham-operation group,an I/R group,and four sevoflurane postconditioning groups (S2,S5,S10,and S15).In the S2,S5,S10,and S15 groups,the duration times of sevoflurane administration were 2,5,10,and 15 min after the onset of reperfusion,respectively.The isolated rat hearts were mounted on the Langendorff system,and after a period of equilibrium were subjected to 40 min global ischemia and 120 min reperfusion.Left ventricular (LV) hemodynamic parameters were monitored throughout each experiment and the data at 30 min of equilibrium and 30,60,90,and 120 min of reperfusion were analyzed.Myocardial infarct size at the end of reperfusion (n=7 in each group) and the expression of myocardial phosphorylated Akt (p-Akt) after 15-min reperfusion were determined in a duplicate set of six groups of rat hearts (n=5 in each group).Compared with the I/R group,the S5,S10,and S15 groups had significantly improved left ventricular end-diastolic pressure (LVEDP),left ventricular developed pressure (LVDP),and the maximal rate of rise or fall of the LV pressure (±dP/dtmax),and decreased myocardial infarct size (P<0.05),but not the S2 group.After 15 min of reperfusion,the expression of p-Akt was markedly up-regulated in the S5,S10,and S15 groups compared with that in the I/R group (P<0.05),but not in the S2 group.Sevoflurane postconditioning for 5 min was sufficient to activate Akt and exert maximal cardioprotection against I/R injury in isolated rat hearts.

  16. KR-31762, a novel KATP channel opener, exerts cardioprotective effects by opening SarcKATP channels in rat models of ischemia/reperfusion-induced heart injury.

    Science.gov (United States)

    Lee, Sung-Hun; Yang, Min-Kyu; Lim, Jong-Hyun; Seo, Ho-Won; Yi, Kyu-Yang; Yoo, Sung-Eun; Lee, Byung-Ho; Won, Hyung-Sik; Lee, Chang-Soo; Choi, Wahn-Soo; Shin, Hwa-Sup

    2008-04-01

    The cardioprotective effects of KR-31762, a newly synthesized K+(ATP) opener, were evaluated in rat models of ischemia/reperfusion (I/R) heart injury. In isolated rat hearts subjected to 30-min global ischemia followed by 30-min reperfusion, KR-31762 (3 and 10 microM) significantly increased the left ventricular developed pressure (LVDP) and double product (heart rate x LVDP) after 30-min reperfusion in a concentration-dependent manner, while decreasing the left ventricular end-diastolic pressure (LVEDP). KR-31762 also significantly increased the time to contracture (TTC) during ischemic period (20.0, 22.4 and 26.4 min for control, 3 and 10 microM, respectively), while decreasing the release of lactate dehydrogenase (LDH) from the heart during 30 min reperfusion (30.4, 14.3 and 19.7 U/g heart weight, respectively). All these parameters except LDH release were reversed by glyburide (1 microM), a nonselective blocker of K+(ATP) channel, but not by 5-hydroxydecanoate, a selective blocker of mitoK+(ATP) channel. In anesthetized rats subjected to 45-min occlusion of left anterior descending coronary artery followed by 90-min reperfusion, KR-31762 significantly decreased the infarct size (60.8, 40.5 and 37.8% for control, 0.3 and 1.0 mg/kg, iv, respectively). KR-31762 slightly relaxed the isolated rat aorta precontracted with methoxamine (IC(50): 23.5 microM). These results suggest that KR-31762 exerts potent cardioprotective effects through the opening of sarcolemmal K(ATP) channel in rat hearts with the minimal vasorelaxant effects.

  17. Quantitative Mitochondrial Proteomics Study on Protective Mechanism of Grape Seed Proanthocyanidin Extracts Against Ischemia/Reperfusion Heart Injury in Rat

    Institute of Scientific and Technical Information of China (English)

    LU Wei-da; QIU Jie; ZHAO Gai-xia; QIE Liang-yi; WEI Xin-bing; GAO Hai-qing

    2012-01-01

    Cardiac ischemia/reperfusion(I/R) injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts(GSPE) against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia(VT)and ventricular fibrillation(VF),the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation(iTRAQ) profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A(MAOA) was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.

  18. Antioxidant effects of ethyl acetate extract of Desmodium gangeticum root on myocardial ischemia reperfusion injury in rat hearts

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    Raman Archana

    2010-01-01

    Full Text Available Abstract Background This study aims to evaluate the antioxidant potential of the ethyl acetate extract of Desmodium gangeticum root for cardioprotection from ischemia reperfusion-induced oxidative stress. Methods The in vitro antioxidant potential of the extract was in terms of hydroxyl radical scavenging activity, lipid peroxide scavenging activity, nitric oxide scavenging activity and diphenylpicrylhydrazyl radical scavenging activity. The in vivo antioxidant potential of the extract was assessed in an isolated rat heart model. Results Free radicals were scavenged by the extract in a concentration-dependent manner within the range of the given concentrations in all models. Administration of the ethyl acetate extract of Desmodium gangeticum root (100 mg per kg body weight before global ischemia caused a significant improvement of cardiac function and a decrease in the release of lactate dehydrogenase in coronary effluent, as well as the level of malondialdehyde in myocardial tissues. Conclusion The ethyl acetate extract of Desmodium gangeticum root protects the myocardium against ischemia-reperfusion-induced damage in rats. The effects of the extract may be related to the inhibition of lipid peroxidation.

  19. Cardioprotective Effect of Angiotensin Ⅱ Receptor Antagonist on Perfused Ischemic Reper-fusion Injury of Whole Isolated Rat Hearts

    Institute of Scientific and Technical Information of China (English)

    徐延敏; 黄体钢; 陈元禄; 李广平

    2003-01-01

    Objectives Investigated the cardioprotective and mechanisms of losartan onwhole isolated ischemic reperfused rat heart. Meth-ods Langendorff perfused systems was used to in-vestigate losartan effect on whole isolated rat hearts inCPK, LDH, MDA, SOD, ang Ⅱ and arrhythmia. Re-sults Losartan decreased incidence of arrhythmia,improved atrial ventricular block recovery in reperfu-sion period, during ischemic period, CPK and LDH inI/R group increased significantly compared with con-trol group, 51.33±27.02 vs 22.42±13.33, 31.80±4.56 vs 22.28 ± 15.96, respectively, but greatlydecreased in losartan group compared with I/R group,23.90±21.74 vs 51.33±27.02 and 11.50±13.20vs 31.80 ± 4. 56, respectively. During reperfusion pe-riod CPK, LDH increased significantly in I/R groupcompared with control group, 49.11 ± 20.63 vs 12.14±5.92 and 28.70±4.69 vs 23.10±21.38, re-spectively, but decreased greatly in losartan groupcompared with I/R group, 39.40 ± 9.60 vs 49.11 ±20.63 and 14.50±13.75 vs 28.70±4.69. Thecontent of MDA, ang Ⅱ in I/R group myocytes ishigher than control group's , 26. ±9. 25 vs 17.2 ±3.37 and 8.43±3.81 vs 4. 80±0.20. However thecontent of SOD in two groups has no significantlychange, 148. 20 ± 8. 72 vs 145.08±6.82. the con-tent of MDA in losartan group myocardial tissue ismuch lower than control group, 15.92±4.05 vs26.80± 9.25 and the content of ang Ⅱ in losartangroup myocardial tissue is much higher than I/Rgroup, 12.44 ± 6.09 vs 8.43 ± 3.21. The departmentof cardiology of second hospital of Tianjin medical u-niversity Tianjin 300211 However, SOD has nosignificant change in two groups, 143.47 ±7.91 vs145.08 ± 6.82. Conclusions Losartan against is-chemic-reperfusion injury of whole isolated rathearts, those beneficial effects are mediate primarily bythe inhibited of angiotensin Ⅱ binding with its receptorand inhibited oxygen free radical scavenging potential.

  20. Evaluation of Chronic Physical and Psychological Stress Induction on Cardiac Ischemia / Reperfusion Injuries in Isolated Male Rat Heart: The Role of Sympathetic Nervous System.

    Science.gov (United States)

    Rakhshan, Kamran; Imani, Alireza; Faghihi, Mahdieh; Nabavizadeh, Fatemeh; Golnazari, Masoumeh; Karimian, SeyedMorteza

    2015-08-01

    Exposure to stress leads to physiological changes called "stress response" which are the result of the changes in the adrenomedullary hormone system, hypothalamus-pituitary-adrenal (HPA) and sympathetic nervous system (SNS) activity. In the present study, the effects of chronic physical and psychological stress and also the role of sympathetic system effects in stress on ischemia/reperfusion (I/R) injuries have been studied in isolated rat heart. Rat heart was isolated and subjected to 30 min regional ischemia and 120 min reperfusion. The daily stress was induced for one week prior to I/R induction. Sympathectomy was done chemically by injection of hydroxyl-dopamine prior to stress induction. There were no significant changes in heart rate and Coronary Flow between groups. Left ventricular developed pressure (LVDP) and rate product pressure (RPP) in both physical and psychological stress groups decreased significantly compared to those in control group (Pphysical and psychological stress groups. Infarct size significantly increased in both physical and psychological stress groups and control group(Pstress led to the elimination of the deleterious effects of stress as compared with stress groups (Presults show that induction of chronic physical and psychological stress prior to ischemia/reperfusion causes enhancement of myocardial injuries and it seems that increased sympathetic activity in response to stress is responsible for these adverse effects of stress on ischemic/reperfused heart.

  1. Role of Opioid Receptors Signaling in Remote Electrostimulation--Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts.

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    Hsin-Ju Tsai

    Full Text Available Our previous studies demonstrated that remote electro-stimulation (RES increased myocardial GSK3 phosphorylation and attenuated ischemia/ reperfusion (I/R injury in rat hearts. However, the role of various opioid receptors (OR subtypes in preconditioned RES-induced myocardial protection remains unknown. We investigated the role of OR subtype signaling in RES-induced cardioprotection against I/R injury of the rat heart.Male Spraque-Dawley rats were used. RES was performed on median nerves area with/without pretreatment with various receptors antagonists such as opioid receptor (OR subtype receptors (KOR, DOR, and MOR. The expressions of Akt, GSK3, and PKCε expression were analyzed by Western blotting. When RES was preconditioned before the I/R model, the rat's hemodynamic index, infarction size, mortality and serum CK-MB were evaluated. Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype. Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group. The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left, RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left were 50%, 20%, 67%, 13%, 50% and 55%, respectively.The mechanism of RES-induced myocardial protection against I/R injury seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling.

  2. 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.

  3. Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway

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    Heng-Fei Luan

    2012-10-01

    Full Text Available The JAK2/STAT3 signal pathway is an important component of survivor activating factor enhancement (SAFE pathway. The objective of the present study was to determine whether the JAK2/STAT3 signaling pathway participates in hydrogen sulfide (H2S postconditioning, protecting isolated rat hearts from ischemic-reperfusion injury. Male Sprague-Dawley rats (230-270 g were divided into 6 groups (N = 14 per group: time-matched perfusion (Sham group, ischemia/reperfusion (I/R group, NaHS postconditioning group, NaHS with AG-490 group, AG-490 (5 µM group, and dimethyl sulfoxide (DMSO; <0.2% group. Langendorff-perfused rat hearts, with the exception of the Sham group, were subjected to 30 min of ischemia followed by 90 min of reperfusion after 20 min of equilibrium. Heart rate, left ventricular developed pressure (LVDP, left ventricular end-diastolic pressure (LVEDP, and the maximum rate of increase or decrease of left ventricular pressure (± dp/dt max were recorded. Infarct size was determined using triphenyltetrazolium chloride (TTC staining. Myocardial TUNEL staining was used as the in situ cell death detection method and the percentage of TUNEL-positive nuclei to all nuclei counted was used as the apoptotic index. The expression of STAT3, bcl-2 and bax was determined by Western blotting. After reperfusion, compared to the I/R group, H2S significantly improved functional recovery and decreased infarct size (23.3 ± 3.8 vs 41.2 ± 4.7%, P < 0.05 and apoptotic index (22.1 ± 3.6 vs 43.0 ± 4.8%, P < 0.05. However, H2S-mediated protection was abolished by AG-490, the JAK2 inhibitor. In conclusion, H2S postconditioning effectively protects isolated I/R rat hearts via activation of the JAK2/STAT3 signaling pathway.

  4. Effects of broad band electromagnetic fields on HSP70 expression and ischemia-reperfusion in rat hearts.

    Science.gov (United States)

    Ronchi, Raffaella; Marano, Lidia; Braidotti, Paola; Bianciardi, Paola; Calamia, Mario; Fiorentini, Cesare; Samaja, Michele

    2004-09-03

    Although exposure to broad band (0.2-20 MHz) electromagnetic fields (EMF) is part of the treatment of several diseases, little is known as to their effects on myocardial protein expression and resistance to ischemia-reperfusion (I/R). We exposed Sprague-Dawley rats to either high (H, 10 min/day at 200 V/m, 36.1 microT) or low (L, 2 min/day at 30 V/m, 11.4 microT) intensity broad band EMF for 15 days. At the end of the treatment, myocardial HSP70 was 32 +/- 8% (mean +/- SEM) higher in L (P = 0.01) than in control (C), whereas in H it remained the same as in C. Electron microscopy revealed sporadic ruptures of mitochondrial cristae in H hearts, with no differences in other parameters. Malondialdehyde was increased in treated hearts (P < 0.05), but especially in H (P = 0.008). To assess the protective role of HSP70 during I/R, hearts were Langendorff-perfused with Krebs-Henseleit. After I/R, C hearts displayed depressed rate. pressure (-13 +/- 7%) and increased end-diastolic (+9.2 +/- 2.8 mmHg) and perfusion pressures (+30 +/- 10 mmHg). In H and L, rate. pressure recovery was similar to C (-2 +/- 21% and -12 +/- 16%, respectively, P = NS). In contrast, both end-diastolic and perfusion pressures were higher in L than in H (30.8 +/- 5.4 vs 18.2 +/- 3.5, P = 0.01, and 54 +/- 8 vs 21 +/- 8 mmHg, P = 0.01, respectively) indicating diastolic derangement in L. In conclusion, the effects of broad band EMF on HSP70 appear to be biphasic, and HSP70 overexpression might not be directly related to improved protection against I/R.

  5. Acute ethanol exposure increases the susceptibility of the donor hearts to ischemia/reperfusion injury after transplantation in rats.

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    Shiliang Li

    contractility and relaxation, oxidative stress and altered protein expression were observed. CONCLUSIONS: These results demonstrate acute alcohol abuse increases the susceptibility of donor hearts to ischemia/reperfusion in a rat heart transplant model even though the global contractile function recovers 6 h after ethanol-administration.

  6. Methanol extract of Desmodium gangeticum roots preserves mitochondrial respiratory enzymes, protecting rat heart against oxidative stress induced by reperfusion injury.

    Science.gov (United States)

    Kurian, Gino A; Yagnesh, N; Kishan, R Sanchit; Paddikkala, Jose

    2008-04-01

    Ischaemia and reperfusion result in mitochondrial dysfunction, with decreased oxidative capacity, loss of cytochrome c and generation of reactive oxygen species. The aim of this study was to evaluate the effect of a methanol extract of Desmodium gangeticum (L) DC (Fabaceae) (DG) on lipid peroxidation and antioxidants in mitochondria and tissue homogenates of normal, ischaemic and ischaemia-reperfused rats. Myocardial lipid peroxidation products (thiobarbituric acid reactive substances; TBARS) in cardiac tissue homogenates and mitochondrial fractions were significantly increased during ischaemia reperfusion. Antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase (GPx) and glutathione reductase) in the myocardial tissue homogenate and mitochondria decreased significantly during ischaemia reperfusion, accompanied by a decreased activity of mitochondrial respiratory enzymes. Daily pretreatment of rats with DG (50 or 100 mgkg(-1)) orally for 30 days had a significant effect on the activity of mitochondrial and antioxidant enzymes. In-vitro studies showed that DG inhibited lipid peroxidation, and also scavenged hydroxyl and superoxide radicals. The concentrations required to scavenge 50% of the superoxide and hydroxyl radicals were 21 and 50.5 microgmL(-1), respectively. Administration of DG to normal rats did not have any significant effect on any of the parameters studied. The results of our study showed that DG possesses the ability to scavenge the free radicals generated during ischaemia and ischaemia reperfusion and thereby preserves the mitochondrial respiratory enzymes that eventually lead to cardioprotection.

  7. Chronic Losartan Treatment Up-Regulates AT1R and Increases the Heart Vulnerability to Acute Onset of Ischemia and Reperfusion Injury in Male Rats.

    Science.gov (United States)

    Song, Minwoo A; Dasgupta, Chiranjib; Zhang, Lubo

    2015-01-01

    Inhibition of angiotensin II type 1 receptor (AT1R) is an important therapy in the management of hypertension, particularly in the immediate post-myocardial infarction period. Yet, the role of AT1R in the acute onset of myocardial ischemia and reperfusion injury still remains controversial. Thus, the present study determined the effects of chronic losartan treatment on heart ischemia and reperfusion injury in rats. Losartan (10 mg/kg/day) was administered to six-month-old male rats via an osmotic pump for 14 days and hearts were then isolated and were subjected to ischemia and reperfusion injury in a Langendorff preparation. Losartan significantly decreased mean arterial blood pressure. However, heart weight, left ventricle to body weight ratio and baseline cardiac function were not significantly altered by the losartan treatment. Of interest, chronic in vivo losartan treatment significantly increased ischemia-induced myocardial injury and decreased post-ischemic recovery of left ventricular function. This was associated with significant increases in AT1R and PKCδ expression in the left ventricle. In contrast, AT2R and PKCε were not altered. Furthermore, losartan treatment significantly increased microRNA (miR)-1, -15b, -92a, -133a, -133b, -210, and -499 expression but decreased miR-21 in the left ventricle. Of importance, addition of losartan to isolated heart preparations blocked the effect of increased ischemic-injury induced by in vivo chronic losartan treatment. The results demonstrate that chronic losartan treatment up-regulates AT1R/PKCδ and alters miR expression patterns in the heart, leading to increased cardiac vulnerability to ischemia and reperfusion injury.

  8. Evaluation of Chronic Physical and Psychological Stress Induction on Cardiac Ischemia / Reperfusion Injuries in Isolated Male Rat Heart: The Role of Sympathetic Nervous System

    Directory of Open Access Journals (Sweden)

    Kamran Rakhshan

    2015-10-01

    Full Text Available Exposure to stress leads to physiological changes called “stress response” which are the result ofthe changes in the adrenomedullary hormone system, hypothalamus-pituitary-adrenal (HPA and sympatheticnervous system (SNS activity. In the present study, the effects of chronic physical and psychological stressand also the role of sympathetic system effects in stress on ischemia/reperfusion (I/R injuries have beenstudied in isolated rat heart. Rat heart was isolated and subjected to 30 min regional ischemia and 120 minreperfusion. The daily stress was induced for one week prior to I/R induction. Sympathectomy was donechemically by injection of hydroxyl-dopamine prior to stress induction. There were no significant changes inheart rate and Coronary Flow between groups. Left ventricular developed pressure (LVDP and rate productpressure (RPP in both physical and psychological stress groups decreased significantly compared to those incontrol group (Pgroups. Infarct size significantly increased in both physical and psychological stress groups and control group(Pas compared with stress groups (Ppsychological stress prior to ischemia/reperfusion causes enhancement of myocardial injuries and it seemsthat increased sympathetic activity in response to stress is responsible for these adverse effects of stress onischemic/reperfused heart.

  9. Metformin induces cardioprotection against ischaemia/reperfusion injury in the rat heart 24 hours after administration.

    Science.gov (United States)

    Solskov, Lasse; Løfgren, Bo; Kristiansen, Steen B; Jessen, Niels; Pold, Rasmus; Nielsen, Torsten T; Bøtker, Hans Erik; Schmitz, Ole; Lund, Sten

    2008-07-01

    The UK Prospective Diabetes Study demonstrated that the hypoglycaemic drug metformin is associated with a reduction in cardiovascular events in a group of obese type 2 diabetes patients. The energy sensing enzyme AMP-activated protein kinase (AMPK) has been indicated to play an important protective role in the ischaemic heart and is activated by metformin. The aim of this study was to determine whether a single dose of metformin protects the myocardium against experimentally induced ischaemia 24 hr after the administration, and furthermore to determine whether a single dose of metformin results in an acute increase in myocardial AMPK activity. Wistar rats were given either a single oral dose of metformin (250 mg/kg body weight), or a single oral dose of saline. After 24 hr, the hearts were Langendorff-perfused and subjected to 45 min. of coronary artery occlusion. Infarct size was determined by staining with triphenyltetrazoliumchloride (TTC) and Evans Blue and expressed as a percentage of the risk zone (IS/AAR %). Isoform specific AMPK activity was measured 2 hr after administration of metformin or saline. Infarct size was significantly reduced in the metformin treated (I/R: 19.9 +/- 3.9%versus 36.7 +/- 3.6%, P < 0.01, n = 8-14) compared to the control group. A single oral dose of metformin resulted in an approximately ~2-fold increase in AMPK-alpha2 activity 2 hr after administration (P < 0.015, n = 10). In conclusion, a single dose of metformin results in an acute increase in myocardial AMPK activity measured 2 hr after administration and induces a significant reduction in myocardial infarct size 24 hr after metformin administration. Increased AMPK activity may be an important signal mediator involved in the mechanisms behind the cardioprotective effects afforded by metformin.

  10. Distinct effects of acute pretreatment with lipophilic and hydrophilic statins on myocardial stunning, arrhythmias and lethal injury in the rat heart subjected to ischemia/reperfusion.

    Science.gov (United States)

    Čarnická, S; Adameová, A; Nemčeková, M; Matejíková, J; Pancza, D; Ravingerová, T

    2011-01-01

    Although both lipophilic and more hydrophilic statins share the same pathway of the inhibition of HMG-CoA reductase, their pleiotropic cardioprotective effects associated with the ability to cross cellular membranes, including membranes of heart cells, may differ. To test this hypothesis, isolated rat hearts were Langendorff-perfused either with simvastatin (S, 10 micromol/l) or pravastatin (P, 30 micromol/l), 15 min prior to ischemia. Control untreated hearts (C) were perfused with perfusion medium only. Postischemic contractile dysfunction, reperfusion-induced ventricular arrhythmias and infarct size were investigated after exposure of the hearts to 30-min global ischemia and 2-h reperfusion. Both lipophilic S and hydrophilic P reduced the severity of ventricular arrhythmias (arrhythmia score) from 4.3 +/- 0.2 in C to 3.0 +/- 0 and 2.7 +/- 0.2 in S and P, respectively, (both P statins indicating a different ability to cross cardiac membranes may underlie their distinct cardioprotective effects on myocardial stunning and lethal injury induced by ischemia/reperfusion.

  11. Protection of the reperfused heart by L-propionylcarnitine.

    Science.gov (United States)

    Leipälä, J A; Bhatnagar, R; Pineda, E; Najibi, S; Massoumi, K; Packer, L

    1991-10-01

    The effects of L-propionylcarnitine on mechanical function, creatine phosphate and ATP content, and lactate dehydrogenase leakage were studied in isolated perfused rat hearts exposed to global no-flow ischemia for 30 min followed by reperfusion for 20 min. Five and 10 mM L-propionylcarnitine resulted in a 100% recovery of left ventricular-developed pressure, whereas the recovery was only 40% in the hearts perfused without this agent. Ischemia-reperfusion caused a 85% loss of creatine phosphate and a 77% loss of ATP, which was prevented by 10 mM L-propionylcarnitine. Five millimolar L-propionylcarnitine protected the heart from the loss of creatine phosphate but not from the loss of ATP. Ten millimolar L-propionylcarnitine failed to improve the postischemic left ventricular-developed pressure, when it was added to the perfusate only after ischemia. L-propionylcarnitine alleviated the decrease of coronary flow in the reperfused hearts. Lactate dehydrogenase leakage was aggravated in the beginning of the reperfusion period by 10 mM L-propionylcarnitine. This adverse effect was, however, transient. L-Propionylcarnitine provides protection for the postischemic reperfused heart in a dose-dependent manner. The optimal time for administration is before the ischemic insult. High doses of this compound may perturb cell membrane integrity. Moreover, the present data point to an intracellular, metabolic, and perhaps anaplerotic mechanism of action of L-propionylcarnitine in cardiac ischemia-reperfusion injury.

  12. Effect of HEMADO on Level of CK-MB and LDH Enzymes after Ischemia/Reperfusion Injury in Isolated Rat Heart

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    Mohammad Amani

    2013-01-01

    Full Text Available Introduction: Ischemia/Reperfusion (IR injury mainly causes the increase of enzymes involved in myocytes injury including CK-MB (creatine kinase-MB isoenzyme and LDH (lactate dehydrogenase. Leakage of CK-MB isoenzyme and LDH from myocardial tissues to blood is indicator of acute myocardial infarction. The aim of this study was to assess the effect of HEMADO on IR injury and its relationship with mitochondrial ATP-sensitive K+ channels (mitoKATP in rat heart. Methods: Twenty eight male Wistar rats (250-300g were divided into four groups (seven members in each group: control (without ischemia, I/R (with ischemia+without HEMADO, ischemia received HEMADO (HEMADO, ischemia received HEMADO and 5-HD (5-hydroxydecanoate, specific mitoKATP channel blocker (HEMADO+5-HD. The animals were anesthetized and the hearts were quickly removed and mounted on Langendorff apparatus and perfused by Krebs-Henseleit solution under constant pressure and temperature of 37ºC. After 20 minutes of stabilization, ischemic groups were exposed to 40 minutes of global ischemia and consecutive 90 minutes of reperfusion. Results: IR injury increased the level of LDH and CK-MB in the collected coronary flow during 5 minutes since start of reperfusion. HEMADO reduced the enzymes’ levels and using 5-HD abolished the effect of HEMADO. Conclusion: Our findings indicated that HEMADO could protect the heart against ischemia-reperfusion injury by decreasing the CK-MB and LDH levels. The cardioprotective effect of HEMADO may be mediated in part by mitoKATP.

  13. C1q/TNF-Related Protein 9 Protects Diabetic Rat Heart against Ischemia Reperfusion Injury: Role of Endoplasmic Reticulum Stress

    Science.gov (United States)

    Bai, Sanxing; Cheng, Liang; Yang, Yang; Fan, Chongxi; Zhao, Dajun; Qin, Zhigang; Feng, Xiao; Zhao, Lin; Ma, Jipeng; Wang, Xiaowu; Yang, Jian; Xu, Xuezeng

    2016-01-01

    As a newly identified adiponectin paralog, C1q/TNF-related protein 9 (CTRP9) reduces myocardial ischemia reperfusion (IR) injury through partially understood mechanisms. In the present study, we sought to identify the role of endoplasmic reticulum stress (ERS) in CTRP9 induced cardioprotection in diabetic heart. Isolated hearts from high-fat-diet (HFD) induced type 2 diabetic Sprague-Dawley rats were subjected to ex vivo IR protocol via a Langendorff apparatus at the presence of globular CTRP9. CTRP9 significantly improved post-IR heart function and reduced cardiac infarction, cardiomyocytes apoptosis, Caspase-3, Caspase-9, Caspase-12, TNF-α expression, and lactate dehydrogenase activity. The cardioprotective effect of CTRP9 was associated with reduced ERS and increased expression of disulfide-bond A oxidoreductase-like protein (DsbA-L) in diabetic heart. CTRP9 reduced ERS in thapsigargin (TG) treated cardiomyocytes and protected endoplasmic reticulum (ER) stressed H9c2 cells against simulated ischemia reperfusion (SIR) injury, concurrent with increased expression of DsbA-L. Knockdown of DsbA-L increased ERS and attenuated CTRP9 induced protection against SIR injury in H9c2 cells. Our findings demonstrated for the first time that CTRP9 exerts cardioprotection by reducing ERS in diabetic heart through increasing DsbA-L.

  14. The influence of experimental hyperlipidemia on the time course of contractility during simulated ischaemia and reperfusion and responsiveness to phenylephrine of rat heart papillary muscle.

    Science.gov (United States)

    Kocić, I; Dworakowska, D; Konstański, Z; Dworakowski, R

    1998-09-01

    The aim of this study was to examine the influence of simulated ischaemia on the contractility and responsiveness to phenylephrine of rat isolated papillary muscle in standard diet fed (SD) and hyperlipidemic diet fed (HLD) rats. The following parameters were measured: force of contraction (Fc), rate of rise (+dF/dt) and rate of fall (-dF/dt) of force of contraction, time to peak contraction (ttp) and relaxation time at 10% of total amplitude of contraction (tt10). The baseline values of Fc and +dF/dt, but, not -dF/dt, were significantly lower in HLD group than in SD group. Tissues from HLD rats were more sensitive to ischaemia regarding Fc, +dF/dt and -dF/dt. Moreover, reprefusion completely reversed the effects of ischaemia only in SD rats, but not in HLD rats, regarding Fc and +dF/dt. In contrast, a recovery of -dF/dt during reperfusion occurred only in the HLD group. In SD rats, phenylephrine (10 and 30 microM) had no effect on the contractility or induced megative inotropic effects (100 and 300 microM). Propranolol (1 microM), a non-selective blocker of beta-adrenoceptors, had no effects on this action. Chloroethylclonidine (CEC) (1 microM), a selectivw blocker of alpha 1b-adrenoceptor subtype, but not WB-4101(2-((2,6-dimethoxyphenoxyethyl)amino-methyl-1,4-benzodioxane), a selective blocker of alpha 1a adrenoceptor subtype, abolishes the negative inotropic action of phenylephrine. In HLD rats, phenylephrine had positive inotropic action (10 and 30 microM). The results indicate that hyperlipidemic diet in rats leads to the suppression of force of contraction and velocity of contraction, but not velocity of relaxation of isolated heart muscle. Under such a condition, heart muscle is more sensitive to ischaemia, but has better responsiveness to phenylephrine after ischeamia-reperfusion period.

  15. Combined subthreshold dose inhibition of myosin light chain phosphorylation and MMP-2 activity provides cardioprotection from ischaemic/reperfusion injury in isolated rat heart.

    Science.gov (United States)

    Cadete, Virgilio J J; Sawicka, Jolanta; Bekar, Lane K; Sawicki, Grzegorz

    2013-09-01

    Phosphorylation and degradation of myosin light chain 1 (MLC1) during myocardial ischaemia/reperfusion (I/R) injury is a well-established phenomenon. It has been established that MMP-2 is involved in MLC1 degradation and that this degradation is increased when MLC1 is phosphorylated. We hypothesized that simultaneous inhibition of MLC1 phosphorylation and MMP-2 activity will protect hearts from I/R injury. As phosphorylation of MLC1 and MMP-2 activity is important for normal heart function, we used a cocktail consisting combination of low (subthreshold for any protective effect alone) doses of MLC kinase, MMP-2 inhibitors and subthreshold dose of an MLC phosphatase activator. Isolated rat hearts were subjected to 20 min of global, no-flow ischaemia and 30 min reperfusion in the absence and presence of inhibitors of MLC1 phosphorylation and degradation. The recovery of cardiac function was improved in a concentration-dependent manner by the MLC kinase inhibitor, ML-7 (1-5 μM), the MLC phosphatase activator, Y-27632 (0.05-1 μM) or the MMP inhibitor, doxycycline (Doxy, 1-30 μM). Co-administration of subthreshold doses of ML-7 (1 μM) and Y-27632 (0.05 μM) showed a potential synergistic effect in protecting cardiac contractility and MLC1 levels in I/R hearts. Further combination with a subthreshold concentration of Doxy (1 μM) showed additional protection that resulted in full recovery to control levels. The results of this study exemplify a novel low-dose multidrug approach to pharmacological prevention of reperfusion injury that will enable a reduction of unwanted side effects and/or cytotoxicity associated with currently available MMP-2 and kinase inhibiting drugs. © 2013 The British Pharmacological Society.

  16. Cardioprotective Effects of Total Flavonoids Extracted from Xinjiang Sprig Rosa rugosa against Acute Ischemia/Reperfusion-Induced Myocardial Injury in Isolated Rat Heart.

    Science.gov (United States)

    Hou, Xuejiao; Han, Jichun; Yuan, Changsheng; Ren, Huanhuan; Zhang, Ya; Zhang, Tao; Xu, Lixia; Zheng, Qiusheng; Chen, Wen

    2016-01-01

    This study evaluated the antioxidative and cardioprotective effects of total flavonoids extracted from Xinjiang sprig Rosa rugosa on ischemia/reperfusion (I/R) injury using an isolated Langendorff rat heart model. The possible mechanism of Xinjiang sprig rose total flavonoid (XSRTF) against I/R injury was also studied. XSRTF (5, 10, and 20 µg/mL) dissolved in Krebs-Henseleit buffer was administered to isolated rat heart. The XSRTF showed remarkable scavenging effects against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and superoxide anion radicals in vitro. XSRTF pretreatment improved the heart rate, increased LVDP, and decreased CK and LDH levels in coronary flow. This pretreatment also increased SOD activity and GSH/GSSG ratio but decreased MDA, TNF-α, and CRP levels and IL-8 and IL-6 activities. The infarct size and cell apoptosis in the hearts from the XSRTF-treated group were lower than those in the hearts from the I/R group. Therefore, the cardioprotective effects of XSRTF may be attributed to its antioxidant, antiapoptotic, and anti-inflammatory activities.

  17. A lipophilic nitric oxide donor and a lipophilic antioxidant compound protect rat heart against ischemia-reperfusion injury if given as hybrid molecule but not as a mixture.

    Science.gov (United States)

    Rastaldo, Raffaella; Raffaella, Rastaldo; Cappello, Sandra; Sandra, Cappello; Di Stilo, Antonella; Antonella, Di Stilo; Folino, Anna; Anna, Folino; Losano, Gianni; Gianni, Losano; Pagliaro, Pasquale; Pasquale, Pagliaro

    2012-03-01

    Low concentrations of a hydrophilic nitric oxide donor (NOD) are reported to reduce myocardial reperfusion injury only when combined with a lipophilic antioxidant (AOX) to form a hybrid molecule (HYB). Here we tested whether liposoluble NOD requires to be combined with AOX to be protective. Isolated rat hearts underwent 30 minutes of ischemia and 120 minutes of reperfusion. To induce postconditioning, 1 μM solutions of the following liposoluble compounds were given during the first 20 minutes of reperfusion: NOD with weak (w-NOD) or strong NO-releasing potency (s-NOD); weak HYB built up with w-NOD and a per se ineffective AOX lead; strong HYB built up with s-NOD and the same AOX; mixtures of w-NOD plus AOX or s-NOD plus AOX. A significant reduction of infarct size with improved recovery of cardiac function was obtained only with weak HYB. We suggest that w-NOD requires the synergy with a per se ineffective AOX to protect. The synergy is possible only if the 2 moieties enter the cell simultaneously as a hybrid, but not as a mixture. It seems that strong HYB was ineffective because an excessive intracellular NO release produces a large amount of reactive species, as shown from the increased nitrotyrosine production.

  18. Overexpression of heat-shock protein 20 in rat heart myogenic cells confers protection against simulated ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Yan-hui ZHU; Xian WANG

    2005-01-01

    Aim: To explore whether overexpression of the small heat shock protein HSP20 in rat cardiomyocytes protects against simulated ischemia/reperfusion (SI/R) injury.Methods: Recombinant adenovirus expressing HSP20 was used to infect rat H9c2cardiomyocytes at high efficiency, as assessed by green fluorescent protein. H9c2cells were subjected to SI/R stress; survival was estimated through assessment of lactate dehydrogenase and cell apoptosis through caspase-3 activity. Results:Overexpression of HSP20 decreased lactate dehydrogenase release by 21.5% and caspase-3 activity by 58.8%. Pretreatment with the protein kinase C inhibitor Ro31-8220 (0.1 μmol/L) for 30 min before SI/R canceled the protective effect of HSP20.The selective mitochondrial K+ATP channel inhibitor 5-hydroxydecanoate ( 100 μmol/L)had a similar effect. However, the non-selective K+ATP channel inhibitor glibenclamide (100 μmol/L) had no significant effect. Conclusion: These data indicate that the protective effect of HSP20 in vitro is primarily due to reduced necrotic and apoptotic death of cardiomyocytes, possibly via the protein kinase C/mitochondrial K+ATP pathway.

  19. Cardioprotective effects of the novel Na+/H+ exchanger-1 inhibitor KR-32560 in a perfused rat heart model of global ischemia and reperfusion: Involvement of the Akt-GSK-3beta cell survival pathway and antioxidant enzyme.

    Science.gov (United States)

    Jung, In-Sang; Lee, Sung-Hun; Yang, Min-Kyu; Park, Jung-Woo; Yi, Kyu-Yang; Yoo, Sung-Eun; Kwon, Suk-Hyung; Chung, Hun-Jong; Choi, Wahn-Soo; Shin, Hwa-Sup

    2010-08-01

    To investigate the cardioprotective effects and mechanism of action of KR-32560 {[5-(2-methoxy-5-fluorophenyl)furan-2-ylcarbonyl]guanidine}, a newly synthesized NHE-1 inhibitor, we evaluated the effects of KR-32560 on cardiac function in a rat model of ischemia/reperfusion (I/R)-induced heart injury as well as the role antioxidant enzymes and pro-survival proteins play these observed effects. In isolated rat hearts subjected to 25 min of global ischemia followed by 30 min of reperfusion, KR-32560 (3 and 10 microM) significantly reversed the I/Rinduced decrease in left ventricular developed pressure and increase in left ventricular enddiastolic pressure. In rat hearts reperfused for 30 min, KR-32560 (10 microM) significantly decreased the malondialdehyde content while increasing the activities of both glutathione peroxidase and catalase, two important antioxidant enzymes. Western blotting analysis of left ventricles subjected to I/R showed that KR-32560 significantly increased phosphorylation of both Akt and GSK-3beta in a dose-dependent manner, with no effect on the phosphorylation of eNOS. These results suggest that KR-32560 exerts potent cardioprotective effects against I/Rinduced rat heart injury and that its mechanism involves antioxidant enzymes and the Akt-GSK-3beta cell survival pathway.

  20. 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.

  1. Remifentanil-induced preconditioning has cross-talk with A1 and A2B adenosine receptors in ischemic-reperfused rat heart

    Directory of Open Access Journals (Sweden)

    Yong-Cheol Lee

    2016-01-01

    Full Text Available The purpose of this study was to determine whether there is a cross-talk between opioid receptors (OPRs and adenosine receptors (ADRs in remifentanil preconditioning (R-Pre and, if so, to investigate the types of ADRs involved in the cross-talk. Isolated rat hearts received 30 min of regional ischemia followed by 2 hr of reperfusion. OPR and ADR antagonists were perfused from 10 min before R-Pre until the end of R-Pre. The heart rate, left ventricular developed pressure (LVDP,velocity of contraction (+dP/dtmax, and coronary flow (CF were recorded. The area at risk and area of necrosis were measured. After reperfusion, the LVDP, +dP/dtmax,and CF showed a significant increase in the R-Pre group compared with the control group (no intervention before or after regional ischemia. These increases in the R-Pre group were blocked by naloxone, a nonspecific ADR antagonist, an A1 ADR antagonist, and an A2B ADR antagonist. The infarct size was reduced significantly in the R-Pre group compared with the control group. The infarct-reducing effect in the R-Pre group was blocked by naloxone, the nonspecific ADR antagonist, the A1 ADR antagonist, and the A2B ADR antagonist. The results of this study demonstrate that there is cross-talk between ADRs and OPRs in R-Pre and that A1 ADR and A2B ADR appear to be involved in the cross-talk.

  2. [The effect of argan oil on heart function during ischemia and reperfusion].

    Science.gov (United States)

    Benajiba, N; Morel, S; De Leiris, J; Boucher, F; Charrouf, Z; Mokhtar, N; Aguenaou, H

    2002-01-01

    The aim of this study was to evaluate the effect of organ oil on isolated heart function before and after ischemia and on the activity of cardiac antioxidant enzymes. 16 Wistar rats were divided into 2 groups; control group and treated group receiving 5 mL/kg/day of organ oil. After 8 weeks of treatment, hearts were perfused and subjected to a global ischemia followed by reperfusion. Activity of cardiac antioxidant enzymes was assessed in freeze-clamped hearts at the end of reperfusion. Results showed that organ oil induces: 1--damage to heart function during the preischemic period, 2--decreased functional recovery during reperfusion and 3--significant increase in catalase activity. It seems that, in our experimental conditions, organ oil increases heart sensitivity to ischemia and reperfusion. However, the mechanism involved has yet to be understood.

  3. Ischemic Postconditioning-Regulated miR-499 Protects the Rat Heart Against Ischemia/Reperfusion Injury by Inhibiting Apoptosis through PDCD4

    Directory of Open Access Journals (Sweden)

    Jianbing Zhu

    2016-11-01

    Full Text Available Background: Here, we determined miR-499 involvement in the protective effect of ischemic postconditioning (IPC against myocardial ischemia/reperfusion (I/R injury and identified the underlying mechanisms. Methods: To investigate the cardioprotective effect of IPC-induced miR-499, rats were divided into the following five groups: sham, I/R, IPC, IPC + scramble, and IPC + antagomiR-499. Hemodynamic indexes were measured by carotid-artery intubation to assess left ventricular function . Ischemia and infarction areas of rat hearts were determined by Evans blue and triphenyltetrazolium chloride staining, and cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end-labeling assay. Results: IPC attenuated I/R-induced infarct size of the left ventricle (45.28 ± 5.40% vs. 23.56 ± 6.20%, P vs. 990.21 ± 172.39%, P vs. 1289.11 ± 347.28%, P vs. 4.85 ± 1.52%, P in vivo and in vitro by knockdown of cardiac miR-499, suggesting that miR-499 may participate in the protective function of IPC against I/R injury through targeting programmed cell death 4 (PDCD4. Conclusion: Our data revealed that IPC-regulated miR-499 plays an important role in IPC-mediated cardiac protection against I/R injury by targeting PDCD4.

  4. NADPH oxidase inhibitor apocynin attenuates ischemia/reperfusion induced myocardial injury in rats

    Institute of Scientific and Technical Information of China (English)

    罗秀菊

    2013-01-01

    Objective To explore the role of NADPH oxidase inhibitor apocynin on ischemia/reperfusion(I/R)-induced myocardial injury. Methods Male SD rat hearts were divided into the normal control group; sham group;I/R group(1 h ischemia followed by 3 h reperfusion); I/R+ apocynin group(50 mg/kg,administrated at 30 min

  5. Schisandrin B decreases the sensitivity of mitochondria to calcium ion-induced permeability transition and protects against ischemia-reperfusion injury in rat hearts

    Institute of Scientific and Technical Information of China (English)

    Po-yee CHIU; Hoi-yan LEUNG; Ada HL SIU; Michel KT POON; Kam-ming KO

    2007-01-01

    Aim: In order to elucidate the molecular mechanism underlying the cardioprotection afforded by schisandrin B (Sch B), the effect of Sch B treatment on the sensitivity of mitochondria to Ca2+-stimulated permeability transition (PT) was investigated in rat hearts under normal and ischemia-reperfusion (I-R) conditions. Results:Myocardial I-R injury caused an increase in the sensitivity of mitochondria to Ca2+-stimulated PT in vitro. The enhanced sensitivity to mitochondrial PT was associated with increases in mitochondrial Ca2+ content as well as the extent of reactive oxidant species production in vitro and cytochrome c release in vivo.The cardioprotection afforded by Sch B pretreatment against I-R-induced injury was paralleled by the decrease in the sensitivity of myocardial mitochondria to Ca2+-stimulated PT, particularly under I-R conditions. Conclusion: The results suggest that Sch B treatment increases the resistance of myocardial mitochondria to Ca2+-stimulated PT and protects against I-R-induced tissue injury.

  6. KR-31761, a novel K+(ATP)-channel opener, exerts cardioprotective effects by opening both mitochondrial K+(ATP) and Sarcolemmal K+(ATP) channels in rat models of ischemia/reperfusion-induced heart injury.

    Science.gov (United States)

    Yang, Min-Kyu; Lee, Sung-Hun; Seo, Ho-Won; Yi, Kyu-Yang; Yoo, Sung-Eun; Lee, Byung-Ho; Chung, Hun-Jong; Won, Hyung-Sik; Lee, Chang-Soo; Kwon, Suk-Hyung; Choi, Wahn-Soo; Shin, Hwa-Sup

    2009-02-01

    The cardioprotective effects of KR-31761, a newly synthesized K+(ATP) opener, were evaluated in rat models of ischemia/reperfusion (I/R) heart injury. In isolated rat hearts subjected to 30-min global ischemia/30-min reperfusion, KR-31761 perfused prior to ischemia significantly increased both the left ventricular developed pressure (% of predrug LVDP: 17.8, 45.1, 54.2, and 62.6 for the control, 1 microM, 3 microM, and 10 microM, respectively) and double product (DP: heart rate x LVDP; % of predrug DP: 17.5, 44.9, 56.2, and 64.5 for the control, 1 microM, 3 microM, and 10 microM, respectively) at 30-min reperfusion while decreasing the left ventricular end-diastolic pressure (LVEDP). KR-31761 (10 microM) significantly increased the time to contracture during the ischemic period, whereas it concentration-dependently decreased the lactate dehydrogenase release during reperfusion. All these parameters were significantly reversed by 5-hydroxydecanoate (5-HD, 100 microM) and glyburide (1 microM), selective and nonselective blockers of the mitochondrial K+(ATP) (mitoK+(ATP)) channel and K+(ATP) channel, respectively. In anesthetized rats subjected to 30-min occlusion of left anterior descending coronary artery/2.5-h reperfusion, KR-31761 administered 15 min before the onset of ischemia significantly decreased the infarct size (72.2%, 55.1%, and 47.1% for the control, 0.3 mg/kg, i.v., and 1.0 mg/kg, i.v., respectively); and these effects were completely and almost completely abolished by 5-HD (10 mg/kg, i.v.) and HMR-1098, a selective blocker of sarcolemmal K+(ATP) (sarcK+(ATP)) channel (6 mg/kg, i.v.) administered 5 min prior to KR-31761 (72.3% and 67.9%, respectively). KR-31761 only slightly relaxed methoxamine-precontracted rat aorta (IC50: > 30.0 microM). These results suggest that KR-31761 exerts potent cardioprotective effects through the opening of both mitoK+(ATP) and sarcK+(ATP) channels in rat hearts with a minimal vasorelaxant effect.

  7. Cardioprotective Activity of Ganoderma lucidum Extract during Total Ischemia and Reperfusion of Isolated Heart.

    Science.gov (United States)

    Lasukova, T V; Maslov, L N; Arbuzov, A G; Burkova, V N; Inisheva, L I

    2015-04-01

    The cardioprotective effects of Ganoderma lucidum extract were examined in experiments with global ischemia (45 min) and reperfusion (30 min) of isolated and perfused rat heart. The course of preventive administration of the extract in a dose of 400 mg/kg for 15 days diminished necrotic death of cardiomyocytes and reduced reperfusion contracture. Ganoderma lucidum extract demonstrated antioxidant properties. The authors believe that the cardioprotective properties of Ganoderma lucidum extract are largely determined by its antioxidant properties.

  8. Prolonged Helium Postconditioning Protocols during Early Reperfusion Do Not Induce Cardioprotection in the Rat Heart In Vivo: Role of Inflammatory Cytokines

    Directory of Open Access Journals (Sweden)

    Gezina Tanya Mei Ling Oei

    2015-01-01

    Full Text Available Postconditioning of myocardial tissue employs short cycles of ischemia or pharmacologic agents during early reperfusion. Effects of helium postconditioning protocols on infarct size and the ischemia/reperfusion-induced immune response were investigated by measurement of protein and mRNA levels of proinflammatory cytokines. Rats were anesthetized with S-ketamine (150 mg/kg and diazepam (1.5 mg/kg. Regional myocardial ischemia/reperfusion was induced; additional groups inhaled 15, 30, or 60 min of 70% helium during reperfusion. Fifteen minutes of helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes of helium inhalation led to an infarct size of 47% and 39%, respectively. Increased protein levels of cytokine-induced neutrophil chemoattractant (CINC-3 and interleukin-1 beta (IL-1β were found after 30 or 60 min of helium inhalation, in comparison to control. 30 min of helium increased mRNA levels of CINC-3, IL-1β, interleukin 6 (IL-6, and tumor necrosis factor alpha (TNF-α in myocardial tissue not directly subjected to ischemia/reperfusion. These results suggest that the effectiveness of the helium postconditioning protocol is very sensitive to duration of noble gas application. Additionally, helium was associated with higher levels of inflammatory cytokines; however, it is not clear whether this is causative of nature or part of an epiphenomenon.

  9. Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts Efeitos benéficos da perfusão hiperosmótica no miocárdio após lesão isquemia/reperfusão em corações isolados de ratos

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    Yong Cao

    2013-03-01

    Full Text Available OBJECTIVE: A simple method to reduce the ischemia/reperfusion injury that can accompany cardiac surgery would have great clinical value. This study was to investigate the effect of hyperosmotic perfusion on ischemia/reperfusion injury in isolated perfused rat hearts. METHOD: Forty male Sprague-Dawley rats were randomly divided either to have their isolated hearts perfused with normal osmotic buffer or buffer made hyperosmotic by addition of glucose. Hearts were then subjected to 30 min ischemia followed by 30 min reperfusion. Coronary flow, time to ischemic arrest, reperfusion arrhythmia, and ventricular function were recorded. Creatine phosphokinase leakage into the coronary artery, and myocardial content and activity of superoxide dismutase and catalase were also examined. RESULTS: Rat hearts with hyperosmotic perfusion showed higher coronary flow, a prolonged time to ischemic arrest (10.60 vs. 5.63 min, POBJETIVO: Um método simples para reduzir a lesão de isquemia/reperfusão que pode acompanhar a cirurgia cardíaca teria grande valor clínico. O objetivo deste estudo foi investigar o efeito da perfusão hiperosmótica na isquemia/reperfusão em corações isolados de ratos perfundidos. MÉTODOS: Quarenta ratos machos Sprague-Dawley foram divididos aleatoriamente e tiveram os seus corações isolados perfundidos com tampão osmótico normal ou tampão hiperosmótico com a adição de glucose. Os corações foram então submetidos a 30 minutos de isquemia, seguida de 30 min de reperfusão. O fluxo coronariano, tempo de parada isquêmica, arritmia de reperfusão e da função ventricular foram registrados. Vazamento creatinofosfoquinase na artéria coronária, o miocárdio e atividade de superóxido dismutase e catalase foram também examinados. RESULTADOS: Crações de ratos com perfusão hiperosmótica apresentaram maior fluxo coronariano, tempo prolongado de parada isquêmica (10,60 vs. 5,63 min, P<0,005, menor pontuação de reperfus

  10. COMPARATIVE STUDY OF CARDIOPROTECTIVE EFFECT OF VARIOUS DIAMETER AND COMPOSITION LIPOSOMES DURING REPERFUSION OF THE ISOLATED RAT HEARTS AFTER NORMOTHERMIC ISCHEMIA

    Directory of Open Access Journals (Sweden)

    Ya. G. Toropova

    2013-01-01

    Full Text Available The wide application of cardiac surgery using the aorto-pulmonary bypass technique needs the development of new drugs, capable to minimize the heart damaging during ischemia and reperfusion. But the direct delivery of drugs into the damaged tissues and cells is a big problem. The liposomes as unique transport system can be used to solve this problem.The aim of the study was to evaluate the influence of "empty" liposomes of various diameter and the liposomes of different composition on the myocardium contractile function which has underwent the ischemia and the subsequent reperfusion. The obtained results allowed us to make the conclusion that liposomes of 50 nanometers in diameter are most effective to cardiac protection versus liposomes of 100 nanometers.Inclusion the emoxipine into the composition of liposomes provide the best results on contractile function of an ischemic myocardium.

  11. 大豆异黄酮对大鼠离体心肌缺血/再灌注损伤的保护作用%Protective Effect of Soy Isoflavones on Myocardial Ischemia-Reperfusion Injury in Isolated Rat Hearts

    Institute of Scientific and Technical Information of China (English)

    贾强; 杨锐; 刘小粉; 马善峰

    2011-01-01

    Objective To study the effect of soy isoflavones(SI) against myocardium iscahemia-reperfusion injury in isolated rat hearts. Methods The isolated Langendorff heart perfusion method was used. The effect of soy isofiavones(SI) against myocardium iscahemia-reperfusion was studied by hemodynamics experiment. Results Hemodynamic experiment in vitro showed that cardiac dysfunction was induced by ischemia-reperfusion, the changes of left ventricular pressure, dp/dt and CF in groups of ischemia-reperfusion containing soy isoflavones (SI) was smaller than those groups of ischemia-reperfusion without soy isofiavones ( SI ). It suggested that soy isoflavones(SI) could protect myocardium against ischemia-reperfusion lesion. Conclusion It was shown that soy isofiavones(SI) played an important role on protection ischemia-reperfusion induced cardiac dysfunction.%目的 观察大豆异黄酮对离体大鼠心脏缺血-再灌注(I/R)损伤的保护效应.方法 本文采用Langendorff离体心脏灌流方法,通过心脏动力学实验对大豆异黄酮抗I/R效应进行研究.结果 通过离体大鼠心脏动力学实验显示,缺血前药物各组心功能参数与对照组相比较,差异没有统计学意义(P>0.05);缺血后药物各组与对照组相比较,dp/dtmax与-dp/dtmax差异有统计学意义(P<0.01);再灌注后药物各组与对照组相比较,心率有改善,低剂量组差异有统计学意义(P<0.05).低剂量、高剂量组与对照组相比较dp/dtmax与-dp/dtmax有显著改善(P<0.01).结论 心肌缺血再灌注可抑制心脏的舒缩功能,大豆异黄酮不影响离体心脏的正常功能,但能改善缺血后再灌注引起的心律失常的离体心脏功能,可促进I/R后心功能的恢复.

  12. [Mechanisms of coronary flow recovery in the isolated heart during reperfusion with cardioprotective liposomal emoxipin form].

    Science.gov (United States)

    Toropova, Ia G; Antonova, L V; Mukhamadiiarov, R A; Bogdanov, M V; Golovkin, A S

    2013-06-01

    In the experiments on the isolated perfused rat heart the effects of liposomes, containing different concentrations (0.25 and 0.1 mg/mL) of emoxipine, on coronary flow restoration after total normothermic ischemia and reperfusion were studied. The coronary flow, levels of nitrates and nitrites in the outflowing perfusate from heart and level of free radical processes were assessed, The obtained results showed that 0.1 mg/mL liposomal emoxipine provide with stronger increase coronary flow during reperfusion mostly due to the increase concentration of endothelial nitric oxide compare with treatments at 0.25 mg/mL.

  13. Heart ischemia-reperfusion induces local upregulation of vasoconstrictor endothelin receptor type B in rat coronary arteries downstream of occlusion

    DEFF Research Database (Denmark)

    Skovsted, Gry Freja; Kruse, L.S.; Larsen, R;

    2014-01-01

    . However, under pathophysiological conditions ETB receptors may also be expressed in vascular smooth muscle cells mediating vasoconstriction. We aimed to investigate whether vasoconstrictor ETB receptors are upregulated in coronary arteries after experimental myocardial ischemia in rats.......Endothelins act via two receptor subtypes, endothelin receptor type A (ETA ) and type B (ETB ). Under physiological conditions in coronary arteries ETA receptors expressed in smooth muscle cells mediate vasoconstriction whereas ETB receptors mainly found in endothelial cells mediate vasorelaxation...

  14. COMPARATIVE STUDY OF CARDIOPROTECTIVE EFFECT OF VARIOUS DIAMETER AND COMPOSITION LIPOSOMES DURING REPERFUSION OF THE ISOLATED RAT HEARTS AFTER NORMOTHERMIC ISCHEMIA

    OpenAIRE

    Ya. G. Toropova; R. A. Mukhamadiyarov; Golovkin, A. S.

    2013-01-01

    The wide application of cardiac surgery using the aorto-pulmonary bypass technique needs the development of new drugs, capable to minimize the heart damaging during ischemia and reperfusion. But the direct delivery of drugs into the damaged tissues and cells is a big problem. The liposomes as unique transport system can be used to solve this problem.The aim of the study was to evaluate the influence of "empty" liposomes of various diameter and the liposomes of different composition on the myo...

  15. Activation of the elastin-laminin receptor (S-Gal) induces preconditioning in isolated rat heart submitted to ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    ArnaudROBINET; GeorgesBELLON; WilliamHORNEBECK; HerveMILLART

    2004-01-01

    AIM: Elastin-laminin receptor (S-Gal), was described to belong to G-protein-coupled receptors (GPCRs). Using an isolated nonworking rat heart model, we investigated whether S-Gal stimulation was able to mimic ischemic preconditioning as observed with some other GPCRs. METHODS: Hearts, after 6-hydroxydopamine pretreatment and a 20-min stabilization period,

  16. Proteção da recuperação funcional do miocárdio pelo omeprazol após isquemia-reperfusão em corações isolados de ratos Myocardium functional recovery protection by omeprazole after ischemia-reperfusion in isolated rat hearts

    Directory of Open Access Journals (Sweden)

    Otoni Moreira Gomes

    2010-09-01

    Full Text Available OBJETIVO: Analisar efeitos do omeprazol na proteção da recuperação funcional de corações isolados de ratos submetidos à lesão de isquemia-reperfusão. MÉTODOS: Foram estudados 12 ratos Wistar, peso corpóreo médio de 280g. Após anestesia com injeção intra-abdominal de 10mg de cetamina e 2mg de xilazina, os corações foram removidos e mantidos em perfusão com solução Krebs-Henseleit (95%O2 e 5% CO2, 37ºC, 110-120mmHg de pressão de perfusão e pressão diastólica de 8 mmHg em sistema Langendorff, modificado, descartável, modelo FCSFA-ServCor (Comex Ltda.. Os seis corações do Grupo I (GI e os seis do Grupo II (GII foram submetidos a 20 minutos de isquemia e 30 minutos de reperfusão. Nos corações do Grupo II, imediatamente antes da isquemia, foram administrados via perfusão coronária 200mcg de omeprazol. Foram controlados frequência cardíaca (FC, fluxo coronário (FCo, pressão sistólica (PS, +dP/dt e -dP/dt, após estabilização (t0 e no final da reperfusão (t30. Empregou-se método não paramétrico de Kruskal-Wallis (P0,05 entre os valores de FCo e FC nos dois grupos. No final do período de reperfusão (t30, foram significantes (POBJECTIVE: To evaluate the myocardium contractility alterations of isolated hearts of rats, submitted to ischemia and reperfusion with and without administration of the omeprazole. METHODS: Twelve Wistar breed rats with 270g mean body weight was studied. After anesthesia by intraperitoneal injection of ketamine 10mg and xylazine 2mg, their hearts were removed and perfused with Krebs-Henseleit solution (95% of O2 and 5% of CO2, 37ºC, 110-120 mmHg perfusion pressure, 8 mmHg ventricular diastolic pressure in the São Francisco de Assis disposable Langendorff system model Comex Ltda, MG. The six hearts of Group I (GI and of the Group II (GII were submitted to 20 min ischemia and 30 min reperfusion. In GII hearts, intracoronary injection of omeprazole 200 mcg was done immediately before the

  17. Urotensin-ⅡReceptor Antagonist SB-710411 Protects Rat Heart against Ischemia-Reperfusion Injury via RhoA/ROCK Pathway.

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    Sheng-Yong Luo

    Full Text Available SB-710411 is a rat selective urotensin-II (U-II receptor antagonist, which can block U-II-induced contraction of the aorta and inhibit U-II-induced myocardial fibrosis in rats. However, the effect of SB-710411 on myocardial ischemia-reperfusion (I/R injury is unclear. The present study was designed to investigate whether SB-710411 has a protective effect on myocardial I/R injury in rats and the possible mechanisms.Myocardial I/R injury was induced by occluding the left anterior descending coronary artery in adult male Sprague-Dawley rats. Hemodynamic parameters, electrocardiogram (ECG, infarct size, histological alteration, lactate dehydrogenase (LDH, creatine phosphokinase-MB (CK-MB, cardiac troponin I (cTnI, RhoA, and the protein expressions of U-II receptor (UTR, ROCK1 and ROCK2 were evaluated. Cardiac I/R injury significantly up-regulated the expressions of UTR, ROCK1 and ROCK2 proteins in rat myocardium. SB-710411 1.0 and 2.0 μg/kg significantly reduced cardiac I/R-induced the infarct size and histological damage in rat myocardium, markedly inhibited the changes of hemodynamic parameters and the increases of ST-segment in ECG, the serum LDH and CK-MB activities and cTnI level in rats subjected to myocardial I/R injury. Furthermore, SB-710411 obviously prevented myocardial I/R-increased RhoA activity and UTR, ROCK1 and ROCK2 protein expressions.Our results indicate that cardiac I/R injury increases myocardial UTR expression, and SB-710411 has a potent protective effect on myocardial I/R injury in rats. The cardioprotection may be associated with the inhibition of UTR-RhoA/ROCK pathway.

  18. Selective heart rate reduction with ivabradine slows ischaemia-induced electrophysiological changes and reduces ischaemia–reperfusion-induced ventricular arrhythmias

    Science.gov (United States)

    Ng, Fu Siong; Shadi, Iqbal T.; Peters, Nicholas S.; Lyon, Alexander R.

    2013-01-01

    Heart rates during ischaemia and reperfusion are possible determinants of reperfusion arrhythmias. We used ivabradine, a selective If current inhibitor, to assess the effects of heart rate reduction (HRR) during ischaemia–reperfusion on reperfusion ventricular arrhythmias and assessed potential anti-arrhythmic mechanisms by optical mapping. Five groups of rat hearts were subjected to regional ischaemia by left anterior descending artery occlusion for 8 min followed by 10 min of reperfusion: (1) Control n = 10; (2) 1 μM of ivabradine perfusion n = 10; (3) 1 μM of ivabradine + 5 Hz atrial pacing throughout ischaemia–reperfusion n = 5; (4) 1 μM of ivabradine + 5 Hz pacing only at reperfusion; (5) 100 μM of ivabradine was used as a 1 ml bolus upon reperfusion. For optical mapping, 10 hearts (ivabradine n = 5; 5 Hz pacing n = 5) were subjected to global ischaemia whilst transmembrane voltage transients were recorded. Epicardial activation was mapped, and the rate of development of ischaemia-induced electrophysiological changes was assessed. HRR observed in the ivabradine group during both ischaemia (195 ± 11 bpm vs. control 272 ± 14 bpm, p hearts (27.7 ± 4.3 min vs. 14.5 ± 0.6 min, p Heart rate during ischaemia is a major determinant of reperfusion arrhythmias. Heart rate at reperfusion alone was not a determinant of reperfusion VF, as neither a bolus of ivabradine nor pacing immediately prior to reperfusion significantly altered reperfusion VF incidence. This anti-arrhythmic effect of heart rate reduction during ischaemia may reflect slower development of ischaemia-induced electrophysiological changes. PMID:23402927

  19. Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

    Energy Technology Data Exchange (ETDEWEB)

    Savergnini, S.Q.; Reis, A.M. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Santos, R.A.S. [1Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Santos, P.E.B. [Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ferreira, A.J. [Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Almeida, A.P. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2012-11-01

    Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E{sub 2}; 5 µg·100 g{sup −1}·day{sup −1}) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E{sub 2} treatment caused an increase in uterine weight. Although E{sub 2} administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E{sub 2}-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval.

  20. Antioxidative and cardioprotective effects of total flavonoids extracted from Dracocephalum moldavica L. against acute ischemia/reperfusion-induced myocardial injury in isolated rat heart.

    Science.gov (United States)

    Jiang, Jiangtao; Yuan, Xuan; Wang, Ting; Chen, Hongmei; Zhao, Hong; Yan, Xinyan; Wang, Zhiping; Sun, Xiling; Zheng, Qiusheng

    2014-03-01

    This study evaluates antioxidative and cardioprotective effects of total flavonoids extracted from Dracocephalum moldavica L. (DML). The total flavonoids showed remarkable scavenging effects against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl and superoxide anion radicals in vitro. Compared with the ischemia/reperfusion (I/R) group as demonstrated by the use of improved Langendorff retrograde perfusion technology, the total flavonoids (5 μg/mL) pretreatment improved the heart rate and coronary flow, rised left ventricular developed pressure and decreased creatine kinase, lactate dehydrogenase levels in coronary flow. The infarct size/ischemic area at risk of DML-treated hearts was smaller than that of I/R group; the superoxide dismutase activity and glutathione/glutathione disulfide ratio increased and malondialdehyde content reduced obviously (P total flavonoids treatment groups. In conclusion, the total flavonoids possess obvious protective effects on myocardial I/R injury, which may be related to the improvement of myocardial oxidative stress states.

  1. Protective Effects of Kaempferol against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart via Antioxidant Activity and Inhibition of Glycogen Synthase Kinase-3β

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    Mingjie Zhou

    2015-01-01

    Full Text Available Objective. This study aimed to evaluate the protective effect of kaempferol against myocardial ischemia/reperfusion (I/R injury in rats. Method. Left ventricular developed pressure (LVDP and its maximum up/down rate (±dp/dtmax were recorded as myocardial function. Infarct size was detected with 2,3,5-triphenyltetrazolium chloride staining. Cardiomyocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling (TUNEL. The levels of creatine kinase (CK, lactate dehydrogenase (LDH, malondialdehyde (MDA, superoxide dismutase (SOD, glutathione/glutathione disulfide (GSH/GSSG ratio, and tumor necrosis factor-alpha (TNF-α were determined using enzyme linked immunosorbent assay (ELISA. Moreover, total glycogen synthase kinase-3β (GSK-3β, phospho-GSK-3β (P-GSK-3β, precaspase-3, cleaved caspase-3, and cytoplasm cytochrome C were assayed using Western blot analysis. Results. Pretreatment with kaempferol significantly improved the recovery of LVDP and ±dp/dtmax, as well as increased the levels of SOD and P-GSK-3β and GSH/GSSG ratio. However, the pretreatment reduced myocardial infarct size and TUNEL-positive cell rate, as well as decreased the levels of cleaved caspase-3, cytoplasm cytochrome C, CK, LDH, MDA, and TNF-α. Conclusion. These results suggested that kaempferol provides cardioprotection via antioxidant activity and inhibition of GSK-3β activity in rats with I/R.

  2. Prevention of reperfusion lung injury by lidocaine in isolated rat lung ventilated with higher oxygen levels.

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    Das K

    2003-01-01

    Full Text Available BACKGROUND: Lidocaine, an antiarrhythmic drug has been shown to be effective against post-ischaemic reperfusion injury in heart. However, its effect on pulmonary reperfusion injury has not been investigated. AIMS: We investigated the effects of lidocaine on a postischaemic reperfused rat lung model. MATERIALS AND METHODS: Lungs were isolated and perfused at constant flow with Krebs-Henseilet buffer containing 4% bovine serum albumin, and ventilated with 95% oxygen mixed with 5% CO2. Lungs were subjected to ischaemia by stopping perfusion for 60 minutes followed by reperfusion for 10 minutes. Ischaemia was induced in normothermic conditions. RESULTS: Postischaemic reperfusion caused significant (p < 0.0001 higher wet-to-dry lung weight ratio, pulmonary arterial pressure and peak airway pressure compared to control lungs. Lidocaine, at a dose of 5mg/Kg b.w. was found to significantly (p < 0.0001 attenuate the increase in the wet-to-dry lung weight ratio, pulmonary arterial pressure and peak airway pressure observed in post-ischaemic lungs. CONCLUSION: Lidocaine is effective in preventing post-ischaemic reperfusion injury in isolated, perfused rat lung.

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

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    Hamed Ashrafzadeh Takhtfooladi

    2015-01-01

    Full Text Available Background: 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. Objective: This study evaluated the effects of tramadol on the heart as a remote organ after acute hindlimb IR. Methods: 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. Results: 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. Conclusion: From the histological and biochemical perspectives, treatment with tramadol alleviated the myocardial injuries induced by skeletal muscle IR in this experimental model.

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

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    Mehmet Salih Aydin

    2015-02-01

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

  5. 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.

  6. Role of mitochondrial ATP-sensitive potassium channel-mediated PKC-ε in delayed protection against myocardial ischemia/reperfusion injury in isolated hearts of sevoflurane-preconditioned rats

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    C. Wang

    2015-06-01

    Full Text Available This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP channels and protein kinase C (PKC-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9. The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group or 33% oxygen inhalation (I/R group 24 h before coronary occlusion. The control group (CON and the sevoflurane group (SEVO group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD was given 30 min before sevoflurane preconditioning (5-HD+SWOP group. Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05 in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05 compared with the SWOP group. The results suggest that mitoKATP channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.

  7. Role of mitochondrial ATP-sensitive potassium channel-mediated PKC-ε in delayed protection against myocardial ischemia/reperfusion injury in isolated hearts of sevoflurane-preconditioned rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, C. [Department of Anesthesiology and Critical Care, The Second Affiliate Hospital, Soochow University, Suzhou (China); Institute of Neuroscience, Soochow University, Suzhou (China); Hu, S.M. [Institute of Neuroscience, Soochow University, Suzhou (China); Xie, H.; Qiao, S.G. [Department of Anesthesiology and Critical Care, The Second Affiliate Hospital, Soochow University, Suzhou (China); Liu, H. [Department of Anesthesiology and Pain Medicine, University of California Davis Health System, Davis, CA (United States); Liu, C.F. [Institute of Neuroscience, Soochow University, Suzhou (China)

    2015-03-27

    This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoK{sub ATP}) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoK{sub ATP} channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoK{sub ATP} channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.

  8. 山奈酚预处理对大鼠心脏缺血再灌注损伤的影响%Effects of Kaempferol Against Myocardial Ischemia-Reperfusion Injury in Rat Heart

    Institute of Scientific and Technical Information of China (English)

    周明杰; 刘立群

    2015-01-01

    目的:观察山奈酚预处理对大鼠心肌缺血再灌注损伤的影响。方法应用Langendorff灌流装置构建大鼠心脏缺血再灌注模型,120只雄性Sprague-Dawley(SD)大鼠随机分为3组,对照组(n=40),单纯缺血再灌注组( n=40)和山奈酚处理组( n=40)。心功能指标从Langendorff灌流装置上获取;采用ELISA法检测CK-MB( Creatine Kinase Isoenzyme)及SOD( superoxide dismutase)含量;采用TUNEL法检测心肌细胞凋亡。结果山奈酚预处理能显著提高大鼠心脏缺血再灌注后心功能的恢复及心肌组织内SOD的含量,同时显著降低灌流液中CK-MB的含量,减少再灌注后心肌细胞凋亡。结论山奈酚预处理对缺血再灌注后大鼠心脏具有明显的保护作用。%Objective To evaluate the effect of kaempferol against myocardial ischemia-reperfusion injury in rats.Methods Application of Langendorff simulated the model of ischemia-reperfusion.One hundred and twenty male SD rats were randomly divided into 3 groups,group A was the control group(n=40);group B was the ischemia-reperfu-sion group(n=40);group C was the kaempferol-treated group(n=40).Myocardial function were recorded at the screen of Langendorff.The levels of CK-MB and SOD were determined by enzyme linked immunosorbent assay( ELISA) ,Cardio-myocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling(TUNEL).Results Pretreatment with kaempferol significantly improved the recovery of heart function as well as increased the levels of SOD.However, pretreatment with kaempferol reduced TUNEL-positive cell rate as well as decreased the levels of CK-MB.Conclusion Pretreatment with kaempferol provides cardioprotection in rats with I/R.

  9. Effects of ischemic preconditioning and iloprost on myocardial ischemia-reperfusion damage in rats.

    Science.gov (United States)

    Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi

    2013-01-01

    This study investigates the effects of cardiac ischemic preconditioning and iloprost on reperfusion damage in rats with myocardial ischemia/reperfusion. 38 male Wistar Albino rats used in this study were divided into 5 groups. The control group (Group 1) (n=6), ischemia/reperfusion (IR) group (Group 2) (n=8), cardiac ischemic preconditioning (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic preconditioning + iloprost (CIP+ILO) group (Group 5) (n=8). Pre-ischemia, 15 minutes post-ischemia, 45 minutes post-reperfusion, mean blood pressure (MBP), and heart rates (HR) were recorded. The rate-pressure product (RPP) was calculated. Post-reperfusion plasma creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin (cTn) vlaues, and infarct size/area at risk (IS/AAR) were calculated from myocardial tissue samples. Arrhythmia and ST segment elevations were evaluated during the ischemia and reperfusion stages. Although the MBP, HR, RPP values, biochemical parameters of CK-MB and LDH levels, IS/AAR rates, ST segment elevation values were found to be similar in CIP and CIP+ILO groups and the IR and ILO groups (p>0.05), CIP-containing group values had a positively meaningful difference (pILO group. While mild-moderate findings of damage were observed in Group 3 and Group 5, severely findings of damage were releaved in Group 2 and Group 4. The arrhythmia score of the ILO group was meaningfully lower (F: 41.4, p<0.001) than the IR group. We can conclude that the effects of myocardial reperfusion damage can be reduced by cardiac ischemic preconditioning, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes.

  10. Na+ overload during ischemia and reperfusion in rat hearts : Comparison of the Na+/H+ exchange blockers EIPA, cariporide and eniporide

    NARCIS (Netherlands)

    ten Hove, M; van Emous, JG; van Echteld, CJA

    2003-01-01

    Intracellular myocardial Na+ overload during ischemia is an important cause of reperfusion injury via reversed Na+/Ca2+ exchange. Prevention of this Na+ overload can be accomplished by blocking the different Na+ influx routes. In this study the effect of ischemic inhibition of the Na+/H+ exchanger (

  11. Quercetin protects rat skeletal muscle from ischemia reperfusion injury.

    Science.gov (United States)

    Ekinci Akdemir, Fazile Nur; Gülçin, İlhami; Karagöz, Berna; Soslu, Recep

    2016-01-01

    In this study, we investigated the potential beneficial effects of quercetin on skeletal muscle ischemia reperfusion injury. Twenty-four Sprague-Dawley type rats were randomly divided into four groups. In the sham group, only gastrocnemius muscle were removed and given no quercetin. In ischemia group, all the femoral artery, vein and collaterals were occluded in the left hindlimb by applying tourniquate under general anaesthesia for three hours but reperfusion was not done. In the Quercetin + Ischemia reperfusion group, quercetin (200 mg kg(-1) dose orally) was given during one-week reoperation and later ischemia reperfusion model was done. Finally, gastrocnemius muscle samples were removed to measure biochemical parameters. The biomarkers, MDA levels, SOD, CAT and GPx activities, were evaluated related to skeletal muscle ischemia reperfusion injury. MDA levels reduced and SOD, CAT and GPx activities increased significantly in Quercetin + Ischemia reperfusion group. Results clearly showed that Quercetin have a protective role against oxidative damage induced by ischemia reperfusion in rats.

  12. Effects of reperfusion arrhythmias and myocardial connexin 43 by Compound Astragalus Mixture Nourishing Heart in a rat model of acute myocardial ischemic reperfusion injury%复方黄芪养心合剂对大鼠缺血再灌注心肌缝隙连接蛋白43的影响

    Institute of Scientific and Technical Information of China (English)

    陈启兰; 龚一萍; 祝光礼; 齐国安; 赫小龙; 任兴昌; 王骋

    2013-01-01

    目的:观察复方黄芪养心合剂对SD大鼠缺血再灌注心肌细胞缝隙连接蛋白43(Cx43)分布的改变和表达的影响.方法:应用复方黄芪养心合剂按每天14g/kg剂量、琥珀酸美托洛尔缓释片按每天(MSSRT) 9.5mg/kg剂量灌胃2周后,对SD大鼠行冠状动脉左前降支结扎30min后再灌注60min造成心肌缺血再灌注(I/R)损伤模型,记录Ⅱ导联心电图,采用免疫组织化学法(IHC)观察心肌细胞Cx43分布的改变;运用Image Pro Plus 6.0图像分析软件对Cx43的表达进行半定量分析.结果:Cx43平均光密度(AOD)I/R组心肌内膜下缺血区Cx43的AOD显著低于假手术组(P<0.01),且MSSRT组、复方组较1/R组升高(P<0.05).结论:对冠状动脉左前降支结扎术后再灌注SD大鼠,复方黄芪养心合剂对心肌细胞Cx43分布的改变有改善作用,有促进心肌内膜下缺血区域Cx43表达的作用,其作用与MSSRT相近.%Objective: To evaluate the effects of Compound Astragalus Mixture Nourishing Heart (CAMNH) antiarrhythmia and myocardial connexin 43 (Cx43) in a rat model of acute myocardial ischemic reperfusion injury. Methods: Myocardial infarction (MI) was induced by ligating left anterior descending coronary artery (LAD) for 30 minutes, followed by reperfusion of 60 minutes in rats. Rats were treated with CAMNH (14g·kg-1·d-1) or metoprolol succinate sustained-release tablets (MSSRT, 9.5mg·kg-1d-1) for 14 days before MI. The distribution of myocardial Cx43 was observed by Immunohistochemistry (IHC), and the expression of myocardial Cx43, which were represented by average optical density (AOD), was measured by Image Pro Plus 6.0. Results: The expression of myocardial Cx43 in infarction region was significantly reduced, disordered and even all disappearing, the expression of myocardial Cx43 from infarction region into ischemic region and normal region had a gradual recovery of transitional variability. Ischemia/reperfusion(I/R) group vs sham-operated (SO

  13. Endomorphins and β-Endorphin Do Not Affect Heart Tolerance to the Pathogenic Effect of Reperfusion.

    Science.gov (United States)

    Mukhomedzyanov, A V; Maslov, L N; Tsibulnikov, S Yu; Pei, J M

    2016-11-01

    Selective agonists of μ1- and μ2-opioid receptors endomorphin-2 and endomorphin-1 injected intravenously in a dose of 4500 nmol/kg in 5 min before coronary blood flow resumption had no effect on cardiac reperfusion damage. Consequently, μ1- and μ2-opioid receptors are not involved in the regulation of heart tolerance to reperfusion injury. Nonselective opioid receptor agonist β-endorphin (100 nmol/kg) also did not affect heart tolerance to the pathogenic effect of reperfusion.

  14. Paracrine systems in the cardioprotective effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Liu, Y H; Yang, X P; Sharov, V G; Sigmon, D H; Sabbath, H N; Carretero, O A

    1996-01-01

    After transient episodes of ischemia, benefits of thrombolytic or angioplastic therapy may be limited by reperfusion injury. Angiotensin-converting enzyme inhibitors protect the heart against ischemia/reperfusion injury, an effect mediated by kinins. We examined whether the protective effect of the angiotensin-converting enzyme inhibitor ramiprilat on myocardial ischemia/reperfusion is due to kinin stimulation of prostaglandin and/or nitric oxide release. The left anterior descending coronary artery of Lewis inbred rats was occluded for 30 minutes, followed by 120 minutes of reperfusion. Immediately before reperfusion rats were treated with vehicle, ramiprilat, or the angiotensin II type 1 receptor antagonist losartan. We tested whether pretreatment with the kinin receptor antagonist Hoe 140, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor indomethacin blocked the effect of ramiprilat on infarct size and reperfusion arrhythmias. In controls, infarct size as a percentage of the area at risk was 79 +/- 3%; ramiprilat reduced this to 49 +/- 4% (P < .001), but losartan had little effect (74 +/- 6%, P = NS). Pretreatment with Hoe 140, NG-nitro-L-arginine methyl ester, or indomethacin abolished the beneficial effect of ramiprilat. Compared with the 30-minute ischemia/120-minute reperfusion group, nonreperfused hearts with 30 minutes of ischemia had significantly smaller infarct size as a percentage of the area at risk, whereas in the 150-minute ischemia group it was significantly larger. This suggests that reperfusion caused a significant part of the myocardial injury, but it also suggests that compared with prolonged ischemia, reperfusion salvaged some of the myocardium. Ventricular arrhythmias mirrored the changes in infarct size. Thus, angiotensin-converting enzyme inhibitors protect the myocardium against ischemia/reperfusion injury and arrhythmias; these beneficial effects are mediated primarily by a kinin

  15. Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Jun Li

    Full Text Available BACKGROUND AND PURPOSE: Mitochondrial dysfunction has been implicated in the cell death observed after cerebral ischemia, and several mechanisms for this dysfunction have been proposed. Reperfusion after transient cerebral ischemia may cause continued and even more severe damage to the brain. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. The purpose of this study was to observe the features of mitochondrial dysfunction in isolated mitochondria during the reperfusion period following focal cerebral ischemia. METHODS: Male Wistar rats were subjected to focal cerebral ischemia. Mitochondria were isolated using Percoll density gradient centrifugation. The isolated mitochondria were fixed for electron microscopic examination; calcium-induced mitochondrial swelling was quantified using spectrophotometry. Cyclophilin D was detected by Western blotting. Fluorescent probes were used to selectively stain mitochondria to measure their membrane potential and to measure reactive oxidative species production using flow cytometric analysis. RESULTS: Signs of damage were observed in the mitochondrial morphology after exposure to reperfusion. The mitochondrial swelling induced by Ca(2+ increased gradually with the increasing calcium concentration, and this tendency was exacerbated as the reperfusion time was extended. Cyclophilin D protein expression peaked after 24 hours of reperfusion. The mitochondrial membrane potential was decreased significantly during the reperfusion period, with the greatest decrease observed after 24 hours of reperfusion. The surge in mitochondrial reactive oxidative species occurred after 2 hours of reperfusion and was maintained at a high level during the reperfusion period. CONCLUSIONS: Reperfusion following focal cerebral ischemia induced significant mitochondrial morphological damage and Ca(2+-induced mitochondrial swelling. The mechanism of this swelling may be mediated by

  16. Ketamine anesthesia reduces intestinal ischemia/reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Carlos Roddgo Cámara; Francisco Javier Guzmán; Ernesto Alexis Barrera; Andrés Jesús Cabello; Armando Garcia; Nancy Esthela Fernández; Eloy Caballero; Jesus Ancer

    2008-01-01

    AIM:To investigate the effects of ketamine anesthesia on the motility alterations and tissue injury caused by ischemia/reperfusion in rats.METHODS:Thirty maIe Wistar rats weighing 200-250 g were used.Ischemia was induced by obstructing blood flow in 25% of the total small intestinal length(ileum)with a vascular clamp for 45 min,after which either 60 min or 24 h of reperfusion was allowed.Rats were either anesthetized with pento-barbital sodium(50 mg/kg)or ketamine(100 mg/kg).Control groups received sham surgery,After 60 min of reperfusion,the intestine was examined for mor-phological alterations,and after 24 h intestinal basic electrical rhythm(BER)frequency was calculated,and intestinal transit determined in all groups.RESULTS:The intestinal mucosa in rats that were anesthetized with ketamine showed moderate alterations such as epithelial lifting,while ulceration and hemorrhage was observed in rats that received pento-barbital sodium after 60 min of reperfusion.Quantitative analysis of structural damage using the Chiu scale showed significantly Iess injury in rats that received ketamine than in rats that did not(2.35±1.14 vs 4.58 ±0.50,P<0.0001).The distance traveled by a marker,expressed as percentage of total intestinal length,in rats that received pentobarbital sodium was 20% ± 2% in comparison with 25.9% ±1.64% in rats that received ketamine(P=0.017).BER was not statistically different between groups.CONCLUSION:Our results show that ketamine anesthesia is associated with diminished intestinal iniury and abolishes the intestinal transit delay induced by ischemia/reperfusion.(C)2008 The WJG Press.All rights reserved.

  17. Ketamine anesthesia reduces intestinal ischemia/reperfusion injury in rats

    Science.gov (United States)

    Cámara, Carlos Rodrigo; Guzmán, Francisco Javier; Barrera, Ernesto Alexis; Cabello, Andrés Jesús; Garcia, Armando; Fernández, Nancy Esthela; Caballero, Eloy; Ancer, Jesus

    2008-01-01

    AIM: To investigate the effects of ketamine anesthesia on the motility alterations and tissue injury caused by ischemia/reperfusion in rats. METHODS: Thirty male Wistar rats weighing 200-250 g were used. Ischemia was induced by obstructing blood flow in 25% of the total small intestinal length (ileum) with a vascular clamp for 45 min, after which either 60 min or 24 h of reperfusion was allowed. Rats were either anesthetized with pentobarbital sodium (50 mg/kg) or ketamine (100 mg/kg). Control groups received sham surgery. After 60 min of reperfusion, the intestine was examined for morphological alterations, and after 24 h intestinal basic electrical rhythm (BER) frequency was calculated, and intestinal transit determined in all groups. RESULTS: The intestinal mucosa in rats that were anesthetized with ketamine showed moderate alterations such as epithelial lifting, while ulceration and hemorrhage was observed in rats that received pentobarbital sodium after 60 min of reperfusion. Quantitative analysis of structural damage using the Chiu scale showed significantly less injury in rats that received ketamine than in rats that did not (2.35 ± 1.14 vs 4.58 ± 0.50, P < 0.0001). The distance traveled by a marker, expressed as percentage of total intestinal length, in rats that received pentobarbital sodium was 20% ± 2% in comparison with 25.9% ± 1.64% in rats that received ketamine (P = 0.017). BER was not statistically different between groups. CONCLUSION: Our results show that ketamine anesthesia is associated with diminished intestinal injury and abolishes the intestinal transit delay induced by ischemia/reperfusion. PMID:18777596

  18. Effects of doxycycline on the distribution of gap junction and susceptibility of arrhythmias in isolated ischemia-reperfusion rat hearts%多西环素对离体大鼠心肌缺血再灌注后缝隙连接分布及心律失常的影响

    Institute of Scientific and Technical Information of China (English)

    李镇; 严激; 徐健; 朱红军; 余华; 程敏; 陈康玉; 沈伟

    2011-01-01

    目的 研究多西环素对离体大鼠心肌缺血再灌注后心律失常易感性的影响,并通过分析缝隙连接的重新分布探讨其可能机制.方法 48只大鼠随机分为空白对照组、缺血再灌组、多西环素干预组.采用Langendorff灌注系统,制备离体大鼠缺血再灌注模型,用ELISA方法检测各组间大鼠心肌基质金属蛋白酶-9(MMP-9)的含量,通过Western-blot方法及免疫荧光标记方法检测心肌Cx43的分布及含量.用电生理方法观察多西环素对缺血再灌注后室性快速性心律失常发生的影响.结果 缺血再灌组及多西环素干预组较空白对照组MMP-9水平显著增高(P0.05).结论 多西环素可通过减少MMP-9的表达,减轻缺血后缝隙连接的侧化分布并减少再灌注心律失常发生.%Aim To investigate the effects and the possible mechanisms of doxycycline on the susceptibility of ventricular tachyarrhythmias in isolated ischemia-reperfusion rat hearts. Methods 48 isolated rat hearts perfused with a langendorff instrument were divided into blank group,ischemia-reperfusion group and doxycycline intervention group( n = 16 , respectively ). Matrix metalloproteinase-9( MMP-9 )were detected hy ELISA. Cx43 in the cardiomyocytes were quantified by western-blotting and localized by immunofluorescence. The risk of inducible ventricular tachyarrhythmias was evaluated by electrophysiological study. Results Doxycycline could significantly dilute MMP-9 in the ischemia-reperfusion rat hearts( P < 0. 001 ). Ventricular tachyarrhythmias tended to he reduced in doxycycline-perfused hearts( P < 0. 05 ). Redistrihution of Cx43 can he ohserved in the tissue of doxycycline-perfused hearts. Conclusion Doxycycline can prevent gap junction redistrihution hy reducing MMP-9 in the heart tissue, thereby decrease inducihle ventricular tachyarrhythmias in ischemia-reperfusion hearts.

  19. Protective effects of GLP-1 analogues exendin-4 and GLP-1(9-36) amide against ischemia-reperfusion injury in rat heart

    DEFF Research Database (Denmark)

    Sonne, David P; Engstrøm, Thomas; Treiman, Marek

    2007-01-01

    Glucagon-Like Peptide-1 (GLP-1) is an incretin peptide secreted from intestinal L-cells, whose potent plasma glucose-lowering action has prompted intense efforts to develop GLP-1 receptor-targeting drugs for treatment of diabetic hyperglycemia. More recently, GLP-1 and its analogues have been shown...... the last 60 min of reperfusion. These effects were only partially antagonized by Exe(9-39). We suggest that Exe-4, in addition to being currently exploited in treatment of diabetes, may present a suitable candidate for postconditioning trials in clinical settings of IRI. The divergent agonist effects...... to exert cardiovascular effects in a number of experimental models. Here we tested exendin-4 (Exe-4), a peptide agonist at GLP-1 receptors, and GLP-1(9-36) amide, the primary endogenous metabolite of GLP-1 (both in the concentration range 0.03-3.0 nM), for their protective effects against ischemia...

  20. Transient Acidosis during Early Reperfusion Attenuates Myocardium Ischemia Reperfusion Injury via PI3k-Akt-eNOS Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xin Qiao

    2013-01-01

    Full Text Available In this paper, we concluded that transient acidosis reperfusion conferred cardioprotection against myocardial ischemia reperfusion injury in isolated rat hearts through activating PI3K-Akt-eNOS pathway.

  1. Effects of anabolic steroid nandrolone decanoate on ischemic preconditioning in isolated heart of sedentary rats

    Directory of Open Access Journals (Sweden)

    Zahra Akbari

    2014-11-01

    Full Text Available Background: Previous studies have shown that use of supraphysiologocal doses of anabolic adrogenic steroids (AAS associated with detrimental cardiovascular effects including ventricular hypertrophy, increased susceptibility to ischaemia/reperfusion injury, impairment of exercise-induced cardioprotection and sudden cardiac death. The aim of the present study was to evaluate the impact of 8 weeks treatment of AAS nandrolone decanoate (10 mg/kg/week, on ischemic preconditioning (IPC phenomena in isolated hearts of sedentary rats. Materials and Methods: Three groups of animals were studied in the present study. Control ischemia/reperfusion injury group (IR, 2- Ischemic preconditioned group before main test ischemia and reperfusion (IPC+IR, and 3- Nandrolone treated ischemic preconditioned group before main test ischemia and reperfusion (Nan+IPC+IR. After two months of nandrolone and/or its solvent, the isolated Langendorff perfused rat hearts were subjected to 30 min of ischemia followed by 120 min reperfusion. The IPC was induced by three cycles of 3-min occlusion and 3-min reperfusion of the left anterior descending coronary artery (LAD before main test ischemia. Heart rate, left ventricular developed pressure (LVDP, rate pressure product (RPP, Max dp/dt, Min dp/dt and coronary flow were recorded during experiment. Infarction size was measured after 120 min reperfusion by TTC staining. Results: Eight weeks’ nandrolone treatment decreased body weight and increased cardiac to body weight ratio in treated rats. Nandrolone increased pre-ischemic base line cardiac function parameters in the rat hearts. Cardiac function recovery parameters in different time points during reperfusion were also greater in nandrolone treated rats compared to their respective controls. IPC decreased infarct size in the rats (P<0.05. Nandrolone could not significantly change the infarct size lowering effect of IPC in the rat heart. Conclusion: The present study revealed

  2. The neuroprotection of Aspirin on Cerebral Ischemia-Reperfusion rats

    Institute of Scientific and Technical Information of China (English)

    QiuLi-ying; YuJuan; ChenChong-hong; ZhouYu

    2004-01-01

    AIM: Aspirin (aeetylsalicylic acid, ASA as a nonsteroidal anti-inflammatory drug not only has well-established efficacy in anti-thromboxane, but also has direct neuroprotective effect. In this study, we design to investigate its neuroprotective effect on focal cerebral ischemia-reperfusion injury (CIRI rats, and its effect on ATP level from occluded brain tis-

  3. Glycine preconditioning to ameliorate pulmonary ischemia reperfusion injury in rats

    NARCIS (Netherlands)

    Sommer, Sebastian-Patrick; Sommer, Stefanie; Sinha, Bhanu; Leyh, Rainer G.

    2012-01-01

    This study examines the impact of glycine (Gly) preconditioning on ischemia reperfusion (IR)-induced pulmonary mitochondrial injury to research the previously, in pig lungs, demonstrated Gly-dependent amelioration of pulmonary IR injury. IR injury was induced in rat lungs by 30 min pulmonary hilum c

  4. Effect and mechanism of salvianolic acid B on the myocardial ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Ling Xue; Zhen Wu; Xiao-Ping Ji; Xia-Qing Gao; Yan-Hua Guo

    2014-01-01

    Objective: To investigate the effect of salvianolic acid B on rats with myocardial ischemia-reperfusion injury. Methods: SD rats were randomly divided into five groups (n=10 in each group): A sham operation group, B ischemic reperfusion group model group, C low dose salvianolic acid B group, D median dose salvianolic acid B group, E high dose salvianolic acid B group. One hour after establishment of the myocardial ischemia-reperfusion model, the concentration and the apoptotic index of the plasma level of myocardial enzymes (CTnⅠ, CK-MB), SOD, MDA, NO, ET were measured. Heart tissues were obtained and micro-structural changes were observed. Results: Compared the model group, the plasma CTnⅠ, CK-MB, MDA and ET contents were significantly increased, NO, T-SOD contents were decreased in the treatment group (group C, D, and E) (P<0.05); compared with group E, the plasma CTnⅠ, CK-MB, MDA and ET levels were increased, the NO, T-SOD levels were decreased in groups C and D (P<0.05). Infarct size was significantly reduced, and the myocardial ultrastructural changes were improved significantly in treatment group. Conclusions: Salvianolic acid B has a significant protective effect on myocardial ischemia-reperfusion injury. It can alleviate oxidative stress, reduce calcium overload, improve endothelial function and so on.

  5. Activation of big conductance Ca(2+)-activated K (+) channels (BK) protects the heart against ischemia-reperfusion injury

    DEFF Research Database (Denmark)

    Bentzen, Bo Hjorth; Osadchii, Oleg; Jespersen, Thomas;

    2009-01-01

    complexes, while producing no effect on cardiac K(ATP) channels. The cardioprotective effects of NS11021-induced BK channel activation were studied in isolated, perfused rat hearts subjected to 35 min of global ischemia followed by 120 min of reperfusion. 3 microM NS11021 applied prior to ischemia...... (3 microM) antagonized the protective effect. These findings suggest that tissue damage induced by ischemia and reperfusion can be reduced by activation of cardiac BK channels.......Activation of the large-conductance Ca(2+)-activated K(+) channel (BK) in the cardiac inner mitochondrial membrane has been suggested to protect the heart against ischemic injury. However, these findings are limited by the low selectivity profile and potency of the BK channel activator (NS1619...

  6. N-acetylcysteine attenuates ischemia/reperfusion-induced cardiocyte apoptosis in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Li Ma; Shanglong Yao; Kezhong Li

    2006-01-01

    Objective: To study the effects of N-acetylcysteine (NAC) on iscbemia/ reperfusion (I/R)-induced myocyte apoptosis in diabetic rats. Methods:The I/R heart model was made by ligation of the left anterior descending coronary artery (LAD) close to its origin. The LAD was occluded for 30 min followed by removal of ligation to allow subsequent reperfusion for 3 h. 72 rats were randomly divided into two groups: non-diabetic group (C, n = 36) and diabetic group (D, n = 36).The animals in C group were randomly reassigned into sham-ope rated group (CS, n = 12) , I/R group (C I/R, n = 12) and treated with NAC group (CN, n = 12). The rats in D group were also reassigned to sham-operated group (DS, n = 12) , I/R group (DI/R, n = 12) and treated with NAC group (DN, n = 12). Malondialdehyde (MDA) and creatine kinase isoenzyme-MB (CK-MB) were measured. Infarct size(IS/AAR%), the apoptosis index(AI) by TUNEL staining, the number of the cells positive for Caspase-3 and positive expression index (PEI) were calculated. Results:After I/R, the IS/AAR%, CK-MB, MDA, AI and Caspase-3 PEI were higher in diabetic group than those in non-diabetic group. Treatment with NAC decreased the above parameters in both non-diabetic and diabetic rats, but the parameters in diabetic rats were higher than those in non-diabetic rats. Conclusion:Diabetic rat hearts are more susceptible to I/R-induced myocardial necrosis and myocyte apoptosis. NAC can decrease the infarct size and attenuate cardiomyocyte apoptosis in both non-diabetic and diabetic rats, but the therapeutic effects are less effective in diabetic rats than those in non-diabetic rats.

  7. Effect of Electroacupuncture on Reperfusion Ventricular Arrhythmia in Rat

    Institute of Scientific and Technical Information of China (English)

    ZENG Qing; LI Man; OUYANG Xingbiao; NONG Yi; LIU Xiaochun; SHI Jing; GUAN Xinmin

    2006-01-01

    Protective effect and mechanism of electroacupuncture (EA) on acute reperfusion ventricular arrhthmia was investigated. Ventricular arrhythmia was induced by occlusion of the proximal left anterior descend (LAD) branch of coronary artery for 5 min and followed with 15 min reperfusion . EA on acupoint "Neiguan", "Jianshi" was performed at 30 min before ligation and continued another 5 min during ischemia. Isoprenaline (20, 30 and 50 μg/kg) or atropine (1 mg/kg) was intravenously injected at 5min before ischemia. The results showed that EA significantly decreased the incidence of ischemia/reperfusion (I/R) induced ventricular tachycardia (VT), ventricular fibrillation (VF) and mortality as compared to I/R group. Atropine partially suppressed the EA's effect of antiarrhythmia; Isoprenaline increased the incidence and severity of reperfusion arrhythmia, which was inhibited by EA, but this inhibition of EA was blocked with increasing dose of isoprenaline. The results indicated that EA treatment could prevent the occurrence of reperfusion ventricular arrhythmia in rats with myocardial ischemia, and its mechanism might be related to the regulation of EA on the β-adrenoceptors and M-cholinergic receptor activation in myocardium.

  8. Ginkgolide B Reduces the Degradation of Membrane Phospholipids to Prevent Ischemia/Reperfusion Myocardial Injury in Rats.

    Science.gov (United States)

    Pei, Hong-Xia; Hua, Rong; Guan, Cha-Xiang; Fang, Xiang

    2015-01-01

    Platelet-activating factor (PAF), a bioactive phospholipid, plays an important role in the integrity of the cellular membrane structure, and is involved in the pathogenesis of myocardial ischemia/reperfusion (IR) injuries. In this study, we tested the hypothesis that blockage of PAF receptor by BN 52021 (Ginkgolide B) can prevent IR-induced degradation of the myocardial membrane phospholipid, and deterioration of the cardiac function. Rat hearts in situ were subjected to 5 min ischemia and followed by 10 min reperfusion. Cardiac performances during periods of ischemia and reperfusion were monitored, and the amount of membrane phospholipids was analyzed. Myocardial total phospholipids, phosphatidylcholine, and phosphatidylethanolamine were decreased significantly in ischemia-reperfusion rat hearts compared with those of sham-operated rat hearts. Degradation of the membrane phospholipid was accompanied by the deterioration of cardiac functions and increase in serum lactate dehydrogenase (LDH) activity. BN 52021 (15 mg/kg), given by intravenous infusion 10 min prior to the left anterior descending coronary artery occlusion, reduced IR-related degradation of the myocardial phospholipids, the activity of serum LDH, and was concomitant with improvement of cardiac function. Furthermore, we demonstrated that the production of PAF was increased and BN 52021 decreased cellular damage in cultured anoxic cardiomyocytes. These results indicated that PAF antagonist BN 52021 has a protective effect against IR-induced myocardial dysfunction and degradation of the membrane phospholipids.

  9. 大鼠心脏缺血再灌注对心肌基质金属蛋白酶-1的影响%THE EFFECT OF ISCHEMIA-REPERFUSION ON MATRIX METALLOPROTEINASE-1 IN RAT HEART

    Institute of Scientific and Technical Information of China (English)

    郭志坤; 史福军; 朱武岭; 王华; 李和

    2007-01-01

    Objective To investigate the effect of ischemia and ischemia/reperfusion(I/R)in rat heart on matrix metalloproteinase-1(MMP-1).Methods The I/R animal models were established by shutting down and reopening the anterior interventricular branch with a silver clamp,then the distribution and amount of MMP-1 of the normal and I/R rat hearts were observed by immunohistochemical staining and Western blotting and analyzed by computer image analysis.Results 1.Immunohistochemical staining showed MMP-1 existed mainly in the cardiac matrix.There were strong positive reactions in fibrocytes,smooth muscle cells of the blood vessel and endotheliaI cells of capillaries.MMP-1 didn't show distinct changes 30 minutes after ischemia,while its concentration increased dramatically 60 minutes after ischemia.The positive reaction of MMP-1 increased 30 minutes after I/R,and 60 minutes after I/R there was large fusion areas in MMP-1 existing reglons.2.Quantitative analysis showed no dramatic changes of MMP-1 after ischemia for 30 minutes(P>0.05),while dramatic changes were seen 60 minutes after ischemia(P<0.05).MMP-1 changed dramatically 30 minutes and 60 minutes after I/R.3.Western blotting showed that there were no distinct naked-eye-observable changes.The bands of MMP-1 became widened 30 minutes after I/R,and became obviously widened 60 minutes after I/R.Conclusion 1.MMP-1 is secreted by fibrocytes,smooth muscle cells and endothelial cells of cardiac tissue under physiological conditions,and cardiomyocytes has the potential to secrete MMP-1 under ischemia or I/R.2.The longer time the heart ischemia lasts,the greater MMP-1 concentration will increase.Reperfusion can increase MMP-1 concentration to an even higher level,which may be the main cause of the collagen destruction after heart I/R.%目的 探讨缺血和缺血-再灌注状态下对大鼠心肌基质金属蛋白酶-1(MMP-1)的影响.方法 取正常大鼠心脏和通过钳夹大鼠心脏冠状动脉旋支制造缺血-再灌注

  10. CaMKII-dependent responses to ischemia and reperfusion challenges in the heart

    Directory of Open Access Journals (Sweden)

    James eBell

    2014-05-01

    Full Text Available Ischemic heart disease is a leading cause of death, and there is considerable imperative to identify effective therapeutic interventions. Cardiomyocyte Ca2+ overload is a major cause of ischemia and reperfusion injury, initiating a cascade of events culminating in cardiomyocyte death, myocardial dysfunction and occurrence of lethal arrhythmias. Responsive to fluctuations in intracellular Ca2+, Ca2+/calmodulin-dependent protein kinase II (CaMKII has emerged as an enticing therapeutic target in the management of ischemic heart injury. CaMKII is activated early in ischemia and to a greater extent in the first few minutes of reperfusion, at a time when reperfusion arrhythmias are particularly prominent. CaMKII phosphorylates and upregulates many of the key proteins involved in intracellular Na+ and Ca2+ loading in ischemia and reperfusion. Experimentally, selective inhibition of CaMKII activity reduces cardiomyocyte death and arrhythmic incidence post-ischemia. New evidence is emerging that CaMKII actions in ischemia and reperfusion involve specific splice variant targeted actions, selective and localized post-translational modifications, and organelle-directed substrate interactions. A more complete mechanistic understanding of CaMKII mode of action in ischemia and reperfusion is required to optimize intervention opportunities. This review summarizes the current experimentally-derived understanding of CaMKII participation in mediating the pathophysiology of the heart in ischemia and in reperfusion, and highlights priority future research directions.

  11. Achyranthes bidentata Polypeptides Reduces Oxidative Stress and Exerts Protective Effects against Myocardial Ischemic/Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Haifeng Zhang

    2013-09-01

    Full Text Available Achyranthes bidentata, a Chinese medicinal herb, is reported to be neuroprotective. However, its role in cardioprotection remains largely unknown. Our present study aimed to investigate the effects of Achyranthes bidentata polypeptides (ABPP preconditioning on myocardial ischemia/reperfusion (MI/R injury and to test the possible mechanisms. Rats were treated with ABPP (10 mg/kg/d, i.p. or saline once daily for one week. Afterward, all the animals were subjected to 30 min of myocardial ischemia followed by 4 h of reperfusion. ABPP preconditioning for one week significantly improved cardiac function following MI/R. Meanwhile, ABPP reduced infarct size, plasma creatine kinase (CK/lactate dehydrogenase (LDH activities and myocardial apoptosis at the end of reperfusion in rat hearts. Moreover, ABPP preconditioning significantly inhibited superoxide generation, gp91phox expression, malonaldialdehyde formation and enhanced superoxide dismutase activity in I/R hearts. Furthermore, ABPP treatment inhibited PTEN expression and increased Akt phosphorylation in I/R rat heart. PI3K inhibitor wortmannin blocked Akt activation, and abolished ABPP-stimulated anti-oxidant effect and cardioprotection. Our study demonstrated for the first time that ABPP reduces oxidative stress and exerts cardioprotection against MI/R injury in rats. Inhibition of PTEN and activation of Akt may contribute to the anti-oxidant capacity and cardioprotection of ABPP.

  12. Intestinal microflora in rats with ischemia/reperfusion liver injury

    Institute of Scientific and Technical Information of China (English)

    XING Hui-chun; LI Lan-juan; XU Kai-jin; SHEN Tian; CHEN Yun-bo; SHENG Ji-fang; YU Yun-song; CHEN Ya-gang

    2005-01-01

    Objectives: To investigate the intestinal microflora status related to ischemia/reperfusion (I/R) liver injury and explore the possible mechanism. Methods: Specific pathogen free grade Sprague-Dawley rats were randomized into three groups: Control group (n=8), sham group (n=6) and I/R group (n=10). Rats in the control group did not receive any treatment, rats in the I/R group were subjected to 20 min of liver ischemia, and rats in the sham group were only subjected to sham operation. Twenty-two hours later, the rats were sacrificed and liver enzymes and malondialdehyde (MDA), superoxide dismutase (SOD), serum endotoxin,intestinal bacterial counts, intestinal mucosal histology, bacterial translocation to mesenteric lymph nodes, liver, spleen, and kidney were studied. Results: Ischemia/reperfusion increased liver enzymes, MDA, decreased SOD, and was associated with plasma endotoxin elevation in the I/R group campared to those in the sham group. Intestinal Bifidobacteria and Lactobacilli decreased and intestinal Enterobacterium and Enterococcus, bacterial translocation to kidney increased in the I/R group compared to the sham group. Intestinal microvilli were lost, disrupted and the interspace between cells became wider in the I/R group.Conclusion: I/R liver injury may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function,which contributes to endotoxemia and bacterial translocation to kidney.

  13. 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.

  14. Methylprednisolone improves microcirculation in streptozotocin-induced diabetic rats after myocardial ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    HU Zhi-cheng; CHEN Yun-dai; REN Yi-hong

    2011-01-01

    Background Methylprednisolone has been demonstrated to decrease inflammation, and it may protect organs from ischemia/reperfusion (I/R) injury. This study aimed to investigate the effects of methylprednisolone on diabetic myocardial I/R injury.Methods Forty adult male Sprague-Dawley (SD) rats were randomized into five groups (n=8 in each group) including a sham operation (sham) group, I/R group, diabetic sham operation (DMS) group, diabetic I/R (DM-I/R) group and methylprednisolone intervention (MP+DM-I/R) group. The diabetic model was produced by injection of streptozotocin (STZ). Body weight and blood glucose levels were determined after diabetes was established. Twelve weeks after induction of diabetes, a segmental I/R of the heart was induced by occluding the left anterior descending artery for one hour and then three hours of reperfusion in the I/R, DM-I/R and MP+DM-I/R groups. Blood pressure and electrocardiogram were continuously recorded during the procedure. IL-1β, IL-6 and TNF-α were measured at certain time points during the surgery. After reperfusion, a microcirculation scan was performed; myocardial biomarkers and tissue structure were utilized to evaluate the reperfusion damage. Intercellular adhesion molecule (ICAM)-1 and NF-κBp65 expression were quantified by immunohistological staining. Total Toil-like receptor 4 (TLR4) and nuclear NF-κBp65 protein were determined by Western blotting.Results Twelve weeks after diabetes was established, blood glucose levels were elevated and body weights were lower in diabetic rats. After reperfusion, infarction size was increased, myocardial biomarkers and inflammatory cytokines levels were elevated. Microcirculation perfusion was significantly reduced in the DM-I/R group compared with the I/R group, however it was improved in the MP+DM-I/R group. The expression of NF-κBp65 and ICAM-1 were increased in the DM-I/R group and decreased in the MP+DM-I/R group, Compared with the non-diabetic I/R group, TLR4 and NF

  15. Cardioprotective effects of Guanxinshutong (GXST) against myocardial ischemia/reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Zhuo Liang; Li-Feng Liu; Tian-Ming Yao; Yu Huo; Ya-Ling Han

    2012-01-01

    Background The protective effects against reperfusion injury of cardioprotective drugs have recently been evaluated and found to be inadequate. Guanxinshutong (GXST), a combination of the traditional herb and Mongolian medicine, is effective and safe in treating angina pectoris in clinical trials. We assess the cardioprotective effects of GXST against myocardial ischemia and reperfusion (MI/R) injury in rats and explore its possible mechanism. Methods Forty-five male Sprague Dawley rats were randomized into three groups: non-MI/R group (Sham, n = 15), MI/R group treated with vehicle (Control, n = 15) and MI/R group treated with GXST (Drug, n = 15). MI/R was induced by ligation of the left anterior descending coronary artery (LAD) for 30 minutes, followed by 2/24 hour reperfusion in the Control and Drug groups. In the Sham group, the LAD was exposed without occlusion. GXST powder (in the Drug group) or saline (in the Control and Sham groups) were administered via direct gastric gavage from 7 day prior to surgery. Blood samples were collected from the carotid artery (10 rats each group) after 2 hours of reperfusion, to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) using enzyme-linked immunosorbent assays. The animals were then sacrificed and the hearts were harvested for histopathology and western blot analysis. Infarct size was measured in the remaining five rats in each group after 24 hours reperfusion. Results GXST significantly decreased levels of TNF-α, IL-1β, IL-6, ICAM-1, apoptosis index (AI) and infarct size. GXST also obviously inhibited nuclear factor kappa B (NF-κB) activity when compared with the Control group (all P < 0.05). Conclusions GXST is effective in protecting the myocardium against MI/R injury in rats. Its possible cardioprotective mechanism involves inhibition of the inflammatory response and apoptosis following MI/R injury.

  16. Attenuation of reperfusion hyperalgesia in the rat by systemic administration of benzodiazepines.

    OpenAIRE

    1993-01-01

    1. An investigation into whether reperfusion hyperalgesia is modulated by prior systemic administration of two benzodiazepine agonists (diazepam and chlordiazepoxide), and an antagonist (flumazenil) was conducted. 2. Transient ischaemia was induced in conscious rats by applying an inflatable tourniquet to the base of the tail; when the rats exhibited a co-ordinated escape response, the tourniquet was deflated and reperfusion of the tail was allowed. Reperfusion hyperalgesia manifested as a de...

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

    Science.gov (United States)

    Jeddi, Sajad; Khalifi, Saeedeh; Ghanbari, Mahboubeh; Bageripour, Fatemeh; Ghasemi, Asghar

    2016-01-01

    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. PMID:27849257

  18. 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.

  19. Preconditioning in globally ischemic isolated rat hearts: effect on function and metabolic indices of myocardial damage

    NARCIS (Netherlands)

    M. Arad; J.W. de Jong (Jan Willem); R. de Jonge (Robert); T. Huizer (Tom); B. Rabinowitz

    1996-01-01

    textabstractWe assessed the effects of ischemic preconditioning on heart recovery and metabolic indices of damage following global ischemia and reperfusion, in relationship to post-ischemic lactate release. Three groups of Langendorff rat hearts were studied: (1) A control group of

  20. Preconditioning in globally ischemic isolated rat hearts: effect on function and metabolic indices of myocardial damage

    NARCIS (Netherlands)

    M. Arad; J.W. de Jong (Jan Willem); R. de Jonge (Robert); T. Huizer (Tom); B. Rabinowitz

    1996-01-01

    textabstractWe assessed the effects of ischemic preconditioning on heart recovery and metabolic indices of damage following global ischemia and reperfusion, in relationship to post-ischemic lactate release. Three groups of Langendorff rat hearts were studied: (1) A control group of

  1. ω-3脂肪酸后处理保护大鼠心肌缺血-再灌注损伤的血流动力学及形态学研究%Hemodynamic and morphological investigation of the protective effect of omega-3 fatty acids postconditioning against ischemia reperfusion injury in rat hearts

    Institute of Scientific and Technical Information of China (English)

    王颖博; 童健; 张福伟

    2011-01-01

    Objective To observe the protective effect of omega - 3 fatty acids on myocardial ischemia reperfusion injury in isolated working hearts of rats and to explore the possible mechanism involved. Methods Forty Sprague - Dawley rats were randomly divided into 4 groups. The control group of rats were perfused for 150 minutes without cardioplegia ischemia. The rat hearts of other three groups (I - R,Post and Post - ω) were subjected to 30 - minute ischemia and 90 - minute reperfusion after the perfusion for 30 minutes. At the onset of reperfusion, the process of 20 seconds reperfusion followed by 20 seconds ischemia was repeated for 4 times in the Post group. The Post - ω group was treated by 15 -minutes omega - 3 fatty acids at the onset of reperfusion. The left ventricular end - diastolic pressure ( LVEDP) ,left ventricular developed pressure( LVDP) , rising and descending rate of left ventricular pressure( ± dp/dtmax) and heart rate( HR) were measured after perfusion and 30, 60 , 90 minutes after reperfusion. Finally, infarction sizes in heart were determined by staining with TTC and morphologic changes of mitochondria were observed by the method of transnmission electron microscope. Results Hemodynamic index±dp/dtmax at different times( 30 , 60 and 90 minutes after the reperfusion) were improved significantly in the Post - ω group compared with the I - R group ( P < 0.01,P < 0.05 ) . The Post group had no effect on myocardial functions as compared with the I - R group. The percentage of myocardial infarction size was less in the Post - ω group and the Post group than in I - R group ( P<0.05 ) . Myocardial mitochondrial impairment was reduced significantly in the Post -ω group and the Post group as compared with the I - R group. Conclusion Omega - 3 fatty acids postconditioning can increase the systolic and diastolic function of heart. The protective effect on myocardial ischemia -reperfusion injury in isolated working hearts of rats depend on reducing

  2. The cardioprotective effect of brief acidic reperfusion after ischemia in perfused rat hearts is not mimicked by inhibition of the Na+/H+ exchanger NHE1

    DEFF Research Database (Denmark)

    Andersen, Ann-Dorit; Bentzen, Bo Hjorth; Salling, H.

    2011-01-01

    Ischemic postconditioning (PostC), i.e. brief ischemia-reperfusion cycles before full reperfusion, is protective against cardiac ischemia/reperfusion (I/R) injury. Inhibition of the Na(+)/H(+) exchanger NHE1 and delayed intracellular pH-normalization have been proposed to underlie protection...

  3. Evaluation of the relationship between hyperinsulinaemia and myocardial ischaemia/reperfusion injury in a rat model of depression.

    Science.gov (United States)

    Solskov, Lasse; Løfgren, Bo; Pold, Rasmus; Kristiansen, Steen B; Nielsen, Torsten T; Overstreet, David H; Schmitz, Ole; Bøtker, Hans Erik; Lund, Sten; Wegener, Gregers

    2009-11-09

    Major depression is associated with medical co-morbidity, such as ischaemic heart disease and diabetes, but the underlying pathophysiological mechanisms remain unclear. The FSL (Flinders Sensitive Line) rat is a genetic animal model of depression exhibiting features similar to those of depressed individuals. The aim of the present study was to compare the myocardial responsiveness to I/R (ischaemia/reperfusion) injury and the effects of IPC (ischaemic preconditioning) in hearts from FSL rats using SD (Sprague-Dawley) rats as controls and to characterize differences in glucose metabolism and insulin sensitivity between FSL and SD rats. Hearts were perfused in a Langendorff model and were subjected or not to IPC before 40 min of global ischaemia, followed by 120 min of reperfusion. Myocardial infarct size was found to be significantly larger in the FSL rats than in the SD rats following I/R injury (62.4+/-4.2 compared with 46.9+/-2.9%; P<0.05). IPC reduced the infarct size (P<0.01) and improved haemodynamic function (P<0.01) in both FSL and SD rats. No significant difference was found in blood glucose levels between the two groups measured after 12 h of fasting, but fasting plasma insulin (70.1+/-8.9 compared with 40.9+/-4.7 pmol/l; P<0.05) and the HOMA (homoeostatic model assessment) index (P<0.01) were significantly higher in FSL rats compared with SD rats. In conclusion, FSL rats had larger infarct sizes following I/R injury and were found to be hyperinsulinaemic compared with SD rats, but appeared to have a maintained cardioprotective mechanism against I/R injury, as IPC reduced infarct size in these rats. This animal model may be useful in future studies when examining the mechanisms that contribute to the cardiovascular complications associated with depression.

  4. Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes.

    Science.gov (United States)

    Korkmaz-Icöz, Sevil; Lehner, Alice; Li, Shiliang; Vater, Adrian; Radovits, Tamás; Hegedűs, Péter; Ruppert, Mihály; Brlecic, Paige; Zorn, Markus; Karck, Matthias; Szabó, Gábor

    2015-01-01

    Despite clinical studies indicating that diabetic hearts are more sensitive to ischemia/reperfusion injury, experimental data is contradictory. Although mild diabetes prior to ischemia/reperfusion may induce a myocardial adaptation, further research is still needed. Nondiabetic Wistar (W) and type 2 diabetic Goto-Kakizaki (GK) rats (16-week-old) underwent 45 min occlusion of the left anterior descending coronary artery and 24 h reperfusion. The plasma glucose level was significantly higher in diabetic rats compared to the nondiabetics. Diabetes mellitus was associated with ventricular hypertrophy and increased interstitial fibrosis. Inducing myocardial infarction increased the glucose levels in diabetic compared to nondiabetic rats. Furthermore, the infarct size was smaller in GK rats than in the control group. Systolic and diastolic functions were impaired in W + MI and did not reach statistical significance in GK + MI animals compared to the corresponding controls. Among the 125 genes surveyed, 35 genes showed a significant change in expression in GK + MI compared to W + MI rats. Short-term diabetes promotes compensatory mechanisms that may provide cardioprotection against ischemia/reperfusion injury, at least in part, by increased antioxidants and the upregulation of the prosurvival PI3K/Akt pathway, by the downregulation of apoptotic genes, proinflammatory cytokine TNF-α, profibrogenic TGF-β, and hypertrophic marker α-actin-1.

  5. The role of muscarinic receptors in the beneficial effects of adenosine against myocardial reperfusion injury in rats.

    Directory of Open Access Journals (Sweden)

    Lei Sun

    Full Text Available Adenosine, a catabolite of ATP, displays a wide variety of effects in the heart including regulation of cardiac response to myocardial ischemia and reperfusion injury. Nonetheless, the precise mechanism of adenosine-induced cardioprotection is still elusive. Isolated Sprague-Dawley rat hearts underwent 30 min global ischemia and 120 min reperfusion using a Langendorff apparatus. Both adenosine and acetylcholine treatment recovered the post-reperfusion cardiac function associated with adenosine and muscarinic receptors activation. Simultaneous administration of adenosine and acetylcholine failed to exert any additive protective effect, suggesting a shared mechanism between the two. Our data further revealed a cross-talk between the adenosine and acetylcholine receptor signaling in reperfused rat hearts. Interestingly, the selective M(2 muscarinic acetylcholine receptor antagonist methoctramine significantly attenuated the cardioprotective effect of adenosine. In addition, treatment with adenosine upregulated the expression and the maximal binding capacity of muscarinic acetylcholine receptor, which were inhibited by the selective A(1 adenosine receptor antagonist 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX and the nitric oxide synthase inhibitor N(ω-nitro-L-arginine methyl ester (L-NAME. These data suggested a possible functional coupling between the adenosine and muscarinic receptors behind the observed cardioprotection. Furthermore, nitric oxide was found involved in triggering the response to each of the two receptor agonist. In summary, there may be a cross-talk between the adenosine and muscarinic receptors in ischemic/reperfused myocardium with nitric oxide synthase might serve as the distal converging point. In addition, adenosine contributes to the invigorating effect of adenosine on muscarinic receptor thereby prompting to regulation of cardiac function. These findings argue for a potentially novel mechanism behind the adenosine

  6. Effect of Batroxobin on Neuronal Apoptosis During Focal Cerebral Ischemia and Reperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    吴卫平; 匡培根; 李振洲

    2001-01-01

    We have found that Batroxobin plays a protactive role in ischemic brain injury, which attracted us to investigate the effect of Batroxobin on apoptosis of neurons during cerebral ischemia and reperfusion. The apoptotic cells in ischemic rat brains at different reperfusion intervals were tested with method of TdT-mediated dUTP-DIG nick end labeling (TUNEL) and the effect of Batroxobin on the apoptosis of neurons was studied in left middle cerebral artery (LMCA) occlusion and reperfusion in rat models (n=18). The results showed that few scattered apoptosis cells were observed in right cerebral hemispheres after LMCA occlusion and reperfusion, and that a lot of apoptosis cells were found in left ischemic cortex and caudoputamen at 12h reperfusion, and they reached peak at 24h~48h reperfusion. However, in the rats pretreated with Batroxobin, the number of apoptosis cells in left cerebral cortex and caudoputamen reduced significantly and the neuronal damage was much milder at 24h reperfusion than that of saline-treated rats. The results indicate that administration of Batroxobin may reduce the apoptosis of neurons induced by cerebral ischemia and reperfusion and afford significant cerebroprotection in the model of focal cerebral ischemia and reperfusion.

  7. Intralipid, a Clinically Safe Compound, Protects the Heart Against Ischemia-Reperfusion Injury More Efficiently Than Cyclosporine-A

    Science.gov (United States)

    Li, Jingyuan; Iorga, Andrea; Sharma, Salil; Youn, Ji-Youn; Partow-Navid, Rod; Umar, Soban; Cai, Hua; Rahman, Siamak; Eghbali, Mansoureh

    2013-01-01

    Background We have recently shown that post-ischemic administration of intralipid protects the heart against ischemia/reperfusion injury. Here we compared the cardioprotective effects of intralipid with cyclosporine-A, a potent inhibitor of the mitochondrial permeability transition pore opening. Methods In-vivo rat hearts or isolated Langendorff-perfused mouse hearts were subjected to ischemia followed by reperfusion with Intralipid (0.5%, 1% and 2% ex-vivo and 20% in-vivo), cyclosporine-A (0.2μM, 0.8μM and 1.5μM ex-vivo and 10mg/kg in-vivo) or vehicle. The hemodynamic function, infarct size, calcium retention capacity, mitochodrial superoxide production and phosphorylation levels of Akt/GSK-3β were measured. The values are mean±SEM. Results Administration of intralipid at reperfusion significantly reduced myocardial infarct size compared with cyclosporine-A in-vivo ((infarct size/area at risk)%: 22.9±2.5% vs. 35.2±3.5%; p=0.030, n=7/group). Postischemic administration of intralipid at its optimal dose (1%) was more effective than cyclosporine-A (0.8μM) in protecting the ex-vivo heart against ischemia/reperfusion injury as the rate pressure product at the end of reperfusion was significantly higher (mmHg*beats/min:12740±675(n=7) vs. 9203±10781(n=5), p=0.024), and the infarct size was markedly smaller (17.3±2.9(n=7) vs. 29.2±2.7(n=5), p=0.014). Intralipid was as efficient as cyclosporine-A in inhibiting the mPTP opening (calcium retention capacity=280±8.2 vs. 260.3±2.9nmol/mg-mitochondria-protein in cyclosporine-A, p=0.454, n=6) and in reducing cardiac mitochondrial superoxide production. Unlike intralipid, which increased phosphorlyation of Akt (6-fold) and GSK-3β (5-fold), cyclosporine-A had no effect on the activation of these pro-survival kinases. Conclusions Although intralipid inhibits the opening of the mitochondrial permeability transition pore as efficiently as cyclosporine-A, intralipid is more effective in reducing the infarct size and

  8. Melatonin protects liver from intestine ischemia reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Jian-Yi Li; Hong-Zhuan Yin; Xi Gu; Yong Zhou; Wen-Hai Zhang; Yi-Min Qin

    2008-01-01

    AIM:To investigate the protective effect of melatonin on liver after intestinal ischemia-reperfusion injury in rats.METHODS:One hundred and fifty male Wistar rats,weighing 190-210 g,aged 7 wk,were randomly divided into melatonin exposure group,alcohol solvent control group and normal saline control group.Rats in the melatonin exposure group received intraperitoneal (IP) melatonin (20 mg/kg) 30 min before intestinal ischemia-reperfusion (IR),rats in the alcohol solvent control group received the same concentration and volume of alcohol,and rats in the normal saline control group received the same volume of normal saline.Serum samples were collected from each group 0.5,1,6,12,and 24 h after intestinal IR.Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured with an auto-biochemical analyzer.Serum TNF-a was tested by enzyme-linked immunosorbent assay (ELISA).Malondialdehyde (MDA) in liver was detected by colorimetric assay.Pathological changes in liver and immunohistochemical straining of ICAM-1 were observed under an optical microscope.RESULTS:The levels of ALT measured at various time points after intestinal IR in the melatonin exposure group were significantly lower than those in the other two control groups (P<0.05).The serum AST levels 12 and 24 h after intestinal IR and the ICAM-1 levels (%) 6,12 and 24 h after intestinal IR in the melatonin exposure group were also significantly lower than those in the other two control groups (P<0.05).CONCLUSION:Exotic melatonin can inhibit the activity of ALT,AST and TNF-a decrease the accumulation of MDA,and depress the expression of ICAM-1 in liver after intestinal IR injury,thus improving the liver function.

  9. Intraperitoneal Bilirubin Administration Decreases Infarct Area in a Rat Coronary Ischemia/Reperfusion Model

    Directory of Open Access Journals (Sweden)

    Ron eBen-Amotz

    2014-02-01

    Full Text Available Bilirubin was previously considered a toxin byproduct of heme catabolism. However, a mounting body of evidence suggests that at physiological doses, bilirubin is a powerful antioxidant and anti-atherosclerotic agent. Recent clinical studies have shown that human beings with genetically-induced hyperbilirubinemia (Gilbert Syndrome are protected against coronary heart disease. The purpose of this study was to investigate whether administration of exogenous bilirubin to normal rats would convey similar protective effects in an experimental model of coronary ischemia. We hypothesized that intraperitoneal bilirubin administration 1 hour before injury would decrease infarct area and preserve left ventricular (LV systolic function when compared to non-treated rats. Coronary ischemia was induced by temporary (30 min ligation of the left anterior descending coronary artery in control or bilirubin treated rats, followed by a 1-hour period of reperfusion. LV function was estimated by measurements of fractional shortening and fractional area shortening using echocardiography. LV function decreased in both experimental groups after ischemia and reperfusion, although in bilirubin-treated rats fractional shortening was less depressed during the period of ischemia (18.8 vs 25.8%, p = 0.034. Infarct size was significantly reduced in the bilirubin treated group compared to the non-treated group (13.34% vs 25.5%, p = 0.0067. Based on the results of this study, bilirubin supplementation appears to provide significant decrease in infarct size although protective effects on LV function were noted only during the period of ischemia. This result also suggests that lipid soluble antioxidant bilirubin prevents the oxidation of cardiolipin and decreases the infarct size in the heart during ischemia.

  10. Sulforaphane improves oxidative status without attenuating the inflammatory response or cardiac impairment induced by ischemia-reperfusion in rats.

    Science.gov (United States)

    Bonetto, Jéssica Hellen Poletto; Fernandes, Rafael Oliveira; Seolin, Bruna Gazzi de Lima; Müller, Dalvana Daneliza; Teixeira, Rayane Brinck; Araujo, Alex Sander; Vassallo, Dalton; Schenkel, Paulo Cavalheiro; Belló-Klein, Adriane

    2016-05-01

    Sulforaphane, a natural isothiocyanate, demonstrates cardioprotection associated with its capacity to stimulate endogenous antioxidants and to inhibit inflammation. The aim of this study was to investigate whether sulforaphane is capable of attenuating oxidative stress and inflammatory responses through the TLR4/MyD88/NFκB pathway, and thereby could modulate post-ischemic ventricular function in isolated rat hearts submitted to ischemia and reperfusion. Male Wistar rats received sulforaphane (10 mg·kg(-1)·day(-1)) or vehicle i.p. for 3 days. Global ischemia was performed using isolated hearts, 24 h after the last injection, by interruption of the perfusion flow. The protocol included a 20 min pre-ischemic period followed by 20 min of ischemia and a 20 min reperfusion. Although no changes in mechanical function were observed, sulforaphane induced a significant increase in superoxide dismutase and heme oxygenase-1 expression (both 66%) and significantly reduced reactive oxygen species levels (7%). No differences were observed for catalase and glutathione peroxidase expression or their activities, nor for thioredoxin reductase, glutaredoxin reductase and glutathione-S-transferase. No differences were found in lipid peroxidation or TLR4, MyD88, and NF-κB expression. In conclusion, although sulforaphane was able to stimulate endogenous antioxidants modestly, this result did not impact inflammatory signaling or cardiac function of hearts submitted to ischemia and reperfusion.

  11. Ischemic conditioning by short periods of reperfusion attenuates renal ischemia/reperfusion induced apoptosis and autophagy in the rat

    Directory of Open Access Journals (Sweden)

    Chien Chiang-Ting

    2009-02-01

    Full Text Available Abstract Prolonged ischemia amplified iscehemia/reperfusion (IR induced renal apoptosis and autophagy. We hypothesize that ischemic conditioning (IC by a briefly intermittent reperfusion during a prolonged ischemic phase may ameliorate IR induced renal dysfunction. We evaluated the antioxidant/oxidant mechanism, autophagy and apoptosis in the uninephrectomized Wistar rats subjected to sham control, 4 stages of 15-min IC (I15 × 4, 2 stages of 30-min IC (I30 × 2, and total 60-min ischema (I60 in the kidney followed by 4 or 24 hours of reperfusion. By use of ATP assay, monitoring O2-. amounts, autophagy and apoptosis analysis of rat kidneys, I60 followed by 4 hours of reperfusion decreased renal ATP and enhanced reactive oxygen species (ROS level and proapoptotic and autophagic mechanisms, including enhanced Bax/Bcl-2 ratio, cytochrome C release, active caspase 3, poly-(ADP-ribose-polymerase (PARP degradation fragments, microtubule-associated protein light chain 3 (LC3 and Beclin-1 expression and subsequently tubular apoptosis and autophagy associated with elevated blood urea nitrogen and creatinine level. I30 × 2, not I15 × 4 decreased ROS production and cytochrome C release, increased Manganese superoxide dismutase (MnSOD, Copper-Zn superoxide dismutase (CuZnSOD and catalase expression and provided a more efficient protection than I60 against IR induced tubular apoptosis and autophagy and blood urea nitrogen and creatinine level. We conclude that 60-min renal ischemia enhanced renal tubular oxidative stress, proapoptosis and autophagy in the rat kidneys. Two stages of 30-min ischemia with 3-min reperfusion significantly preserved renal ATP content, increased antioxidant defense mechanisms and decreased ischemia/reperfusion enhanced renal tubular oxidative stress, cytosolic cytochrome C release, proapoptosis and autophagy in rat kidneys.

  12. Ischemia/reperfusion injury in the rat colon.

    Science.gov (United States)

    Murthy, S; Hui-Qi, Q; Sakai, T; Depace, D E; Fondacaro, J D

    1997-04-01

    This study investigated metabolic and biochemical consequences of colonic ischemia/reperfusion (I/R) in the rat and evaluated whether antioxidants prevent I/R-induced functional damage in the rat colon. The surgical preparation involved a 10 cm segment of the colon and occlusion of the superior mesenteric artery (SMA) to induce I/R. Arterial blood from the aorta and venous blood from the superior mesenteric vein (SMV) was collected to measure blood gases, lactic acid (LA) and arachidonic acid (AA) metabolites. Tissue xanthine oxidase (XO) and thiobarbituric acid (TBA) derivatives were measured before and after reperfusion. In addition, vascular and mucosal permeability, and the effect of MDL 73404 (a water soluble vitamin E analog) and 5-aminosalicylic acid on LA, AA, XO and TBA was measured. After ischemia, the colon displayed a metabolic shift from aerobic to anaerobic course by increasing lactic acid production in the colon (183% increase in SMV lactate level compared 87% in the SMA; p < 0.03). After 10 minutes of reperfusion, circulating 6-keto-prostaglandin F1 alpha increased by 3.85 fold (p < 0.001) and thromboxane B2 increased by 2 to 3 fold. An Ischemia time longer than 60 minutes was required to cause changes in tissue XO levels. Tissue TBA levels showed a good dose response corresponding with I/R time. I/R (60 minutes) caused a three and 16 fold increase (p < 0.01) in vascular and mucosal permeability, respectively. MDL 73404 and 5-aminosalicylic acid significantly inhibited the vascular permeability and decreased LA, AA, XO and TBA. These observations provide the first direct experimental evidence for I/R-induced damage in the colon and some of its effects can be reversed by conventional and novel antioxidants.

  13. Adaptation in properties of skeletal muscle to coronary artery occlusion/reperfusion in rats

    Energy Technology Data Exchange (ETDEWEB)

    Ogoh, Shigehiko [Univ. of North Texas, Fort Worth, TX (United States). Health Science Center; Hirai, Taku [Kyoto Univ. (Japan). Graduate School of Medicine; Nohara, Ryuuji [Kitano Hospital, Osaka (Japan); Taguchi, Sadayoshi [Kyoto Univ. (Japan). Graduate School of Human and Environmental Studies

    2002-10-01

    The present study was designed to determine if changes in function and metabolism of heart muscle induce alterations in characteristics of skeletal muscle. We investigated the histochemical and biochemical properties of soleus (SOL) and extensor digitorum longus (EDL) muscles in Wistar rats at the chronic phase after coronary artery occlusion/reperfusion. The size of myocardial infarct region was evaluated using a high resolution pinhole single photo emission computed tomography (SPECT) system. 4wk after left coronary artery occlusion/reperfusion, the SOL and EDL of hindlimb were dissected out and immersed in isopentane cooled with liquid nitrogen for subsequent histochemical and biochemical analysis. From SPECT imaging, the blood circulation was recovered, but the recovery of fatty acid metabolism was not observed in infarct region of heart. Citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HAD) activities in infarct region of heart were lower in the myocardial infarction (MI, n=6) group compared with that of age-matched sham-operated (Sham, n=6) group. In addition, heart muscle hypertrophy caused by the dysfunction in MI group was observed. In skeletal muscle, the atrophy and transition of fiber type distribution in MI group, reported in previous studies of heart failure, were not observed. However, the succinate dehydrogenase (SDH) activity in the slow twitch oxidative (SO) from SOL of MI group decreased by 9.8% and in the fast twitch oxidative glycolytic fibers (FOG), 8.0% as compared with sham group. Capillary density of the SO fibers from SOL of MI group also reduced by 18.5% and in the FOG fibers, 18.2% as compared with Sham group. Decreased capillary density in this study related significantly to decreased SDH activity of single muscle fibers in chronic phase of perfusion after surgical infarction. Our results make it clear that there is a difference in the reaction of skeletal muscle to coronary artery occlusion/reperfusion compared with chronic

  14. Effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart.

    Science.gov (United States)

    Kansal, Sunil Kumar; Jyoti, Uma; Sharma, Samridhi; Kaura, Arun; Deshmukh, Rahul; Goyal, Sandeep

    2015-06-01

    Hyperlipidemia is regarded as independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia-/reperfusion (I/R)-induced injury. Hyperlipidemia attenuates the cardioprotective response of ischemic preconditioning (IPC). The present study investigated the effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat hearts. Hyperlipidemia was induced in rat by feeding high-fat diet (HFD) for 6 weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4 cycles of ischemic preconditioning (IPC), then 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was elaborated morphologically by triphenyltetrazolium chloride (TTC) staining and biochemically by lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) release from coronary effluent and left ventricular collagen content. However, the effect of zinc supplement, i.e., zinc pyrithione (10 μM) perfused during reperfusion for 120 min, significantly abrogated the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart whereas administration of chelator of this zinc ionophore, i.e., N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN; 10 μM), perfused during reperfusion 2 min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion.

  15. Isorhamnetin protects rat ventricular myocytes from ischemia and reperfusion injury.

    Science.gov (United States)

    Zhang, Najuan; Pei, Fei; Wei, Huaying; Zhang, Tongtong; Yang, Chao; Ma, Gang; Yang, Chunlei

    2011-01-01

    Ischemia/reperfusion (I/R) has been known to cause damages to ventricular myocytes. Isorhamnetin, one member of flavonoid compounds, has cardioprotective effect, the effect that suggests a possible treatment for I/R damages. In the present investigation, we found that isorhamnetin could significantly promote the viability of neonatal rat ventricular myocytes that were exposed to ischemia/reperfusion (I/R) in vitro. Ventricular myocytes were obtained from neonatal SD rats, and then were divided randomly into three groups, namely I/R-/isor-, I/R+/isor- and I/R+/isor+ group. Before the whole experiment, the most appropriate concentration of isorhamnetin (4 μM) was determined by MTT assay. Our results showed that isorhamnetin could alleviate the damages of I/R to ventricular myocytes through inhibiting lactate dehydrogenase (LDH) activity, and repressing apoptosis. Compared with the counterpart of the I/R+/isor- group, LDH activity in the isorhamnetin-treated group weakened, halving from 24.1 ± 2.3 to 11.4 ± 1.2U/L. Additionally, flow cytometry showed the apparently increased apoptosis rate induced by I/R, the result that was further confirmed by transmission electron microscope. Administration of isorhamnetin, however, assuaged the apoptosis induced by I/R. Corresponding to the reduced apoptosis rate in the I/R+/isor+ group, western blotting assay showed increased amount of Bcl-2 and p53, decreased amount of Bax, and nuclear accumulation of NF-κB/p65.

  16. The role of different concentrations of nitroglycerin on cardiac ischemia and reperfusion injury in isolated perfused rat hearts%不同浓度硝酸甘油对大鼠离体心脏缺血/再灌注损伤的作用

    Institute of Scientific and Technical Information of China (English)

    姜翠荣; 高琴; 王晓梅; 李正红

    2011-01-01

    目的:探讨不同浓度硝酸甘油(nitroglycerin,GTN)对大鼠离体心脏缺血/再灌注损伤的作用.方法:采用离体大鼠心脏Langendorff灌流方法,结扎冠状动脉左前降支30 min和再灌注120 min复制局部缺血/再灌注损伤模型,测定各项心室动力学指标、冠状动脉流出液中乳酸脱氢酶(lactatede hydrogenase,LDH)含量及心肌梗死面积.结果:与单纯缺血/再灌注组相比,GTN高浓度组(2×10-6 mol/L)抑制了再灌注后心功能的恢复(P<0.05~P<0.01),增大了心肌梗死面积(P<0.01),再灌注时冠状动脉流出液中LDH释放增加(P<0.05);GTN中浓度组(1×10-7 mol/L)与单纯缺血/再灌注组相比,对心功能的恢复、心肌梗死面积和LDH含量改变不明显;GTN低浓度组(1×10-8 mol/L)明显促进了再灌注后心功能的恢复,减小了心肌梗死面积,冠状动脉流出液中LDH释放减少(P<0.05~P<0.01).结论:高浓度GTN加重心肌缺血/再灌注损伤,中浓度GTN对缺血/再灌注心肌作用不明显,低浓度GTN可保护缺血/再灌注心肌.%Objective:To examine the effects of different concentrations of nitroglycerin(GTN) on cardiac ischemia and reperfusion injury in isolated perfused rat hearts. Methods: Male Sprague-Dawley rats were used for Langendoff isolated heart perfusion. The hearts were subjected to 30 min regional ischemia( occlusion of left anterior descending artery) and 120 min reperfusion. The ventricular hemodynamic parameters,lactate dehydrogenase (LDH) release during reperfusion and myocardial infarct size were measured. Results: Administration of GTN at high concentration(2 x 10-6 mol/L) significantly aggravated post-ischemic myocardial injury characterized by depressed cardiac function recovery( P < 0.05 - P < 0.01 ), enlarged myocardial infarct size ( P < 0.01 ) and increased LDH release (P < 0. 05 ). GTN at middle concentration( 1 × 10 -7 mol/L) did not change the cardiac function recovery, myocardial infarct size and LDH release

  17. Role of JAK2/STAT3 signaling pathway in hydrogen sulfide postconditioning on isolated ischemia/reperfusion rat hearts%Janus激酶-信号转导子与转录激活子信号通路在硫化氢后处理离体缺血再灌注大鼠心肌中的作用

    Institute of Scientific and Technical Information of China (English)

    栾恒飞; 李振; 赵其宏; 王乐; 季永; 曾因明

    2011-01-01

    目的 探讨Janus激酶-信号转导子与转录激活子(JAK2/STAT3)信号通路在硫化氢后处理(H2S)减轻离体大鼠心脏缺血/再灌注(I/R)损伤的作用.方法 应用Langendorff离体心脏灌流装置、通过停灌30 min/复灌60 min的方法建立SD大鼠I/R模型.按照处理及再灌注成分分为持续灌注对照组,I/R组,NaHS 10 μmol·L-1组,NaHS +AG490 10 μmol·L-1组,AG490组和DMSO组.持续测定心率(HR)、左心室发展压(LVDP)、左心室舒张末压(LVEDP)、左室内压上升最大速率(+dp/dtmax)、左室内压下降最大速率(-dp/dtmax);再灌注末取心肌TTC法测心肌梗死面积,TUNEL法测心肌细胞凋亡率,Western blotting半定量测p-STAT3和总的STAT3表达水平.结果 平衡灌注末各组间心功能指标无统计学差异.再灌注后,与I/R组比较,NaHS组明显改善再灌注损伤心功能的各项指标(P<0.05),减少心肌梗死面积[(23±4)% vs(41±5)%](P<0.05);并降低凋亡指数[(22±4)% vs(43±5)%](P<0.05),p-STAT3表达水平明显升高[(0.0450±0.0034) vs (0.0238±0.0021)](P<0.05).AG490逆转了硫化氢后处理产生的心肌保护效应及p-STAT3表达水平的增加(P<0.05).结论 JAK2/STAT3信号通路参与了H2S减轻离体大鼠心脏I/R损伤过程.%OBJECTIVE To investigate whether JAK2/STAT3 signaling pathway participated in hydrogen sulfide postconditioning protecting isolated rat hearts against ischemia/reperfusion (I/R)injury. METHODS Isolated perfused rat hearts were exposed to ischemia 30 min followed by reperfusion for 60 min to establish a rat I/R model using Langendorff apparatus. According to the different experimental protocols, SD rats were randomly assigned to the following groups: control,I/R, NaHS 10 μmol·L-1, NaHS + AG490 10 μmol·L-1, AG490 and DMSO groups. Left ventricular hemodynamics including the heart rate ( HR), left ventricular developed pressure ( LVDP), left ventricular end-diastolic pressure (LVEDP) , the maximum rate of increase or decrease of

  18. Reducing the oxidative stress mediates the cardioprotection of bicyclol against ischemia-reperfusion injury in rats

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    Jie CUI; Zhi LI; Ling-bo QIAN; Qin GAO; Jue WANG; Meng XUE; Xiao-e LOU

    2013-01-01

    Objective:To investigate the beneficial effect of bicyclol on rat hearts subjected to ischemia-reperfusion (IR) injuries and its possible mechanism.Methods:Male Sprague-Dawley rats were intragastrically administered with bicyclol (25,50 or 100 mg/(kg·d)) for 3 d.Myocardial IR was produced by occlusion of the coronary artery for 1 h and reperfusion for 3 h.Left ventricular hemodynamics was continuously monitored.At the end of reperfusion,myocardial infarct was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining,and serum lactate dehydrogenase (LDH) level and myocardial superoxide dismutase (SOD) activity were determined by spectrophotometry.Isolated ventricular myocytes from adult rats were exposed to 60 min anoxia and 30 min reoxygenation to simulate IR injuries.After reperfusion,cell viability was determined with trypan blue; reactive oxygen species (ROS) and mitochondrial membrane potential of the cardiomyocytes were measured with the fluorescent probe.The mitochondrial permeability transition pore (mPTP) opening induced by Ca2+ (200 μmol/L) was measured with the absorbance at 520 nm in the isolated myocardial mitochondria.Results:Low dose of bicyclol (25 mg/(kg·d)) had no significant improving effect on all cardiac parameters,whereas pretreatment with high bicyclol markedly reduced the myocardial infarct and improved the left ventricular contractility in the myocardium exposed to IR (P<0.05).Medium dose of bicyclol (50 mg/(kg·d))markedly improved the myocardial contractility,left ventricular myocyte viability,and SOD activity,as well decreased infarct size,serum LDH level,ROS production,and mitochondrial membrane potential in rat myocardium exposed to IR.The reduction of ventricular myocyte viability in IR group was inhibited by pretreatment with 50 and 100 mg/(kg.d) bicyclol (P<0.05 vs.IR),but not by 25 mg/(kg·d) bicyclol.The opening of mPTP evoked by Ca2+ was significantly inhibited by medium bicyclol.Conclusions:Bicyclol exerts

  19. Cardioprotective effect of the Hibiscus rosa sinensis flowers in an oxidative stress model of myocardial ischemic reperfusion injury in rat

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    Krishnamoorthy Karthikeyan K

    2006-09-01

    Full Text Available Abstract Background The present study investigates the cardioprotective effects of Hibiscus rosa sinensis in myocardial ischemic reperfusion injury, particularly in terms of its antioxidant effects. Methods The medicinal values of the flowers of Hibiscus rosa sinensis (Chinese rose have been mentioned in ancient literature as useful in disorders of the heart. Dried pulverized flower of Hibiscus rosa sinensis was administered orally to Wistar albino rats (150–200 gms in three different doses [125, 250 and 500 mg/kg in 2% carboxy methyl cellulose (CMC], 6 days per week for 4 weeks. Thereafter, rats were sacrificed; either for the determination of baseline changes in cardiac endogenous antioxidants [superoxide dismutase, reduced glutathione and catalase] or the hearts were subjected to isoproterenol induced myocardial necrosis. Results There was significant increase in the baseline contents of thiobarbituric acid reactive substances (TBARS [a measure of lipid per oxidation] with both doses of Hibiscus Rosa sinensis. In the 250 mg/kg treated group, there was significant increase in superoxide dismutase, reduced glutathione, and catalase levels but not in the 125 and 500 mg/kg treated groups. Significant rise in myocardial thiobarbituric acid reactive substances and loss of superoxide dismutase, catalase and reduced glutathione (suggestive of increased oxidative stress occurred in the vehicle treated hearts subjected to in vivo myocardial ischemic reperfusion injury. Conclusion It may be concluded that flower of Hibiscus rosa sinensis (250 mg/kg augments endogenous antioxidant compounds of rat heart and also prevents the myocardium from isoproterenol induced myocardial injury.

  20. Protective effects of tumor necrosis factor antibody and ulinastatin on liver ischemic reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Yan-Ling Yang; Ji-Peng Li; Xiao-Ping Xu; Ke-Feng Dou; Shu-Qiang Yue; Kai-Zong Li

    2004-01-01

    AIM: To study the protective effects of tumor necrosis factor α(TNFα) antibody and ulinastatin on liver ischemic reperfusion in rats.METHODS: One hundred and twenty male SD rats were randomly divided into four groups: normal control group,ischemic group, TNFα antibody group and TNFα antibody + ulinastatin group. The animals were killed at 0, 3, 6, 9,12 h after ischemia for 60 min and followed by reperfusion.Serum alanine aminotransferase (ALT), malondialdehyde (MDA) and liver histopathology were observed.RESULTS: After ischemic reperfusion, the serum ALT and MDA were remarkably increased, and the hepatic congestion was obvious. Treatment of TNFα antibody and ulinastatin could significantly decrease serum ALT and MDA levels,and relieve hepatic congestion.CONCLUSION: Ulinastatin and TNFα antibody can suppress the inflammatory reaction induced by hepatic ischemic reperfusion, and have protective effects on rat hepatic ischemic reperfusion injury.

  1. Efficacy of Melissa officinalis in suppressing ventricular arrhythmias following ischemia-reperfusion of the heart: a comparison with amiodarone.

    Science.gov (United States)

    Joukar, Siyavash; Zarisfi, Zahra; Sepehri, Gholamreza; Bashiri, Alireza

    2014-01-01

    We aimed to assess the influence of Melissa officinalis (lemon balm), a well-known herbal drug with numerous applications in traditional and modern medicine, on cardiac conduction and susceptibility to lethal ventricular arrhythmia. Forty-two male Wistar rats were divided into a control group (CTL), an M. officinalis group that received the aqueous extract of M. officinalis L. intraperitoneally (i.p.) at dosages of 50, 100, 200 and 400 mg/ml/kg, respectively, and an amiodarone group (Amio group) that received 30 mg/ml/kg i.p. of amiodarone. Heart ischemia/reperfusion was induced by the ligation and release of the left anterior descending branch of the left coronary artery. There were no statistical differences between the groups in the basal heart rate and blood pressure. PR, corrected QT (QTc) and QRS intervals increased in the M. officinalis and Amio groups. PR and QTc were statistically significant only in the Amio group and QRS was significant only in the group receiving 400 mg of M. officinalis (M400 group) in comparison with the CTL group. During the reperfusion period, the decrease in ventricular fibrillations was statistically significant in all groups (except the M400 group) when compared with the CTL group. The score of arrhythmia severity also decreased, but was statistically significant only in the Amio group (p < 0.05 vs. CTL group). Our findings suggest that M. officinalis extract has a mild protective effect against reperfusion-induced lethal ventricular arrhythmias in rats. © 2014 S. Karger AG, Basel.

  2. Arginase induction and activation during ischemia and reperfusion and functional consequences for the heart

    Directory of Open Access Journals (Sweden)

    Klaus-Dieter eSchlüter

    2015-03-01

    Full Text Available Induction and activation of arginase is among the fastest responses of the heart to ischemic events. Induction of arginase expression and enzyme activation under ischemic conditions shifts arginine consumption from nitric oxide formation (NO to the formation of ornithine and urea. In the heart such a switch in substrate utilisation reduces the impact of the NO/cGMP-pathway on cardiac function that requires intact electromechanical coupling but at the same time it induces ornithine-dependent pathways such as the polyamine metabolism. Both effects significantly reduce the recovery of heart function during reperfusion and thereby limits the success of reperfusion strategies. In this context, changes in arginine consumption trigger cardiac remodelling in an unfavourable way and increases the risk of arrhythmia, specifically in the initial post-ischemic period in which arginase activity is dominating. However, during the entire ischemic period arginase activation might be a meaningful adaptation that is specifically relevant for reperfusion following prolonged ischemic periods. Therefore, a precise understanding about the underlying mechanism that leads to arginase induction as well as of it’s mechanistic impact on post-ischemic hearts is required for optimizing reperfusion strategies. In this review we will summarize our current understanding of these processes and give an outlook about possible treatment options for the future.

  3. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury

    Science.gov (United States)

    Masuzawa, Akihiro; Black, Kendra M.; Pacak, Christina A.; Ericsson, Maria; Barnett, Reanne J.; Drumm, Ciara; Seth, Pankaj; Bloch, Donald B.; Levitsky, Sidney; Cowan, Douglas B.

    2013-01-01

    Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 ± 1.7 × 106/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased (P mitochondria (7.9 ± 2.9%) compared with RI-vehicle (34.2 ± 3.3%, P mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2–8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury. PMID:23355340

  4. Buyang Huanwu decoction enhances cell membrane fluidity in rats with cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Chenxu Li

    2012-01-01

    After bilateral carotid artery occlusion for 30 minutes and reperfusion for 2 hours, distinct patho-logical changes presented in the cerebral cortex and cerebellum of rats. Compared with normal rats, nerve cell membrane fluidity significantly decreased in ischemia/reperfusion rats as detected by spin-labeling electron spin resonance, consistent with order parameter S and rotational correlation time TC measurements. Brain nerve cells from rats with ischemia/reperfusion injury were cultured with 1-100 mg/mL Buyang Huanwu decoction. Results showed that Buyang Huanwu decoction gradually increased membrane fluidity dose-dependently to normal levels, and eliminated hydroxide (OH·) and superoxide (O2·) free radicals dose-dependently. These findings suggest that Buyang Huanwu decoction can protect against cell membrane fluidity changes in rats with ischemia/ reper-fusion injury by scavenging free radicals.

  5. Protective Effects of L-Malate against Myocardial Ischemia/Reperfusion Injury in Rats

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    Shiao Ding

    2016-01-01

    Full Text Available Objective. To investigate the protective effects of L-malate against myocardial ischemia/reperfusion (I/R injury in rats. Methods. Male Sprague-Dawley rats were randomly assigned to the following groups: sham (sham, an ischemia/reperfusion (I/R model group (model, an DMF pretreated group (DMF, and 5 L-malate pretreated groups (15, 60, 120, 240, or 480 mg/kg, gavage before inducing myocardial ischemia. Plasma LDH, cTn-I, TNF-α, hs-CRP, SOD, and GSH-PX were measured 3 h later I/R. Areas of myocardial infarction were measured; hemodynamic parameters during I/R were recorded. Hearts were harvested and Western blot was used to quantify Nrf2, Keap1, HO-1, and NQO-1 expression in the myocardium. Results. L-malate significantly reduced LDH and cTn-I release, reduced myocardial infarct size, inhibited expression of inflammatory cytokines, and partially preserved heart function, as well as increasing antioxidant activity after myocardial I/R injury. Western blot confirmed that L-malate reduced Kelch-like ECH-associated protein 1 in ischemic myocardial tissue, upregulated expression of Nrf2 and Nrf2 nuclear translocation, and increased expression of heme oxygenase-1 and NAD(PH:quinone oxidoreductase 1, which are major targets of Nrf2. Conclusions. L-malate may protect against myocardial I/R injury in rats and this may be associated with activation of the Nrf2/Keap1 antioxidant pathway.

  6. Rosmarinic acid attenuates hepatic ischemia and reperfusion injury in rats.

    Science.gov (United States)

    Ramalho, Leandra Naira Z; Pasta, Ângelo Augusto C; Terra, Vânia Aparecida; Augusto, Marlei Josiele; Sanches, Sheila Cristina; Souza-Neto, Fernando P; Cecchini, Rubens; Gulin, Francine; Ramalho, Fernando Silva

    2014-12-01

    Rosmarinic acid (RosmA) demonstrates antioxidant and anti-inflammatory properties. We investigated the effect of RosmA on liver ischemia/reperfusion injury. Rats were submitted to 60 min of ischemia plus saline or RosmA treatment (150 mg/kg BW intraperitoneally) followed by 6 h of reperfusion. Hepatocellular injury was evaluated according to aminotransferase activity and histological damage. Hepatic neutrophil accumulation was also evaluated. Oxidative/nitrosative stress was estimated by measuring the reduced glutathione, lipid hydroperoxide and nitrotyrosine levels. Endothelial and inducible nitric oxide synthase (eNOS/iNOS) and nitric oxide (NO) were assessed with immunoblotting and chemiluminescence assays. Hepatic tumor necrosis factor-alpha (TNF-α) and interleukin-1beta mRNA were assessed using real-time PCR, and nuclear factor-kappaB (NF-κB) activation was estimated by immunostaining. RosmA treatment reduced hepatocellular damage, neutrophil infiltration and all oxidative/nitrosative stress parameters. RosmA decreased the liver content of eNOS/iNOS and NO, attenuated NF-κB activation, and down-regulated TNF-α and interleukin-1beta gene expression. These data indicate that RosmA exerts anti-inflammatory and antioxidant effects in the ischemic liver, thereby protecting hepatocytes against ischemia/reperfusion injury. The mechanisms underlying these effects may be related to the inhibitory potential of RosmA on the NF-κB signaling pathway and the reduction of iNOS and eNOS expressions and NO levels, in addition to its natural antioxidant capability.

  7. The protective activity of noscapine on renal ischemia–reperfusion injury in male Wistar rat

    OpenAIRE

    Mehrangiz Khanmoradi; Seyyed Ali Mard; Nahid Aboutaleb; Malihe Nobakht; Masoud Mahmoudian

    2014-01-01

    Objective(s): Bradykinin is a part of the kinin-kallikrein system which is involved in ischemia-reperfusion injury via B1 and B2 receptors. Noscapine is a non-competitive antagonist of bradykinin receptors. Noscapine has been reported to to be able to protect some organs against ischemia-reperfusion injury but its effect on renal ischemia-reperfusion injury (RIR) in rats is unknown. Therefore, the present study was designed to evaluate the effect of noscapine on renal ischemia-reperfusion inj...

  8. Moxonidine prevents ischemia/reperfusion-induced renal injury in rats.

    Science.gov (United States)

    Tsutsui, Hidenobu; Sugiura, Takahiro; Hayashi, Kentaro; Ohkita, Mamoru; Takaoka, Masanori; Yukimura, Tokihito; Matsumura, Yasuo

    2009-01-28

    Enhancement of renal sympathetic nerve activity during renal ischemia and its consequent effect on norepinephrine overflow from nerve endings after reperfusion play important roles in the development of ischemic acute kidney injury. In the present study, we evaluated whether moxonidine, an alpha(2)-adrenaline/I(1)-imidazoline receptor agonist which is known to elicit sympathoinhibitory action, would prevent the post-ischemic renal injury. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Intravenous (i.v.) injection of moxonidine at a dose of 360 nmol/kg to ischemic acute kidney injury rats suppressed the enhanced renal sympathetic nerve activity during the ischemic period, to a degree similar to findings with intracerebroventricular (i.c.v.) injection of moxonidine at a dose of 36 nmol/kg. On the other hand, suppressive effects of the i.v. treatment on renal venous norepinephrine overflow, renal dysfunction and tissue injury in the post-ischemic kidney were significantly greater than those elicited by the i.c.v. treatment. These results suggest that renoprotective effects of moxonidine on ischemic acute kidney injury probably result from its suppressive action on the ischemia-enhanced renal sympathetic nerve activity followed by norepinephrine spillover from the nerve endings of the post-ischemic kidney.

  9. Cardioprotective effect of connexin 43 expression regulated by PI3K/Akt on hydrogen sulfide postconditioning in isolated ischemic and reperfused rat hearts%PI3K/Akt调节线粒体Cx43蛋白表达在H2S后处理离体大鼠心肌中的保护作用

    Institute of Scientific and Technical Information of China (English)

    张可璇; 毛洪雅; 孟雪; 惠夏; 张邓新; 季永

    2013-01-01

    Aim To investigate whether the PBK/Akt signaling pathway regulates connexin 43 expression to protect isolated rat hearts against ischemia/reperfusion ( I/R ) injury in hydrogen sulfide postconditioning. Methods Hearts of 56 male SD rats were isolated and linked to the Langendorff apparatus. They were randomly divided into 4 groups( n = 14): ischemia reper-fusion group ( I/R ), PBK/Akt signaling pathway inhibitor LY294002 group ( LY ), hydrogen sulfide post-conditioning group ( NP ), and hydrogen sulfide with to all the nuclei counted was used as apoptotic index ( AI ). The expression of total Cx43 and phosphoryla-tion Cx43 in mitochondria were determined with Western blot analysis at the end of reperfusion. Results No differences in baseline hemodynamics were observed a-mong the experimental groups ( P > 0. 05 ). After reperfusion, compared with I/R group, NP group had better hemodynamics; the myocardial infarct size and cardiocyte apoptotic index were much lower ( P < 0. 05 ); the expression of tCx43 ( total connexin 43 , tCx43 ) and pCx43 ( phosphorylated connexin 43, pCx43 ) in mitochondria increased significantly. How- LY294002 group( N + L ). The heart rate ( HR ) , the left ventricular diastolic pressure ( LVEDP ), the left ventricular developed pressure ( LVDP ), the maximum rate of increase or decrease of left ventricular pressure ( ± dp/dtmax ) were recorded at 20 min of equilibrium at 30 min of reperfusion and at the end of reperfusion, respectively. Myocardial infarct size was measured by triphenyltet tetrazolium chloride ( TTC ) staining. Myocardial TUNEL staining was determined by in situ cell death detection kit. The ratio of TUNEL positive nuclei ever , LY294002 abolished the cardioprotection offered by hydrogen sulfide postconditioning and the increase in tCx43 and pCx43 expression in mitochondria. Conclusion The PI3K/Akt pathway upregulates connexin 43 expression to protect isolated rat hearts against is-chemia/reperfusion ( I/R ) injury in

  10. 七氟烷后处理对不同病程糖尿病大鼠离体心肌缺血再灌注损伤的影响%Sevoflurane postconditioning protects hearts isolated from rats with diabetes mellitus of different duration against ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    郑瑛慧; 张洪松; 钱敏; 孟雪; 许鹏程; 刘金东

    2012-01-01

    目的 评价七氟烷后处理对不同病程糖尿病大鼠离体心肌缺血再灌注损伤的影响.方法 清洁级健康雄性SD大鼠72只,体重200 ~ 240 g,采用随机数字法,将其随机分成6组(n=12):非糖尿病缺血再灌注组(I/R组)、非糖尿病七氟烷后处理组(I/R+ sevo组)、2周糖尿病缺血再灌注组(2DM组)、2周糖尿病七氟烷后处理组(2DM+ sevo组)、6周糖尿病缺血再灌注组(6DM组)、6周糖尿病七氟烷后处理组(6DM+ sevo组).制备离体心脏Langendorff灌注模型,各组经主动脉灌注K-H液,平衡灌注15 min后停灌30 min,I/R组、2DM组及6DM组均采用K-H液灌注75 min; I/R+ sevo组、2DM+ sevo组及6DM+ sevo组均采用含有3%七氟烷的K-H液灌注15 min,随后用K-H液继续灌注60 min.于平衡末、再灌注15和75 min时记录左室舒张末压、左室发展压、左心室压力上升最大速率、左心室压力下降最大速率以及心率.于再灌注15 min时取心肌组织,用Western blot法测定磷酸化Akt(p-Akt)和总Akt的表达,于再灌注75 min时采用TTC法测定心肌梗死体积,计算心肌梗死体积比.结果 与2DM组比较,2DM+ sevo组心功能改善,心肌梗死体积比减小,p-Akt表达上调(P<0.05);与I/R组比较,I/R+ sevo组再灌注期间心功能改善,心肌梗死体积比减小,p-Akt表达上调(P<0.05);与6DM组比较,6DM+ sevo组心功能指标、心肌梗死体积比及p-Akt表达差异无统计学意义(P>0.05).结论 随着糖尿病病程进展,七氟烷后处理减轻大鼠心肌缺血再灌注损伤的作用减弱,可能与PI3K/Akt信号通路受损有关.%Objective To investigate the protective effect of sevoflurane postconditioning (Sevo-Postcon)on the hearts isolated from rats with diabetes mellitus (DM) of different duration against ischemia-reperfusion (I/R)injury.Methods Seventy-two pathogen-free male SD rats weighing 200-240 g were randomly divided into 3 groups ( n =24 each):group Ⅰ rats without DM (C) ; group

  11. Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury.

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    Laila Elsherif

    Full Text Available Mice expressing the tetracycline transactivator (tTA transcription factor driven by the rat α-myosin heavy chain promoter (α-MHC-tTA are widely used to dissect the molecular mechanisms involved in cardiac development and disease. However, these α-MHC-tTA mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury in both in vitro and in vivo models in the absence of associated cardiac hypertrophy or remodeling. Cardiac function, as assessed by echocardiography, did not differ between α-MHC-tTA and control animals, and there were no noticeable differences observed between the two groups in HW/TL ratio or LV end-diastolic and end-systolic dimensions. Protection against ischemia/reperfusion injury was assessed using isolated perfused hearts where α-MHC-tTA mice had robust protection against ischemia/reperfusion injury which was not blocked by pharmacological inhibition of PI3Ks with LY294002. Furthermore, α-MHC-tTA mice subjected to coronary artery ligation exhibited significantly reduced infarct size compared to control animals. Our findings reveal that α-MHC-tTA transgenic mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury similar to cardiac pre- and post-conditioning effects. However, in contrast to classical pre- and post-conditioning, the α-MHC-tTA phenotype is not inhibited by the classic preconditioning inhibitor LY294002 suggesting involvement of a non-PI3K-AKT signaling pathway in this phenotype. Thus, further study of the α-MHC-tTA model may reveal novel molecular targets for therapeutic intervention during ischemic injury.

  12. Diverse Effects of L-arginine on Cardiac Function of Rats Subjected to Myocardial Ischemia and Reperfusion in vivo

    Institute of Scientific and Technical Information of China (English)

    Xiaoliang WANG; Feng LIANG; Xiangying JIAO; Lei LIU; Xiaojie BAI; Meixia LI; Jianmin ZHI; Huirong LIU

    2007-01-01

    In vivo administration of L-arginine at different time points during the course of myocardial ischemia and reperfusion (MI/R) has been shown to differentially regulate postischemic apoptosis.Cardiac function is one of the most important indexes used to judge the degree of myocardial injury.The present study attempted to determine whether in vivo administration of L-arginine at different stages of MI/R has a diverse influence on cardiac function of ischemic reperfused hearts and,if So,to investigate the mechanisms involved.Male adult rats were subjected to 30 min myocardial ischemia followed by 5 h reperfusion.An intravenous L-arginine bolus was given either 10 min before and 50 min after reperfusion (early treatment) or 3 h and 4 h after reperfusion (late treatment).Early treatment with L-arginine markedly increased the left ventricular systolic pressure (LVSP) and dP/dtmax,and decreased myocardial nitrotyrosine content.In strict contrast,late treatment with L-arginine resulted in a significant decrease in LVSP and dP/dtmx from 4 h to 5h after reperfusion,and increase in toxic peroxynitrite formation as measured by nitrotyrosine.These results suggest that the administration of L-arginine at different time points during the course of MI/R leads to diverse effects on cardiac dysfunction.Early supplementation decreased the nitrative stress and improved left ventricular function.However,late treatment with L-arginine increased the formation of peroxynitrite and aggravated cardiac functional injury.

  13. Dissecting the Effects of Ischemia and Reperfusion on the Coronary Microcirculation in a Rat Model of Acute Myocardial Infarction.

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    Maurits R Hollander

    Full Text Available Microvascular injury (MVI after coronary ischemia-reperfusion is associated with high morbidity and mortality. Both ischemia and reperfusion are involved in MVI, but to what degree these phases contribute is unknown. Understanding the etiology is essential for the development of new potential therapies.Rats were divided into 3 groups receiving either 30 minutes ischemia, 90 minutes ischemia or 30 minutes ischemia followed by 60 minutes reperfusion. Subsequently hearts were ex-vivo perfused in a Langendorff-model. Fluorescence and electron microscopy was used for analysis of capillary density, vascular permeability and ultrastructure. Most MVI was observed after 30 minutes ischemia followed by 60 minutes reperfusion. In comparison to the 30' and 90' ischemia group, wall thickness decreased (207.0±74 vs 407.8±75 and 407.5±71, p = 0.02. Endothelial nuclei in the 30'-60' group showed irreversible damage and decreased chromatin density variation (50.5±9.4, 35.4±7.1 and 23.7±3.8, p = 0.03. Cell junction density was lowest in the 30'-60' group (0.15±0.02 vs 2.5±0.6 and 1.8±0.7, p<0.01. Microsphere extravasation was increased in both the 90' ischemia and 30'-60' group.Ischemia alone for 90 minutes induces mild morphological changes to the coronary microcirculation, with increased vascular permeability. Ischemia for 30 minutes, followed by 60 minutes of reperfusion, induces massive MVI. This shows the direct consequences of reperfusion on the coronary microcirculation. These data imply that a therapeutic window exists to protect the microcirculation directly upon coronary revascularization.

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

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    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.

  15. Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial Ischemia/Reperfusion Injury via Mitochondria Apoptosis Pathway

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    Yang Wu

    2017-01-01

    Full Text Available Background. Histone deacetylases (HDACs play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion. H9C2 cardiomyocytes were exposed to high glucose for 24 h, followed by 4 h of hypoxia and 2 h of reoxygenation (H/R. Results. Both MI/R injury and diabetes mellitus elevated myocardium HDACs activity. MI/R induced apoptotic cell death was significantly decreased in diabetic rats treated with HDACs inhibitor trichostatin A (TSA. TSA administration markedly moderated dissipation of mitochondrial membrane potential, protected the integrity of mitochondrial permeability transition pore (mPTP, and decreased cell apoptosis. Notably, cotreatment with Akt inhibitor partly or absolutely inhibited the protective effect of TSA in vivo and in vitro. Furthermore, TSA administration activated Akt/Foxo3a pathway, leading to Foxo3a cytoplasm translocation and attenuation proapoptosis protein Bim expression. Conclusions. Both diabetes mellitus and MI/R injury increased cardiac HDACs activity. Suppression of HDACs activity triggered protective effects against MI/R and H/R injury under hyperglycemia conditions through Akt-modulated mitochondrial apoptotic pathways via Foxo3a/Bim.

  16. Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial Ischemia/Reperfusion Injury via Mitochondria Apoptosis Pathway

    Science.gov (United States)

    Wu, Yang; Leng, Yan; Meng, Qingtao; Xue, Rui; Zhao, Bo; Zhan, Liying

    2017-01-01

    Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion. H9C2 cardiomyocytes were exposed to high glucose for 24 h, followed by 4 h of hypoxia and 2 h of reoxygenation (H/R). Results. Both MI/R injury and diabetes mellitus elevated myocardium HDACs activity. MI/R induced apoptotic cell death was significantly decreased in diabetic rats treated with HDACs inhibitor trichostatin A (TSA). TSA administration markedly moderated dissipation of mitochondrial membrane potential, protected the integrity of mitochondrial permeability transition pore (mPTP), and decreased cell apoptosis. Notably, cotreatment with Akt inhibitor partly or absolutely inhibited the protective effect of TSA in vivo and in vitro. Furthermore, TSA administration activated Akt/Foxo3a pathway, leading to Foxo3a cytoplasm translocation and attenuation proapoptosis protein Bim expression. Conclusions. Both diabetes mellitus and MI/R injury increased cardiac HDACs activity. Suppression of HDACs activity triggered protective effects against MI/R and H/R injury under hyperglycemia conditions through Akt-modulated mitochondrial apoptotic pathways via Foxo3a/Bim. PMID:28191472

  17. 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.

  18. Effects of KR-33028, a novel Na+/H+ exchanger-1 inhibitor, on ischemia and reperfusion-induced myocardial infarction in rats and dogs.

    Science.gov (United States)

    Oh, Kwang-Seok; Seo, Ho Won; Yi, Kyu Yang; Lee, Sunkyung; Yoo, Sung-eun; Lee, Byung Ho

    2007-06-01

    The present study was performed to evaluate the cardioprotective effects of KR-33028, a novel Na+/H+ exchanger subtype 1 (NHE-1) inhibitor, in rat and dog models of coronary artery occlusion and reperfusion. In anesthetized rats subjected to a 45-min coronary occlusion and a 90-min reperfusion, KR-33028 at 5 min before occlusion (i.v. bolus) dose-dependently reduced myocardial infarct size from 58.0% to 46.6%, 40.3%, 39.7%, 33.1%, and 27.8% for 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg respectively (P KR-33028 (3 mg/kg, i.v. bolus) markedly decreased infarct size from 45.6% in vehicle-treated group to 16.4% (P KR-33028 (1 mg/kg, i.v. bolus) given 10 min before or at reperfusion in rat models also significantly reduced the myocardial infarct size (46.3% and 44.1% respectively) compared with vehicle-treated group. In all studies, KR-33028 caused no significant changes in any hemodynamic profiles. In an isolated rat heart model of hypothermic cardioplegia, KR-33028 (30 mum), which was added to the heart preservation solution (histidin-tryptophan-ketoglutarate) during hypothermic cardioplegic arrest, significantly improved the recovery of left ventricular developed pressure, heart rate and dP/dt(max) after reperfusion. Taken together, these results indicate that KR-33028 significantly reduced the myocardial infarction induced by ischemia and reperfusion in rats and dogs, without affecting hemodynamic profiles.

  19. Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats

    Science.gov (United States)

    Li, Shadan; Liu, Bin; Guan, Qiunong; Chafeeva, Irina; Brooks, Donald E; Nguan, Christopher YC; Kizhakkedathu, Jayachandran N; Du, Caigan

    2017-01-01

    Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation. PMID:28337272

  20. Dexmedetomidine preconditioning protects isolated rat hearts against ischemia/reperfusion injuries and its mechanism%右美托咪定预处理减轻离体大鼠心脏缺血/再灌注损伤的线粒体相关机制

    Institute of Scientific and Technical Information of China (English)

    姜翠翠; 夏满莉; 王敏; 陈士票

    2013-01-01

    Objective:To investigate the protective effect of dexmedetomidine (Dex) preconditioning against ischemia/reperfusion (I/R) injuries in isolated rat hearts and its relation to mitochondrial permeability transition pore (mPTP) and mitochondrial ATP-sensitive K+ channel (mitoKATP).Methods:The hearts of male SD rats were isolated to mount on the Langendorff apparatus and subjected to 30 min global ischemia followed by 120 min reperfusion.The isolated hearts were treated with Dex (10nmol/L) before ischemia for 15 min.The left ventricular hemodynamic parameters,coronary flow (CF)and the lactate dehydrogenase (LDH) release in the coronary effluent at 5 min reperfusion were measured.The formazan content was assayed to determine the myocardial viability at the end of reperfusion.Results:Compared with normal controls,I/R markedly decreased the left ventricular developed pressure and CF during the whole reperfusion period and the formazan content; while the left ventricular end diastolic pressure and LDH release were significantly increased.Dex preconditioning markedly improved the myocardial viability and cardiac function (P <0.01),which were reversed by the treatment with both atractyloside (20 μmol/L before ischemian),an opener of mPTP,and 5-hydroxydecanoate (100 μmol/L at the beginning of repeffusion),an inhibitor of mitoKATP,for 20 min.Conclusion:Dex has protective effect against I/R injuries in isolated rat hearts,which may be related to inhibiting the opening of mPTP at the beginning of reperfusion and activating mitoKATP before ischemia.%目的:研究右美托咪定(dexmedetomidine,Dex)预处理对心肌缺血/再灌注(I/R)损伤的作用及其与线粒体渗透性转换孔(mPTP)和/或线粒体ATP敏感性钾通道(mitoKATP)的关系.方法:分离SD雄性大鼠心脏置于Langendorff系统行全心停灌30 min,再灌注120 min建立心肌I/R损伤模型,停灌前15 min给予Dex(10 nmol/L)处理.测定左心室动力学、再灌注期间冠脉流量及再灌注5

  1. Histological and biochemical alterations in early-stage lobar ischemia-reperfusion in rat liver

    Institute of Scientific and Technical Information of China (English)

    Hossein Ali Arab; Farhang Sasani; Mohammad Hossein Rafiee; Ahmad Fatemi; Abbas Javaheri

    2009-01-01

    AIM: To investigate the structural and biochemical changes in the early stage of reperfusion in the rat livers exposed to lobar ischemia-reperfusion (IR).METHODS: The median and left lobes of the liver were subjected to 60 min ischemia followed by 5, 10,30, 45, 60 and 120 min reperfusion. Blood samples were taken at different time intervals to test enzyme activities and biochemical alterations induced by reperfusion. At the end of each reperfusion period, the animals were killed by euthanasia and tissue samples were taken for histological examination and immunohistochemistry.RESULTS: Cell vacuolation, bleb formation and focal hepatitis were the most important changes occur during ischemia. While some changes including bleb formation were removed during reperfusion, other alterations including portal hepatitis, inflammation and the induction of apoptosis were seen during this stage. The occurrence of apoptosis, as demonstrated by apoptot i c cel l s and bodies , was the mos t important histological change during reperfusion. The severity of apoptosis was dependent on the time of reperfusion, and by increasing the time of reperfusion,the numbers of apoptotic bodies was significantly enhanced. The amounts of lactate dehydrogenase,alanine aminotransferase, aspartate aminotransferase,creatinine and urea were significantly increased in serum obtained from animals exposed to hepatic IR.

  2. Ratiometric imaging of calcium during ischemia-reperfusion injury in isolated mouse hearts using Fura-2

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    Venkataraman Raghav

    2012-07-01

    Full Text Available Abstract Background We present an easily implementable method for measuring Fura-2 fluorescence from isolated mouse hearts using a commercially available switching light source and CCD camera. After calibration, it provides a good estimate of intracellular [Ca2+] with both high spatial and temporal resolutions, permitting study of changes in dispersion of diastolic [Ca2+], Ca2+ transient dynamics, and conduction velocities in mouse hearts. In a proof-of-principle study, we imaged isolated Langendorff-perfused mouse hearts with reversible regional myocardial infarctions. Methods Isolated mouse hearts were perfused in the Landendorff-mode and loaded with Fura-2. Hearts were then paced rapidly and subjected to 15 minutes of regional ischemia by ligation of the left anterior descending coronary artery, following which the ligation was removed to allow reperfusion for 15 minutes. Fura-2 fluorescence was recorded at regular intervals using a high-speed CCD camera. The two wavelengths of excitation light were interleaved at a rate of 1 KHz with a computer controlled switching light source to illuminate the heart. Results Fura-2 produced consistent Ca2+ transients from different hearts. Ligating the coronary artery rapidly generated a well defined region with a dramatic rise in diastolic Ca2+ without a significant change in transient amplitude; Ca2+ handling normalized during reperfusion. Conduction velocity was reduced by around 50% during ischemia, and did not recover significantly when monitored for 15 minutes following reperfusion. Conclusions Our method of imaging Fura-2 from isolated whole hearts is capable of detecting pathological changes in intracellular Ca2+ levels in cardiac tissue. The persistent change in the conduction velocities indicates that changes to tissue connectivity rather than altered intracellular Ca2+ handling may be underlying the electrical instabilities commonly seen in patients following a myocardial infarction.

  3. Pretreatment of cromolyn sodium prior to reperfusion attenuates early reperfusion injury after the small intestine ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effects of Cromolyn Sodium (CS) pretreated prior to reperfusion on the activity of intestinal mucosal mast cells (IMMC) and mucous membrane of the small intestine in ischemia-reperfusion (IR) injury of rats.METHODS: Thirty-two Sprague-Dawley (SD) rats were randomly divided into four groups: sham group (group S), model group (group M), high and low dosage of CS groups, (treated with CS 50 mg/kg or 25 mg/kg,group C1 and C2). Intestinal IR damage was induced by clamping the superior mesenteric artery for 45 min followed by reperfusion for 60 min. CS was intravenouly administrated 15 min before reperfusion. Ultrastructure and counts of IMMC, intestinal structure, the expression of tryptase, levels of malondisldehyde (MDA), TNF-α,histamine and superoxide dismutase (SOD) activity of the small intestine were detected at the end of experiment.RESULTS: The degranulation of IMMC was seen in group M and was attenuated by CS treatment. Chiu's score of group M was higher than the other groups. CS could attenuate the up-regulation of the Chiu's score,the levels of MDA, TNF-α, and expression of tryptase and the down-regulation of SOD activity and histamine concentration. The Chiu's score and MDA content were negatively correlated, while SOD activity was positively correlated to the histamine concentration respectively in the IR groups.CONCLUSION: Pretreated of CS prior to reperfusion protects the small intestine mucous from ischemiareperfusion damage, the mechanism is inhibited IMMC from degranulation.

  4. The Effect of Sleep Deprivation on Cardiac Function and Tolerance to Ischemia-Reperfusion Injury in Male Rats

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    Sajad Jeddi

    2015-01-01

    Full Text Available AbstractBackground:Sleep deprivation (SD is strongly associated with elevated risk for cardiovascular disease.Objective:To determine the effect of SD on basal hemodynamic functions and tolerance to myocardial ischemia-reperfusion (IR injury in male rats.Method:SD was induced by using the flowerpot method for 4 days. Isolated hearts were perfused with Langendorff setup, and the following parameters were measured at baseline and after IR: left ventricular developed pressure (LVDP; heart rate (HR; and the maximum rate of increase and decrease of left ventricular pressure (±dp/dt. Heart NOx level, infarct size and coronary flow CK-MB and LDH were measured after IR. Systolic blood pressure (SBP was measured at start and end of study.Results:In the SD group, the baseline levels of LVDP (19%, +dp/dt (18%, and -dp/dt (21% were significantly (p < 0.05 lower, and HR (32% was significantly higher compared to the controls. After ischemia, hearts from SD group displayed a significant increase in HR together with a low hemodynamic function recovery compared to the controls. In the SD group, NOx level in heart, coronary flow CK-MB and LDH and infarct size significantly increased after IR; also SD rats had higher SBP after 4 days.Conclusion:Hearts from SD rats had lower basal cardiac function and less tolerance to IR injury, which may be linked to an increase in NO production following IR.

  5. Effect of Shenfu injection on nuclear factor-kB during myocardial ischemia/reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ben-jing; WANA Yan-lin; WANG Cheng-yao; KE Jian-juan

    2005-01-01

    Objective: To investigate effects of Shenfu injection on the concentrations of plasma tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), activity of Nuclear Factor kappa B (NF-κB) and heart tissue ultrastructure during myocardial ischemia/reperfusion (I/R) injury in rats and its potential mechanism.Methods: Myocardial ischemia/reperfusion (I/R) was produced by ligation and release of the left anterior descending coronary artery. Ischemia lasted for 30 min and reperfusion for 60 min. Twenty-four healthy male SD rats weighing 230-280 g were randomly divided into three groups (n=8, each): Group I (Sham-operation group); Group II (I/R group); Group III (Shenfu group), in which Shenfu injection (10 ml/kg) was intraperitoneally injected 30 min before ischemia in animals with I/R. The plasma concentrations of IL-6 and TNF-α were measured by ELISA, and the heart was harvested for determination of NF-κB levels by Ecl-western blot analysis. Electron microscopy was used to study its ultrastructure.Results: After reperfusion, NF-κB binding activity in myocardial nuclei and the plasma concentrations of IL-6 and TNF-α were significantly increased in Group II, compared with Group I (P<0.01), and they were markedly reduced in Group III, compared with Group II (P<0.01). In addition, electron microscopic examination showed more serious injury of the myocardium ultrastructure in Group II, while in Group III the myocardial ultrastructure was similar to normal state.Conclusions: Shenfu injection inhibits NF-κB activity in I/R myocardium and leads to down-regulation of proinflammatory cytokine expression, which might be one of the molecular mechanisms of Shenfu injection in cardioprotection.

  6. Endothelin receptor mediated Ca(2+) signaling in coronary arteries after experimentally induced ischemia/reperfusion injury in rat

    DEFF Research Database (Denmark)

    Kristiansen, Sarah Brøgger; Haanes, Kristian A; Sheykhzade, Majid

    2017-01-01

    a phenotypical shift, which includes increased evoked ETB induced contraction in the smooth muscle cell, and also a higher basal tone development which both are dependent on Ca(2+) influx through VGCCs. This is combined with alterations in the ETA calcium handling, which has a stronger dependence on Ca(2...... greatly exacerbate the damage. For the latter, no medical treatment exist. In this study the aim was to characterize Ca(2+) sensitivity in coronary arteries following experimental ischemia/reperfusion injury. METHODS: Arteries were isolated from hearts exposed to a well-established rat ischemia...

  7. Antioxidant Activity and Cardioprotective Effect of a Nonalcoholic Extract of Vaccinium meridionale Swartz during Ischemia-Reperfusion in Rats

    Directory of Open Access Journals (Sweden)

    Yasmin E. Lopera

    2013-01-01

    Full Text Available Our objective was to assess the antioxidant properties and the effects against the reperfusion injury of a nonalcoholic extract obtained by fermentation from the Colombian blueberry, mortiño (Vaccinium meridionale Swartz, Ericaceae. Antioxidant properties were assessed by in vitro systems. To examine the postischemic myocardial function, isolated rat hearts were treated 10 min before ischemia and during the first 10 min of reperfusion with the extract. To analyze the participation of nitric oxide (NO, other experiments were performed in the presence of nitric oxide synthase (NOS inhibition with NG-nitro-L-arginine methyl ester (L-NAME. In cardiac tissue thiobarbituric acid reactive substances (TBARS concentration, reduced glutathione (GSH content, endothelial NOS (eNOS, and Akt expression were also measured. The blueberry extract showed higher total phenols and anthocyanins contents, scavenging activity of superoxide radical and systolic and diastolic function was improved, TBARS diminished, GSH was partially preserved, and both NOS and Akt expression increased in hearts treated with the extract. These beneficial effects were lost when eNOS was inhibited. In resume, these data show that the increase of eNOS expression via Akt and the scavenging activity contribute to the cardioprotection afforded by acute treatment with Colombian blueberry extract against ischemia and reperfusion injury.

  8. Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats

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    J.G.P. Tavares

    2015-02-01

    Full Text Available The present study evaluated electrocardiographic alterations in rats with epilepsy submitted to an acute myocardial infarction (AMI model induced by cardiac ischemia and reperfusion. Rats were randomly divided into two groups: control (n=12 and epilepsy (n=14. It was found that rats with epilepsy presented a significant reduction in atrioventricular block incidence following the ischemia and reperfusion procedure. In addition, significant alterations were observed in electrocardiogram intervals during the stabilization, ischemia, and reperfusion periods of rats with epilepsy compared to control rats. It was noted that rats with epilepsy presented a significant increase in the QRS interval during the stabilization period in relation to control rats (P<0.01. During the ischemia period, there was an increase in the QRS interval (P<0.05 and a reduction in the P wave and QT intervals (P<0.05 for both in rats with epilepsy compared to control rats. During the reperfusion period, a significant reduction in the QT interval (P<0.01 was verified in the epilepsy group in relation to the control group. Our results indicate that rats submitted to an epilepsy model induced by pilocarpine presented electrical conductivity alterations of cardiac tissue, mainly during an AMI episode.

  9. Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats

    Energy Technology Data Exchange (ETDEWEB)

    Tavares, J.G.P. [Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Universidade Iguaçu, Campos V, Itaperuna, RJ (Brazil); Faculdade de Minas, Muriaé, MG (Brazil); Vasques, E.R. [Departamento de Gastroenterologia, LIM 37, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Arida, R.M. [Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Cavalheiro, E.A. [Departamento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Cabral, F.R.; Torres, L.B. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Menezes-Rodrigues, F.S.; Jurkiewicz, A.; Caricati-Neto, A. [Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Godoy, C.M.G. [Departamento de Ciência e Tecnologia, Universidade Federal de São Paulo, São José dos Campos, SP (Brazil); Gomes da Silva, S. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Núcleo de Pesquisas Tecnológicas, Programa Integrado em Engenharia Biomédica, Universidade de Mogi das Cruzes, Mogi das Cruzes, SP (Brazil)

    2015-01-13

    The present study evaluated electrocardiographic alterations in rats with epilepsy submitted to an acute myocardial infarction (AMI) model induced by cardiac ischemia and reperfusion. Rats were randomly divided into two groups: control (n=12) and epilepsy (n=14). It was found that rats with epilepsy presented a significant reduction in atrioventricular block incidence following the ischemia and reperfusion procedure. In addition, significant alterations were observed in electrocardiogram intervals during the stabilization, ischemia, and reperfusion periods of rats with epilepsy compared to control rats. It was noted that rats with epilepsy presented a significant increase in the QRS interval during the stabilization period in relation to control rats (P<0.01). During the ischemia period, there was an increase in the QRS interval (P<0.05) and a reduction in the P wave and QT intervals (P<0.05 for both) in rats with epilepsy compared to control rats. During the reperfusion period, a significant reduction in the QT interval (P<0.01) was verified in the epilepsy group in relation to the control group. Our results indicate that rats submitted to an epilepsy model induced by pilocarpine presented electrical conductivity alterations of cardiac tissue, mainly during an AMI episode.

  10. The Effect of Sleep Deprivation on Cardiac Function and Tolerance to Ischemia-Reperfusion Injury in Male Rats.

    Science.gov (United States)

    Jeddi, Sajad; Asl, Amir Nezami; Asgari, Alireza; Ghasemi, Asghar

    2016-01-01

    Sleep deprivation (SD) is strongly associated with elevated risk for cardiovascular disease. To determine the effect of SD on basal hemodynamic functions and tolerance to myocardial ischemia-reperfusion (IR) injury in male rats. SD was induced by using the flowerpot method for 4 days. Isolated hearts were perfused with Langendorff setup, and the following parameters were measured at baseline and after IR: left ventricular developed pressure (LVDP); heart rate (HR); and the maximum rate of increase and decrease of left ventricular pressure (± dp/dt). Heart NOx level, infarct size and coronary flow CK-MB and LDH were measured after IR. Systolic blood pressure (SBP) was measured at start and end of study. In the SD group, the baseline levels of LVDP (19%), +dp/dt (18%), and -dp/dt (21%) were significantly (p function recovery compared to the controls. In the SD group, NOx level in heart, coronary flow CK-MB and LDH and infarct size significantly increased after IR; also SD rats had higher SBP after 4 days. Hearts from SD rats had lower basal cardiac function and less tolerance to IR injury, which may be linked to an increase in NO production following IR.

  11. Effects of ulinastatin on renal ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Cong-cong CHEN; Zi-ming LIU; Hui-hua WANG; Wei HE; Yi WANG; Wei-dong WU

    2004-01-01

    AIM: To investigate the effect and possible mechanism of ulinastatin on renal ischemia-reperfusion injury in rats.METHODS: Male Sprague-Dawley rats were subjected to 45-min bilateral renal ischemia, treated with intravenously 12 500 U ulinastatin at 30 min prior to ischemia and at the beginning of reperfusion, compared with a nontreated group without ulinastatin and a sham-operation group without bilateral renal ischemia. After 0 h, 2 h, 6 h, 12 h, and 24 h of reperfusion, serum creatinine and blood urea nitrogen were measured for the assessment of renal function, renal sections were used for histologic grading of renal injury, for immunohistochemical localization of Bcl-2 and heat shock protein 70. Renal ultrastructure was observed through a transmission electron microscope.RESULTS: Ulinastatin significantly reduced the increase in blood urea nitrogen and creatinine produced by renal ischemia-reperfusion, suggesting an improvement in renal function. Ulinastatin reduced the histologic evidence of renal damage associated with ischemia-reperfusion and accompanied with an up-regulation in the expression of Bcl-2 protein, but it had no significent effect on the expression of HSP 70. Ulinastatin also significantly reduced kidney ultrastructure damage caused by renal ischemia-reperfusion. CONCLUSION: The protease inhibitor, ulinastatin,reduced the renal dysfunction and injury associated with ischemia-reperfusion of the kidney. The protective effect of ulinastatin might be associated with the up-regulation of Bcl-2 expression and the effect on membrane fragility.

  12. Hydrogen sulfide intervention in focal cerebral ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Li, Xin-Juan; Li, Chao-Kun; Wei, Lin-Yu; Lu, Na; Wang, Guo-Hong; Zhao, Hong-Gang; Li, Dong-Liang

    2015-06-01

    The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.

  13. Hydrogen sulfide intervention in focal cerebral ischemia/reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Xin-juan Li

    2015-01-01

    Full Text Available The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X 7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X 7 receptors.

  14. Hydrogen sulifde intervention in focal cerebral ischemia/reperfusion injur y in rats

    Institute of Scientific and Technical Information of China (English)

    Xin-juan Li; Chao-kun Li; Lin-yu Wei; Na Lu; Guo-hong Wang; Hong-gang Zhao; Dong-liang Li

    2015-01-01

    The present study aimed to explore the mechanism underlying the protective effects of hydro-gen sulifde against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulifde donor compound sodium hydrosulifde. Immunolfuorescence revealed that the immu-noreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treat-ment of these rats with hydrogen sulifde signiifcantly lowered mortality, the Longa neurological deifcit scores, and infarct volume. These results indicate that hydrogen sulifde may be protec-tive in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.

  15. Effect of U-74500A, a 21-aminosteroid on renal ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Kaur, Hitchintan; Satyanarayana, Padi S V; Chopra, Kanwaljit

    2003-03-01

    Renal ischemia-reperfusion injury constitutes the most common pathogenic factor for acute renal failure and is the main contributor to renal dysfunction in allograft recipients and revascularization surgeries. Many studies have demonstrated that reactive oxygen species play an important role in ischemic acute renal failure. The aim of the present study was to investigate the effects of the synthetic antioxidant U-74500A, a 21-aminosteroid in a rat model of renal ischemia-reperfusion injury. Renal ischemia-reperfusion was induced by clamping unilateral renal artery for 45 min followed by 24 h of reperfusion. Two doses of U-74500A (4.0 mg/kg, i.v.) were administered 45 min prior to renal artery occlusion and then 15 min prior to reperfusion. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS) in kidney homogenates. Renal function was assessed by estimating serum creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed by histopathological examination of hematoxylin-eosin stained sections of the kidneys. Ischemia-reperfusion produced elevated levels of TBARS and deteriorated the renal function as assessed by increased serum creatinine, BUN and decreased creatinine and urea clearance as compared to sham operated rats. The ischemic kidneys of rats showed severe hyaline casts, epithelial swelling, proteinaceous debris, tubular necrosis, medullary congestion and hemorrhage. U-74500A markedly attenuated elevated levels of TBARS as well as morphological changes, but did not improve renal dysfunction in rats subjected to renal ischemia-reperfusion. These results clearly demonstrate the in vivo antioxidant effect of U-74500A, a 21-aminosteroid in attenuating renal ischemia-reperfusion injury.

  16. Sildenafil citrate protects skeletal muscle of ischemia-reperfusion injury: immunohistochemical study in rat model

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    Dinani Matoso Fialho de Oliveira Armstrong

    2013-04-01

    Full Text Available PURPOSE: To investigate the effect of sildenafil citrate (SC on skeletal muscle ischemia-reperfusion (IR injury in rats. METHODS: Adult male Wistar rats were randomized into three groups: vehicle-treated control (CTG, sildenafil citrate-treated (SCG, and sham group (SG. CTG and SCG had femoral artery occluded for 6 hours. Saline or 1 mg/kg of SC was given 5.5 hours after occlusion. SG had a similar procedure without artery occlusion. Soleus muscle samples were acquired 4 or 24h after the reperfusion. Immunohistochemistry caspase-3 analysis was used to estimate apoptosis using the apoptotic ratio (computed as positive/negative cells. Wilcoxon rank-sum or Kruskal-Wallis tests were used to assess differences among groups. RESULTS: Eighteen animals were included in the 4h reperfusion groups and 21 animals in the 24h reperfusion groups. The mean apoptotic ratio was 0.18±0.1 for the total cohort; 0.14±0.06 for the 4h reperfusion groups and 0.19±0.08 for the 24h groups (p<0.05. The SCG had lower caspase-3 ratio compared to the control groups at the 24h reperfusion time point (p<0.05. CONCLUSION: Sildenafil citrate administration after the onset of the ischemic injury reduces IR-induced cellular damage in skeletal muscle in this rat hindlimb ischemia model.

  17. Protective effects of sitagliptin on myocardial injury and cardiac function in an ischemia/reperfusion rat model.

    Science.gov (United States)

    Chang, Guanglei; Zhang, Peng; Ye, Lin; Lu, Kai; Wang, Ying; Duan, Qin; Zheng, Aihua; Qin, Shu; Zhang, Dongying

    2013-10-15

    The purpose of this study is to investigate the effects and the underlying mechanisms of sitagliptin pretreatment on myocardial injury and cardiac function in myocardial ischemia/reperfusion (I/R) rat model. The rat model of myocardial I/R was constructed by coronary occlusion. Rats were pretreated with sitagliptin (300 mg/kg/day) for 2 weeks, and then subjected to 30 min ischemia and 2h reperfusion. The release of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB), cardiac function and cardiomyocyte apoptosis were evaluated. The levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in heart and glucagon-like peptide-1 (GLP-1) level in plasma were measured. Western blot analysis was performed to detect the target proteins of sitagliptin. Our results showed that sitagliptin pretreatment decreased LDH and CK-MB release, and MDA level in I/R rats. More importantly, we revealed for the first time that sitagliptin pretreatment decreased cardiomyocyte apoptosis while increased the levels of GSH-Px and SOD in heart. Sitagliptin also increased GLP-1 level and enhanced cardiac function in I/R rats. Furthermore, sitagliptin pretreatment up-regulated Akt(serine473) and Bad(serine136) phosphorylation, reduced the ratio of Bax/Bcl-2, and decreased expression levels of cleaved caspase-3 and caspase-3. Interestingly, the above observed effects of sitagliptin were all abolished when co-administered with GLP-1 receptor antagonist exendin-(9-39) or PI3K inhibitor LY294002. Taken together, our data indicate that sitagliptin pretreatment could reduce myocardial injury and improve cardiac function in I/R rats by reducing apoptosis and oxidative damage. The underlying mechanism might be the activation of PI3K/Akt signaling pathway by GLP-1/GLP-1 receptor. Crown Copyright © 2013 Published by Elsevier B.V. All rights reserved.

  18. High-fat, low-carbohydrate diet alters myocardial oxidative stress and impairs recovery of cardiac function after ischemia and reperfusion in obese rats.

    Science.gov (United States)

    Liu, Jian; Lloyd, Steven G

    2013-04-01

    Obesity is associated with elevated risk of heart disease. A solid understanding of the safety and potential adverse effects of high-fat, low-carbohydrate diet (HFLCD) similar to that used by humans for weight loss on the heart is crucial. High fat intake is known to promote increases in reactive oxygen species and mitochondrial damage. We hypothesized that there would be adverse effects of HFLCD on myocardial ischemia/reperfusion injury through enhancing oxidative stress injury and impairing mitochondrial biogenesis in a nongenetic, diet-induced rat model of obesity. To test the hypothesis, 250-g male Sprague-Dawley rats were fed an obesity-promoting diet for 7 weeks to induce obesity, then switched to HFLCD or a low-fat control diet for 2 weeks. Isolated hearts underwent global low flow ischemia for 60 minutes and reperfusion for 60 minutes. High-fat, low-carbohydrate diet resulted in greater weight gain and lower myocardial glycogen, plasma adiponectin, and insulin. Myocardial antioxidant gene transcript and protein expression of superoxide dismutase and catalase were reduced in HFLCD, along with increased oxidative gene NADPH oxidase-4 transcript and xanthine oxidase activity, and a 37% increase in nitrated protein (nitrotyrosine) in HFLCD hearts. The cardiac expression of key mitochondrial regulatory factors such as nuclear respiratory factor-1 and transcription factor A-mitochondrial were inhibited and myocardial mitochondrial DNA copy number decreased. The cardiac expression of adiponectin and its receptors was down-regulated in HFLCD. High-fat, low-carbohydrate diet impaired recovery of left ventricular rate-pressure product after ischemia/reperfusion and led to 3.5-fold increased injury as measured by lactate dehydrogenase release. In conclusion, HFLCD leads to increased ischemic myocardial injury and impaired recovery of function after reperfusion and was associated with attenuation of mitochondrial biogenesis and enhanced oxidative stress in obese rats

  19. Anti-arrhythmic effect of diosgenin in reperfusion-induced myocardial injury in a rat model: activation of nitric oxide system and mitochondrial KATP channel.

    Science.gov (United States)

    Badalzadeh, Reza; Yousefi, Bahman; Majidinia, Maryam; Ebrahimi, Hadi

    2014-11-01

    This study was designed to investigate the anti-arrhythmic effect of diosgenin preconditioning in myocardial reperfusion injury in rat, focusing on the involvement of the nitric oxide (NO) system and mitochondrial ATP-dependent potassium (mitoKATP) channels in this scenario. After isolation of the hearts of male Wister rats, the study was conducted in an isolated buffer-perfused heart model. Global ischemia (for 30 min) was induced by interruption of the aortic supply, which was followed by 90-min reperfusion. Throughout the experiment, the electrocardiograms of hearts were monitored using three golden surface electrodes connected to a data acquisition system. Arrhythmias were assessed based on the Lambeth convention and were categorized as number, duration and incidence of ventricular tachycardia (VT), ventricular fibrillation (VF), and premature ventricular complexes (PVC), and arrhythmic score. Additionally, lactate dehydrogenase (LDH) levels in coronary effluent were estimated colorimetrically. Diosgenin pre-administration for 20 min before ischemia reduced the LDH release into the coronary effluent, as compared with control hearts (P PVC, VT and VF, a reduced duration and incidence of VT and VF, and less severe arrhythmia at reperfusion phase, in comparison with controls. Blocking the mitoKATP channels using 5-hydroxydecanoate as well as inhibiting the NO system through prior administration of L-NAME significantly reduced the positive effects of diosgenin. Our finding showed that pre-administration of diosgenin could provide cardioprotection through anti-arrhythmic effects against ischemia-reperfusion (I/R) injury in isolated rat hearts. In addition, mitoKATP channels and NO system may be the key players in diosgenin-induced cardioprotective mechanisms.

  20. Effects of Potassium Aspartate and Magnesium on Ventricular Arrhythmia in Ischemia-reperfusion Rabbit Heart

    Institute of Scientific and Technical Information of China (English)

    Jun PU; Ben HE; Cuntai ZHANG; Xiaoqing QUAN; Guoan ZHAO; Jiagao LV; Bo LI; Rong BAI; Nian LIU; Yanfei RUAN

    2008-01-01

    Summary: The aim of this study was to determine if the potassium aspartate and magnesium (PAM) prevent reperfusion-induced ventricular arrhythmias (RIVA) in ischcmia-reperfusion (IR) rabbit heart. Thirty rabbits were randomly divided into control, ischemia and PAM groups. Arterially-perfused rabbit left ventricular preparations were made, and transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments. In control group rabbit ventricular wedge preparations were continuously perfused with Tyrode's solution, and in ischemia group and PAM groups the perfusion of Tyrode's solution was stopped for 30 min. Then the ischemia group was reperfused with Tyrode's solution and the PAM group with Tyrode's solution containing 2.42 mg/L PAM, respectively. ECG, QT interval, transmural repolarization dispersion (TDR) and action potentials from epicardium and endocardium were simultaneously recorded, and the RIVA of the wedge preparation was observed. Compared with control group, TDR and incidence of RIVA were significantly increased in ischemia group (P<0.05). The incidence of RIVA in control, ischemia and PAM group was 0/10, 9/10 and 1/10, respectively. Compared with ischemia group, TDR and incidence of RIVA were significantly reduced in PAM group (P<0.05). Potassium aspartate and magnesium significantly reduce TDR and prevent ventricular arrhythmia in ischemic rabbit heart.

  1. Curcuma oil reduces endothelial cell-mediated inflammation in postmyocardial ischemia/reperfusion in rats.

    Science.gov (United States)

    Manhas, Amit; Khanna, Vivek; Prakash, Prem; Goyal, Dipika; Malasoni, Richa; Naqvi, Arshi; Dwivedi, Anil K; Dikshit, Madhu; Jagavelu, Kumaravelu

    2014-09-01

    Endothelial cells initiated inflammation persisting in postmyocardial infarction needs to be controlled and moderated for avoiding fatal complications. Curcuma oil (C.oil, Herbal Medicament), a standardized hexane soluble fraction of Curcuma longa has possessed neuroprotective effect. However, its effect on myocardial ischemia/reperfusion (MI/RP) and endothelial cells remains incompletely defined. Here, using in vivo rat MI/RP injury model and in vitro cellular approaches using EA.hy926 endothelial cells, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and myograph, we provide evidence that with effective regimen and preconditioning of rats with C.oil (250 mg/kg, PO), before and after MI/RP surgery protects rats from MI/RP-induced injury. C.oil treatment reduces left ventricular ischemic area and endothelial cell-induced inflammation, specifically in the ischemic region (*P < 0.0001) and improved endothelial function by reducing the expression of proinflammatory genes and adhesion factors on endothelial cells both in vitro and in vivo. Furthermore, mechanistic studies have revealed that C.oil reduced the expression of adhesion factors like E-selectin (#P = 0.0016) and ICAM-1 ($P = 0.0069) in initiating endothelial cells-induced inflammation. In line to the real-time polymerase chain reaction expression data, C.oil reduced the adhesion of inflammatory cells to endothelial cells as assessed by the interaction of THP-1 monocytes with the endothelial cells using flow-based adhesion and under inflammatory conditions. These studies provide evidence that salutary effect of C.oil on MI/RP could be achieved with pretreatment and posttreatment of rats, C.oil reduced MI/RP-induced injury by reducing the endothelial cell-mediated inflammation, specifically in the ischemic zone of MI/RP rat heart.

  2. Protective effect of olmesartan against cardiac ischemia/reperfusion injury in spontaneously hypertensive rats.

    Science.gov (United States)

    Lu, Xin; Bi, Yan-Wen; Chen, Ke-Biao; Wang, Hong-Yue

    2015-06-01

    Olmesartan, as a new angiotensin II receptor blocker, has shown beneficial effects on cardiovascular diseases. Nevertheless, the effect of olmesartan on ischemia/reperfusion (I/R) injury in the hypertensive heart has not been investigated. Therefore, the present study aimed to investigate the effect of olmesartan on I/R injury in spontaneously hypertensive rats (SHRs). Experimental groups were designed with a 2×2 factorial design for olmesartan and I/R effects. In the I/R group, the left anterior descending coronary artery (LAD) was ligated for 40 min followed by a 180-min reperfusion. In the sham group, SHRs underwent the same surgical procedure as the I/R group, with the exception that the suture passed under the LAD without being tightened. In the Olm-I/R group, the SHRs received olmesartan (5 mg/kg) for 4 weeks prior to surgery and other procedures were the same as for the I/R group. In the Olm-sham group, the SHRs received olmesartan (5 mg/kg) for 4 weeks prior to surgery and other procedures were the same as for the sham group. Infarct size was measured for the I/R and Olm-I/R groups. Blood pressure (BP), serum creatine kinase (CK), left ventricular mass index (LVMI), high mobility group box 1 (HMGB1) protein expression levels and hypoxia-inducible factor-1α (HIF-1α) mRNA expression levels were measured for all four groups. Olmesartan significantly reduced BP and LVMI in the olmesartan-treated SHRs compared with those in the SHRs that were not treated with olmesartan. HMGB1 and HIF-1α expression levels were significantly decreased in the Olm-sham and Olm-I/R groups compared with those in the sham and I/R groups, respectively. The proportional increase in HIF-1α expression due to I/R was greater in the olmesartan-treated rats than in the untreated rats. Serum CK levels were significantly reduced in the Olm-I/R group compared with those in the I/R group. In conclusion, olmesartan ameliorates left ventricular hypotrophy and protects the heart against I

  3. Inhibition of Sevoflurane Postconditioning Against Cerebral Ischemia Reperfusion-Induced Oxidative Injury in Rats

    Directory of Open Access Journals (Sweden)

    Shi-Dong Zhang

    2011-12-01

    Full Text Available The volatile anesthetic sevoflurane is capable of inducing preconditioning and postconditioning effects in the brain. In this study, we investigated the effects of sevoflurane postconditioning on antioxidant and immunity indexes in cerebral ischemia reperfusion (CIR rats. Rats were randomly assigned to five separate experimental groups I–V. In the sham group (I, rats were subjected to the same surgery procedures except for occlusion of the middle cerebral artery and exposed to 1.0 MAC sevoflurane 90 min after surgery for 30 min. IR control rats (group II were subjected to middle cerebral artery occlusion (MCAO for 90 min and exposed to O2 for 30 min at the beginning of reperfusion. Sevoflurane 0.5, 1.0 and 1.5 groups (III, IV, V were all subjected to MCAO for 90 min, but at the beginning of reperfusion exposed to 0.5 MAC, 1.0 MAC or 1.5 MAC sevoflurane for 30 min, respectively. Results showed that sevoflurane postconditioning can decrease serum tumor necrosis factor-alpha (TNF-α, interleukin-1 beta (IL-1β, nitric oxide (NO, nitric oxide synthase (NOS and increase serum interleukin-10 (IL-10 levels in cerebral ischemia reperfusion rats. In addition, sevoflurane postconditioning can still decrease blood lipid, malondialdehyde (MDA levels, infarct volume and increase antioxidant enzymes activities, normal pyramidal neurons density in cerebral ischemia reperfusion rats. It can be concluded that sevoflurane postconditioning may decrease blood and brain oxidative injury and enhance immunity indexes in cerebral ischemia reperfusion rats.

  4. Superior Cardiac Function Via Anaplerotic Pyruvate in the Immature Swine Heart After Cardiopulmonary Bypass and Reperfusion

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Aaron; Hyyti, Outi M.; Cohen, Gordon A.; Ning, Xue-Han; Sadilek, Martin; Isern, Nancy G.; Portman, Michael A.

    2008-12-01

    Pyruvate produces inotropic responses in the adult reperfused heart. Pyruvate oxidation and anaplerotic entry into the citric acid cycle (CAC) via carboxylation are linked to stimulation of contractile function. The goals of this study were to determine if these metabolic pathways operate and are maintained in the developing myocardium after reperfusion. Immature male swine (age 10-18 days) were subjected to cardiopulmonary bypass (CPB). Intracoronary infusion of [2]-13C-pyruvate (to achieve a final concentration of 8 mM) was given for 35 minutes starting either during weaning (Group I), after discontinuation (Group II) or without (Control) CPB. Hemodynamic data was collected. 13C NMR spectroscopy was used to determine the fraction of pyruvate entering the CAC via pyruvate carboxylation (PC) to total CAC entry (PC plus decarboxlyation via pyruvate dehydrogenase). Liquid chromatography-mass spectrometry was used to determine total glutamate enrichment.

  5. [L-propionylcarnitine taurine amide induces the metabolic recovery of the isolated postischemic rat heart].

    Science.gov (United States)

    Lazzarino, G; Corsico, N; Tavazzi, B; di Pierro, D; Arrigoni-Martelli, E; Giardina, B

    1992-10-01

    The effect of reperfusion with L-propionyl-carnitine-taurinammide 1 mM was evaluated on the metabolic recovery of the isolated postischemic rat heart. Data referring to the tissue concentration of the high-energy phosphates, oxypurines, nucleosides, nicotinic coenzymes, lactate and pyruvate indicate that L-propionyl-carnitine-taurinammide significantly improves the metabolism of the reperfused myocardium. In particular, ATP, creatinphosphate, GTP, sum of adenine nucleotides and the energy charge resulted 1.80, 1.83, 3.47, 1.47 and 1.20 times higher respectively than the corresponding values recorded in control reperfused heart (p < 0.01 all). These data, out of supplying the necessary biochemical support to the beneficial effects of L-propionyl-carnitine-taurinammide on hemodynamics obtained in previous studies, suggest that L-propionyl-carnitine-taurinammide might represent a useful tool for the pharmacological treatment of myocardial infarction.

  6. Creatine phosphate decreases the apoptosis and autophagy in myocardial ischemia/reperfusion rat heart%磷酸肌酸减少大鼠缺血再灌注心肌细胞凋亡及自噬泡的数量

    Institute of Scientific and Technical Information of China (English)

    刘艺; 徐卫娟; 柯丽; 李云桥; 彭雯

    2013-01-01

    Objective To investigate the role of Creatine phosphate in myocardial ischemia-reperfusion (I/R) injury of rat heart.Methods Twenty-four male SD rats weighing 200 ~250 g,were randomly divided into a Sham group; a I/R group and a phosphocreative (CP)group.CP group were taken the intravenous administration of 4 mg/kg creatine phosphate sodium before the reperfusion.TUNEL method was used to detect apoptosis of cardiomyocytes.The formation of autophagosomes was observed by electron microscopy.Expression of LC3-Ⅱ was measured by the Western blot.Results Comparing with sham group,I/R aggravated injury of mitochondria,and increased autophagic vacuoles (AVs) (P < 0.01) and apoptosis of cardiomyocytes (P < 0.01).However,CP group alleviated injury of mitochondria and reduced autophagic vacuoles(P < 0.05) and apoptosis of cardiomyocytes(P <0.05) comparing to I/R group.LC3-Ⅱ formation,an autophagy marker,was down-regulated in the CP group (P < 0.01),which was less increased than I/R-injured rats (P < 0.05).Conclusions Creatine phosphate inhibits apoptosis and excessive autophagy to diminish the cell death induced by the myocardial I/R injury.%目的 研究磷酸肌酸减少大鼠缺血再灌注心肌细胞凋亡及白噬的能力.方法 雄性SD大鼠24只,体质量200 ~ 250 g,随机均分为假手术(sham)组、缺血/再灌注(ischemia-reperfusion,I/R)组和磷酸肌酸钠(phosphocreatine,CP)干预组.其中CP组按4 mg/kg磷酸肌酸钠剂量于再灌注前经右股静脉注射.用TUNEL法检测心肌细胞凋亡;电子显微镜观察心肌细胞自噬泡的发生和线粒体的形态学改变;Western blot检测微管相关蛋白1轻链3-Ⅱ(LC3-Ⅱ)蛋白的表达.结果 I/R组与sham组相比,线粒体超微结构损伤加重,自噬泡数量增多(P<0.01),心肌细胞凋亡率明显增加(P<0.01);CP干预组可减轻I/R组线粒体超微结构损伤,自噬泡数量减少(P<0.05),降低心肌细胞凋亡率(P <0.05);LC3-Ⅱ作为评价

  7. Protective effects of remote ischemic preconditioning in rat hindlimb on ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Ying Zhang; Xiangrong Liu; Feng Yan; Lianqiu Min; Xunming Ji; Yumin Luo

    2012-01-01

    Three cycles of remote ischemic pre-conditioning induced by temporarily occluding the bilateral femoral arteries (10 minutes) prior to 10 minutes of reperfusion were given once a day for 3 days before the animal received middle artery occlusion and reperfusion surgery. The results showed that brain infarct volume was significantly reduced after remote ischemic pre-conditioning. Scores in the forelimb placing test and the postural reflex test were significantly lower in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. Thus, neurological function was better in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. These results indicate that remote ischemic pre-conditioning in rat hindlimb exerts protective effects in ischemia-reperfusion injury.

  8. Chronic testosterone replacement exerts cardioprotection against cardiac ischemia-reperfusion injury by attenuating mitochondrial dysfunction in testosterone-deprived rats.

    Directory of Open Access Journals (Sweden)

    Wanpitak Pongkan

    Full Text Available Although testosterone deficiency is associated with increased risks of heart disease, the benefits of testosterone therapy are controversial. Moreover, current understanding on the cardiac effect of testosterone during cardiac ischemia-reperfusion (I/R periods is unclear. We tested the hypothesis that testosterone replacement attenuates the impairment of left ventricular (LV function and heart rate variability (HRV, and reduces the infarct size and arrhythmias caused by I/R injury in orchiectomized (ORX rats.ORX or sham-operated male Wistar rats (n = 24 were randomly divided and received either testosterone (2 mg/kg, subcutaneously administered or the vehicle for 8 weeks. The ejection fraction (EF and HRV were determined at baseline and the 4th and 8th week. I/R was performed by left anterior descending coronary artery ligation for 30 minutes, followed by a 120-minute reperfusion. LV pressure, arrhythmia scores, infarct size and cardiac mitochondrial function were determined.Prior to I/R, EF and HRV were impaired in the ORX group, but were restored in the testosterone-treated group. During I/R, arrhythmia scores and the infarct size were greater, and cardiac mitochondrial function was impaired, whereas the time to 1st VT/VF onset and the LV end-systolic pressure were decreased in the ORX group when compared to the sham group. Testosterone replacement attenuated the impairment of these parameters in ORX rats during I/R injury, but did not show any benefit or adverse effect in non-ORX rats.Testosterone replacement restores cardiac function and autonomic regulation, and exerts cardioprotective effects during the I/R period via mitochondrial protection in ORX rats.

  9. Chronic Testosterone Replacement Exerts Cardioprotection against Cardiac Ischemia-Reperfusion Injury by Attenuating Mitochondrial Dysfunction in Testosterone-Deprived Rats

    Science.gov (United States)

    Pongkan, Wanpitak; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2015-01-01

    Background Although testosterone deficiency is associated with increased risks of heart disease, the benefits of testosterone therapy are controversial. Moreover, current understanding on the cardiac effect of testosterone during cardiac ischemia-reperfusion (I/R) periods is unclear. We tested the hypothesis that testosterone replacement attenuates the impairment of left ventricular (LV) function and heart rate variability (HRV), and reduces the infarct size and arrhythmias caused by I/R injury in orchiectomized (ORX) rats. Methodology ORX or sham-operated male Wistar rats (n = 24) were randomly divided and received either testosterone (2 mg/kg, subcutaneously administered) or the vehicle for 8 weeks. The ejection fraction (EF) and HRV were determined at baseline and the 4th and 8th week. I/R was performed by left anterior descending coronary artery ligation for 30 minutes, followed by a 120-minute reperfusion. LV pressure, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. Results Prior to I/R, EF and HRV were impaired in the ORX group, but were restored in the testosterone-treated group. During I/R, arrhythmia scores and the infarct size were greater, and cardiac mitochondrial function was impaired, whereas the time to 1st VT/VF onset and the LV end-systolic pressure were decreased in the ORX group when compared to the sham group. Testosterone replacement attenuated the impairment of these parameters in ORX rats during I/R injury, but did not show any benefit or adverse effect in non-ORX rats. Conclusions Testosterone replacement restores cardiac function and autonomic regulation, and exerts cardioprotective effects during the I/R period via mitochondrial protection in ORX rats. PMID:25822979

  10. The effect of aloe vera on ischemia--Reperfusion injury of sciatic nerve in rats.

    Science.gov (United States)

    Guven, Mustafa; Gölge, Umut Hatay; Aslan, Esra; Sehitoglu, Muserref Hilal; Aras, Adem Bozkurt; Akman, Tarik; Cosar, Murat

    2016-04-01

    Aloe vera is compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of aloe vera treatment in rats with experimental sciatic nerve ischemia/reperfusion injury. Twenty-eight male Wistar Albino rats were divided equally into 4 groups. Groups; Control group (no surgical procedure or medication), sciatic nerve ischemia/reperfusion group, sciatic nerve ischemia/reperfusion+aloe vera group and sciatic nerve ischemia/reperfusion+methylprednisolone group. Ischemia was performed by clamping the infrarenal abdominal aorta. 24 hours after ischemia, all animals were sacrificed. Sciatic nerve tissues were also examined histopathologically and biochemically. Ischemic fiber degeneration significantly decreased in the pre-treated with aloe vera and treated with methylprednisolone groups, especially in the pre-treated with aloe vera group, compared to the sciatic nerve ischemia/reperfusion group (paloe vera group was not statistically different compared to the MP group (p>0.05). Aloe vera is effective neuroprotective against sciatic nerve ischemia/reperfusion injury via antioxidant and anti-inflammatory properties. Also aloe vera was found to be as effective as MP. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. The effect of erythropoietin on platelet distribution width during ischemia reperfusion injury in rats

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    Constantinos Tsompos

    2014-04-01

    Full Text Available OBJECTIVE: Aim of this experiment study was the erythropoietin (Epo testing, on rat model and particularly on ischemia reperfusion protocol. The benefit or the non effect of that molecule was studied hematologically on platelet distribution width (PDW. METHODS: 40 rats were used of mean weight 247,7 gr. PDW was measured on these time points: on 60 min after reperfusion (groups A and C, and on 120 min after reperfusion (groups B and D, A and B without but C and D with Epo administration. RESULTS: Epo administration increased significantly the PDW levels by 0.22 % [0.034374 % - 0.4056259 %] (P= 0.0214, in accordance also with paired t-test (P= 0.0196, 2 reperfusion time decreased significantly the PDW levels by 0.27 % [-0.4483669 % - 0.0916332 %] (P= 0.0040, in accordance also with paired t-test (P= 0.0012, and 3 interaction of Epo administration and reperfusion time increased non significantly the PDW levels by 0.06 % [-0.054648 % - 0.1819207 %] (P= 0.0615. CONCLUSION: Epo administration has significant increasing short-term effects on PDW levels. However, reperfusion time attenuates significantly this effect. Their interaction seems to resemble the action of Epo administration. The following question is whether these PDW levels alterations are the cause or the result of diseases process modification.

  12. Genistein attenuates ischemia/reperfusion injury in rat kidneys via ...

    African Journals Online (AJOL)

    by oral gavage for 7 consecutive days and then subjected to 45 min of renal bilateral ... Keywords: Oxidative stress, Genistein, Ischemic reperfusion injury, Renal ... radical production ultimately leading to cellular ... serum biomarker analysis.

  13. Fucoidan reduces inflammatory response in a rat model of hepatic ischemia-reperfusion injury.

    Science.gov (United States)

    Li, Xiao-Jing; Ye, Qi-Fa

    2015-11-01

    Ischemia-reperfusion (I/R) injury after a liver transplant is a major cause of severe complications that lead to graft dysfunction. Fucoidan, a complex of sulfated polysaccharides derived from marine brown algae, demonstrated antiapoptotic as well as potential anti-inflammatory properties in previous studies. Fucoidan has also shown protective effects on I/R-injured kidney and heart. However, whether fucoidan can attenuate hepatic I/R injury has not been examined. To clarify the role of fucoidan in hepatic I/R injury, Sprague-Dawley rats were subjected to sham operation or ischemia followed by reperfusion with treatment of saline or fucoidan (50, 100, or 200 mg·(kg body mass)(-1)·d(-1)). The fucoidan-treated group showed decreased levels of alanine aminotransferase and aspartate aminotransferase compared with the control group. Myeloperoxidase and malondialdehyde activities and mRNA levels of CD11b in the fucoidan-treated group were significantly decreased. Hepatocellular swelling/necrosis, sinusoidal/vascular congestion, and inflammatory cell infiltration were also attenuated in the fucoidan group. The expression of TNF-α, IL-6, IL-1β, CXCL-10, VCAM-1, and ICAM-1 were markedly decreased in the samples from the fucoidan-treated group. Fucoidan largely prevented activation of the inflammatory signaling pathway, compared with the control group. In summary, fucoidan can protect the liver from I/R injury through suppressing activation of the inflammatory signaling pathway, as well as the expression of inflammatory mediators, and inflammatory cell infiltration.

  14. Adenosine A2 receptor activation ameliorates mitochondrial oxidative stress upon reperfusion through the posttranslational modification of NDUFV2 subunit of complex I in the heart.

    Science.gov (United States)

    Xu, Jingman; Bian, Xiyun; Liu, Yuan; Hong, Lan; Teng, Tianming; Sun, Yuemin; Xu, Zhelong

    2017-02-20

    While it is well known that adenosine receptor activation protects the heart from ischemia/reperfusion injury, the precise mitochondrial mechanism responsible for the action remains unknown. This study probed the mitochondrial events associated with the cardioprotective effect of 5'-(N-ethylcarboxamido) adenosine (NECA), an adenosine A2 receptor agonist. Isolated rat hearts were subjected to 30min ischemia followed by 10min of reperfusion, whereas H9c2 cells experienced 20min ischemia and 10min reperfusion. NECA prevented mitochondrial structural damage, decreases in respiratory control ratio (RCR), and collapse of mitochondrial membrane potential (ΔΨm). Both the adenosine A2A receptor antagonist SCH58261 and A2B receptor antagonist MRS1706 inhibited the action of NECA. NECA reduced mitochondrial proteins carbonylation, H2O2, and superoxide generation at reperfusion, but did not change superoxide dismutase (SOD) activity. In support, the protective effects of NECA and Peg-SOD on ΔΨm upon reperfusion were additive, implying that NECA's protection is attributable to the reduced superoxide generation but not to the enhancement of the superoxide-scavenging capacity. NECA increased the mitochondrial Src tyrosine kinase activity and suppressed complex I activity at reperfusion in a Src-dependent manner. NECA also reduced mitochondrial superoxide through Src tyrosine kinase. Studies with liquid chromatography-mass spectrometer (LC-MS) identified Tyr118 of the NDUFV2 subunit of complex 1 as a likely site of the tyrosine phosphorylation. Furthermore, the complex I activity of cells transfected with the Y118F mutant was increased, suggesting that this site might be a negative regulator of complex I activity. In support, NECA failed to suppress complex I activity at reperfusion in cells transfected with the Y118F mutant of NDUFV2. In conclusion, NECA prevents mitochondrial oxidative stress by decreasing mitochondrial superoxide generation through inhibition of complex I

  15. Nrf2-ARE通路在缺血后处理和吡那地尔后处理减轻大鼠离体心脏缺血再灌注损伤中的作用%Role of nuclear factor-E2 related factor 2-antioxidant response element pathway in cardio-protection by ischemic or pinacidil postconditioning against ischemia-reperfusion injury in isolated rat hearts

    Institute of Scientific and Technical Information of China (English)

    王海英; 杨义辉; 喻田; 刘兴奎

    2012-01-01

    目的 探讨核转录因子NF-E2相关因子2(Nrf2)-抗氧化反应元件(ARE)通路在缺血后处理和吡那地尔后处理减轻大鼠离体心脏缺血再灌注损伤中的作用.方法 健康雄性SD大鼠,体重200~250 g,4~5月龄,采用Langendorff灌注装置建立离体心脏灌注模型,取模型制备成功的心脏56个,采用随机数字表法,将其随机分为7组(n=8):正常对照组(C组)、缺血再灌注组(I/R组)、缺血后处理组(IP组)和不同浓度的吡那地尔后处理组(PP1组、PP2组、PP3组、PP4组).平衡灌注20min后,C组继续灌注100 min;I/R组停止灌注40 min,复灌60min;IP组停止灌注40 min,于再灌注开始给予6次间隔灌注10 s停止灌注10 s,复灌58 min;PP1组、PP2组、PP3组、PP4组停止灌注40 min,于再灌注开始时灌注含5、10、30、50 μmol/L吡那地尔的K-H液5min,继续灌注55 min.于平衡灌注末及复灌结束时测定左室发展压(LVDP)和左室舒张期末压(LVEDP);于复灌结束时取左心室心肌,分别采用RT-PCR法和Western blot法检测心肌Nrf2、醌氧化还原酶1(NQO1)、超氧化物歧化酶1(SOD1)及血红素加氧酶1(HO-1)的mRNA及蛋白表达水平.结果 与C组比较,其余各组Nrf2、NQO1、SOD1及HO-1的mRNA和蛋白表达均上调,I/R组、PP1组和PP2组复灌结束时LVDP降低,LVEDP升高(P<0.05).与I/R组比较,IP组、PP3组和PP4组Nrf2、NQO1、SODI及HO-1的mRNA和蛋白表达均上调,IP组、PP1组、PP2组、PP3组和PP4组复灌结束时LVDP升高,LVEDP降低(P<0.05).结论 缺血后处理和吡那地尔后处理可通过激活Nrf2-ARE通路减轻大鼠心肌缺血再灌注损伤.%Objective To evaluate the role of nuclear factor-E2 related factor 2 (Nrf2)-antioxidant response element (ARE) pathway in cardio-protection by ischemic or pinacidil postconditioning ( IP,PP) against ischemia-reperfusion (I/R) injury in isolated rat hearts.Methods Fifty-six male SD rats of both sexes weighing 200-250 g were anesthetized with

  16. The protective activity of noscapine on renal ischemia–reperfusion injury in male Wistar rat

    Science.gov (United States)

    Khanmoradi, Mehrangiz; Ali Mard, Seyyed; Aboutaleb, Nahid; Nobakht, Malihe; Mahmoudian, Masoud

    2014-01-01

    Objective(s): Bradykinin is a part of the kinin-kallikrein system which is involved in ischemia-reperfusion injury via B1 and B2 receptors. Noscapine is a non-competitive antagonist of bradykinin receptors. Noscapine has been reported to to be able to protect some organs against ischemia-reperfusion injury but its effect on renal ischemia-reperfusion injury (RIR) in rats is unknown. Therefore, the present study was designed to evaluate the effect of noscapine on renal ischemia-reperfusion injury in rats. Materials and Methods: Twenty four rats were randomly assigned to four groups; sham, RIR control, pre-and post-treatment with noscapine. To induce RIR injury, 20 days after right nephrectomy, animals underwent a midline laparotomy and the renal artery was clamped for 40 min to induce ischemia, and the clamp was then removed to allow reperfusion for 48 hr. Animals received noscapine or vehicle 1 hr before RIR or just prior to reperfusion. At the end of the experiment, animals were killed by cardiac exsanguination. Blood samples were collected to assess blood urea nitrogen (BUN) and creatinine. The kidneys were also removed for histopathlogical and western-blot analysis. Results: Noscapine treatment 1 hr before RIR or just prior to reperfusion protects the renal tissue structure as compared with the control. The expression levels of the studied inflammatory mediators, TNF-α and MCP-1in pretreated-, and treated-noscapine groups decreased as compared with the control group. The levels of BUN and creatinine in pre-, and post-treated noscapine groups were significantly lower than in control animals. Conclusion: Noscapine protects renal tissue structure and function against RIR through down-regulation of the inflammatory mediators. PMID:24904716

  17. Effects of Ischemic Postconditioning on the Hemodynamic Parameters and Heart Nitric Oxide Levels of Hypothyroid Rats

    Directory of Open Access Journals (Sweden)

    Sajad Jeddi

    2015-02-01

    Full Text Available Background: Ischemic postconditioning (IPost is a method of protecting the heart against ischemia-reperfusion (IR injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear. Objective: The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats. Methods: Propylthiouracil in drinking water (500 mg/L was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia. Results: Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP and peak rates of positive and negative changes in left ventricular pressure (±dp/dt during reperfusion in control rats (p < 0.05. However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NOx levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05 and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05. Heart NOx concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05 higher and lower after IR and IPost, respectively, in the control groups. Conclusion: Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group.

  18. Effects of Ischemic Postconditioning on the Hemodynamic Parameters and Heart Nitric Oxide Levels of Hypothyroid Rats

    Energy Technology Data Exchange (ETDEWEB)

    Jeddi, Sajad; Zaman, Jalal; Ghasemi, Asghar, E-mail: ghasemi@endocrine.ac.ir [Endocrine Physiology Research Center - Research Institute for Endocrine Sciences - Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Endocrine Research Center - Research Institute for Endocrine Sciences - Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2015-02-15

    Ischemic postconditioning (IPost) is a method of protecting the heart against ischemia-reperfusion (IR) injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear. The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats. Propylthiouracil in drinking water (500 mg/L) was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia. Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) during reperfusion in control rats (p < 0.05). However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NO{sub x}) levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05) and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05). Heart NO{sub x} concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05) higher and lower after IR and IPost, respectively, in the control groups. Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO) levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group.

  19. Comparative analysis of different cyclosporine A doses on protection after myocardial ischemia/reperfusion injury in rat

    Institute of Scientific and Technical Information of China (English)

    Kang Huang; Shi-Juan Lu; Jiang-Hua Zhong; Qun Xiang; Liu Wang; Miao Wu

    2014-01-01

    Objective:To investigate the protective effect of different cyclosporinA(CsA) doses on myocardial ischemia/reperfusion injury in rat models.Methods:A rat model of myocardial ischemia/reperfusion injury was established in vivoand the rats were randomly divided into four groups: placebo(PBS;T1), low-dose(CsA dose:1.0 mg/kg;T2), medium-dose(CsA dose:2.5 mg/kg;T3), and high-dose(CsA dose:5.0 mg/kg;T4) groups.Heart function indexes were monitored at different time points, the extent of myocardial infarction was assessed byEvans Blue-TTC staining, and creatine kinase MB mass and cardiac troponinI values were measured by biochemical assays.Results:Compared with theT1 andT2 groups, both the creatine kinase MB mass and cardiac troponinI were significantly lower in theT3 andT4 groups(P<0.05).The mean arterial pressure(MAP) and left ventricular systolic pressure(LVSP) decreased sequentially in each group, with the extending reperfusion time.Significant decreases inLVSP andMAP were observed in theT3 andT4 groups as compared to theT1 andT2 group(P<0.05), and theT2 group showed a significantly lowerLVSP andMAP decline than theT1 group(P<0.05).Compared with theT1 group, the rats from theT2,T3, andT4 groups suffered from a significantly lower extent of myocardial infarction(P<0.05).Also, the animals in theT3 andT4 groups had a significantly smaller extent of myocardial infarction than those in theT2 group(P<0.05).Conclusions:Various CsA doses exert different degrees of protection against ischemia/reperfusion injury, and this protective effect peaks at approximately2.5 mg/kg in rat models.

  20. Activation of ALDH2 with Low Concentration of Ethanol Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetes Rat Model

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    Pin-Fang Kang

    2016-01-01

    Full Text Available The aim of this paper is to observe the change of mitochondrial aldehyde dehydrogenase 2 (ALDH2 when diabetes mellitus (DM rat heart was subjected to ischemia/reperfusion (I/R intervention and analyze its underlying mechanisms. DM rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vitro and pretreated with ALDH2 activator ethanol (EtOH; cardiomyocyte in high glucose (HG condition was pretreated with ALDH2 activator Alda-1. In control I/R group, myocardial tissue structure collapse appeared. Compared with control I/R group, left ventricular parameters, SOD activity, the level of Bcl-2/Bax mRNA, ALDH2 mRNA, and protein expressions were decreased and LDH and MDA contents were increased, meanwhile the aggravation of myocardial structure injury in DM I/R group. When DM I/R rats were pretreated with EtOH, left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 expression were increased; LDH, MDA, and myocardial structure injury were attenuated. Compared with DM + EtOH I/R group, cyanamide (ALDH2 nonspecific blocker, atractyloside (mitoPTP opener, and wortmannin (PI3K inhibitor groups all decreased left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 and increased LDH, MDA, and myocardial injury. When cardiomyocyte was under HG condition, CCK-8 activity and ALDH2 protein expression were decreased. Alda-1 increased CCK-8 and ALDH2. Our findings suggested enhanced ALDH2 expression in diabetic I/R rats played the cardioprotective role, maybe through activating PI3K and inhibiting mitoPTP opening.

  1. Effects of ischemia and omeprazole preconditioning on functional recovery of isolated rat heart

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    Nevena Jeremic

    2015-04-01

    Full Text Available AbstractObjective:The aim of this study was to compare protective effects of ischemic and potential protective effects of pharmacological preconditioning with omeprazole on isolated rat heart subjected to ischemia/reperfusion.Methods:The hearts of male Wistar albino rats were excised and perfused on a Langendorff apparatus. In control group (CG after stabilization period, hearts were subjected to global ischemia (perfusion was totally stopped for 20 minutes and 30 minutes of reperfusion. Hearts of group II (IPC were submitted to ischemic preconditioning lasting 5 minutes before 20 minutes of ischemia and 30 minutes of reperfusion. In third group (OPC hearts first underwent preconditioning lasting 5 minutes with 100μM omeprazole, and then submitted 20 minutes of ischemia and 30 minutes of reperfusion.Results:Administration of omeprazole before ischemia induction had protective effect on myocardium function recovery especially regarding to values of systolic left ventricular pressure and dp/dt max. Also our findings are that values of coronary flow did not change between OPC and IPC groups in last point of reperfusion.Conclusion:Based on our results it seems that ischemic preconditioning could be used as first window of protection after ischemic injury especially because all investigated parameters showed continuous trend of recovery of myocardial function. On the other hand, preconditioning with omeprazole induced sudden trend of recovery with positive myocardium protection, although less effective than results obtained with ischemic preconditioning not withstand, we must consider that omeprazole may be used in many clinical circumstances where direct coronary clamping for ischemic preconditioning is not possible.

  2. Neuregulin-1 preconditioning protects the heart against ischemia/reperfusion injury through a PI3K/Akt-dependent mechanism

    Institute of Scientific and Technical Information of China (English)

    FANG Shan-juan; WU Xue-si; HAN Zhi-hong; ZHANG Xiao-xia; WANG Chun-mei; LI Xin-yan; LU Ling-qiao; ZHANG Jing-lan

    2010-01-01

    Background Neuregulin-1 (NRG-1), the ligand of the myocardial ErbB receptor, is a protein mediator with regulatory actions in the heart. This study investigated whether NRG-1 preconditioning has protective effects on myocardial ischemia/reperfusion (I/R) injury and its potential mechanism.Methods We worked with an in vivo rat model with induced myocardial ischemia (45 minutes) followed by reperfusion (3 hours). NRG-1 message was detected in the heart using RT-PCR and the protein levels of NRG-1 and ErbB4 were detected by Western blotting analysis. Infarct size was assessed using the staining agent triphenyltetrazolium chloride and cardiac function was continuously monitored. The levels of creatine kinase and lactate dehydrogenase in plasma were analyzed to assess the degree of cardiac injury. The extent of cardiac apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and by Western blotting analysis of cleaved caspase-3. We examined the phosphorylation of Akt in the myocardium and the effect of PI3K/Akt inhibition on NRG-1-induced cardioprotection.Results Transcription and expression of NRG-1 and phosphorylation of its ErbB4 receptor were significantly upregulated in the I/R hearts. NRG-1 pretreatment reduced the infarct size following cardiac I/R in a concentration-dependent manner with an optimal concentration of 4 μg/kg in vivo. NRG-1 pretreatment with 4 μg/kg, i.v.markedly reduced the plasma creatine kinase and lactate dehydrogenase levels. Pretreatment with NRG-1 also significantly reduced the percentage of TUNEL positive myocytes and the level of cleaved caspase-3 in the I/R hearts.Pretreatment with NRG-1 significantly increased phosphorylation of Akt following I/R. Furthermore, the cardioprotective effect limiting the infarct size that was induced by NRG-1 was abolished by co-administration of the PI3K inhibitor LY294002.Conclusions The concentration of NRG-1, a new autacoid, was rapidly upregulated

  3. Does closure of acid-sensing ion channels reduce ischemia/reperfusion injury in the rat brain?

    Institute of Scientific and Technical Information of China (English)

    Jie Wang; Yinghui Xu; Zhigang Lian; Jian Zhang; Tingzhun Zhu; Mengkao Li; Yi Wei; Bin Dong

    2013-01-01

    Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2+-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain and various intracranial diseases. However, the mechanism associated with expression of these channels remains unclear. This study sought to observe the expression characteristics of permeable Ca2+-acid-sensing ion channels during different reperfusion inflows in rats after cerebral ischemia. The rat models were randomly divided into three groups: adaptive ischemia/reperfusion group, one-time ischemia/reperfusion group, and severe cerebral ischemic injury group. Western blot assays and immunofluorescence staining results exhibited that when compared with the one-time ischemia/reperfusion group, acid-sensing ion channel 3 and Bcl-x/l expression decreased in the adaptive ischemia/reperfusion group. Calmodulin expression was lowest in the adaptive ischemia/reperfusion group. Following adaptive reperfusion, common carotid artery flow was close to normal, and the pH value improved. Results verified that adaptive reperfusion following cerebral ischemia can suppress acid-sensing ion channel 3 expression, significantly reduce Ca2+ influx, inhibit calcium overload, and diminish Ca2+ toxicity. The effects of adaptive ischemia/reperfusion on suppressing cell apoptosis and relieving brain damage were better than that of one-time ischemia/reperfusion.

  4. Myocardial ischemia-reperfusion induces upregulation of contractile endothelin ETB receptor in rat coronary arteries

    DEFF Research Database (Denmark)

    Skovsted, Gry Freja; Sheykhzade, Majid; Trautner, Simon;

    2011-01-01

    ETB receptor upregulation. Methods and Results Thirteen Sprague-Dawley male rats (body weight 260-410 g) were anaesthetized with Hypnorm-Midazolam and subjected to 15 min occlusion of left anterior descending coronary artery (LAD) followed by 22 h of reperfusion. The contractile response...

  5. Inhibition of classical complement activation attenuates liver ischaemia and reperfusion injury in a rat model

    NARCIS (Netherlands)

    B.H.M. Heijnen; I.H. Straatsburg; N.D. Padilla; G.J. Mierlo; C.E. Hack; T.M. van Gulik

    2006-01-01

    Activation of the complement system contributes to the pathogenesis of ischaemia/reperfusion (I/R) injury. We evaluated inhibition of the classical pathway of complement using C1-inhibitor (C1-inh) in a model of 70% partial liver I/R injury in male Wistar rats (n = 35). C1-inh was administered at 10

  6. Inhibitory effect of zileuton on inflammatory injury to myocardium following ischemia/reperfusion in rats

    Directory of Open Access Journals (Sweden)

    Hua-di QIN

    2014-03-01

    Full Text Available Objective  To investigate the protective effect of zileuton, an inhibitor of 5-lipoxygenase (5-LO, on ischemia/ reperfusion (I/R injury of rat myocardium, and its probable mechanisms. Methods  Thirty female SD rats were randomly divided into 3 groups (10 each: sham group (S group, ischemic/reperfusion group (I/R group, and zileuton group (Z group. The I/ R model was reproduced by left anterior descending (LAD artery occlusion for 45min followed by 120-min reperfusion. To rats of Z group 3mg/kg zileuton was given 15min before ischemia. Animals were sacrificed after reperfusion. The degree of myocardial damage was determined by means of pathological examination. Myocardial apoptosis was identified by TUNEL assay. The levels of leukotriene B4 (LTB4, interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α in plasma were determined by ELISA; the distribution of 5-LO in neutrophils was determined by immunofluorescence and Western blotting. Results  Compared with I/ R group, zileuton attenuated the I/R-induced myocardial damage significantly. TUNEL assay demonstrated a significant decrease in myocardial apoptosis by zileuton (P0.05. Conclusion  Zileuton may protect myocardium from I/R injury in rats through suppressing myocardial apoptosis and inflammation by inhibiting the 5-LO activation and redistribution. DOI: 10.11855/j.issn.0577-7402.2014.03.05

  7. Myocardial ischemia-reperfusion induces upregulation of contractile endothelin ETB receptor in rat coronary arteries

    DEFF Research Database (Denmark)

    Skovsted, Gry Freja; Sheykhzade, Majid; Trautner, Simon

    2011-01-01

    ETB receptor upregulation. Methods and Results Thirteen Sprague-Dawley male rats (body weight 260-410 g) were anaesthetized with Hypnorm-Midazolam and subjected to 15 min occlusion of left anterior descending coronary artery (LAD) followed by 22 h of reperfusion. The contractile response...

  8. [Antioxidant and cardioprotective effects of N-tyrosol in myocardial ischemia with reperfusion in rats].

    Science.gov (United States)

    Smol'iakova, V I; Chernyshova, G A; Plotnikov, M B; Aliev, O I; Krasnov, E A

    2010-01-01

    We demonstrated in experiments on rats with left coronary artery occlusion that intravenous administration of 20 mg/kg n-tyrosol during ischemia limited manifestations of oxidative stress in myocardial tissue during early post reperfusion period: content of diene and triene conjugates lowered 16 and 20%, respectively. This was associated with higher preservation of cardiomyocytes and reduction of the infarction zone.

  9. Human thioredoxin exerts cardioprotective effect and attenuates reperfusion injury in rats partially via inhibiting apoptosis

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-wei; TENG Zong-yan; JIANG Li-hong; FAN Ying; ZHANG Yu-hua; LI Xiu-rong; ZHANG Yi-na

    2008-01-01

    Background Thioredoxin is one of the most important redox regulating proteins. Although thioredoxin has been shown to protect cells against different kinds of oxidative stress, the role of thioredoxin in myocardial ischemia and reperfusion injury has not been fully understood. This study was conducted to explore the protective role of human thioredoxin on myocardial ischemia and reperfusion injury and its potential mechanisms.Methods Purified human thioredoxin was injected into adult Wister rats, which were subjected to 30 minutes of myocardial ischemia followed by 2 or 24 hours of reperfusion. We detected 1) the infarct size; 2) the level of malondisldehyde (MDA) in serum; 3) the expression of caspase-9, and cytochrome c in/out of mitochondia by Western blotting; 4) apoptosis by terminal-deoxynucleotidyl transferase mediated nick end labeling ('rUNEL) assay and caspase-3 and its protein by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting; 5) the expression of bcl-2 and bax in cardium by immunohistochemical (IHC) assay.Results Human thioredoxin reduced myocardial ischemia/reperfusion injury as evidenced by significant decrease of myocardial infarct size (P<0.01), notable reduction of myocyte apoptosis (P <0.01), lower systemic oxidative stress level (P <0.01) after reperfusion for 2 hours, and few inflammatory cell infiltration after reperfusion for 24 hours in rats. Furthermore, treatment with human thioredoxin significantly reduced the release of mitochondrial cytochrome C (P<0.05),and inhibited the activity of caspase-9 (P <0.05) and caspase-3 (P <0.01 in mRNA and P <0.05 at protein level).Meanwhile, human thioredoxin markedly increased bcl-2 expression (P <0.05).Conclusions These results strongly suggest that human thioredoxin has cardioprotective effects on myocardial ischemia/reperfusion and its anti-apoptotic role may be mediated by modulating bcl-2 and the mitochondria-dependent apoptotic signaling pathway.

  10. Neuroprotective effects of SMADs in a rat model of cerebral ischemia/reperfusion

    Directory of Open Access Journals (Sweden)

    Fang-fang Liu

    2015-01-01

    Full Text Available Previous studies have shown that up-regulation of transforming growth factor β1 results in neuroprotective effects. However, the role of the transforming growth factor β1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inflammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phosphorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats via delivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor necrosis factor-α and interleukin-1β mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These findings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inflammatory and anti-apoptotic pathways.

  11. Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats.

    Science.gov (United States)

    Guo, Wei; Feng, Guoying; Miao, Yanying; Liu, Guixiang; Xu, Chunsheng

    2014-06-01

    Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48 h of reperfusion. The effects of rapamycin (250 μg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin.

  12. Ischemia and reperfusion injury of the rat liver: the role of nimodipine.

    Science.gov (United States)

    Chávez-Cartaya, R E; Pino DeSola, G; Ramirez-Romero, P; Calne, R Y; Jamieson, N V

    1996-01-01

    The protective effect of the calcium channel blocker nimodipine on liver ischemia and reperfusion was studied in the rat. The homeostasis of intracellular calcium ions seems to be a determinant factor in the cell injury that appears after ischemia and reperfusion. Nimodipine was used to downregulate the calcium levels in the cytosol of the ischemic cell, the hypothetical role of Ca2+ in the pathogenesis of ischemia and reperfusion injury. The experimental procedure consisted of the temporary interruption of blood flow to the left lateral and medial lobes of the rat liver and subsequent reperfusion after a period of 45 min of ischemia. Nimodipine (10 micrograms/kg body wt) was administered either before or after the onset of ischemia. The postischemic liver blood flow and liver oxyhemoglobin saturation were recorded using a He-Ne laser Doppler flowmeter and photometer, which showed, in the pretreated group, a recovery of reperfusion blood flow (58.1%) and liver reflectance (85.5%) significantly better (P flow (32.8%) and reflectance (70.5%). In the group that received nimodipine after ischemia, the recovery of the blood flow and the postreperfusion liver reflectance were not significantly better than those in the untreated control group. ALT levels (P < 0.05), galactose elimination capacity (P < 0.001), and histological studies also showed a protective effect of calcium antagonist nimodipine when administered before ischemia.

  13. Pharmacokinetics of ligustrazine ethosome patch in rats and anti-myocardial ischemia and anti-ischemic reperfusion injury effect

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    Liu X

    2011-07-01

    Full Text Available Xingyan Liu1, Hong Liu1, Zhaowu Zeng2, Weihua Zhou3, Jianqiang Liu2, Zhiwei He11China-America Cancer Research Institute, Guangdong Medical College, 2Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical College, Dongguan, Guangdong, 3Yichun University, Yichun, Jiangxi, People's Republic of ChinaAbstract: The objective of this study was to investigate the pharmacokinetics of the ligustrazine ethosome patch and antimyocardial ischemia and anti-ischemic reperfusion injury effect. Male Sprague Dawley rats were divided randomly into 3 groups: Group A (intragastric ligustrazine, Group B (transdermal ligustrazine ethosome patch, and Group C (conventional transdermal ligustrazine patch. After treatment, samples of blood and of various tissues such as heart, liver, spleen, lung, kidney, brain, and muscle samples were taken at different time points. Drug concentration was measured with HPLC, and the drug concentration–time curve was plotted. Pharmacokinetic software 3p97 was applied to calculate pharmacokinetic parameters and the area under the drug concentration–time curve (AUC in various tissues. The rat model of acute myocardial ischemia was constructed with intravenous injection of pituitrin and the model of myocardial ischemia-perfusion injury was constructed by tying off the left anterior descending coronary artery of rats to observe the effect of ligustrazine ethosome patches on ischemic myocardium and ischemia-reperfusion injury. Results showed that AUC was highest in the transdermal drug delivery group of ligustrazine ethosome patch. There were significant differences in whole blood viscosity, plasma viscosity, hematocrit, red blood cell aggregation index, and deformation index between ligustrazine the ethosome patch group and ischemic control group (P < 0.01. Moreover, ligustrazine ethosome patches could reduce the scope of myocardial infarction induced by long-term ischemia. Ligustrazine ethosome patches

  14. Effects of ischemic preconditioning on cyclinD1 expression during early ischemic reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Fang-Gang Cai; Jian-Sheng Xiao; Qi-Fa Ye

    2006-01-01

    AIM: To observe the effect of ischemic preconditioning on cyclinD1 expression in rat liver cells during early ischemic reperfusion.METHODS: Fifty-four SD rats were randomly divided into ischemic preconditioning group (IP), ischemia/reperfusion group (IR) and sham operation group (SO). The IP and IR groups were further divided into four sub-groups (n = 6). Sham operation group (SO)served as the control group (n = 6). A model of partial liver ischemia/reperfusion was used, in which rats were subjected to liver ischemia for 60 min prior to reperfusion. The animals in the IP group underwent ischemic preconditioning twice for 5 min each time prior to the ischemia/reperfusion challenge. After 0, 1, 2, and 4 h of reperfusion, serum and liver tissue in each group were collected to detect the level of serum ALT, liver histopathology and expression of cyclinD1 mRNA and protein. Flow cytometry was used to detect cell cycle as the quantity indicator of cell regeneration.RESULTS: Compared with IR group, IP group showed asignificantly lower ALT level in 1 h to 4 h sub-groups (P< 0.05). Proliferation index(PI) indicated by the S-phase and G2/M-phase ratio [(S+G2/M)/(G0/G1+S+G2/M)] was significantly increased in IP group at 0 and 1 h (26.44± 7.60% vs 18.56 ± 6.40%,41.87 ± 7.27% vs 20.25 ±6.70%, P < 0.05). Meanwhile, cyclinD1 protein expression could be detected in IP group. But in IR group, cyclinD1 protein expression occurred 2 h after reperfusion. The expression of cyclinD1 mRNA increased significantly in IP group at 0 and 1 h (0.568 ± 0.112 vs 0.274 ± 0.069, 0.762± 0.164 vs 0.348 ± 0.093, P < 0.05).CONCLUSION: Ischemic preconditioning can protect liver cells against ischemia/reperfusion injury, which may be related to cell proliferation and expression of cyclinD1 during early ischemic reperfusion.

  15. The protecting effects and mechanism of betaine hydrochloride on hepatic ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    XIN Xiao-ming; MA Lian-long; GAO Yong-feng; WANG Hao; WANG Xiao-dan; ZHU Yu-yun; GAO Yun-sheng

    2008-01-01

    Objective To study the protecting effects and mechanism of betaine hydrochloride on hepatic ischemia-reperfusion injury in rats. Methods Fourty SD rats were randomly divided into 5 groups (8 animals in each group) : sham-operated control group (A), hepatic ischemia-reperfusion group (B), 200 mg·kg-1 400 mg·kg-1 800 mg·kg-1 betaine hydrochloride + hepatic ischemia-reperfusion group (C、D、E). betaine hydrochloride was administered to animals byoral route in group C、D、E for 7 days before ischemia. A、B group was administered with NS. Made the animal model of part hepatic ischemia-reperfusion. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in the blood and themalondialdehyde (MDA), superoxide dismutase (SOD), protein content in hepatic tissue were determined after the liver had been reperfused for 24 hours; the hepatic tissue was examined under lightmieroscope and the cell apoptosis was demonstrated with flow cytometry. Results ALT, AST, MDA increased and SOD decreased significantly in B group when compared those in the A group (P<0.05), Hepatic apoptosis was significantly increased; ALT, AST, MDA decreased and SOD increased significantly in betaine hydrochloride 200 mg·kg-1(C) group when compared those in the B group(P<0.05). Hepatic apoptosis was significantly lower, The histologic changes of the liver tissue under lightmicroscope in the C group was more easer than in the I/R group (B). Conclusions Betaine hydrochloride has the ability to scavenge oxygen free radical (OFR), reduce lipid peroxidation and inhibition of apoptosis. So it can protect the rats liver damaged by ischemia-reperfusion.

  16. Saffron (Crocus sativus) pretreatment confers cardioprotection against ischemia-reperfusion injuries in isolated rabbit heart.

    Science.gov (United States)

    Nader, Moni; Chahine, Nathalie; Salem, Charelle; Chahine, Ramez

    2016-12-01

    Restoration of blood flow to the ischemic myocardium is imperative to avoid demise of cardiomyocytes, but is paradoxically associated with irreversible damage to cardiac tissues due to the excessive generation of reactive oxygen species (ROS). We have previously reported that saffron, a natural antioxidant, attenuated ischemia-reperfusion (IR) injuries in vitro; however, its role in a meaningful cardiac recovery remains unknown. Here, we show that saffron supplement (oral administration for 6 weeks) reduced myocardial damage and restored cardiac function in an IR model of rabbit hearts. This was evidenced by improved left ventricle pressure, heart rate and coronary flow, and left ventricle end diastolic pressure (LVEDP) in IR hearts (isolated from rabbits pre-exposed to saffron (S/IR)). Electrophysiological recordings revealed a significant decline in both premature ventricle contraction and ventricle tachycardia/fibrillation in S/IR compared to IR hearts. This was paralleled by increased expression of the contractile proteins α-actinin and Troponin C in the myocardium of S/IR hearts. Histological examination combined to biochemical analysis indicated that hearts pre-exposed to saffron exhibited reduced infarct size, lower lipid peroxidation, with increased glutathione peroxidase activity, and oxidation of nitro blue tetrazolium (by reactive oxygen species). Furthermore, in contrast with IR hearts, saffron pretreatment induced restoration of the phosphorylation level of the survival proteins Akt and 4EBP1 and reduced activity of p38. Collectively, our data demonstrate that the natural antioxidant saffron plays a pivotal role in halting IR-associated cardiac injuries and emerges as a novel preventive tool for ischemic heart disease.

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

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    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.

  18. Cardioprotection Afforded by Norepinephrine-mediated Postconditioning in Isolated Rat Hearts

    Institute of Scientific and Technical Information of China (English)

    Xinhua Huang; Dai Li; Yishuai Zhang; Nianshen Li; Benmei Chen; Jun Peng; Yuanjian Li

    2008-01-01

    Objectives Previous studies have demonstrated that endogenous norepinephrine (NE) plays an important role in the mediation of ischemic preconditioning. The present study is designed to determine whether NE is also involved in medi-ation of the protective effects of postconditioning. Methods The rat hearts were rapidly excised under anesthesia and attached to a Langendorff apparatus via the aorta for retrograde perfusion with Krebs-Henseleit buffer solution. All hearts were subjected to 30 min of left coronary artery occlusion followed by 60 rain of reperfusion, except the control group. Animals were randomly divided into 5 groups as follows: ① control group, the hearts were underwent same procedures without ischemic insult; ② ischemia reperfusion group, the left coronary artery was occluded for 30 min and followed by 60 min of reperfusion;③ ischemic postconditioning (Ipost) group, immediately at the onset of reperfusion, the heart was initiated with 1 min of full coronary flow, followed by 1 min of re-occlusion, repeated for a total of three cycles; ④ Ipost plus prazosin group, the heart was perfused with prazosin for 10 min before ischemia; ⑤ Ipost plus reserpine group, a single dose of reserpine was administered by I.m. Injection, 24 hours before the experiment. Coronary flow was measured by timed collection of coronary effluent and sample of coronary effluent at 5 rain of reperfusion were collected for the measurement of ereatine kinase (CK). Infarct size and risk area were determined at the end of experiments. Results 30 rain of ischemia and followed by 60 min of reperfusion caused a significant decrease in cardiac function and a significant increase in CK release and infarct size. Postconditioning with three cycles of 1-min ischemia and 1-min reperfusion markedly improved cardiac function and reduced CK release and infarct size. However,the cardioprotection afforded by postconditioning was abolished by prazosin (10-6M), a selective α1 adrenergic

  19. {sup 41}Ca as a tracer for calcium uptake and deposition in heart tissue during ischemia and reperfusion

    Energy Technology Data Exchange (ETDEWEB)

    Southon, J.R. [Lawrence Livermore National Lab., CA (United States); Bishop, M.S.; Kost, G.J. [California Univ., Davis, CA (United States). Dept. of Medical Pathology and Biomedical Engineering

    1993-09-17

    We have developed techniques and are commencing experiments using enriched {sup 41}Ca as a tracer in isolated rabbit heart preparations. The aims of the study are to measure calcium uptake and deposition in response to cardiac ischemia and reperfusion, and to investigate events and mechanism leading to irreversible myocyte injury.

  20. Reducing mitochondrial bound hexokinase II mediates transition from non-injurious into injurious ischemia/reperfusion of the intact heart

    NARCIS (Netherlands)

    R. Nederlof (Rianne); Gürel-Gurevin, E. (Ebru); O. Eerbeek (Otto); C. Xie (Chaoqin); Deijs, G.S.; Konkel, M. (Moritz); Hu, J. (Jun); N.C. Weber (Nina); C. Schumacher (Cees); A. Baartscheer (Antonius); E.G. Mik (Egbert); M.W. Hollmann (Markus); F.G. Akar (Fadi); C.J. Zuurbier (Coert J.)

    2016-01-01

    textabstractIschemia/reperfusion (I/R) of the heart becomes injurious when duration of the ischemic insult exceeds a certain threshold (approximately ≥20 min). Mitochondrial bound hexokinase II (mtHKII) protects against I/R injury, with the amount of mtHKII correlating with injury. Here, we examine

  1. Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Na Zhang; Gen-Yang Cheng; Xian-Zhi Liu; Feng-Jiang Zhang

    2014-01-01

    Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue. Methods:Fourty eight rats were randomly divided into four groups(n=12): sham operation group,30 min ischemia60 min reperfusion group,60 min ischemia60 min reperfusion group, and 120 min ischemia60 min reperfusion group.The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreasedBcl-2 expression, increasedBax expression, upregulated expression ofNF-κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation.

  2. Estudo da isquemia e reperfusão em retalhos cutâneos de ratos The study of the ischemia and reperfusion in skin flaps of rats

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    Frederico Alonso Sabino de Freitas

    2002-01-01

    Full Text Available INTRODUÇÃO: Múltiplos fatores têm sido implicados na patogênese da lesão de isquemia/reperfusão da pele, incluindo as espécies reativas de oxigênio. OBJETIVO: Estudar a lesão de isquemia/reperfusão em retalhos cutâneos de ratos avaliando os níveis teciduais do malonildialdeído (MDA e xantina oxidase (XO. MÉTODOS: Foram utilizados 8 ratos Wistar, com peso entre 300 - 400g, sendo confeccionados 2 retalhos epigástricos por animal (controle e experimento, um deles submetido à 16h de isquemia (RI seguida de 45 min de reperfusão (RR e o outro controle (RC. Foram colhidas 3 biópsias de pele dos retalhos (RC, RI, RR e encaminhadas para dosagem de MDA e XO. RESULTADOS: A análise bioquímica mostrou aumento significativo dos níveis teciduais de MDA e XO após a reperfusão em relação aos retalhos controles. CONCLUSÃO: Retalhos epigástricos de ratos submetidos à 16h de isquemia e 45min de reperfusão apresentam elevação dos níveis teciduais de MDA e XO, caracterizando a lipoperoxidação da membrana celular.INTRODUCTION: Multiple factors have been implicated in the pathogenesis of reperfusion injury in the skin, including the reactive oxygen species. OBJECTIVE: The aim was to evaluate the effect of reperfusion injury in the rat skin flap evaluated by tissue assay for malonyldialdehyde (MDA and xanthine oxidase (XO. METHODS: 8 Wistar rats were used, between 300-400g weight and two identical epigastric flaps were raised in each animal (control and experiment, the vasculature of one flap was left intact and in the second flap the arterial pedicle was clamped for 16 hours and reperfused for 45 minutes. Skin samples were obtained from each flap after these periods of time and submitted to MDA and XO analysis. RESULTS: Reperfused flaps had significantly increased MDA and XO values compared to the control flaps biopsies. CONCLUSION: The lipid peroxidation levels were higher in the rat epigastric skin flaps subjected to 16 hours of

  3. The protective effect of erdosteine on short-term global brain ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Ozerol, Elif; Bilgic, Sedat; Iraz, Mustafa; Cigli, Ahmet; Ilhan, Atilla; Akyol, Omer

    2009-02-01

    Experimental studies have demonstrated that free radicals play a major role on neuronal injury during ischemia/reperfusion (I/R) in rats. Erdosteine is a thioderivative endowed with mucokinetic, mucolytic and free-radical-scavenging properties. The aim of the present study was to investigate the effect of erdosteine treatment against short-term global brain ischemia/reperfusion injury in rats. The study was carried out on Wistar rats divided into four groups. (i) Control group, (ii) ischemia/reperfusion group, (iii) ischemia/reperfusion+erdosteine group, and (iv) erdosteine group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as thiobarbituric acid reactive substances (TBARSs) and nitric oxide (NO) levels were analysed in erythrocyte and plasma of rats. Plasma NO levels were significantly higher in the ischemia/reperfusion group than the other groups. The activities of SOD and GSH-Px were decreased, while TBARS levels increased in the ischemia/reperfusion group compared to other groups in both plasma and erythrocyte. The erythrocyte CAT activity was higher in erdosteine group and there was a statistically significant increase, when compared with the erdosteine plus ischemia/reperfusion group. By treating the rats with erdosteine, the depletion of endogenous antioxidant enzymes (SOD, CAT, GSH-Px) and increase of TBARS and NO levels were prevented. This study, therefore, suggests that erdosteine reduces parameters of oxidative stress is well supported by the data.

  4. Iloprost reduces myocardial edema in a rat model of myocardial ischemia reperfusion.

    Science.gov (United States)

    Caliskan, A; Yavuz, C; Karahan, O; Yazici, S; Guclu, O; Demirtas, S; Mavitas, B

    2014-05-01

    Myocardial ischemia severely reduces myocyte longevity and function. Extensive interstitial edema and cell damage occur as a result of myocardial reperfusion injury. Current therapies are directed at prevention of ischemia-induced damage to cardiac tissue. Iloprost is a novel pharmaceutical agent for the treatment of ischemia. Twenty rats were segregated into four experimental groups. The procedure control group consisted of four rats undergoing a sham operation. The remaining 16 rats were divided into two equal groups. The first group (control group) received a continuous intravenous infusion of physiological serum immediately prior to the procedure. Iloprost was administered by a continuous intravenous infusion into the right jugular vein at an infusion rate of 100 ng/kg/min for 30 minutes prior to reperfusion in the experimental group (study group). Following the infusion treatments, ligation of the left coronary artery was conducted for 30 minutes to induce myocardial ischemia. The rats were euthanized 24 hours after reperfusion and cardiac tissue was harvested from all specimens for analysis. Histological examination revealed three myocardial tissue specimens with grade II damage and five myocardial tissue specimens with grade III reperfusion injury in the control group. However, the study group consisted of two grade III myocardial tissue specimens, five grade II myocardial tissue specimens and one grade I myocardial tissue specimen. Moreover, a statistically significant reduction in myocardial edema was observed in the study group (p=0.022). Our results support the hypothesis that iloprost enhances protection against cardiac ischemia reperfusion injury. This protective effect may be associated with vasodilation, antioxidant or anti-edema mechanisms.

  5. [Effect of electroacupuncture on inflammatory injury induced by intestinal ischemia/reperfusion in rats].

    Science.gov (United States)

    Yao, Jia-Rui; Shi, Xian; Hu, Sen; Zhong, Yu-Xian; Liu, Wei-Wei; Zhao, Ying

    2012-07-01

    To observe the protective effect of electroacupuncture (EA) at "Zusanli" (ST 36) on inflammatory injury induced by intestinal ischemia/reperfusion (I/R) in rats. Forty-eight Wistar rats were randomly divided into a sham injury group, a model group, an EA group and a sham EA group, 12 rats in each group. Intestinal I/R rat models were established by method of clamping with occlusion of superior mesenteric artery (SMA) for 45 min followed by reperfusion. The EA group was treated with EA (2.5 mA, 2 Hz/100 Hz, 0.5 h) at "Zusanli" (ST 36) 30 min before reperfusion, and at the same time, the sham EA group was treated with fast insertion at two non-meridian acupoints on skin surface (2 cm horizontally away from linea alba abdominis and about 5 cm paralleled to cartilago ensiformis downward). No interventions were added on the sham injury group and the model group. The degree of pathological injury in intestines, water rate of intestines, diamine oxidase (DAO) activity and intestinal mucosal blood flow (IMBF) were examined at 1 h and 3 h after reperfusion. At 1 h and 3 h after reperfusion, the intestinal pathological injury in EA group was significantly attenuated compared with that in model group, and the intestinal water rate of (74.00 +/- 2.11)% and (78.78 +/- 0.80)% in EA group were significantly lower than (80.69 +/- 1.66)% and (83.17 +/- 2.08)% in model group (both P 0.05). Electroacupuncture can not only reduce the inflammatory injury induced by intestinal IR but also increase intestinal blood supply so as to protect the intestine function.

  6. Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage

    Science.gov (United States)

    Turamanlar, Ozan; Özen, Oğuz Aslan; Songur, Ahmet; Yağmurca, Murat; Akçer, Sezer; Mollaoğlu, Hakan; Aktaş, Cevat

    2015-01-01

    Background: Alpha lipoic acid is a potent antioxidant that plays numerous roles in human health. This study examined the effect of ALA on rat sciatic nerve ischemia reperfusion damage. Aims: Protective effect of alpha lipoic acid (ALA) on sciatic nerve following ischemia-reperfusion in rats was investigated by using light microscopy and biochemical methods. Provided that the protective effect of ALA on sciatic nerve is proven, we think the damage to the sciatic nerve that has already occurred or might occur in patients for various reasons maybe prevented or stopped by giving ALA in convenient doses. Study Design: Animal experiment. Methods: Forty-two adult male Sprague-Dawley rats (250–300 grams) were used in this study. Rats were randomly divided into six groups including one control (Group 1), one sham (Group 2), two ischemia-reperfusion (Groups 3 and 4) and two treatment groups (Groups5 and 6). Doses of 60 and 100 mg/kg ALA were given (Group 5 and 6) intra peritoneally twice, 1 and 24 hours before the ischemia to each treatment group. Ischemia was carried out the abdominal aorta starting from the distal part of the renal vein for two hours followed by reperfusion for three hours. In immunohistochemical methods, fibronectin immunoreactivity was analyzed. For biochemical analyses, the tissues were taken in eppendorf microtubes and superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) enzyme activities as well as malondialdehyde (MDA) and nitricoxide (NO) levels were measured. Results: Fibronectin was observed to have increased significantly in the ischemia group; on the other hand, it was observed to have decreased in parallel to the doses in the ALA groups. Biochemical studies showed that SOD and GSHPx declined with ischemia-reperfusion, but the activities of these enzymes were increased in the treatment groups in parallel with the dose. It was found that increased MDA levels with ischemia-reperfusion were decreased in parallel with ALA dose. There were

  7. Protection Against Hepatic Ischemia-reperfusion Injury in Rats by Oral Pretreatment With Quercetin

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To investigate the possible protection provided by oral quercetin pretreatment against hepatic ischemia-reperfusion injury in rats. Methods The quercetin (0.13 mmol/kg) was orally administrated in 50 min prior to hepatic ischemia-reperfusion injury. Ascorbic acid was also similarly administered. The hepatic content of quercetin was assayed by high performance liquid chromatography (HPLC). Plasma glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) activities and malondialdehyde (MDA) concentration were measured as markers of hepatic ischemia-reperfusion injury. Meanwhile, hepatic content of glutathione (GSH), activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO), total antioxidant capacity (TAOC), contents of reactive oxygen species (ROS) and MDA, DNA fragmentation were also determined. Results Hepatic content of quercetin after intragastric administration of quercetin was increased significantly. The increases in plasma GPT, GOT activities and MDA concentration after hepatic ischemia-reperfusion injury were reduced significantly by pretreatment with quercetin. Hepatic content of GSH and activities of SOD, GSH-Px and TAOC were restored remarkably while the ROS and MDA contents were significantly diminished by quercetin pretreatment after ischemia-reperfusion injury. However, quercetin pretreatment did not reduce significantly hepatic XO activity and DNA fragmentation. Ascorbic acid pretreatment had also protective effects against hepatic ischemia-reperfusion injury by restoring hepatic content of GSH, TAOC and diminishing ROS and MDA formation and DNA fragmentation. Conclusion It is indicated that quercetin can protect the liver against ischemia-reperfusion injury after oral pretreatment and the underlying mechanism is associated with improved hepatic antioxidant capacity.

  8. [The influence of inhibiting no formation on metabolic recovery of ischemic rat heart by apelin-12].

    Science.gov (United States)

    Pisarenko, O I; Pelogeĭkina, Iu A; Shul'zhenko, V S; Studneva, I M; Bespalova, Zh D; Az'muko, A A; Sidorova, M V; Pal'keeva, M E

    2012-01-01

    Apelin 12 (A-12) was synthesized by the automatic solid phase method with use of Fmoc 1H-NMR spectroscopy and mass spectrometry. Effects of apelin-12 (a peptide comprised of 12 aminoacids, A-12) on recovery of energy metabolism and cardiac function were studied in isolated working rat hearts perfused with Krebs buffer (KB) containing 11 mM glucose that were subjected to global ischemia and reperfusion. A short-term infusion of microM 140 A-12 in KB prior to ischemia enhanced myocardial ATP, the total adenine nucleotide pool (SigmaAN = ATP + ADP + AMP) and the energy charge of cardiomyocites ((ATP + 0.5ADP)/SigmaAN) at the end of reperfusion compared with control (KB infusion) and reduced lactate content and lactate/pyruvate ratio in reperfused myocardium to the initial values. This effect was accompanied by improved recovery of coronary flow and cardiac function. Coadministration of 140 microM A-12 and 100 microM L-NAME (the nonspecific NOS inhibitor) profoundly attenuated the peptide influence on metabolic and functional recovery of reperfused hearts. The results indicate involvement of NO, formed under the peptide action, in mechanisms of cardioprotection that are tightly associated with recovery of energy metabolism in postischemic heart.

  9. Ischemic preconditioning and the gene expression of enteric endothelial cell biology of rats submitted to intestinal ischemia and reperfusion

    Directory of Open Access Journals (Sweden)

    Murched Omar Taha

    2013-03-01

    Full Text Available PURPOSE: To investigate the effects of ischemic preconditioning (IPC on the expression of pro and anti-apoptotic genes in rat endothelial cells undergoing enteric ischemia (I and reperfusion (R. METHODS: Thirty rats underwent clamping of the superior mesenteric vessels. Sham group (GS laparotomy only; Ischemia (GI: intestinal ischemia (60 min; Ischemia and Reperfusion (GIR: ischemia (60 min and reperfusion (120 min; Ischemia and intestinal ischemic preconditioning (GI + IPC : 5 minutes of ischemia followed by 10 min of reperfusion before sustained ischemia (60 min ischemia and reperfusion and IPC (GIR + IPC: 5 min ischemia followed by 10 min of reperfusion before sustained ischemia (60min and reperfusion (120 min. Rat Endothelial Cell Biology (PCR array to determine the expression of genes related to endothelial cell biology. RESULTS: Gene expression of pro-apoptotic markers (Casp1, Casp6, Cflar, Fas, and Pgl was down regulated in GI+IPC and in GIR + IPC. In contrast, the expression of anti-apoptotic genes (Bcl2 and Naip2, was up-regulated in GI + IPC and in GIR + IPC. CONCLUSION: Ischemic preconditioning may protect against cell death caused by ischemia and reperfusion.

  10. Protective effects of captopril in diabetic rats exposed to ischemia/reperfusion renal injury.

    Science.gov (United States)

    Fouad, Amr A; Al-Mulhim, Abdulruhman S; Jresat, Iyad; Morsy, Mohamed A

    2013-02-01

    To investigate the potential protective effects of captopril, the angiotensin-converting enzyme inhibitor, in diabetic rats exposed to ischaemia/reperfusion (I/R) renal injury. Following successful induction of diabetes, captopril treatment (50 mg/kg/day, p.o.) was applied for 4 weeks, after which bilateral renal ischaemia was induced for 30 min followed by reperfusion for 24 h. Captopril significantly attenuated hyperglycaemia and hypoinsulinaemia in diabetic rats, and significantly reduced the elevations of serum creatinine and aldosterone levels, and renal malondialdehyde, tumour necrosis factor-α and nitric oxide (NO), and prevented the depletion of reduced glutathione caused by I/R in diabetic rats. Histopathological renal tissue damage induced by I/R in diabetic rats was ameliorated by captopril treatment. Immunohistochemical analysis revealed that captopril significantly attenuated the reduction of insulin content in pancreatic islet β-cells, and decreased the I/R-induced expression of inducible NO synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin and heme oxygenase-1 in the kidney tissue of diabetic rats. Captopril represents a potential candidate to reduce the risk of renal injury induced by ischaemia/reperfusion in type 2 diabetes. © 2012 The Authors. JPP © 2012. Royal Pharmaceutical Society.

  11. Dexamethasone pretreatment attenuates lung and kidney injury in cholestatic rats induced by hepatic ischemia/reperfusion.

    Science.gov (United States)

    Zhou, Liangyi; Yao, Xiangqing; Chen, Yanling

    2012-02-01

    Hepatic ischemia followed by reperfusion (IR) results in mild to severe organ injury, in which tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) seem to be involved. Thus, we aim to assess the influence of hepatic ischemia/reperfusion injury on remote organs in addition to cholestasis and consider the possible efficacy of steroid pretreatment in reducing the injury. A common bile duct ligation model was done on 24 male Sprague-Dawley rats. After 7 days, the rats were divided randomly into control group, IR group, and dexamethasone (DEX) group. The IR group showed significant increases in serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels compared with the control and DEX groups. By ELISA techniques, higher levels of TNF-α and IL-1β in lung and kidney tissues were measured in the IR group than in the control and DEX groups, these were verified by immunohistochemistry. The lung histology of the IR group rats showed neutrophil infiltration, interstitial edema, and alveolar wall thickening. Kidney histology of the IR group rats showed vacuolization of the proximal tubular epithelial cells and tubular dilatation with granular eosinophilic casts. Better morphological aspects were observed in the DEX-pretreated animals. Minimal lesions were observed in the control. The results suggest that hepatic ischemia/reperfusion injury in cholestatic rats induced lung and kidney injuries. Pretreatment with dexamethasone reduced the IR-induced injury in addition to cholestasis.

  12. Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the effects of resveratrol on liver ischemia/reperfusion (I/R) injury in rats. METHODS: A total of 40 male Sprague-Dawley rats weighing 240-290 g were randomized into four groups often: (1) controls: data from unmanipulated animals; (2) sham group: rats subjected to the surgical procedure, except for liver I/R, and given saline; (3) I/R group: rats underwent liver ischemia for 45 min followed by reperfu-sion for 45 min; (4) I-R/Resveratrol group: rats pretreat-ed with resveratrol (10 μmol/L, iv). Liver tissues were obtained to determine antioxidant enzyme levels and for biochemical and histological evaluation. RESULTS: Plasma aminotransferase activities were higher in the I/R group than in the I-R/Resveratrol group. Malondialdehyde levels and the hepatic injury score decreased, while superoxide dismutase, catalase, and glutathione peroxidase levels increased in group 4 compared to group 3. In group 4, histopathological changes were significantly attenuated in resveratrol-treated livers.CONCLUSION: These results suggest that resveratrol has protective effects against hepatic I/R injury, and is a potential therapeutic drug for ischemia reperfusion-related liver injury.

  13. The effect of erythropoietin on serum uric acid levels during renal ischemia reperfusion injury in rats

    Science.gov (United States)

    Tsompos, Constantinos; Panoulis, Constantinos; Toutouzas, Konstantinos; Zografos, George; Papalois, Apostolos

    2014-01-01

    Objective: The aim of this experimental study was to assess the effect of erythropoietin on a rat model, particularly under a renal ischemia reperfusion protocol. The beneficial or lack of effects of that molecule on the excreted renal product of serum uric acid were studied biochemically. Material and methods: Forty rats were used with a mean weight of 247.7 gr. Serum uric acid levels were measured measured at 60 min after reperfusion (Groups A and C) and at 120 min after reperfusion (groups B and D). Results: 1) Erythropoietin administration non-significantly decreased the serum uric acid levels non-significantly by 0.02 mg/dL [−0.2415423 mg/dL-0.2015423 mg/dL] (p=0.8560), in accordance with the paired t-test (p=0.8438). Reperfusion time non-significantly increased the serum uric acid levels non-significantly by 0.17 mg/dL [−0.0444933 mg/dL-0.3844933 mg/dL] (p=0.1169), in accordance with the paired t-test (p=0.1648). 3) The interaction of erythropoietin administration and reperfusion time non-significantly increased the serum uric acid levels non-significantly by 0.1 mg/dL [−0.0295564 mg/dL-0.2295564 mg/dL] (p=0.1264). Conclusion: Erythropoietin administration, reperfusion time and their interaction have no significant short-term alterations on serum uric acid levels. Conclusions cannot be extracted by non-significant p-values within 2 hours. Obviously, longer study times may permit safer results. PMID:26328161

  14. Ischemic post-conditioning attenuates the intestinal injury induced by limb ischemia/reperfusion in rats

    Directory of Open Access Journals (Sweden)

    Y.F. Leng

    2011-05-01

    Full Text Available The purpose of this study was to investigate the protective effects of ischemic post-conditioning on damage to the barrier function of the small intestine caused by limb ischemia-reperfusion injury. Male Wistar rats were randomly divided into 3 groups (N = 36 each: sham operated (group S, lower limb ischemia-reperfusion (group LIR, and post-conditioning (group PC. Each group was divided into subgroups (N = 6 according to reperfusion time: immediate (0 h; T1, 1 h (T2, 3 h (T3, 6 h (T4, 12 h (T5, and 24 h (T6. In the PC group, 3 cycles of reperfusion followed by ischemia (each lasting 30 s were applied immediately. At all reperfusion times (T1-T6, diamine oxidase (DAO, superoxide dismutase (SOD, and myeloperoxidase (MPO activity, malondialdehyde (MDA intestinal tissue concentrations, plasma endotoxin concentrations, and serum DAO, tumor necrosis factor-α (TNF-α, and interleukin-10 (IL-10 concentrations were measured in sacrificed rats. Chiu’s pathology scores for small intestinal mucosa were determined under a light microscope and showed that damage to the small intestinal mucosa was lower in group PC than in group LIR. In group PC, tissue DAO and SOD concentrations at T2 to T6, and IL-10 concentrations at T2 to T5 were higher than in group LIR (P < 0.05; however, tissue MPO and MDA concentrations, and serum DAO and plasma endotoxin concentrations at T2 to T6, as well as TNF-α at T2 and T4 decreased significantly (P < 0.05. These results show that ischemic post-conditioning attenuated the permeability of the small intestines after limb ischemia-reperfusion injury. The protective mechanism of ischemic post-conditioning may be related to inhibition of oxygen free radicals and inflammatory cytokines that cause organ damage.

  15. Caffeine Mitigates Lung Inflammation Induced by Ischemia-Reperfusion of Lower Limbs in Rats

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    Wei-Chi Chou

    2015-01-01

    Full Text Available Reperfusion of ischemic limbs can induce inflammation and subsequently cause acute lung injury. Caffeine, a widely used psychostimulant, possesses potent anti-inflammatory capacity. We elucidated whether caffeine can mitigate lung inflammation caused by ischemia-reperfusion (IR of the lower limbs. Adult male Sprague-Dawley rats were randomly allocated to receive IR, IR plus caffeine (IR + Caf group, sham-operation (Sham, or sham plus caffeine (n=12 in each group. To induce IR, lower limbs were bilaterally tied by rubber bands high around each thigh for 3 hours followed by reperfusion for 3 hours. Caffeine (50 mg/kg, intraperitoneal injection was administered immediately after reperfusion. Our histological assay data revealed characteristics of severe lung inflammation in the IR group and mild to moderate characteristic of lung inflammation in the IR + Caf group. Total cells number and protein concentration in bronchoalveolar lavage fluid of the IR group were significantly higher than those of the IR + Caf group (P<0.001 and P=0.008, resp.. Similarly, pulmonary concentrations of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2 and pulmonary myeloperoxidase activity of the IR group were significantly higher than those of the IR + Caf group (all P<0.05. These data clearly demonstrate that caffeine could mitigate lung inflammation induced by ischemia-reperfusion of the lower limbs.

  16. Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury in rats.

    Science.gov (United States)

    Fouad, Amr A; Jresat, Iyad

    2011-11-16

    The therapeutic potential of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated in rats exposed to ischemia/reperfusion liver injury. Ischemia was induced by clamping the pedicle of the left hepatic lobe for 30 min, and cannabidiol (5mg/kg, i.v.) was given 1h following the procedure and every 24h thereafter for 2 days. Ischemia/reperfusion caused significant elevations of serum alanine aminotransferase and hepatic malondialdehyde, tumor necrosis factor-α and nitric oxide levels, associated with significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters mediated by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced liver damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin protein in ischemic/reperfused liver tissue. These results emphasize that cannabidiol represents a potential therapeutic option to protect the liver against hypoxia-reoxygenation injury.

  17. Effect of Salvia leriifolia Benth. root extracts on ischemia-reperfusion in rat skeletal muscle

    Directory of Open Access Journals (Sweden)

    Nassiri-Asl Marjan

    2007-07-01

    Full Text Available Abstract Background Salvia leriifolia have been shown to decrease ischemia-reperfusion (I/R injury in brain tissues. In this study, the effects of S. leriifolia aqueous and ethanolic extracts were evaluated on an animal model of I/R injury in the rat hind limb. Methods Ischemia was induced using free-flap surgery in skeletal muscle. The aqueous and ethanolic extracts of S. leriifolia (100, 200 and 400 mg/kg root and normal saline (10 ml/kg were administered intraperitoneally 1 h prior reperfusion. During preischemia, ischemia and reperfusion conditions the electromyographic (EMG potentials in the muscles were recorded. The markers of oxidative stress including thiobarbituric acid reactive substances (TBARS, total sulfhydryl (SH groups and antioxidant capacity of muscle (using FRAP assay were measured. Results In peripheral ischemia, the average peak-to-peak amplitude during ischemic-reperfusion was found to be significantly larger in extracts groups in comparison with control group. Following extracts administration, the total SH contents and antioxidant capacity were elevated in muscle flap. The MDA level was also declined significantly in test groups. Conclusion It is concluded that S. leriifolia root extracts have some protective effects on different markers of oxidative damage in muscle tissue injury caused by lower limb ischemia-reperfusion.

  18. Hydrogen Gas Ameliorates Hepatic Reperfusion Injury After Prolonged Cold Preservation in Isolated Perfused Rat Liver.

    Science.gov (United States)

    Shimada, Shingo; Wakayama, Kenji; Fukai, Moto; Shimamura, Tsuyoshi; Ishikawa, Takahisa; Fukumori, Daisuke; Shibata, Maki; Yamashita, Kenichiro; Kimura, Taichi; Todo, Satoru; Ohsawa, Ikuroh; Taketomi, Akinobu

    2016-12-01

    Hydrogen gas reduces ischemia and reperfusion injury (IRI) in the liver and other organs. However, the precise mechanism remains elusive. We investigated whether hydrogen gas ameliorated hepatic I/R injury after cold preservation. Rat liver was subjected to 48-h cold storage in University of Wisconsin solution. The graft was reperfused with oxygenated buffer with or without hydrogen at 37° for 90 min on an isolated perfusion apparatus, comprising the H2 (+) and H2 (-) groups, respectively. In the control group (CT), grafts were reperfused immediately without preservation. Graft function, injury, and circulatory status were assessed throughout the perfusion. Tissue samples at the end of perfusion were collected to determine histopathology, oxidative stress, and apoptosis. In the H2 (-) group, IRI was indicated by a higher aspartate aminotransferase (AST), alanine aminotransferase (ALT) leakage, portal resistance, 8-hydroxy-2-deoxyguanosine-positive cell rate, apoptotic index, and endothelial endothelin-1 expression, together with reduced bile production, oxygen consumption, and GSH/GSSG ratio (vs. CT). In the H2 (+) group, these harmful changes were significantly suppressed [vs. H2 (-)]. Hydrogen gas reduced hepatic reperfusion injury after prolonged cold preservation via the maintenance of portal flow, by protecting mitochondrial function during the early phase of reperfusion, and via the suppression of oxidative stress and inflammatory cascades thereafter. Copyright © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  19. Thromboxane A2 release in ischemia and reperfusion of free flaps in rats, studied by microdialysis.

    Science.gov (United States)

    Ionac, M; Schaefer, D; Geishauser, M

    2001-02-01

    Several studies have implicated enhanced eicosanoid production in reperfusion injury. The reported study investigated the use of microdialysis in the in vivo measurement of thromboxane levels during reperfusion in ischemic and reperfused experimental free muscle flaps. Microdialysis probes were inserted, via a guide, into the gracilis and semitendinosus free flap in the rat. The probe was perfused at a flow of 5 microl/min, with samples collected at intervals of 20 min, and analyzed by the ELISA technique. Animals were randomly distributed into three groups. After ischemic periods of 2, 4, and 6 hr, respectively, the free muscle flaps were revascularized on the contralateral femoral vessels. The mean thromboxane level during ischemia was 1785.34 +/- 124.81 pg/ml. The mean levels of thromboxane rose significantly (p ischemia group, 192.33 percent in the 4-hr ischemia group, and 294.69 percent in the 6-hr ischemia group, and correlated well with histologic observations. The results suggest that a microdialysis technique, combined with a sensitive assay for measuring thromboxane, is a useful method for in vivo monitoring of inflammatory processes during ischemia and reperfusion. The evolution of thromboxane release following 6 hr of ischemia indicates that this mediator may be involved in facilitation of cell death, following ischemia and reperfusion, since its tissue level correlates with histologic tissue damage.

  20. Low-dose calcium antagonists reduce energy demand and cellular damage of isolated hearts during both ischemia and reperfusion.

    Science.gov (United States)

    Becker, B F; Möbert, J

    1999-09-01

    Calcium antagonists may protect against postischemic reperfusion injury of the heart, but neither the time and mode of action leading to cardioprotection is resolved, nor is the generality of this effect proven. Accordingly, the functional and metabolic influence of four different Ca2+-antagonists (diltiazem, 3x10(-8) M; nifedipine, 3x10(-9) M; amlodipine, 3x 10(-9) M; barnidipine, 3x10(-11) M) was examined in preparations of guinea pig hearts (n=7/group) performing pressure-volume work after being subjected to low-flow ischemia (30 min) and reperfusion (35 min). The drugs were applied throughout the study at concentrations without negative inotropic or chronotropic effect, as would be mandatory for any therapeutic application, and without overt coronary dilatation. All calcium antagonists improved postischemic recovery of external heart work: from 42% in controls (post- vs. preischemic value) to 59% for diltiazem, 61% for nifedipine, 65% for amlodipine, and 73% for barnidipine (all Pbarnidipine (15% efficiency). Release of lactate dehydrogenase in the first 5 min of reperfusion, a sign of cell damage, increased from basal (65 mU/min) to 208 mU/min in controls. This increase was fully suppressed by all drugs tested. Myocardial release of lactate and of purine catabolites of adenine nucleotides (markers of anaerobic metabolism) was markedly reduced by Ca2+-antagonists. Interestingly, these metabolic effects were evident not only in the reperfusion phase, but already in the period of low-flow ischemia. Oxidative consumption of pyruvate was enhanced, whereas coronary flow and heart rate showed no postischemic effect of treatment. These findings on isolated guinea pig hearts suggest that Ca2+-antagonists generally improve postischemic pump function and aerobic metabolism without any requirements for negative inotropic action or coronary dilatation. The protective effects seemed to rely on an attenuation of both ischemic stress and reperfusion damage. This could

  1. 吡那地尔后处理大鼠缺血再灌注损伤心肌线粒体的蛋白质组学研究%Proteomic study of myocardial mitochondria with ischemia/reperfusion injury and pinacidil postconditioning in isolated rat hearts

    Institute of Scientific and Technical Information of China (English)

    魏义勇; 李科; 刘云; 刘兴奎; 王海英; 喻田

    2015-01-01

    目的:运用蛋白质组学研究方法探讨吡那地尔后处理对缺血再灌注损伤大鼠心肌的保护作用。方法:建立Langendorff大鼠离体心脏缺血再灌注损伤模型,随机分为吡那地尔后处理组( Pina组)和缺血再灌注损伤组(I/R组),每组9只。提取心肌线粒体蛋白质行双向凝胶电泳,应用质谱鉴定差异大于2倍的蛋白质点。结果:Pina组与I/R组比较,共发现7个差异蛋白质:Pina 组NADH 脱氢酶1α亚复合体10亚基( NDUFA10)﹑NADH脱氢酶铁硫蛋白2(NDUFS2)和NADH脱氢酶黄素蛋白2(NDUFV2)表达低于I/R组;Pina组异柠檬酸脱氢酶α亚基(IDHA)和Δ3,5-Δ2,4-二烯酰辅酶A异构酶(ECH1)表达高于I/R组;另有2个蛋白质点均被鉴定为ATP合酶δ亚基,一个蛋白质点表达升高,而另一个表达降低。结论:吡那地尔后处理可能抑制了复合体Ⅰ的亚基(NDUFA10﹑NDUFS2和NDUFV2)代偿性增加,但促进了IDHA和ECH1表达并引发了ATP合酶δ亚基发生磷酸化,这些改变可能均与吡那地尔后处理保护心肌的作用有关。%AIM:To investigate the protective effect of pinacidil postconditioning on rat myocardium suffering ischemia/reperfusion injury by mitochondrial proteomics .METHODS: Langendorff apparatus was used to establish the model of myocardial ischemia/reperfusion injury .Sprague-Dawley rats were randomly divided into 2 groups:pinacidil post-conditioning group (Pina group) and ischemia/reperfusion injury group (I/R group).After 20 min of perfusion with K-H solution, the perfusion was suspended for 40-min (global ischemia) follow by 60 min of reperfusion in I/R group.In Pina group at the end of 40 min global ischemia , the isolated hearts were perfused with K-H solution containing pinacidil ( 50μmol/L) for 2 min followed 58-min perfusion with regular K-H solution.Total proteins extracted from the mitochondria were applied to the two

  2. Modulation of the cardioprotective effect of ischemic preconditioning in hyperlipidaemic rat heart.

    Science.gov (United States)

    Yadav, Harlokesh Narayan; Singh, Manjeet; Sharma, Pyare Lal

    2010-09-15

    Ischemic preconditioning (IPC) produces cardioprotection by phosphorylation of glycogen synthaes kinase-3beta (GSK-3beta) that inhibits the opening of mitochondrial permeability transition pore (MPTP), and this cardioprotective action of IPC is attenuated by hyperlipidaemia. The present study investigated the role of GSK-3beta in attenuation of cardioprotective effect of IPC, by hyperlipidaemia in the rat heart. Hyperlipidaemia was produced in rat by feeding high fat diet for six weeks. Isolated perfused rat heart was subjected to 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) was analyzed from coronary effluent. IPC significantly decreased the myocardial infarct size and the release of LDH and CK-MB from normal rat heart. IPC induced myocardial protection was attenuated in hyperlipidaemic rat heart. However, cardioprotective effect of pharmacological preconditioning with GSK-3beta inhibitors i.e. Lithium Chloride (LiCl) (20mM), Indirubin - 3 Monooxime (1 microM) and 3-(2, 4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2, 5-dione (SB216763) (3 microM), was not attenuated. This differential attenuation by hyperlipidaemia, of IPC and pharmacological preconditioning induced cardioprotection is a new finding in our study. GSK-3beta inhibition is reported to increase the threshold of opening for MPTP during reperfusion. Administration of atractyloside (20 microM), an opener of MPTP, significantly attenuated the cardioprotective effect of IPC in normal heart, and pharmacological preconditioning in the hyperlipidaemic rat heart. Thus, the attenuation of cardioprotective effect of IPC in hyperlipidaemic heart may be due to inhibition of protective signaling pathways upstream of GSK-3beta and inhibition of opening of MPTP.

  3. Comparative research between Bai-hua Qian-hu, a Chinese traditional plant, and its active ingredient on nuclear factor-κB and tumor necrosisfactor-α in isolated ischemia-reperfusion heart of rat

    Institute of Scientific and Technical Information of China (English)

    王弛; 常天辉

    2004-01-01

    @@Ischemia-reperfusion (I/R) injury is a complicated pathophysiological process, which is involved in calcium overload, free radical production, metabolic abnormalities, and inflammatory reaction. With the development of modern molecular biology, the expression and regulation of gene in myocardial I/R injury are focused on NF-κB.1Inflammatory reactions play an important role in I/R injury.2 TNF-α, an important inflammatory cytokine, is regulated by NF-κB and counteracts the activation of NF-κB. Sometimes, improper activation of NF-κB can induce excessive inflammatory responses and injury, so, modulation of NF-κB activation may dedicate a new target in alleviation of myocardial I/R injury.3Our previous studies have proved that Bai-hua Qian-hu (Peucedanum praeruptorum Dunn, BQ), a Chinese traditional plant had cardioprotective action in I/R animals.4 Its active ingredient Pd-Ia, a Ca2+-influx blocker5 and K+-channel opener,6 had similar effects. Meanwhile, it relieved inflammatory reaction and apoptosis in I/R myocardium through inhibition of interleukin-6 and Fas, bax, bcl-2 protein expression.7 However, the effects of BQ and Pd-Ia on the activation of NF-κB and the expression of TNF-α in I/R myocardium have not been clear yet. In this study, the effects of BQ and Pd-Ia on these two factors were investigated to further ascertain the molecular protective mechanism of BQ in I/R myocardium.

  4. The hepatoprotective effects of Hypericum perforatum L. on hepatic ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Bayramoglu, Gokhan; Bayramoglu, Aysegul; Engur, Selin; Senturk, Hakan; Ozturk, Nilgun; Colak, Suat

    2014-05-01

    Little is known about the effective role of Hypericum perforatum on hepatic ischemia-reperfusion (I/R) injury in rats. Hence, albino rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. Hypericum perforatum extract (HPE) at the dose of 50 mg/kg body weight (HPE50) was intraperitonally injected as a single dose, 15 min prior to ischemia. Rats were sacrificed at the end of reperfusion period and then, biochemical investigations were made in serum and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (p < 0.05). Treatment with HPE50 significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats without treatment-control group (p < 0.05). In oxidative stress generated by hepatic ischemia-reperfusion, H. perforatum L. as an antioxidant agent contributes an alteration in the delicate balance between the scavenging capacity of antioxidant defence systems and free radicals in favour of the antioxidant defence systems in the body.

  5. Effect of Gαq/11 Protein and ATP-sensitive Potassium Channels on Ischemic Preconditioning in Rat Hearts

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objectives To investigate the effect of Gαq/11 signaling pathway and ATP-sensitive potassium channel ( KATP channel ) on ischemic preconditioning (IPC) protection in rat hearts.Methods Two series of experiments were performed in Wistar rat hearts. In the first series of experiment,ischemic preconditioning was induced by left anterior descending occlusion (three, 5 min episodes separated by 5 min of reperfusion), ischemia-reperfusion injury was induced by 30 min coronary artery occlusion followed by 90 min reperfusion. Hemodynamics,infarct size and scores of ventricular arrhythmias were measured. The expression of Gαq/11 protein in the heart was measured by Western blot analysis in the second series. Results Ischemic preconditioning rats showed decreased infarct size and scores of ventricular arrhythmia vs non-IP control rats. The effect of IPC was significantly attenuated by glibenclamide (1 mg/kg, ip), a nonselective KATP channel inhibitor. IPC caused a significant increase in the expression of Gαq/11 protein. Conclusions Activations of Gαq/11 signal pathway and KATP channel played significant roles in the classical cardioprotection of ischemic preconditioning rat heart and might be an important mechanism of signal transduction pathway during the ischemic preconditioning.

  6. Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Lifang Lei; Xiaohong Zi; Qiuyun Tu

    2008-01-01

    BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 (MMP-9) is closely related to cerebral ischemia/reperfusion injuryOBJECTIVE: This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability.DESIGN, TIME AND SETTING: This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006.MATERIALS: Ninety healthy male SD rats, aged 3-4 months, weighing 200-280g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody (Boster, Wuhan, China) and Evans blue (Sigma, USA) were also used.METHODS: All rats were randomly divided into 9 groups with 10 rats in each group: normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3,6,12 hours, 1,2,4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled.MAIN OUTCOME MEASURES: BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method.RESULTS: All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter

  7. Effect of N-desulfated heparin on hepatic/renal ischemia reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Tong Zhou; Jin-Lian Chen; Wei Song; Feng Wang; Ming-Jun Zhang; Pei-Hua Ni; Jian-Guo Geng

    2002-01-01

    AIM: To investigate the effect of N-desulfated heparin onhepatic/renal ischemia and reperfusion injury in rats.METHODS: Using rat models of 60 minutes hepatic or renalischemia followed by 1 h,3 h,6 h and 24 h reperfusion,animalswere randomly divided into following groups,the shamoperated controls,ischemic group receiving only normalsaline,and treated group receiving N-desulfated heparin ata dose of 12 mg/kg at 5 minutes before reperfusion. P-selectin expression was detected in bepatic/renal tissueswith immunohistochemistry methodRESULTS: P-selectin expression, serum ALT, AST, BUN andCr levels were significantly increased during 60 minuteischemia and 1 h, 3 h, 6 h and 24 h reperfusion,while theincrement was significantly inhibited,and hepatic/renalpathology observed by light microscopy was remarkablyimproved by treatment with the N-desulfated heparin.Furthermore,the heparin was found no effects on PT and KPTT.CONCLUSION: P-selectin might mediate neutrophilinfiltration and contribute to hepatic/renal ischemia andreperfusion. The N-desulfated heparin might preventhepatic/renal damage induced by ischemia and reperfusioninjury without significant anticoagulant activity.

  8. Selenium protects against ischemia-reperfusion- induced gastric lesions in rats

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    Mobarok Ali Abu Taib

    1997-01-01

    Full Text Available Recent studies have shown that selenium afforded protection against ethanol and stress-induced gastric lesions in rats. The present study was undertaken to investigate the effect of selenium on ischemia-reperfusion-induced gastric injuries in which rats were subjected to 30 minutes of ischemia in the presence of 100 mM HCI and a reperfusion for 60 minutes duration. Intraluminal bleeding was assessed macroscopically and gastric lesions were graded microscopically under an inverted microscope. Nonprotein sulphydryl levels were measured spectrophotometrically. The severity of gastric lesions, intraluminal bleeding as well as the depletion of nonprotein sulphydryls during the reperfusion periods was significantly different from that of control. Pretreatment with selenium (0.125-2.0 mg/kg, intraperitoneally 30 minutes before the ischemia-reperfusion, dose-dependently attenuated the gastric lesions, reduced the severity of intraluminal bleeding and prevented the depletion of nonprotein sulphydryls in the stomach. These results suggest that the gastric protection effect of selenium may be due to its antioxidant properties. Furthermore, endogenous nonprotein sulphydryls may play a significant role in the protective mechanisms of selenium.

  9. Luoyutong Treatment Promotes Functional Recovery and Neuronal Plasticity after Cerebral Ischemia-Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Ning-qun Wang

    2015-01-01

    Full Text Available Luoyutong (LYT capsule has been used to treat cerebrovascular diseases clinically in China and is now patented and approved by the State Food and Drug Administration. In this retrospective validation study we investigated the ability of LYT to protect against cerebral ischemia-reperfusion injury in rats. Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion followed by reperfusion. Capsule containing LYT (high dose and medium dose as treatment group and Citicoline Sodium as positive control treatment group were administered daily to rats 30 min after reperfusion. Treatment was continued for either 3 days or 14 days. A saline solution was administered to control animals. Behavior tests were performed after 3 and 14 days of treatment. Our findings revealed that LYT treatment improved the neurological outcome, decreased cerebral infarction volume, and reduced apoptosis. Additionally, LYT improved neural plasticity, as the expression of synaptophysin, microtubule associated protein, and myelin basic protein was upregulated by LYT treatment, while neurofilament 200 expression was reduced. Moreover, levels of brain derived neurotrophic factor and basic fibroblast growth factor were increased. Our results suggest that LYT treatment may protect against ischemic injury and improve neural plasticity.

  10. Effects of Rosa Canina L. on Ischemia/ Reperfusion Injury in Anesthetized Rats

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    S Karimi

    2012-04-01

    Full Text Available Background: Ischemia/reperfusion induced acute renal failure causes excretory functional disorders of nephrons. Ischemia/reperfusion injury is accompanied by generation of reactive oxygen species that leads to dysfunction, injury, and death of renal cells. Antioxidants of plant origin minimize the harmful effects of reactive oxygen species. The aim of this study was to determine the possible therapeutic potentials of Rosa canina L. in preventing renal functional disturbances during the post-ischemic reperfusion period. Methods: In this experimental study undertaken for evaluating renal excretory function in 30 male Wistar rats, renal ischemia was induced by occluding both renal arteries for 45 min, followed by 24 h of reperfusion. The rats received 2 ml of tap water or a hydroalcoholic extract of Rosa canina (500 mg/kg orally for 7 days before induction of ischemia. In plasma samples, creatinine and urea nitrogen levels were measured, and in renal tissue samples, red blood cells were counted. The data were analyzed using ANOVA and Duncan tests.Results: Renal ischemia for 45 minutes increased plasma levels of creatinine (P<0.001 and nitrogen urea (P<0.01 while reducing red blood cell counts in renal glomeruli (P<0.001. Rosa canina administration diminished the increase in creatinine (P<0.001 and nitrogen urea concentrations (P<0.01, and prevented reductions in red blood cell counts in renal glomeruli (P<0.001. Conclusion: Rosa canina seems to be useful as a preventive agent against renal damages induced by ischemia/reperfusion injuries in rats.

  11. DPP-4 Inhibitor and Estrogen Share Similar Efficacy Against Cardiac Ischemic-Reperfusion Injury in Obese-Insulin Resistant and Estrogen-Deprived Female Rats

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    Sivasinprasasn, Sivaporn; Tanajak, Pongpan; Pongkan, Wanpitak; Pratchayasakul, Wasana; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2017-01-01

    Estrogen deprivation aggravates cardiac injury after myocardial ischemia and reperfusion (I/R) injury. Although either estrogen or the dipeptidyl peptidase-4 (DPP-4) inhibitor, vildagliptin, reduces myocardial damage following cardiac I/R, their effects on the heart in obese-insulin resistant and estrogen deprived conditions remain unknown. Ovariectomized (O) rats (n = 36) were divided to receive either normal diet (NDO) or high-fat diet (HFO) for 12 weeks, followed by treatment with a vehicle, estrogen or vildagliptin for 4 weeks. The setting of in vivo cardiac I/R injury, 30-min ischemia and 120-min reperfusion, was performed. At 12 weeks after ovariectomy, both NDO and HFO rats exhibited an obese-insulin resistant condition. Both NDO and HFO rats treated with estrogen and vildagliptin showed reduced fasting plasma glucose, insulin and HOMA index. Both treatments improved cardiac function indicated by restoration of heart rate variability and increased %left ventricular ejection fraction (%LVEF). The treatments similarly protected cardiac mitochondrial function against I/R injury, leading to a reduction in the infarct size, oxidative stress and apoptosis in the ischemic myocardium. These findings demonstrate that vildagliptin effectively improves metabolic status, and shares similar efficacy to estrogen in reducing myocardial infarction and protecting cardiac mitochondrial function against I/R injury in estrogen-deprived obese-insulin resistant rats. PMID:28281660

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

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    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.

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

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    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. Differential expression of Bcl-2 and Bax during gastric ischemia-reperfusion of rats

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    Wei-Li Qiao; Guang-Ming Wang; Yue Shi; Jin-Xia Wu; You-Jian Qi; Jian-Fu Zhang; Hong Sun; Chang-Dong Yan

    2011-01-01

    AIM: To investigate expression of Bcl-2 and Bax in gastric ischemia-reperfusion (GI-R) and involvement of extracellular signal-regulated kinase (ERK) 1/2 activation.METHODS: The GI-R model was established by ligature of the celiac artery for 30 min and reperfusion in Sprague-Dawley rats. Rats were assigned to groups in accordancewith their evaluation period: control, 0, 0.5, 1, 3, 6, 24,48, and 72 h. Expression and distribution of Bcl-2 and Bax proteins were analyzed by immunohistochemistry and western blotting in gastric tissue samples after sacrifice.RESULTS: Compared with controls, the percentage of positive cells and protein levels of Bcl-2 decreased in the early phases of reperfusion, reached its minimumat 1 h (P < 0.05); it then increased, reaching its peak at 24 h of reperfusion (P < 0.05). The pattern of Bax expression was opposite to that of Bcl-2. Bax expressionincreased after reperfusion, with its peak at 1 h of reperfusion (P < 0.05), and then it decreased gradually to a minimum at 24 h after reperfusion (P < 0.05).On the other hand, inhibition of activation of ERK1/2 induced by PD98059, a specific upstream MEK inhibitor,had significant effects on Bcl-2 and Bax in GI-R.Compared with GI-R treatment only at 3 h of reperfusion,PD98059 reduced the number of Bcl-2 positive cells (0.58% of R3h group, P < 0.05) and Bcl-2 proteinlevel (74% of R3h group, P < 0.05) but increased the number of Bax-positive cells (1.33-fold vs R3h group, P< 0.05) and Bax protein level (1.35-fold of R3h group,P < 0.05).CONCLUSION: These results indicated that the Bcl-2 and Bax played a pivotal role in the gastric mucosal I-R injury and repair by activation of ERK1/2.

  15. Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats

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    WANG Na; GUO Qu-lian; YE Zhi; XIA Ping-ping; WANG E; YUAN Ya-jing

    2011-01-01

    Background Several studies suggest that oyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats.Methods Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-a (TNF-α) levels. Infarct volume was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining.Results The rats in the I/R group had lower NDSs (P <0.05), larger infarct volume (P <0.05), lower HMGB1 levels (P<0.05), and higher TNF-α levels (P<0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P <0.05).Conclusions Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.

  16. Effect of matrine on Kupffer cell activation in cold ischemia reperfusion injury of rat liver

    Institute of Scientific and Technical Information of China (English)

    Xin-Hua Zhu; Yu-Dong Qiu; Hao Shen; Ming-Ke Shi; Yi-Tao Ding

    2002-01-01

    AIM: To study the effect of matrine on activation of Kupffer cell during cold ischemia and reperfusion injury in rat orthotopic liver transplantation (OLT).METHODS: 168 syngeneic SD rats were randomly divided into four groups: untreated group, small-dose treated group, large-dose treated group and sham operation group. After 5 hours of preservation in Ringer's (LR) solution, orthotopic implantation of the donor liver was performed. At 1 h, 2 h, 4 h and 24 h after reperfusion of the portal vein, 6 rats were killed in each group to collect the serum and the liver for assay and pathology.RESULTS: Matrine markedly inhibited the activation of Kupffer cells and their release of tumor necrosis factor (TNF). TNF cytotoxicity level at 2 h decreased significantly by matrine treatment (7.94±0.42, 2.39±0.19 and 2.01±0.13 U/ml,respectively; P<0.01), so did the other three time points. The level of hylluronic acid (HA) and alanine transaminase (ALT) decreased significantly in both treated groups, and matrine treatment markedly ameliorated focal necrosis of hepatocytes, inflammatory cells aggregating, rounding and detachment of sinusoidal endothelial cells (SEC). And no significant difference was observed between the treated groups.CONCLUSION: Matrine can inhibit the activation of Kupffer cell and prevent the donor liver from cold preservation and reperfusion injury in rat orthotopic liver transplantation.

  17. Combination of tadalafil and diltiazem attenuates renal ischemia reperfusion-induced acute renal failure in rats.

    Science.gov (United States)

    El-Sisi, Alaa E; Sokar, Samia S; Abu-Risha, Sally E; Ibrahim, Hanaa A

    2016-12-01

    Life threatening conditions characterized by renal ischemia/reperfusion (RIR) such as kidney transplantation, partial nephrectomy, renal artery angioplasty, cardiopulmonary bypass and aortic bypass surgery, continue to be among the most frequent causes of acute renal failure. The current study investigated the possible protective effects of tadalafil alone and in combination with diltiazem in experimentally-induced renal ischemia/reperfusion injury in rats. Possible underlying mechanisms were also investigated such as oxidative stress and inflammation. Rats were divided into sham-operated and I/R-operated groups. Anesthetized rats (urethane 1.3g/kg) were subjected to bilateral ischemia for 30min by occlusion of renal pedicles, then reperfused for 6h. Rats in the vehicle I/R group showed a significant (p˂0.05) increase in kidney malondialdehyde (MDA) content; myeloperoxidase (MPO) activity; TNF-α and IL-1β contents. In addition significant (p˂0.05) increase in intercellular adhesion molecule-1(ICAM-1) content, BUN and creatinine levels, along with significant decrease in kidney superoxide dismutase (SOD) activity. In addition, marked diffuse histopathological damage and severe cytoplasmic staining of caspase-3 were detected. Pretreatment with combination of tadalafil (5mg/kg bdwt) and diltiazem (5mg/kg bdwt) resulted in reversal of the increased biochemical parameters investigated. Also, histopathological examination revealed partial return to normal cellular architecture. In conclusion, pretreatment with tadalafil and diltiazem combination protected against RIR injury.

  18. Inhibition of mammalian target of rapamycin protects against reperfusion injury in diabetic heart through STAT3 signaling.

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    Das, Anindita; Salloum, Fadi N; Filippone, Scott M; Durrant, David E; Rokosh, Gregg; Bolli, Roberto; Kukreja, Rakesh C

    2015-05-01

    Diabetic patients suffer augmented severity of myocardial infarction. Excessive activation of the mammalian target of rapamycin (mTOR) and decreased activation of STAT3 are implicated in diabetic complications. Considering the potent cardioprotective effect of mTOR inhibitor, rapamycin, we hypothesized that reperfusion therapy with rapamycin would reduce infarct size in the diabetic hearts through STAT3 signaling. Hearts from adult male db/db or wild type (WT) C57 mice were isolated and subjected to 30 min of normothermic global ischemia and 60 min of reperfusion in Langendorff mode. Rapamycin (100 nM) was infused at the onset of reperfusion. Myocardial infarct size (IS) was significantly reduced in rapamycin-treated mice (13.3 ± 2.4 %) compared to DMSO vehicle control (35.9 ± 0.9 %) or WT mice (27.7 ± 1.1 %). Rapamycin treatment restored phosphorylation of STAT3 and enhanced AKT phosphorylation (target of mTORC2), but significantly reduced ribosomal protein S6 phosphorylation (target of mTORC1) in the diabetic heart. To determine the cause and effect relationship of STAT3 in cardioprotection, inducible cardiac-specific STAT3-deficient (MCM TG:STAT3(flox/flox)) and WT mice (MCM TG:STAT3(flox/flox)) were made diabetic by feeding high fat diet (HFD). Rapamycin given at reperfusion reduced IS in WT mice but not in STAT3-deficient mice following I/R. Moreover, cardiomyocytes isolated from HFD-fed WT mice showed resistance against necrosis (trypan blue staining) and apoptosis (TUNEL assay) when treated with rapamycin during reoxygenation following simulated ischemia. Such protection was absent in cardiomyocytes from HFD-fed STAT3-deficient mice. STAT3 signaling plays critical role in reducing IS and attenuates cardiomyocyte death following reperfusion therapy with rapamycin in diabetic heart.

  19. Protective effect of dietary n-3 polyunsaturated fatty acids on myocardial resistance to ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Zeghichi-Hamri, Sabrina; de Lorgeril, Michel; Salen, Patricia; Chibane, Mohamed; de Leiris, Joël; Boucher, François; Laporte, François

    2010-12-01

    Dietary n-3 polyunsaturated fatty acids (PUFA) reduce coronary heart disease (CHD) complications, such as chronic arrhythmia and sudden cardiac death. Improved myocardial resistance to ischemia-reperfusion injury results in smaller myocardial infarction, which is a major factor in the occurrence of CHD complications. We hypothesized that a specific dietary fatty acid profile (low in saturated and n-6 PUFA but high in plant and marine n-3 PUFA) may improve myocardial resistance to ischemia-reperfusion injury and reduce infarct size. To test this assumption, we used a well-defined rat model of myocardial infarction. Based on our results, in comparison to a diet that is high in either saturated or n-6 PUFA but poor in plant and marine n-3 PUFA, a diet that is low in saturated fats and n-6 PUFA but rich in plant and marine n-3 PUFA results in smaller myocardial infarct size (P fatty acid composition of plasma, erythrocyte cell membranes, and the phospholipids of myocardial mitochondria. The results show a great accumulation of n-3 PUFA and a parallel decrease in arachidonic acid, the main n-6 PUFA, in plasma, cell membranes, and cardiac mitochondria (P < .0001). We conclude that improved myocardial resistance to ischemia-reperfusion may be one of the critical factors explaining the protective effects of dietary n-3 PUFA against CHD complications in humans. In addition to increasing n-3 PUFA intake, an optimal dietary pattern aimed at reducing cardiovascular mortality should include a reduction of the intake of both saturated and n-6 PUFA.

  20. Etanercept protects myocutaneous flaps from ischaemia reperfusion injury: An experimental study in a rat tram flap model.

    Science.gov (United States)

    Ersoy, Burak; Çevik, Özge; Çilingir, Özlem Tuğçe

    2016-08-01

    Background Being an inevitable component of free tissue transfer, ischemia-reperfusion injury tends to contribute to flap failure. TNF-α is an important proinflammatory cytokine and a prominent mediator of the ischemia-reperfusion injury. Etanercept, a soluble TNF-α binding protein, has shown anti-inflammatory and anti-apoptotic effects in animal models of renal and myocardial ischemia-reperfusion injury. We have designed an experimental study to investigate the effect of etanercept on myocutaneous ischemia-reperfusion injury on transverse rectus abdominis myocutaneous flap model in rats. Methods Twenty-four male Sprague-Dawley rats were divided into 3 groups: In group 1 (sham), the TRAM flap was raised and sutured back without further intervention. In group 2 (control), the flap was raised and the ischemia-reperfusion protocol was followed. In group 3, etanercept (10 mg/kg, i.v.) was administered 10 minutes before reperfusion. At the end of the reperfusion period, biochemical and histolopathological evaluations were performed on serum and tissue samples. Results In the etanercept group the IMA and 8-OHdG levels (p = 0.005 and p = 0.004, respectively) were found significantly lower, and the GSH and SOD levels (p = 0.01 and p ischemia-reperfusion injury in skeletal muscle tissue, enhancing the TRAM flap viability. The ability of etanercept to induce ischemic tolerance suggests that it may be applicable in free-flap surgery.

  1. Protective effects of Rosa canina L fruit extracts on renal disturbances induced by reperfusion injury in rats.

    Science.gov (United States)

    Changizi Ashtiyani, Saeed; Najafi, Houshang; Jalalvandi, Sepeideh; Hosseinei, Fatemeh

    2013-07-01

    This study aimed to investigate the effects of Rosa canina L fruit extracts on histological damages, oxidative stress, and functional disturbances induced by bilateral renal ischemia and reperfusion. Ischemia and reperfusion were induced on the kidneys of anesthetized male Sprague-Dawley rats. The rats in the reperfusion and Rosa canina groups were administered extract solvent and Rosa canina extract, respectively. In addition, in the sham group, surgery was done without ischemia. In the last 6 hours of the reperfusion period, urine sample were collected using metabolic cage and at the end of this period, blood samples were taken from the descending aorta. The kidney tissues were collected and subjected to microscopic study for histological damages, while oxidative stress was measured by determining malondialdehyde and ferric reducing/antioxidant power levels. The comparison between the reperfusion and sham groups indicated reductions in creatinine clearance, absolute excretion of potassium, urine osmilarity, and increase in absolute excretion of sodium in the reperfusion group. These changes were less pronounced with Rosa canina fruit extract. In addition, blood creatinine and urea concentrations which increased in the reperfusion group, were significantly lower in the Rosa canina group. In this group, the degree of histological damages and the level of malondialdehyde were lower than the reperfusion group, while ferric reducing/antioxidant power level was significantly higher. The findings of this study showed that Rosa canina fruit extract possesses protective effects against kidney function disturbances, oxidative stress, and histological damages.

  2. Role of Kupffer cells in reperfusion injury in fat-loaded livers from ethanol-treated rats.

    Science.gov (United States)

    Zhong, Z; Connor, H D; Mason, R P; Qu, W; Gao, W; Lemasters, J J; Thurman, R G

    1995-12-01

    Reperfusion injury was studied in blood-free perfused livers from fat-loaded, ethanol-treated rats. Rats were pair-fed a modified Lieber-DeCarli liquid diet containing 36% calories as ethanol or isocaloric maltose-dextrin for 4 to 5 weeks. Reperfusion injury to the liver, which occurs in previously hypoxic regions upon reintroduction of oxygen, was studied in a low-flow, reflow perfusion model. Lactate dehydrogenase in effluent perfusate increased from basal levels of < 1 to 17 IU/g/h in livers from controls, whereas prior alcohol treatment elevated values to 37 IU/g/h. Pretreatment of rats with gadolinium chloride (GdCl3, 20 mg/kg i.v.), a selective Kupffer cell toxicant, minimized lactate dehydrogenase release during reperfusion to 7 to 8 IU/g/h in livers from both groups. Rates of malondialdehyde production were 144 and 166 nmol/g/h during reperfusion in control and alcohol-treated rats, respectively, but values reached only 54 and 79 nmol/g/h after GdCl3 treatment. Interestingly, a typical PBN/carbon-centered free radical adduct signal was detected in bile of livers from ethanol-treated rats, but not in controls or ethanol-treated rats given GdCl3. Portal pressure increased during the reperfusion period in livers from alcohol-treated rats, although not in controls, and GdCl3 reduced it significantly. Taken together, these data indicate that reperfusion injury is greater in fatty livers from alcohol-treated rats in a blood-free model. Inactivation of Kupffer cells minimized reperfusion injury in both control and alcohol-treated rats, most likely by diminishing lipid peroxidation thereby improving hepatic microcirculation.

  3. Effects of dexmedetomidine in conjunction with remote ischemic preconditioning on renal ischemia–reperfusion injury in rats

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    Emine Bagcik

    2014-12-01

    Full Text Available Background and objectives: The aim of this study was to evaluate the effects of remote ischemic preconditioning by brief ischemia of unilateral hind limb when combined with dexmedetomidine on renal ischemia-reperfusion injury by histopathology and active caspase-3 immunoreactivity in rats. Methods: 28 Wistar albino male rats were divided into 4 groups. Group I (Sham, n = 7: Laparotomy and renal pedicle dissection were performed at 65th minute of anesthesia and the rats were observed under anesthesia for 130min. Group II (ischemia-reperfusion, n = 7: At 65th minute of anesthesia bilateral renal pedicles were clamped. After 60 min ischemia 24 h of reperfusion was performed. Group III (ischemia-reperfusion + dexmedetomidine, n = 7: At the fifth minute of reperfusion (100 μg/kg intra-peritoneal dexmedetomidine was administered with ischemia-reperfusion group. Reperfusion lasted 24 h. Group IV (ischemia-reperfusion + remote ischemic preconditioning + dexmedetomidine, n = 7: After laparotomy, three cycles of ischemic preconditioning (10 min ischemia and 10 min reperfusion were applied to the left hind limb and after 5 min with group III. Results: Histopathological injury scores and active caspase-3 immunoreactivity were significantly lower in the Sham group compared to the other groups. Histopathological injury scores in groups III and IV were significantly lower than group II (p = 0.03 and p = 0.05. Active caspase-3 immunoreactivity was significantly lower in the group IV than group II (p = 0.01 and there was no significant difference between group II and group III (p = 0.06. Conclusions: Pharmacologic conditioning with dexmedetomidine and remote ischemic preconditioning when combined with dexmedetomidine significantly decreases renal ischemia- reperfusion injury histomorphologically. Combined use of two methods prevents apoptosis via active caspase-3.

  4. Role of mucus in ischemia/reperfusion-induced gastric mucosal injury in rats.

    Science.gov (United States)

    Mojzis, J; Hegedüsová, R; Mirossay, L

    2000-01-01

    Gastric mucus plays an important role in gastric mucosal protection. Apart from its "barrier" function, it has been demonstrated that mucus protects gastric epithelial cells against toxic oxygen metabolites derived from the xanthine/ xanthine oxidase system. In this study, we investigated the effect of malotilate and sucralfate (mucus production stimulators) and N-acetylcysteine (mucolytic agent) on ischemia/reperfusion-induced gastric mucosal injury. Gastric ischemia was induced by 30 min clamping of the coeliac artery followed by 30 min of reperfusion. The mucus content was determined by the Alcian blue method. Sucralfate (100 mg/kg), malotilate (100 mg/kg), and N-acetylcysteine (100 mg/kg) were given orally 30 min before surgery. Both sucralfate and malotilate increased the mucus production in control rats. On the other hand, N-acetyloysteine significantly decreased mucus content in control (sham) group. A significant decrease of mucus content was found in the control and the N-acetylcysteine pretreated group during the period of ischemia. On the other hand, sucralfate and malotilate prevented the decrease the content of mucus during ischemia. A similar result can be seen after ischemia/reperfusion. In the control group and N-acetylcysteine pretreated group a significant decrease of adherent mucus content was found. However, sucralfate and malotilate increased mucus production (sucralfate significantly). Sucralfate and malotilate also significantly protected the gastric mucosa against ischemia/reperfusion-induced injury. However, N-acetylcysteine significantly increased gastric mucosal injury after ischemia/reperfusion. These results suggest that gastric mucus may be involved in the protection of gastric mucosa after ischemia/reperfusion.

  5. Deguelin attenuates reperfusion injury and improves outcome after orthotopic lung transplantation in the rat.

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    Patrick Paulus

    Full Text Available The main goal of adequate organ preservation is to avoid further cellular metabolism during the phase of ischemia. However, modern preservation solutions do rarely achieve this target. In donor organs hypoxia and ischemia induce a broad spectrum of pathologic molecular mechanisms favoring primary graft dysfunction (PGD after transplantation. Increased hypoxia-induced transcriptional activity leads to increased vascular permeability which in turn is the soil of a reperfusion edema and the enhancement of a pro-inflammatory response in the graft after reperfusion. We hypothesize that inhibition of the respiration chain in mitochondria and thus inhibition of the hypoxia induced mechanisms might reduce reperfusion edema and consecutively improve survival in vivo. In this study we demonstrate that the rotenoid Deguelin reduces the expression of hypoxia induced target genes, and especially VEGF-A, dose-dependently in hypoxic human lung derived cells. Furthermore, Deguelin significantly suppresses the mRNA expression of the HIF target genes VEGF-A, the pro-inflammatory CXCR4 and ICAM-1 in ischemic lungs vs. control lungs. After lung transplantation, the VEGF-A induced reperfusion-edema is significantly lower in Deguelin-treated animals than in controls. Deguelin-treated rats exhibit a significantly increased survival-rate after transplantation. Additionally, a downregulation of the pro-inflammatory molecules ICAM-1 and CXCR4 and an increase in the recruitment of immunomodulatory monocytes (CD163+ and CD68+ to the transplanted organ involving the IL4 pathway was observed. Therefore, we conclude that ischemic periods preceding reperfusion are mainly responsible for the increased vascular permeability via upregulation of VEGF. Together with this, the resulting endothelial dysfunction also enhances inflammation and consequently lung dysfunction. Deguelin significantly decreases a VEGF-A induced reperfusion edema, induces the recruitment of immunomodulatory

  6. Effects of vagus nerve stimulation on cognitive functioning in rats with cerebral ischemia reperfusion

    OpenAIRE

    Liu, Ai-Fen; Zhao, Feng-bo; Wang, Jing; Lu, Yi-Fan; Tian, Jian; Zhao, Yin; Gao, Yan; Hu, Xia-jun; LIU, XIAO-YAN; Tan, Jie; Tian, Yun-li; Shi, Jing

    2016-01-01

    Background Vagus nerve stimulation (VNS) has become the most common non-pharmacological treatment for intractable drug-resistant epilepsy. However, the contribution of VNS to neurological rehabilitation following stroke has not been thoroughly examined. Therefore, we investigated the specific role of acute VNS in the recovery of cognitive functioning and the possible mechanisms involved using a cerebral ischemia/reperfusion (I/R) injury model in rats. Methods The I/R-related injury was modele...

  7. Protective Effects and Mechanism of Puerarin on Learning-Memory Disorder after Global Cerebral Ischemia-Reperfusion Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    WU Hai-qin; GUO He-na; WANG Hu-qing; CHANG Ming-ze; ZHANG Gui-lian; ZHAO Ying-xian

    2009-01-01

    Objective: To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats, and to explore its mechanism of action. Methods: The global cerebral ischemia-reperfusion injury model was established using the modified Pulsinelli four-vessel occlusion in Sprague-Dawley rats. Rats were intraperitoneally injected with puerarin (100 mg/kg) 1 h before ischemia and once every 6 h afterwards. The learning-memory ability was evaluated by the passive avoidance test. The dynamic changes of the cell counts of apoptosis and positive expression of Bcl-2 in the hippocampus CA1 region were determined by the TUNEL and immunohistochemical methods, respectively. Results: (1) Compared with the reperfusion group, the step through latency (STL) in the passive avoidance test in the puerarin group was prolonged significantly (P<0.01). (2) The apoptotic neurons were injured most severely on the 3rd day in the hippocampal CA1 region after global ischemia and reperfusion. In the pueradn group, the number of apoptotic cells decreased at respective time points after ischemia-reperfusion (P<0.01). (3) The level of positive expression of Bcl-2 varied according to the duration of reperfusion and the peak level occurred on day 1 in the hippocampal CA1 region after global cerebral ischemia. Compared with the reperfusion group, the expression of Bcl-2 in the pueradn group was up-regulated at the respective time points after ischemia raperfusion (P<0.01), reaching the peak on day 1. Conclusions: Puerarin could improve the learning-memory ability after global cerebral ischemia and reperfusion in rats. The protective mechanism might be related to the effect of inhibiting or delaying the cell apoptosis through up-regulating the expression of Bcl-2 after ischemia and reperfusion.

  8. EFFECTS OF NITRIC OXIDE ON REPERFUSION INJURY FOLLOWING PANCREATICODUODENAL TRANSPLANTATION IN RATS

    Institute of Scientific and Technical Information of China (English)

    Chun-hui Yuan; Yong-feng Liu; Jian Liang; Ning Zhao; San-guang He

    2005-01-01

    Objective To investigate the effects of nitric oxide (NO) on reperfusion injury following pancreaticoduodenal transplantation in rats.Methods The homologous male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was used. The L-arginine (L-Arg) group received intravenous injection of L-Arg 5 minutes before and after reperfusion at a dose of 200 mg/kg while the N-Nitro-L-Arginine methyl ester (L-NAME) group received intravenous injection of L-NAME at a dose of 10mg/kg, and control group received saline. The amount of NO in the pancreas graft was measured. Serum concentration of cytokine-induced neutrophil chemoattractant (CINC) determined by enzyme-linked immunosorbant assay,expression of CINC mRNA detected by Northern blot assay, and myeloperoxidase (MPO) activity in the pancreas graft were measured. Histological observation was performed.Results The amount of NO in the L-Arg group was higher than in the control group, while in the L-NAME group was lower than in the control group (P < 0.05). The peak of serum CINC concentration occurred 3 hours after reperfusion with significant difference among groups. Expression peak of CINC mRNA in the pancreas graft occurred 3 hours after reperfusion.The expression level in the L-Arg group was lower than in the control group, the L-NAME group was higher than control group (P < 0.05). MPO activity in the L-Arg group obviously decreasd compared with other groups. The pancreas inflammation was ameliorated in L-Arg group, and pancreas damage was aggravated in L-NAME group.Conclusions L-Arg can increase the amount of NO and inhibit the elevation of CINC, CINC mRNA expression, and early neutrophil accumulation in the transplanted pancreas. NO has protective effects on the ischemia/reperfusion injury of pancreaticoduodenal transplantation.

  9. Intestinal ischemia/reperfusion induces bronchial hyperreactivity and increases serum TNF-alpha in rats

    Directory of Open Access Journals (Sweden)

    Arruda Marcio Jose Cristiano de

    2006-01-01

    Full Text Available INTRODUCTION: Intestinal or hepatic ischemia/reperfusion induces acute lung injury in animal models of multiple organ failure. Tumor necrosis factor (TNF- alpha is involved in the underlying inflammatory mechanism of acute respiratory distress syndrome. Although the inflammatory cascade leading to acute respiratory distress syndrome has been extensively investigated, the mechanical components of acute respiratory distress syndrome are not fully understood. Our hypothesis is that splanchnic ischemia/reperfusion increases airway reactivity and serum TNF-alpha levels. OBJECTIVE: To assess bronchial smooth muscle reactivity under methacholine stimulation, and to measure serum TNF-alpha levels following intestinal and/or hepatic ischemia/reperfusion in rats. METHOD: Rats were subjected to 45 minutes of intestinal ischemia, or 20 minutes of hepatic ischemia, or to both (double ischemia, or sham procedures (control, followed by 120 minutes of reperfusion. The animals were then sacrificed, and the bronchial response to increasing methacholine molar concentrations (10-7 to 3 x 10-4 was evaluated in an ex-vivo bronchial muscle preparation. Serum TNF-alpha was determined by the L929-cell bioassay. RESULTS: Bronchial response (g/100 mg tissue showed increased reactivity to increasing methacholine concentrations in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. Similarly, serum TNF-alpha (pg/mL concentration was increased in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. CONCLUSION: Intestinal ischemia, either isolated or associated with hepatic ischemia, increased bronchial smooth muscle reactivity, suggesting a possible role for bronchial constriction in respiratory dysfunction following splanchnic ischemia/reperfusion. This increase occurred in concomitance with serum TNF-alpha increase, but whether the increase in TNF-alpha caused this bronchial contractility remains

  10. Gene expression profile in rat small intestinal allografts after cold preservation/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Shu-Feng Wang; Qi Liang; Guo-Wei Li; Kun Gao

    2005-01-01

    AIM: To determine the changes of gene expression profile in small intestinal allografts in rats after cold preservation/reperfusion, and to identify the genes relevant to cold preservation/reperfusion injury.METHODS: Heterotopic segmental small bowel transplantation was performed in six rats with a sham operation and they were used as controls. Total RNA was extracted from the allografts (experimental group) and normal intestines (control group) 1 h after cold preservation/reperfusion, and then purified to mRNA, which was then reversely transcribed to cDNA, and labeled with fluorescent Cy5-dUTP and Cy3-dUTP to prepare hybridization probes.The mixed probes were hybridized to the cDNA microarray.After high-stringent washing, the fluorescent signals on cDNA microarray chip werescanned and analyzed.RESULTS: Among the 4 096 target genes, 82 differentially expressed genes were identified between the two groups.There were 18 novel genes, 33 expression sequence tags,and 31 previously reported genes. The selected genes may be divided into four classes: genes modulating cellular adhesion, genes regulating cellular energy, glucose and protein metabolism, early response genes and other genes.CONCLUSION: A total of 82 genes that may be relevant to cold preservation/reperfusion injury in small intestinal allografts are identified. Abnormal adhesion between polymorphonuclears and endothelia and failure in energy,glucose and protein metabolism of the grafts may contribute to preservation/reperfusion injury. The functions of the novel genes identified in our study need to be darified further.

  11. Effect of lidocaine on retinal aquaporin-4 expression after ischemia/reperfusion injury in the rat

    Institute of Scientific and Technical Information of China (English)

    Liying He; Li Li

    2008-01-01

    BACKGROUND: Several studies have demonstrated that high doses of lidocaine can reduce edema in rats with brain injury by down-regulating aquaporin-4 (AQP4) expression. The hypothesis for the present study is that lidocaine could retinal edema that is associated with AQP4 expression.OBJECTIVE: This study was designed to investigate the interventional effects of lidocaine on retinal AQP4 expression and retinal edema following ischemia/reperfusion injury in the rat.DESIGN, TIME AND SETTING: This study, a randomized, controlled, animal experiment, was performed at the Basic Research Institute, Chongqing Medical University from September 2006 to May 2007.MATERIALS: Seventy-five, healthy, adult, female, Sprague-Dawley rats were included. A total of 50 rats were used to establish a retinal ischemia/reperfusion injury model using an anterior chamber enhancing perfusion unit. Rabbit anti-rat AQP4 antibody was purchased from Santa Cruz Biotechnology, USA.METHODS: All 75 rats were randomly divided into three groups, with 25 rats in each: control, model, and lidocaine. At each time point (1, 6, 12, 24, and 48 hours after modeling, five rats for each time point), each rat in the lidocaine group was intraperitoneally administered lidocaine with an initial dose of 30 mg/kg, followed by subsequent doses of 15 mg/kg every six hours. The entire treatment process lasted three days for each rat. At each above-mentioned time point, rats in the model group were modeled, but not administered any substances. Rats in the control group received the same treatments as in the lidocaine group except that lidocaine was replaceld by physiological saline.MAIN OUTCOME MEASURES: Following hematoxylin-eosin staining, rat retinal tissue was observed to investigate retinal edema degree through the use of an optical microscope and transmission electron microscope. Retinal AQP4 expression was determined by immunohistochemistry.RESULTS: At each above-mentioned time point, AQP4 expression was

  12. Inhibition of classical complement activation attenuates liver ischaemia and reperfusion injury in a rat model.

    Science.gov (United States)

    Heijnen, B H M; Straatsburg, I H; Padilla, N D; Van Mierlo, G J; Hack, C E; Van Gulik, T M

    2006-01-01

    Activation of the complement system contributes to the pathogenesis of ischaemia/reperfusion (I/R) injury. We evaluated inhibition of the classical pathway of complement using C1-inhibitor (C1-inh) in a model of 70% partial liver I/R injury in male Wistar rats (n = 35). C1-inh was administered at 100, 200 or 400 IU/kg bodyweight, 5 min before 60 min ischaemia (pre-I) or 5 min before 24 h reperfusion (end-I). One hundred IU/kg bodyweight significantly reduced the increase of plasma levels of activated C4 as compared to albumin-treated control rats and attenuated the increase of alanine aminotransferase (ALT). These effects were not better with higher doses of C1-inh. Administration of C1-inh pre-I resulted in lower ALT levels and higher bile secretion after 24 h of reperfusion than administration at end-I. Immunohistochemical assessment indicated that activated C3, the membrane attack complex C5b9 and C-reactive protein (CRP) colocalized in hepatocytes within midzonal areas, suggesting CRP is a mediator of I/R-induced, classical complement activation in rats. Pre-ischaemic administration of C1-inh is an effective pharmacological intervention to protect against liver I/R injury.

  13. Influence of ulinastatin on myocardial enzyme spectrum, inflammatory state and reperfusion injury of patients with extracorporeal circulation heart operation

    Institute of Scientific and Technical Information of China (English)

    Ming-Bin Deng; Ju-Yi Wan; Yi-Bing Fang

    2016-01-01

    Objective:To study the influence of ulinastatin on the myocardial enzymes, the inflammatory state and the reperfusion injury of patients with cardiopulmonary bypass.Methods:A total of 60 patients with extracorporeal circulation heart operation in our hospital from September 2012 to August 2015 were taken as research objects. 60 patients were randomly divided into two groups: observation group (conventional surgery group with ulinastatin, 30 cases) and control group (conventional surgery group, 30 cases), and then detected and compared the related indicators of serum cardiac enzymes, inflammatory state and ischemia-reperfusion injury of two test groups at 12 h, 24 h, 72 h after operation.Results:The serum myocardial zymogram of the observation group at 12 h, 24 h and 72 h after the operation were all lower than those of the control group. Meanwhile, the inflammatory indexes and the reperfusion injury indexes of the observation group were also better than those of the control group. The test result of two groups had significant differences.Conclusions: Ulinastatin can effectively improve the myocardial enzyme spectrum and the inflammatory state of patients with extracorporeal circulation heart operation. Besides, ulinastatin is also plays active role in the prevention of reperfusion injury.

  14. Anti-apoptotic, anti-oxidant, and anti-inflammatory effects of thalidomide on cerebral ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Palencia, Guadalupe; Medrano, Juan Ángel Núñez-; Ortiz-Plata, Alma; Farfán, Dolores Jiménez; Sotelo, Julio; Sánchez, Aurora; Trejo-Solís, Cristina

    2015-04-15

    Thalidomide has shown protective effects in different models of ischemia/reperfusion damage. To elucidate the mechanisms of such protection, this study assessed the effects of thalidomide on the oxidative stress and inflammatory response induced by ischemia/reperfusion episodes in rats. Rats underwent middle cerebral artery occlusion (MCAO) for 2hours. All animals were sacrificed after different reperfusion times. Rats were administered either DMSO or thalidomide (20mg/kg (i.p.)) at different times before or during reperfusion: 1) 1h before reperfusion; the infarct area was measured 2h after reperfusion. 2) 10min before reperfusion and 80min after reperfusion; the infarct area was measured 24h after reperfusion; and 3) 10min before reperfusion and 1h, 24h, 48h, and 68h after reperfusion; the infarct area was measured 72h after reperfusion. Thalidomide reduced the infarct area 24h and 72h after MCAO, and decreased the neurological deficit in all groups with respect to controls. Thalidomide also lowered significantly the number of TUNEL-positive cells, levels of Bax, caspase-3, lipoperoxidation, and pro-inflammatory cytokines, and increased the levels of SOD1, Bcl-2 and pAkt. These results show that thalidomide has neuroprotective effects, apparently due to its anti-apoptotic, anti-oxidant, and anti-inflammatory effects.

  15. Effects of Ethyl Pyruvate on Myocardial Apoptosis and Expression of Bcl-2 and Bax Proteins after Ischemia-reperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    Jialong GUO; Kailun ZHANG; Yanmei JI; Xionggang JIANG; Shunqing ZUO

    2008-01-01

    In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemia/reperfusion (I/R) in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendorff model. Twenty-four rats were randomly divided into 3 groups (n=8 in each group): control group was perfused for 120min. In the I/R group, after 30min stabilization the injury was induced by 30min global ischemia followed by 60min reperfusion. Ethyl pyruvate (EP) group was set up with the same protocol as I/R group except that it was supplied with 2mmol/L EP 15min before ischemia and throughout reperfusion. Myocardial malonaldehyde (MDA) content Was measured. Myocardial apoptotic index (AI) was tested by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in cardiac myocytes was detected by immunohistochemistry. As compared with control group, the content of MDA, myocardial AI and the expression of Bcl-2, Bax proteins were increased significantly in I/R group, but the content of MDA, myocardial AI and the expression of Bax protein were decreased obviously and the expression of Bcl-2 protein was up-regulated in EP group (P<0.05). These results demonstrate that EP could inhibit apoptosis of cardiac myocytes possibly via alleviating oxidative stress, up-regulating Bcl-2 and down-regulating Bax proteins.

  16. Hypothermic protection in rat focal ischemia models: strain differences and relevance to "reperfusion injury".

    Science.gov (United States)

    Ren, Yubo; Hashimoto, Megumi; Pulsinelli, William A; Nowak, Thaddeus S

    2004-01-01

    Hypothermic protection was compared in Long-Evans and spontaneously hypertensive rat (SHR) strains using transient focal ischemia, and in Wistar and SHR strains using permanent focal ischemia. Focal ischemia was produced by distal surgical occlusion of the middle cerebral artery and tandem occlusion of the ipsilateral common carotid artery (MCA/CCAO). Moderate hypothermia of 2 hours' duration was produced by systemic cooling to 32 degrees C, with further cooling of the brain achieved by reducing to 30 degrees C the temperature of the saline drip superfusing the exposed occlusion site. Infarct volume was determined from serial hematoxylin and eosin-stained frozen sections obtained routinely at 24 hours, or in some cases after 3 days' survival. In the SHR, moderate hypothermia was only effective when initiated before recirculation after a 90-minute occlusion period. In contrast, the same intervention was strikingly effective in the Long-Evans rat even when initiated after as long as 30-minute reperfusion after a 3-hour occlusion. This magnitude and duration of cooling was not protective in permanent MCA/CCAO in the SHR, but such transient hypothermia did effectively reduce infarct volume after permanent occlusions in Wistar rats. These results show striking differences in the temporal window for hypothermic protection among rat focal ischemia models. As expected, "reperfusion injury" in the Long-Evans strain is particularly responsive to delayed cooling. The finding that the SHR can be protected by hypothermia initiated immediately before recirculation suggests a rapidly evolving component of injury occurs subsequent to reperfusion in this model as well. Hypothermic protection after permanent occlusion in Wistar rats identifies a transient, temperature-sensitive phase of infarct evolution that is not evident in the unreperfused SHR. These observations confirm that distinct mechanisms can underlie the temporal progression of injury in rat stroke models, and emphasize

  17. Heart fatty acid binding protein and myoglobin after reperfusion of acute myocardial infarction.

    Science.gov (United States)

    Ozdemir, Murat; Durakoğlugil, Emre; Gülbahar, Ozlem; Turkoglu, Sedat; Sancak, Banu; Paşaoğlu, Hatice; Cengel, Atiye

    2007-10-01

    The aim of this study was to disclose the release kinetics of heart fatty acid binding protein (HFABP) and myoglobin in acute myocardial infarction (AMI) reperfused by primary percutaneous coronary intervention (PPCI) and to determine the influence of the quality of coronary flow post PPCI on the release properties of these markers. Twenty-four patients with AMI who underwent successful PPCI and had no evidence of reocclusion within the first 120 minutes were studied. Serum myoglobin and HFABP levels at baseline and at 15, 30, 45, 60, 90 and 120 minutes after reperfusion were measured. Corrected TIMI frame count (CTFC) in the relevant vessel post PPCI was used to categorize patients in group I (CTFC > 21) and group 2 (CTFC < or = 21). Biomarker ratios at each sampling point were calculated by dividing the serum level of the biomarker at the specific sampling time by its baseline level. Baseline myoglobin and HFABP levels rose significantly at 15 minutes (153 +/- 251.5 microg/L vs. 904.3 +/- 542.6 microg/L, 10.9 +/- 8 microg/L vs. 17.8 +/- 9.1 microg/L, both P < 0.0001) after successful PPCI. Group 2 patients tended to have higher biomarker ratios at each time point as compared to group I. Successful PPCI for AMI results in a significant increase of both HFABP and myoglobin levels within 15 minutes of vessel opening and the quality of flow in the infarction-related artery post PCI as evaluated by CTFC does not influence the release kinetics of these biomarkers.

  18. Change and role of heme oxygenase-1 in injured lungs following limb ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    周君琳; 朱晓光; 林源; 凌亦凌; 邵新中; 张桂生

    2004-01-01

    Objective: To study the change and role of hemeoxygenase-1 (HO-1) in injured lungs following limbischemia/reperfusion in rats.Methods: A total of 96 healthy male Sprague-Dawley rats, weighing 250-300 g, were used in this study. Hind limb ischemia was made on 40 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, then limb reperfusion for 0, 4, 8,16 and 24 hours(n =8 in each time point)was performed, respectively. Other 8 rats undergoing full surgical operation including isolation of the infrarenal aorta without occlusion were taken as the sham operation group. Lung tissues were obtained from the 48animals and Northern blotting and Western blotting were employed to measure the changes of HO-1 mRNA and protein expression, respectively. Immunohistochemistry technique was used to determine the cell types responsible for HO-1 expression after limb ischemia/reperfusion. Then hind limb ischemia was made on other 12 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, among whom, 6 rats were given zinc protoporphyrin (ZnPP), an inhibitor of HO. Then limb reperfusion for 16 hours was performed on all the 12 rats.And other 12 rats underwent full surgical operation including isolation of the infrarenal aorta without occlusion,among whom, 6 rats were then given ZnPP. Then lung tissues were obtained from the 24 animals and lung injury markers, lung histology, polymorphonuclear leukocyte (PMN) count and malondialdehyde (MDA) content were detected, respectively. HO activity was determined through measuring the carboxyhemoglobin (COHb) level in artery blood with a CO-oximeter after limb ischemia/reperfusion.And the animal mortality was observed on the other 24rats.Results: Northern blotting analysis showed that HO-1mRNA increased significantly at 4 hours after reperfusion,peaked at 16 hours, and began to decrease at 24 hours. In contrast, no positive signal was observed in the sham and simple ischemia animals. Increased HO

  19. Effect of propofol pretreatment on apoptosis in rat brain cortex after focal cerebral ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Haiyan Xu; Chengwei Zhang; Chunxiao Zhang

    2011-01-01

    The present study aimed to observe cortical expression of Bcl-2 and Bax, cysteine-dependent aspartate directed proteases-3 activity and apoptotic cell death in a rat model of middle cerebral artery occlusion pretreated with propofol. Results showed that, propofol pretreatment significantly reduced oxidative stress levels and attenuated neuronal apoptosis in the cortex of rats. Propofol pretreatment upregulated Bcl-2 expression, and downregulated Bax expression and cysteine-dependent aspartate directed proteases-3 activity. These findings indicate that propofol pretreatment inhibits cell apoptosis during focal cerebral ischemia/reperfusion injury. This neuroprotective effect is most likely achieved through the Bcl-2/Bax/cysteine-dependent aspartate directed proteases-3 pathway.

  20. Insulin Reduces Cerebral Ischemia/Reperfusion Injury in the Hippocampus of Diabetic Rats

    OpenAIRE

    Collino, Massimo; Aragno, Manuela; Castiglia, Sara; Tomasinelli, Chiara; Thiemermann, Christoph; Boccuzzi, Giuseppe; Fantozzi, Roberto

    2009-01-01

    OBJECTIVE—There is evidence that insulin reduces brain injury evoked by ischemia/reperfusion (I/R). However, the molecular mechanisms underlying the protective effects of insulin remain unknown. Insulin is a well-known inhibitor of glycogen synthase kinase-3β (GSK-3β). Here, we investigate the role of GSK-3β inhibition on I/R-induced cerebral injury in a rat model of insulinopenic diabetes. RESEARCH DESIGN AND METHODS—Rats with streptozotocin-induced diabetes were subjected to 30-min occlusio...

  1. Total salvianolic acid improves ischemia-reperfusion-induced microcirculatory disturbance in rat mesentery

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the effect of total salvianolic acid(TSA) on ischemia-reperfusion(I/R)-induced rat mesenteric microcirculatory dysfunctions.METHODS:Male Wistar rats were randomly distributed into 5 groups(n = 6 each):Sham group and I/R group(infused with saline),TSA group,TSA + I/R group and I/R + TSA group(infused with TSA,5 mg/kg per hour).Mesenteric I/R were conducted by a ligation of the mesenteric artery and vein(10 min) and subsequent release of the occlusion.TSA was continuously infused either sta...

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

    Directory of Open Access Journals (Sweden)

    Jakub Bukowczan

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

  3. Low Frequency Electromagnetic Field Conditioning Protects against I/R Injury and Contractile Dysfunction in the Isolated Rat Heart.

    Science.gov (United States)

    Bialy, Dariusz; Wawrzynska, Magdalena; Bil-Lula, Iwona; Krzywonos-Zawadzka, Anna; Wozniak, Mieczyslaw; Cadete, Virgilio J J; Sawicki, Grzegorz

    2015-01-01

    Low frequency electromagnetic field (LF-EMF) decreases the formation of reactive oxygen species, which are key mediators of ischemia/reperfusion (I/R) injury. Therefore, we hypothesized that the LF-EMF protects contractility of hearts subjected to I/R injury. Isolated rat hearts were subjected to 20 min of global no-flow ischemia, followed by 30 min reperfusion, in the presence or absence of LF-EMF. Coronary flow, heart rate, left ventricular developed pressure (LVDP), and rate pressure product (RPP) were determined for evaluation of heart mechanical function. The activity of cardiac matrix metalloproteinase-2 (MMP-2) and the contents of coronary effluent troponin I (TnI) and interleukin-6 (IL-6) were measured as markers of heart injury. LF-EMF prevented decreased RPP in I/R hearts, while having no effect on coronary flow. In addition, hearts subjected to I/R exhibited significantly increased LVDP when subjected to LF-EMF. Although TnI and IL-6 levels were increased in I/R hearts, their levels returned to baseline aerobic levels in I/R hearts subjected to LF-EMF. The reduced activity of MMP-2 in I/R hearts was reversed in hearts subjected to LF-EMF. The data presented here indicate that acute exposure to LF-EMF protects mechanical function of I/R hearts and reduces I/R injury.

  4. Low Frequency Electromagnetic Field Conditioning Protects against I/R Injury and Contractile Dysfunction in the Isolated Rat Heart

    Directory of Open Access Journals (Sweden)

    Dariusz Bialy

    2015-01-01

    Full Text Available Low frequency electromagnetic field (LF-EMF decreases the formation of reactive oxygen species, which are key mediators of ischemia/reperfusion (I/R injury. Therefore, we hypothesized that the LF-EMF protects contractility of hearts subjected to I/R injury. Isolated rat hearts were subjected to 20 min of global no-flow ischemia, followed by 30 min reperfusion, in the presence or absence of LF-EMF. Coronary flow, heart rate, left ventricular developed pressure (LVDP, and rate pressure product (RPP were determined for evaluation of heart mechanical function. The activity of cardiac matrix metalloproteinase-2 (MMP-2 and the contents of coronary effluent troponin I (TnI and interleukin-6 (IL-6 were measured as markers of heart injury. LF-EMF prevented decreased RPP in I/R hearts, while having no effect on coronary flow. In addition, hearts subjected to I/R exhibited significantly increased LVDP when subjected to LF-EMF. Although TnI and IL-6 levels were increased in I/R hearts, their levels returned to baseline aerobic levels in I/R hearts subjected to LF-EMF. The reduced activity of MMP-2 in I/R hearts was reversed in hearts subjected to LF-EMF. The data presented here indicate that acute exposure to LF-EMF protects mechanical function of I/R hearts and reduces I/R injury.

  5. The effect of high intensity interval training on cardioprotection against ischemia-reperfusion injury in wistar rats.

    Science.gov (United States)

    Rahimi, Mostafa; Shekarforoush, Shahnaz; Asgari, Ali Reza; Khoshbaten, Ali; Rajabi, Hamid; Bazgir, Behzad; Mohammadi, Mohammad Taghi; Sobhani, Vahid; Shakibaee, Abolfazl

    2015-01-01

    The aims of the present study were to determine whether short term high intensity interval training (HIIT) could protect the heart against ischemia reperfusion (IR) injury; and if so, to evaluate how long the exercise-associated protection can be lasted. Sixty-three rats were randomly assigned into sedentary (n = 15), sham (n = 7), and exercise groups (n = 41). Rats in the exercise groups performed 5 consecutive days of HIIT on treadmill: 5 min warm up with 50 % VO2max, 6×2 min with 95-105 % VO2max (about 40 to 45 m/min), 5×2 min recovery with 65-75 % VO2max (about 28 to 32 m/min), and 3 min cool down with 50 % VO2max, all at 0 % grade. Animals exposed to an in vivo cardiac IR surgery, performed at days 1, 7, and 14 following the final exercise session. Ischemia-induced arrhythmias, myocardial infarct size (IS), plasma lactate dehydrogenase (LDH) and creatine kinase (CK) activities were measured in all animals. Compared to sedentary rats, exercised animals sustained less IR injury as evidenced by a lower size of infarction and lower levels of LDH and CK at day one and day 7 post exercise. In comparison of sedentary group, IS significantly decreased in EX-IR1 and EX-IR7 groups (50 and 35 %, respectively), but not in EX-IR14 group (19 %). The exercise-induced cardioprotection disappeared 14 days following exercise cessation. There were no significant changes in ischemia-induced arrhythmia between exercised and sedentary rats. The results clearly demonstrate that HIIT protects the heart against myocardial IR injury. This protective effect can be sustained for at least one week following the cessation of the training.

  6. Effect of Aiweixin on isolated rat heart during ischemia/reperfusion injury%维药爱维心对离体大鼠心肌缺血/再灌损伤作用机制研究

    Institute of Scientific and Technical Information of China (English)

    李俊红; 马丽娟; 吴燕倪; 陈勤

    2012-01-01

    目的 探讨维药爱维心在缺血/再灌(I/R)损伤过程中对大鼠离体心脏心功能、心律失常、心肌细胞活性、心肌酶及心肌细胞凋亡的保护作用及其可能的作用机制.方法 采用离体大鼠心脏Langendorff灌流模型,全心停灌30 min,再灌60 min建立I/R模型.用MedLab生物信号采集处理系统记录分析血流动力学及心律失常指标;实验结束检测心肌组织中甲臜(formazan)含量;测定再灌注各时间点心脏流出液中乳酸脱氢酶(lactate dehydrogenase,LDH)的含量;SABC免疫组织化学法检测心肌细胞凋亡指数;透射电子显微镜观察心肌超微结构的改变.结果 与对照组比较,爱维心5 mL/L处理组能够明显降低缺血/再灌引起的大鼠离体灌流心脏左心室舒张末期压力(LVEDP),增强左心室最大舒张速率(-dp/dtmax)和心脏做功(rate-pressure product,LVDP×heart rate,RPP)(P<0.01),降低I/R心肌LDH含量(P<0.01),下调凋亡指数(P<0.01),并且能降低缺血心肌细胞的线粒体损伤程度.结论 爱维心可改善离体大鼠I/R损伤心肌顺应性,保护和稳定心肌细胞膜,并有抑制心肌细胞凋亡的作用.

  7. Protective effects of Saffron hydroalcoholic extract against renal tissue damages induced by ischemia-reperfusion in rats

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    Houshang Najafi

    2014-06-01

    Full Text Available Background: The aim of this study was to investigate the protective effects of saffron hydroalcoholic extract against tissue damages induced by renal ischemia/reperfusion. Methods: In this experimental study, 40 male rats were randomly divided into 5 groups; 1. sham group which underwent surgery with no vessel occlusion and passed equivalent reperfusion period, 2. Ischemia/reperfusion group which received solvent of extract and went through surgery, bilateral renal ischemia for 30 min and 24-h reperfusion period (I/R. The other three groups underwent ischemia/reperfusion receiving saffron extracts of 5, 10 or 20 mg/kg/ip, respectively. At the end of reperfusion period, the left kidney tissue was collected and stained with hematoxylin-eosin for histological studies. Statistical analysis was performed using one-way ANOVA and Mann-Whitney tests. Results: Following ischemia/reperfusion, the size of Bowman's space increased significantly (P<0.001. In addition, cell necrosis in the tubules of the cortex and outer medulla, vascular congestion and tubular casts in the outer and inner medulla increased. However, the number of RBCs in glomerular capillaries decreased. Administration of saffron extract could significantly improve all the injuries by all three doses. Nevertheless, the effect of 20 mg dose was smaller. Conclusion: Intraperitoneal administration of saffron hydroalcoholic extract has protective effects against tissue damages induced by 30 min ischemia and 24-h reperfusion in the rat’s kidney.

  8. Effect of tetramethylpyrazine on P-selectin and hepatic/renal ischemia and reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Jin-Lian Chen; Tong Zhou; Wei-Xiong Chen; Jin-Shui Zhu; Ni-Wei Chen; Ming-Jun Zhang; Yun-Lin Wu

    2003-01-01

    AIM: To investigate the effect of tetramethylpyrazine on hepatic/renal ischemia and reperfusion injury in rats.METHODS: Hepatic/renal function, histopathological changes,and hepatic/renal P-selectin expression were studied with biochemical measurement and immunohistochemistry in hepatic/renal ischemia and reperfusion injury in rat models.RESULTS: Hepatic/renal insufficiency and histopathological damage were much less in the tetramethylpyrazine-treated group than those in the saline-treated groups. Hepatic/ renal P-selectin expression was down regulated in the tetramethylpyrazine-treated group.CONCLUSION: P-selectin might mediate neutrophil infiltration and contribute to hepatic/renal ischemia and reperfusion injury. Tetramethylpyrazine might prevent hepatic/renal damage induced by ischemia and reperfusion injury through inhibition of P-selectin.

  9. The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From in vivo Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway.

    Science.gov (United States)

    Huang, Jiannan; Li, Yi; Zhang, Juan; Liu, Yusheng; Lu, Qinghua

    2017-04-06

    Hexarelin, a synthetic growth hormone-releasing peptide, has been proven to possess cardioprotective actions through its binding to the growth hormone secretagogue receptor (GHSR) 1a and the non-GHSR receptor CD36. However, its effect on myocardial ischemia/reperfusion (I/R) injury has not been fully clarified in vivo. We aimed to determine whether hexarelin treatment could protect cardiomyocytes from I/R injury and to examine the underlying mechanisms. In vivo hearts of male SD rats underwent 30 minutes of ischemia by left coronary artery ligation followed by reperfusion. The rats were then treated subcutaneously twice daily with hexarelin [100 μg/kg·day], ghrelin [400 μg/ kg·day], or saline for 7 days. Echocardiography, malondialdehyde detection, and histochemical staining were performed after treatment. In addition, Western blot was used to examine the expression levels of IL-1β, IL-1Ra, and IL-1RI. Our study showed that hexarelin treatment improved cardiac systolic function, decreased malondialdehyde production, and increased the number of surviving cardiomyocytes. The beneficial effects of hexarelin treatment were slightly superior to those of equimolar ghrelin treatment. We meanwhile confirmed that hexarelin induced down-regulation of IL-1β expression and up-regulation of IL-1Ra expression in I/R myocardium, which could be neutralized by the GHSR antagonist [D-Lys3]-growth hormone releasing peptide-6 ([D-Lys3]-GHRP-6). These findings suggest that hexarelin protects in vivo cardiomyocytes from I/R injury partly by modification of the IL-1 signaling pathway through the activation of cardiac GHSR1a receptors.

  10. Lansoprazole ameliorates intestinal mucosal damage induced by ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Hiroshi Ichikawa; Toshikazu Yoshikawa; Norimasa Yoshida; Tomohisa Takagi; Naoya Tomatsuri; Kazuhiro Katada; Yutaka Isozaki; Kazuhiko Uchiyama; Yuji Naito; Takeshi Okanoue

    2004-01-01

    AIM: To investigate the protective effect of lansoprazole on ischemia and reperfusion (I/R)-induced rat intestinal mucosal injury in vivo.METHODS: Intestinal damage was induced by clamping both the superior mesenteric artery and the celiac trunk for 30 min followed by reperfusion in male Sprague-Dawley rats. Lansoprazole was given to rats intraperitoneally 1 h before vascular clamping.RESULTS: Both the intraluminal hemoglobin and protein levels, as indices of mucosal damage, significantly increased in I/R-groups comparion with those of shamoperation groups. These increases in intraluminal hemoglobin and protein levels were significantly inhibited by the treatment with lansoprazole at a dose of 1 mg/kg. Small intestine exposed to I/R resulted in mucosal inflammation that was characterized by significant increases in thiobarbituric acidreactive substances (TBARS), tissue-associated myeloperoxidase activity (MPO), and mucosal content of rat cytokine-induced neutrophil chemoattractant-1 (CINC-1).These increases in TBARS, MPO activities and CINC-1 content in the intestinal mucosa after I/R were all inhibited by pretreatment with lansoprazole at a dose of 1 mg/kg.Furthermore, the CINC-1 mRNA expression was increased during intestinal I/R, and this increase in mRNA expression was inhibited by treatment with lansoprazole.CONCLUSION: Lansoprazole inhibits lipid peroxidation and reduces development of intestinal mucosal inflammation induced by I/R in rats, suggesting that lansoprazole may have a therapeutic potential for I/R injury.

  11. Akt protects the heart against ischaemia-reperfusion injury by modulating mitochondrial morphology.

    Science.gov (United States)

    Ong, Sang-Bing; Hall, Andrew R; Dongworth, Rachel K; Kalkhoran, Siavash; Pyakurel, Aswin; Scorrano, Luca; Hausenloy, Derek J

    2015-03-01

    The mechanism through which the protein kinase Akt (also called PKB), protects the heart against acute ischaemia-reperfusion injury (IRI) is not clear. Here, we investigate whether Akt mediates its cardioprotective effect by modulating mitochondrial morphology. Transfection of HL-1 cardiac cells with constitutively active Akt (caAkt) changed mitochondrial morphology as evidenced by an increase in the proportion of cells displaying predominantly elongated mitochondria (73 ± 5.0 % caAkt vs 49 ± 5.8 % control: N=80 cells/group; pmitochondrial permeability transition pore (MPTP) opening (by 2.4 ± 0.5 fold; N=80 cells/group: pmitochondrial morphology, MPTP opening, and cell survival post-IRI, were demonstrated with pharmacological activation of Akt using the known cardioprotective cytokine, erythropoietin (EPO). The effect of Akt on inducing mitochondrial elongation was found to be dependent on the mitochondrial fusion protein, Mitofusin-1 (Mfn1), as ablation of Mfn1 in mouse embryonic fibroblasts (MEFs) abrogated Akt-mediated mitochondrial elongation. Finally, in vivo pre-treatment with EPO reduced myocardial infarct size (as a % of the area at risk) in adult mice subjected to IRI (26.2 ± 2.6 % with EPO vs 46.1 ± 6.5 % in control; N=7/group: pmitochondrial fragmentation observed by electron microscopy in adult murine hearts subjected to ischaemia from 5.8 ± 1.0 % to 2.2 ± 1.0 % (N=5 hearts/group; pmitochondrial morphology.

  12. Autofluorescence dynamics during reperfusion following long-term renal ischemia in a rat model

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    Raman, R N; Pivetti, C D; Matthews, D L; Troppmann, C; Demos, S G

    2008-02-08

    Optical properties of near-surface kidney tissue were monitored in order to assess response during reperfusion to long (20 minutes) versus prolonged (150 minutes) ischemia in an in vivo rat model. Specifically, autofluorescence images of the exposed surfaces of both the normal and the ischemic kidneys were acquired during both injury and reperfusion alternately under 355 nm and 266 nm excitations. The temporal profile of the emission of the injured kidney during the reperfusion phase under 355 nm excitation was normalized to that under 266 nm as a means to account for changes in tissue optical properties independent of ischemia as well as changes in the illumination/collection geometrical parameters in future clinical implementation of this technique using a hand-held probe. The scattered excitation light signal was also evaluated as a reference signal and found to be inadequate. Characteristic time constants were extracted using fit to a relaxation model and found to have larger mean values following 150 minutes of injury. The mean values were then compared with the outcome of a chronic survival study where the control kidney had been removed. Rat kidneys exhibiting longer time constants were much more likely to fail. This may lead to a method to assess kidney viability and predict its ability to recover in the initial period following transplantation or resuscitation.

  13. Cardioprotective effects of anesthetic preconditioning in rats with ischemia-reperfusion injury: propofol versus isoflurane

    Institute of Scientific and Technical Information of China (English)

    Xing TAO; Ling-qiao LU; Qing XU; Shu-ren LI; Mao-tsun LIN

    2009-01-01

    Objective: We compare the cardioprotective effects of anesthetic preconditioning by propofol and/or isoflurane in rats with ischemia-reperfusion injury. Methods: Male adult Wistar rats were subjected to 60 min of anterior descending coronary artery occlusion followed by 120 min of reperfusion. Before the long ischemia, anesthetics were administered twice for 10 min followed by 5 min washout. Isoflurane was inhaled at I MAC (0.016) in I group, whereas propofol was inhaled intravenously at 37.5 mg/(kg.h) in P group. A combination ofisoflurane and propofol was administered simultaneously in I+P group. Results: In control (without anesthetic preconditioning, C group), remarkable myocardial infarction and apoptosis accompanied by an increased level of cardiac troponin T were noted 120 rain after ischemia-reperfusion. As compared to those of control group, I and P groups had comparable cardioprotection. In addition, I+P group shares with I and P groups the comparable cardioprotective effects in terms of myocardial infarction and cardiac troponin T elevation. Conclusion: A combination of isoflurane and propofol produced no ad-ditional cardioprotection.

  14. Effect of Nigella sativa on ischemia-reperfusion induced rat kidney damage

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    Shahrzad Havakhah

    2015-12-01

    Full Text Available Objective(s:There are a few previously reported studies about the effect of Nigella sativa oil on renal ischemia-reperfusion injury (IRI. The aim of the present study was to test the hypothesis whether pre- or post-treatment with N. sativa hydroalcoholic extract (NSE would reduce tissue injury and oxidative damages in a clinically relevant rat model of renal IRI.    Materials and Methods: IRI was induced by clamping of bilateral renal arteries for 40 min fallowed by reperfusion for 180 min. NSE was prepared in a Soxhlet extractor and administrated with doses of 150 mg/kg or 300 mg/kg at 1 hr before ischemia induction (P-150 and 300 or at the beginning of reperfusion phase (T-150 and 300, via jugular catheter intravenously. The kidneys were then removed and subjected to biochemical analysis, comet assay or histopathological examination. Results: The kidneys of untreated IRI rats had a higher histopathological score (P

  15. The protective role of montelukast against intestinal ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Wu, Shenbao; Zhu, Xuxing; Jin, Zhonghai; Tong, Xiuping; Zhu, Liqin; Hong, Xiaofei; Zhu, Xianfei; Liu, Pengfei; Shen, Weidong

    2015-10-26

    Several drugs are effective in attenuating intestinal ischemia-reperfusion injury (IRI); however little is known about the effect of montelukast. Fifty rats were randomly assigned to 3 groups: model group (operation with clamping), sham group (operation without clamping), and study group (operation with clamping and 0.2, 2 and 20 mg/kg montelukast pretreatment). Intestinal ischemia-reperfusion was performed by occlusion (clamping) of the arteria mesenterica anterior for 45 min, followed by 24 h reperfusion. Intestinal IRI in the model group led to severe damage of the intestinal mucosa, liver and kidney. The Chiu scores of the intestines from the study group (2 and 20 mg/kg) were lower than that of the model group. Intestinal IRI induced a marked increase in CysLTR1, Caspase-8 and -9 expression in intestine, liver and kidney, which were markedly reduced by preconditioning with 2 mg/kg montelukast. Preconditioning with 2 g/kg montelukast significantly attenuated hepatic tissue injury and kidney damage, and decreased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in plasma after intestinal IRI. In conclusion, preconditioning with montelukast could attenuate intestinal IRI and the subsequent systemic inflammatory response in rats.

  16. Ischemic Postconditioning Does Not Provide Cardioprotection from Long Term Ischemic Injury in Isolated Male or Female Rat Hearts

    Science.gov (United States)

    Lee, Daniel S.; Steinbaugh, Gregory E.; Quarrie, Ricardo; Yang, Fuchun; Talukder, Hassan; Zweier, Jay L.; Crestanello, Juan A.

    2010-01-01

    Background Ischemic postconditioning(PoC) is a cardio-protective strategy in which initial reperfusion is interrupted by episodes of ischemia. It is unclear whether PoC can be achieved in the Langendorff perfused rat heart model. We investigated 1) whether postconditioning occurs in Langendorff perfused rat heart and 2) whether there is a gender specific response to PoC. Materials and methods Male/female rat hearts(n=8/group) were subjected to 30 minutes of equilibration, 30 minutes of ischemia, and 120 minutes of reperfusion (CONTROL). PoC was induced by 6 cycles(PoC 6c10s), 3 cycles(PoC 3c10s), or 2 cycles(PoC 2c10s) of 10 second reperfusion/10 second ischemia. Rate pressure product(RPP) and infarct size were measured. Male rats(n=7/group) were subjected in vivo to 30 minute left coronary ligation followed by 24 hours of reperfusion(CONTROL) or PoC 6c10s and 24 hours of reperfusion. Results Recovery of RPP was 18±4% in male CONTROL vs. 17±2% for 6c10s, 16±1% for 3c10s, and 15±3% for 2c10s. Female CONTROL hearts recovered 25±3% of their RPP vs. 21±2% for 6c10s. Infarct size was 25±3% for male CONTROL vs. 26±3% for 6c10s, 30±2% for 3c10s, 28±1% for 2c10s; and 30±2% for female CONTROL vs. 29±2% in 6c10s. In vivo Infarct size for CONTROL and PoC 6c10s was 44±3% and 28±5%, respectively (p<0.05). Conclusions In the Langendorff perfused rat hearts, none of the PoC protocols improved myocardial tolerance to ischemia reperfusion injury nor decreased infarct size; however, in vivo postconditioning did confer protection. The lack of protection in the isolated hearts was not gender specific. PMID:20934717

  17. Effects of electrical stimulated hypothalamuic paraventricular nucleus ongastric ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Jian Fu Zhang; Yong Mei Zhang; Chang Dong Yan

    2000-01-01

    AIM To investigate the effect and regulation of electrical stimulation on the paraventricular nucleus (PVN)of hypothalamus using rat gastric ischemia-reperfusion injury (I-RI)induced ulcer model.METHODS Adult male Sprague-Dawley rats weighing 150 g-250 g were used. The surgically prepared ratswere kept fasting for 24 h, but allowed free access to water. They were then anesthetized with urathane(1 g/kg), the celiac artery was clamped with a small clip (holding force 145 g) for 30min, reperfusion wasestablished by removal of the clamp, 60min after reperfusion, the rats were killed and their stomachs wereremoved and perfused intragastrically with 100 mL/L formalin for 30min, and the ulcer index was scoredaccording to Guth et al. The PVN was obtained according to atlas of Paxinos and Watson. The electrodesand cannula were inserted into the PVN for the electrical stimulation, electrical injury and PVN injection,RESULTS In control group (30min ischemia and 60ain reperfusion only), ulcer index was 184.70±60.80(n = 8); in electrical stimulations of PVN (0.2mA, 0.4mA and 0.6mA) + I-RI group, ulcer indexes were102.40±20.39, 85.37±39.76 and 45.00±19.04 (n =8) respectively. Compared with the control groupthere was significant difference ( P < 0.01) in a dose-dependent manner. In electrical lesion of bilateral PVN+ I-RI group, ulcer index was greatly increased (230.00±47.30, n = 8). Microinjection of 3% L-glutamate0.5μL into PVN could produce similar effect to that of PVN stimulation (ulcer index 75.14±37.18, n = 8).A further study indicated that the MDA, pepsin activity and gastric acidity were reduced by PVN stimulationbut no obvious changes of gastric juice volume, total acid output and gastric mucus barrier were observed.CONCLUSION The PVN is one of the specific CNS areas capable of protecting the gastric ischemic-reperfusion injury in rats, and related to decreased MPA, pepsin activity, gastric acidity, while gastric juicevolume, total acid output and gastric

  18. The Effect of the Antioxidant Drug “U-74389G” on Creatinine Levels during Ischemia Reperfusion Injury in Rats

    Science.gov (United States)

    Tsompos, Constantinos; Panoulis, Constantinos; Toutouzas, Konstantinos; Zografos, George; Papalois, Apostolos

    2016-01-01

    Objective The aim of this experimental study was to examine the effect of the antioxidant drug “U-74389G” on a rat model using an ischemia reperfusion protocol. The effect of U-74389G was studied biochemically by measuring mean blood creatinine levels. Materials and Methods Forty rats were used in the study. Creatinine levels were measured at 60 min of reperfusion (groups A and C) or at 120 min of reperfusion (groups B and D), where groups A and B were controls and groups C and D received U-74389G administration. Results U-74389G administration significantly decreased the predicted creatinine levels by 21.02 ± 5.06% (p = 0.0001). Reperfusion time non-significantly increased the predicted creatinine levels by 4.20 ± 6.12% (p = 0.4103). However, U-74389G administration and reperfusion time together produced a significant combined effect in decreasing the predicted creatinine levels by 11.69 ± 3.16% (p = 0.0005). Conclusion Independent of reperfusion time, U-74389G administration significantly decreased the creatinine levels in an ischemic rat model. This study demonstrates that short-term U-74389G administration improves renal function by increasing creatinine excretion. PMID:27390579

  19. Synthesis and Protective Effect of Scutellarein on Focal Cerebral Ischemia/Reperfusion in Rats

    Directory of Open Access Journals (Sweden)

    Nian-Guang Li

    2012-09-01

    Full Text Available Scutellarein, the main metabolite of scutellarin in vivo, has relatively better solubility, bioavailability and bio-activity than scutellarin. However, compared with scutellarin, it is very difficult to obtain scutellarein from Nature. Therefore, the present study focused on establishing an efficient route for the synthesis of scutellarein by hydrolyzing scutellarin. Neurological deficit score and cerebral infarction volume with the administration of scutellarein were then used to compare its neuroprotective effects on focal cerebral ischemia/reperfusion in rats induced by middle cerebral artery occlusion (MCAO with those of scutellarin. The results showed that scutellarein had better protective effect on focal cerebral ischemia/reperfusion than scutellarin, which laid the foundation for further research and development of scutellarein as a promising candidate for ischemic cerebro-vascular disease.

  20. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus.

    Science.gov (United States)

    Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

    2014-08-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions.

  1. Thrombin inhibition with melagatran does not attenuate renal ischaemia-reperfusion injury in rats

    DEFF Research Database (Denmark)

    Nitescu, Nicoletta; Grimberg, Elisabeth; Ricksten, Sven-Erik;

    2007-01-01

    to renal IR. METHODS: Sprague-Dawley rats underwent renal IR (35 min of bilateral renal arterial clamping), or sham surgery. Treatment groups were: (i) IR-Saline, (ii) IR-Melagatran, (iii) Sham-Saline, and (iv) Sham-Melagatran. Twenty minutes prior to renal IR, the rats were administered a bolus dose......BACKGROUND: Renal ischaemia-reperfusion (IR) is associated with activation of the coagulation system and inflammation within the kidney. The aim of the present study was to examine the effects of selective thrombin inhibition with melagatran on kidney morphology and function in rats subjected...... of saline vehicle or melagatran [0.5 mumol/kg, subcutaneously (s.c.)] followed by a continuous infusion throughout (0.08 micromol/kg/h, s.c.). Forty-eight hours after IR, renal function was assessed in anaesthetized animals and kidney histology was analysed semi-quantitatively. RESULTS: Rats in group IR...

  2. 雌激素对大鼠心肌缺血再灌注损伤过程中心肌HGF表达的影响%E2 upregulates HGF mRNA expression in rat heart during myocardial ischemia-reperfusion process

    Institute of Scientific and Technical Information of China (English)

    王彦; 王冬梅; 宫德正; 许莹平; 谢玲; 赵赫男

    2009-01-01

    目的 观察17β-雌二醇(E_2)在大鼠心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)过程中对肝细胞生长因子(hepatocyte growth factor,HGF)mRNA的表达影响并探讨其与细胞凋亡的关系.方法 雄性SD大鼠40只,利用随机数字表将其分为缺血再灌注组(即对照组)、17β-雌二醇作用后的缺血再灌注组(即E_2作用组),每组20只.结扎大鼠冠状动脉左前降支20 min,再灌注30 min,造成心肌缺血再灌注损伤模型,观察17β-雌二醇对心肌HGF表达的影响,同时测定心肌细胞的凋亡.结果 心肌缺血20 min及再灌注30 min时,E_2作用组HGF mRNA表达均较对照组相应时点显著增高(P<0.05).TUNEL法检测E_2作用组再灌注30 min单位面积内心肌细胞凋亡较对照组明显减低(P<0.05);同时流式细胞仪检测结果显示,E_2作用组亦显著低于对照组(P<0.05).对照组再灌注30 min及E_2作用组再灌注30 min的HGF mRNA表达变化与相应时间点的心肌细胞凋亡变化成负相关.结论 17β-雌二醇在大鼠心肌缺血再灌注损伤(MIRI)过程中可提高HGF的表达,来发挥抗凋亡作用.%Objective To investigate the effect of 17β-estradiol (E_2) on the expression of hepatocyte growth factor (HGF) mRNA in the myocardial tissues in rats during myocardial ischemia-reperfusion (I/R) process, and explore the relationship between HGF mRNA expression and myocardial apoptosis. Methods U-sing the random number table, 40 male SD rats were divided into 2 groups (20 rats in each group) randomly, ischemia-reperfusion (control) group and E_2 treatment group. Myocardial I/R models of rats were duplicated by ligating the left anterior descending coronary artery for 20 min then reperfusion for 30 min. The expression of HGF and the apoptosis of myocardiocytes were observed with RT-PCR, TUNEL and flow cytometry. Results At the points of cardiac ischemia for 20 min and reperfusion for 30 min, in the E_2 treatment group, the

  3. The stability of the atherosclerotic plaque depends on the extent of injured endothelium: results from a novel model of ischemia /reperfusion induced atherosclerosis in carotid artery of rats

    Institute of Scientific and Technical Information of China (English)

    晋学庆

    2014-01-01

    Objective To observe the atherogenic lesion progress in a novel ischemia/reperfusion induced atherosclerosis model in the carotid artery of rats.Methods Rats were divided into normal control,sham-operated control and ischemia-reperfusion injury(IRI)groups(n=10each).IRI was induced by 30 min carotid artery occlusion with a 2 cm

  4. Proprotein convertase 1 mRNA and protein expression in ischemic rat cortex after reperfusion

    Institute of Scientific and Technical Information of China (English)

    Shuqin Zhan; An Zhou; Jingquan Lan; Tao Yang

    2011-01-01

    Proprotein convertase 1 (PC1) is a member of the family of proprotein convertases (PCs), which are the processing enzymes of neuropeptides. Previous studies have addressed PC1 effects with regard to the neuroendocrine system. In this study, the developing changes of PC1 mRNA and PC1 protein in rat cortices after transient focal cerebral ischemia were investigated by fluorescent double labeling (both in situ hybridization and immunocytochemistry) using a transient focal cerebral ischemia model in rats. The results were compared with those of sham-operated rat cortices. Both the mRNA and protein levels of PC1 in ischemic cortices decreased gradually at 4, 8, and 16 hours of reperfusion after 100 minutes of middle cerebral artery occlusion. After 24 hours of reperfusion, enhanced intensities of signals for PC1 protein were observed, while signals for PC1 mRNA remained low. These results suggest that transient focal cerebral ischemia influences PC1 mRNA and protein expression in cortices of ischemic rats. Thus, PC1 is regulated by ischemic stress.

  5. Protective Effect of Salvia miltiorrhiza Extract Against Renal Ischemia-Reperfusion-Induced Injury in Rats

    Directory of Open Access Journals (Sweden)

    Gang Chen

    2012-01-01

    Full Text Available The present study investigates the effect of pre-treatment with Salvia miltiorrhiza ethanol extracts (SMEE on renal function markers, immunity and antioxidant activities in renal ischemia and reperfusion (IR rats. Wistar rat kidneys were subjected to 60 min of global ischemia at 37 °C followed by 30 min of reperfusion, and were randomly assigned into the sham, IR model and three SMEE-treated groups (n = 8 per group. Results showed that high serum creatinin (Scr, blood urea nitrogen (BUN, interleukin-6 (IL-6, interleukin-8 (IL-8, tumor necrosis factor-alpha (TNF-α and malondialhehyde (MDA levels, and low antioxidant enzyme activities were observed in IR rats compared to the sham rats. Pre-treatment of Salvia miltiorrhiza ethanol extracts for 20 days prior to IR operation improved renal function, reduced IR induced renal inflammatory and oxidative injury. It is concluded that Salvia miltiorrhiza ethanol extracts could be beneficial in the treatment of renal ischemic injury.

  6. Protective role of methylprednisolone and heparin in ischaemic-reperfusion injury of the rat testicle.

    Science.gov (United States)

    Mertoğlu, C; Senel, U; Cayli, S; Tas, U; Küskü Kiraz, Z; Özyurt, H

    2016-09-01

    This study evaluated the therapeutic efficacy of heparin and methylprednisolone in the treatment of ischaemic reperfusion (IR) injury of the testis. Twenty-four male Sprague-Dawley rats were allocated equally into three groups of eight animals each. The left testes were rotated 720° for 2 h in the rats in the torsion-detorsion group. Rats in the treatment groups underwent the same surgical procedure as the torsion-detorsion group but were also given methylprednisolone (group II) or heparin (group III) by an intraperitoneal route 30 min prior to detorsion. Left orchiectomy was performed in all rats from each experimental animal at 2 h after detorsion, and the tissue was harvested for the measurement of malondialdehyde (MDA), protein carbonyl (PC) and nitric oxide (NO) and the endogenous antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase. Additional tissue was evaluated using histopathological and immunohistochemical changes. PC and MDA levels were significantly reduced in the treated groups compared to the control group. There was no statistically significant difference in NO level or SOD, GSH-Px and catalase activity among the treatment groups. Histopathological and immunohistochemical findings supported biochemical changes. It is concluded that pre-treatment with methylprednisolone or heparin protects the testis in ischaemic reperfusion injury caused by testicular torsion-detorsion.

  7. Protective effects of calmodulin antagonists (trifluoperazine and W-7 on hypothermic ischemic rat hearts.

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    Sugawara,Eiji

    1991-06-01

    Full Text Available The cardioprotective effect of calmodulin antagonists, trifluoperazine (TFP and N-(6-aminohexyl-5-chloro-1-naphthalene sulfonamide (W-7 was examined on the isolated rat heart exposed to hypothermic and ischemic conditions by measuring distribution of lysosomal enzymes in myocardial cells, and leakage of creatine kinase (CK during reperfusion and postischemic recovery in myocardial systolic function. Experimental hearts were infused with 20 degrees C Krebs-Henseleit bicarbonate buffer (KHB or KHB containing TFP or W-7 for 2min every 30min during hypothermic ischemia. After ischemia for 120min at 20 degrees C, rat hearts were reperfused at 37 degrees C for 30min. TFP and W-7 improved functional recovery and prevented CK release. In TFP treated hearts, leakage of lysosomal enzymes was reduced significantly, whereas stabilization of lysosomes by W-7 did not occur. These results suggest that calcium-calmodulin dependent enzymes may play an important role in the development of cellular damage of the myocardium during hypothermic ischemia, although levels of leakage of lysosomal enzymes may be unreliable predictors of functional recovery after hypothermic ischemia.

  8. Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

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    Ozkan Onal

    2015-01-01

    Full Text Available Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF intraperitoneally (ip for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD, catalase (CAT, glutathioneperoxidase (GSH-Px, malondyaldehide (MDA, and protein carbonyl (PCO were analyzed in tissue samples. Total oxidant status (TOS, and total antioxidant capacity (TAC were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy

  9. In vivo dynamic imaging of myocardial cell death using {sup 99m}Tc-labeled C2A domain of synaptotagmin I in a rat model of ischemia and reperfusion

    Energy Technology Data Exchange (ETDEWEB)

    Liu Zhonglin [Department of Radiology, University of Arizona, Tucson, AZ 85724 (United States)], E-mail: zliu@radiology.arizona.edu; Zhao Ming; Zhu Xiaoguang [Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Furenlid, Lars R.; Chen Yichun; Barrett, Harrison H. [Department of Radiology, University of Arizona, Tucson, AZ 85724 (United States)

    2007-11-15

    Objectives: This study was designed to investigate the capability of a small-animal SPECT imager, FastSPECT II, for dynamic rat heart imaging and to characterize the in vivo kinetic properties of {sup 99m}Tc-C2A-glutathione-s-transferase (GST), a molecular probe targeting apoptosis and necrosis, in detecting cell death in ischemic-reperfused rat hearts. Methods: C2A-GST was radiolabeled with {sup 99m}Tc via 2-iminothiolane thiolation. Myocardial ischemia-reperfusion was induced by 30-min ligation of the left coronary artery followed by 120-min reperfusion in seven rats. FastSPECT II cardiac images of {sup 99m}Tc-C2A-GST in list-mode acquisition were recorded for 2 h using FastSPECT II. Results: Tomographic images showed a focal radioactive accumulation (hot spot) in the lateral and anterior walls of the left ventricle. The hot spot was initially visualized 10 min after injection and persisted on the 2-h images. Quantitative analysis demonstrated that the hot-spot radioactivity increased significantly within 30 min postinjection and experienced no washout up to the end of the 2-h study. The ratio of the hot spot/viable myocardium was 4.52{+-}0.24, and infarct-to-lung ratio was 8.22{+-}0.63 at 2 h postinjection. The uptake of {sup 99m}Tc-C2A-GST in the infarcted myocardium was confirmed by triphenyl tetrazolium chloride staining and autoradiography analysis. Conclusions: FastSPECT II allows quantitative dynamic imaging and functional determination of radiotracer kinetics in rat hearts. An in vivo kinetic profile of {sup 99m}Tc-C2A-GST in the ischemic-reperfused rat heart model was characterized successfully. The pattern of accelerated {sup 99m}Tc-C2A-GST uptake in the ischemic area at risk after reperfusion may be useful in detecting and quantifying ongoing myocardial cell loss induced by ischemia-reperfusion.

  10. Combined Salvianolic Acid B and Ginsenoside Rg1 Exerts Cardioprotection against Ischemia/Reperfusion Injury in Rats.

    Science.gov (United States)

    Deng, Yanping; Yang, Min; Xu, Feng; Zhang, Qian; Zhao, Qun; Yu, Haitao; Li, Defang; Zhang, Ge; Lu, Aiping; Cho, Kenka; Teng, Fukang; Wu, Peng; Wang, Linlin; Wu, Wanying; Liu, Xuan; Guo, De-An; Jiang, Baohong

    2015-01-01

    Lack of pharmacological strategies in clinics restricts the patient prognosis with myocardial ischemia/reperfusion (I/R) injury. The aim of this study was to evaluate the cardioprotection of combined salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1) against myocardial I/R injury and further investigate the underlying mechanism. I/R injury was induced by coronary artery ligation for Wistar male rats and hypoxia/reoxygenation injury was induced on H9c2 cells. Firstly, the best ratio between SalB and Rg1was set as 2:5 based on their effects on heart function detected by hemodynamic measurement. Then SalB-Rg1 (2:5) was found to maintain mitochondrial membrane potential and resist apoptosis and necrosis in H9c2 cell with hypoxia/reoxygenation injury. Companying with same dose of SalB or Rg1 only, SalB-Rg1 showed more significant effects on down-regulation of myocardial infarct size, maintenance of myocardium structure, improvement on cardiac function, decrease of cytokine secretion including TNF-α, IL-1β, RANTES and sVCAM-1. Finally, the SalB-Rg1 improved the viability of cardiac myocytes other than cardiac fibroblasts in rats with I/R injury using flow cytometry. Our results revealed that SalB-Rg1 was a promising strategy to prevent myocardial I/R injury.

  11. Combined Salvianolic Acid B and Ginsenoside Rg1 Exerts Cardioprotection against Ischemia/Reperfusion Injury in Rats.

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    Yanping Deng

    Full Text Available Lack of pharmacological strategies in clinics restricts the patient prognosis with myocardial ischemia/reperfusion (I/R injury. The aim of this study was to evaluate the cardioprotection of combined salvianolic acid B (SalB and ginsenoside Rg1 (Rg1 against myocardial I/R injury and further investigate the underlying mechanism. I/R injury was induced by coronary artery ligation for Wistar male rats and hypoxia/reoxygenation injury was induced on H9c2 cells. Firstly, the best ratio between SalB and Rg1was set as 2:5 based on their effects on heart function detected by hemodynamic measurement. Then SalB-Rg1 (2:5 was found to maintain mitochondrial membrane potential and resist apoptosis and necrosis in H9c2 cell with hypoxia/reoxygenation injury. Companying with same dose of SalB or Rg1 only, SalB-Rg1 showed more significant effects on down-regulation of myocardial infarct size, maintenance of myocardium structure, improvement on cardiac function, decrease of cytokine secretion including TNF-α, IL-1β, RANTES and sVCAM-1. Finally, the SalB-Rg1 improved the viability of cardiac myocytes other than cardiac fibroblasts in rats with I/R injury using flow cytometry. Our results revealed that SalB-Rg1 was a promising strategy to prevent myocardial I/R injury.

  12. Nuclear factor-κB decoy oligodeoxynucleotides attenuates ischemia/reperfusion injury in rat liver graft

    Institute of Scientific and Technical Information of China (English)

    Ming-Qing Xu; Xiu-Rong Shuai; Mao-Lin Yan; Ming-Man Zhang; Lu-Nan Yan

    2005-01-01

    AIM: To evaluate the protective effect of NF-κB decoy oligodeoxynucleotides (ODNs) on ischemia/reperfusion (I/R) injury in rat liver graft.METHODS: Orthotopic syngeneic rat liver transplantation was performed with 3 h of cold preservation of liver graft in University of Wisconsin solution containing phosphorothioated double-stranded NF-κB decoy ODNs or scrambled ODNs. NF-κB decoy ODNs or scrambled ODNs were injected intravenously into donor and recipient rats 6 and 1 h before operation,respectively. Recipients were killed 0 to 16 h after liver graft reperfusion. NF-κB activity in the liver graft was analyzed by electrophoretic mobility shift assay (EMSA). Hepatic mRNA expression of TNF-α, IFN-γand intercellular adhesion molecule-1 (ICAM-1) were determined by semiquantitative RT-PCR. Serum levels of TNF-α and IFN-γ were measured by enzyme-linked immunosorbent assays (ELISA). Serum level of alanine transaminase (ALT) was measured using a diagnostic kit. Liver graft myeloperoxidase (MPO) content was assessed.RESULTS: NF-κB activation in liver graft was induced in a time-dependent manner, and NF-κB remained activated for 16 h after graft reperfusion. NF-κB activation in liver graft was significant at 2 to 8 h and slightly decreased at 16 h after graft reperfusion. Administration of NF-κB decoy ODNs significantly suppressed NF-κB activation as well as mRNA expression of TNF-α, IFN-γ and ICAM-1 in the liver graft. The hepatic NF-κB DNA binding activity [presented as integral optical density (IOD) value] in the NF-κB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (2.16±0.78 vs 36.78±6.35 and 3.06±0.84 vs 47.62± 8.71 for IOD value after 4 and 8 h of reperfusion, respectively, P<0.001).The hepatic mRNA expression level of TNF-α, IFN-y and ICAM-1 [presented as percent of β-actin mRNA(%)] in the NF-κBdecoy ODNs treatment group rat was significantly lower than that of the I/R group rat (8.31 ±3.48 vs 46.37±10

  13. Effect of remote ischemic postconditioning in inflammatory changes of the lung parenchyma of rats submitted to ischemia and reperfusion

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    Rafael Cantero Dorsa

    2015-09-01

    Full Text Available AbstractObjective:To assess the effects of postconditioning remote in ischemia-reperfusion injury in rat lungs.Methods:Wistar rats (n=24 divided into 3 groups: GA (I/R n=8, GB (R-Po n=8, CG (control n=8, underwent ischemia for 30 minutes artery occlusion abdominal aorta, followed by reperfusion for 60 minutes. Resected lungs and performed histological analysis and classification of morphological findings in accordance with the degree of tissue injury. Statistical analysis of the mean rating of the degree of tissue injury.Results:GA (3.6, GB (1.3 and CG (1.0. (GA GB X P<0.05.Conclusion:The remote postconditioning was able to minimize the inflammatory lesion of the lung parenchyma of rats undergoing ischemia and reperfusion process.

  14. Dietary red palm oil supplementation reduces myocardial infarct size in an isolated perfused rat heart model

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    Esterhuyse Adriaan J

    2010-06-01

    Full Text Available Abstract Background and Aims Recent studies have shown that dietary red palm oil (RPO supplementation improves functional recovery following ischaemia/reperfusion in isolated hearts. The main aim of this study was to investigate the effects of dietary RPO supplementation on myocardial infarct size after ischaemia/reperfusion injury. The effects of dietary RPO supplementation on matrix metalloproteinase-2 (MMP2 activation and PKB/Akt phosphorylation were also investigated. Materials and methods Male Wistar rats were divided into three groups and fed a standard rat chow diet (SRC, a SRC supplemented with RPO, or a SRC supplemented with sunflower oil (SFO, for a five week period, respectively. After the feeding period, hearts were excised and perfused on a Langendorff perfusion apparatus. Hearts were subjected to thirty minutes of normothermic global ischaemia and two hours of reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining. Coronary effluent was collected for the first ten minutes of reperfusion in order to measure MMP2 activity by gelatin zymography. Results Dietary RPO-supplementation decreased myocardial infarct size significantly when compared to the SRC-group and the SFO-supplemented group (9.1 ± 1.0% versus 30.2 ± 3.9% and 27.1 ± 2.4% respectively. Both dietary RPO- and SFO-supplementation were able to decrease MMP2 activity when compared to the SRC fed group. PKB/Akt phosphorylation (Thr 308 was found to be significantly higher in the dietary RPO supplemented group when compared to the SFO supplemented group at 10 minutes into reperfusion. There was, however, no significant changes observed in ERK phosphorylation. Conclusions Dietary RPO-supplementation was found to be more effective than SFO-supplementation in reducing myocardial infarct size after ischaemia/reperfusion injury. Both dietary RPO and SFO were able to reduce MMP2 activity, which suggests that MMP2 activity does not play a major role in

  15. Pre-treatment with a DPP-4 inhibitor is infarct sparing in hearts from obese, pre-diabetic rats.

    Science.gov (United States)

    Huisamen, Barbara; Genis, Amanda; Marais, Erna; Lochner, Amanda

    2011-02-01

    Cardiovascular risk is closely associated with insulin resistance and type 2 diabetes. Therapy based on the actions of GLP-1 is currently seen as a novel approach to treat this disease. The aims of this study was therefore to use an animal model to determine whether (i) pre-treatment of obese, insulin resistant but pre-diabetic rats with a DPP4 inhibitor, PFK275-055, could protect the heart from ischaemia/reperfusion injury and (ii) the possible mechanisms involved in such protection. Obese, pre-diabetic rats (DIO) were treated for 4 weeks with 10 mg/kg/day of the DPP4 inhibitor PFK275-055. Ex vivo perfusion was used to subject hearts to ischaemia/reperfusion to determine infarct size, functional recovery and post-ischaemic activation of proteins associated with cardiac protection. Adult ventricular cardiomyocytes were isolated to determine insulin sensitivity. Other assessments included body weight, intra-peritoneal fat weight, insulin and GLP-1 levels as well as histological evaluation of the pancreata. Results showed that DIO animals had higher body mass and intra-peritoneal fat mass than chow-fed animals. They presented with elevated plasma insulin levels and lower GLP-1 levels. Treatment with the DPP4 inhibitor resulted in smaller infarct size development in hearts from DIO rats after ischaemia/reperfusion accompanied by activation of cardioprotective kinases. GLP-1 levels were elevated and plasma insulin levels lower after treatment. In addition, the beta-cell to alpha-cell ratio of the pancreas was improved. We conclude that treatment with PFK275-055 for 4 weeks protected the heart against ischaemia/reperfusion injury, elevated GLP-1 levels and improved metabolic control in obese, pre-diabetic rats.

  16. The effect of hyperglycemia on blood brain barrier of rats with focal cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective: To determine whether hyperglycemia could aggravate the microvascular damage in ischemic stroke.Methods: Hyperglycemia model was made by injection of streptozocin through subcutaneous injection in wistar rats. Using the suture model, the rats were subjected to 3 h of focal ischemia and different times of reperfusion,including 6,12,24,48,96 h and 7 d. TTC dyeing was used to show the infarction area of rats. The infarctive volume of rats were calculated by computer imaging analysis system;Matrix metalloproteinase (MMP-2) and (MMP-9)were detected by immunohistochemistry and in situ hybridization histochemistry in Wistar rats.Results: The infarctive volume was siginificantly larger in hyperglycemic rats than that of nonhyperglycemic rats. The level of MMP-2,MMP-9 expression in the group of hyperglycemic rats was higher than that of nonhyperglycemic rats. Conclusion: Hyperglycemia aggravated the injury of focal ischmia-reperfusion in wistar rats and the higher expression of MMP-2, MMP-9 might be one of the mechanism in aggravation of focal ischemia/reperfusion injury.

  17. Ischemic Postconditioning Alleviates Brain Edema After Focal Cerebral Ischemia Reperfusion in Rats Through Down-Regulation of Aquaporin-4.

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    Han, Dong; Sun, Miao; He, Ping-Ping; Wen, Lu-Lu; Zhang, Hong; Feng, Juan

    2015-07-01

    Cerebral edema is a serious complication associated with cerebral ischemia/reperfusion (I/R). Aquaporin-4 (AQP4) plays a role in generating postischemic edema after reperfusion. Recently, ischemic postconditioning (Postcond) has been shown to produce neuroprotective effects and reduce brain edema in rats after cerebral I/R. It is unclear if ischemic Postcond alleviates brain edema injury through regulation of AQP4. In this study, middle cerebral artery occlusion (MCAO) was induced in rats by filament insertion for 2 h following 24-h reperfusion: ischemic Postcond treatment was performed before reperfusion in the experimental group. We used the wet-dry weight ratio and transmission electron microscopy to evaluate brain edema after 24 h of reperfusion. We used immunohistochemistry and Western blot analyses to evaluate the distribution and expression of AQP4. Ischemic Postcond significantly reduced the water content of the brain tissue and swelling of the astrocytic foot processes. AQP4 expression increased in the I/R and Postcond groups compared to the sham group, but it decreased in the Postcond group compared to the I/R group. The results of our study suggest that ischemic Postcond effectively reduces brain edema after reperfusion by inhibiting AQP4 expression. The data in this study support the use of ischemic Postcond for alleviating brain edema after cerebral I/R.

  18. The effect of the antioxidant drug U-74389G on urea levels during ischemia reperfusion injury in rats

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    Constantinos Tsompos

    2017-05-01

    Full Text Available This experimental study examined the effect of the antioxidant drug U-74389G, on a rat model and particularly in a renal ischemia- reperfusion protocol. The effects of that molecule were studied biochemically using blood mean urea levels. Forty rats of mean weight 231.875 g were used in the study. Urea levels were measured at 60 min of reperfusion (groups A and C and at 120 min of reperfusion (groups B and D. The drug U-74389G was administered only in groups C and D. U-74389G administration significantly decreased the predicted urea levels by 11.35%±2.73% (P=0.0001. Reperfusion time non-significantly increased the predicted urea levels by 2.26%±3.29% (P=0.4103. However, U-74389G administration and reperfusion time together significantly decreased the predicted urea levels by 6.31%±1.70% (P=0.0005. U-74389G administration whether it interacted or not with reperfusion time had significant decreasing effect on the urea serum levels, reflecting a respective renal function augmentation.

  19. MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats

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    Xian-Yun Wang

    2016-09-01

    Full Text Available As an endoplasmic reticulum (ER stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO. MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs.

  20. The Effect of the Antioxidant Drug U-74389G on Uric Acid Levels during Ischemia Reperfusion Injury in Rats

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    Tsompos Constantinos

    2016-09-01

    Full Text Available This experimental study examined the effect of the anti-oxidant drug U-74389G in a rat model using a renal ischaemia-reperfusion (IR protocol. The effects of the molecule were studied biochemically by assessing mean serum uric acid levels (SUA. In total, 40 rats (mean weight = 231.875 g were used in the study. SUA levels were measured at 60 min of reperfusion for groups A and C and at 120 min of reperfusion for groups B and D. The drug U-74389G was administered only in groups C and D. U-74389G administration non-significantly increased the SUA levels by 15.43%±9.10% (p=0.096 at the representative endpoint of 1.5 h. The reperfusion time non-significantly decreased the SUA levels by 13.61%±9.18% (p=0.126. However, the interaction of U-74389G administration and reperfusion time non-significantly increased the SUA levels by 4.78%±5.64% (p= 0.387. Whether it interacted with the reperfusion time, U-74389G administration non-significantly increased SUA levels. It seems that U-74389G cannot reverse injury to IR tubular epithelial cells within 2 hours.

  1. Huangzhi Oral Liquid Prevents Arrhythmias by Upregulating Caspase-3 and Apoptosis Network Proteins in Myocardial Ischemia-Reperfusion Injury in Rats

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    Xu Ran

    2015-01-01

    Full Text Available To study the effect of Huangzhi oral liquid (HZOL on I/R after 2 h and 4 h and determine its regulatory function on caspase-3 and protein networks. 70 SD male rats were randomly divided into seven groups and established myocardial I/R injury model by ligating the left anterior descending coronary artery. Myocardial infarction model was defined by TTC staining and color of the heart. The levels of CK-MB, CTnI, C-RPL, SOD, and MDA were tested at 2 h and 4 h after reperfusion. HE staining and ultramicrostructural were used to observe the pathological changes. The apoptotic index (AI of cardiomyocyte was marked by TUNEL. The expression levels of caspase-3, p53, fas, Bcl-2, and Bax were tested by immunohistochemistry and western blot. HZOL corrected arrhythmia, improved the pathologic abnormalities, decreased CK-MB, CTnI, C-RPL, MDA, AI, caspase-3, p53, fas, and Bax, and increased SOD ans Bcl-2 with different times of myocardial reperfusion; this result was similar to the ISMOC (P>0.05. HZOL could inhibit arrhythmia at 2 and 4 h after I/R and ameliorate cardiac function, which was more significant at 4 h after reperfusion. This result may be related to decreased expression of caspase-3, p53, and fas and increased Bcl-2/Bax ratio.

  2. Erythropoietin reduces ischemia-reperfusion injury after liver transplantation in rats.

    Science.gov (United States)

    Schmeding, Maximilian; Hunold, Gerhard; Ariyakhagorn, Veravoorn; Rademacher, Sebastian; Boas-Knoop, Sabine; Lippert, Steffen; Neuhaus, Peter; Neumann, Ulf P

    2009-07-01

    Human recombinant Erythropoietin (rHuEpo) has recently been shown to be a potent protector of ischemia- reperfusion injury in warm-liver ischemia. Significant enhancement of hepatic regeneration and survival after large volume partial hepatic resection has also been demonstrated. It was the aim of this study to evaluate the capacities of rHuEpo in the setting of rat liver transplantation. One-hundred-and-twenty Wistar rats were used: 60 recipients received liver transplantation following donor organ treatment (60 donors) with either 1000 IU rHuEpo or saline injection (controls) into portal veins (cold ischemia 18 h, University of Wisconsin (UW) solution). Recipients were allocated to two groups, which either received 1000 IU rHuEpo at reperfusion or an equal amount of saline (control). Animals were sacrificed at defined time-points (2, 4.5, 24, 48 h and 7 days postoperatively) for analysis of liver enzymes, histology [hematoxylin-eosin (HE) staining, periodic acid Schiff staining (PAS)], immunostaining [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Hypoxyprobe] and real-time polymerase chain reaction (RT-PCR) of cytokine mRNA (IL-1, IL-6). Lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) values were significantly reduced among the epo-treated animals 24 and 48 h after liver transplantation (LT). The TUNEL and Hypoxyprobe analyses as well as necrotic index evaluation displayed significant reduction of apoptosis and necrosis in rHuEpo-treated graft livers. Erythropoietin reduces ischemia-reperfusion injury after orthotopic liver transplantation in rats.

  3. Cryotherapy reduces skeletal muscle damage after ischemia/reperfusion in rats.

    Science.gov (United States)

    Puntel, Gustavo O; Carvalho, Nélson R; Dobrachinski, Fernando; Salgueiro, Andréia C F; Puntel, Robson L; Folmer, Vanderlei; Barbosa, Nilda B V; Royes, Luiz F F; Rocha, João Batista T; Soares, Félix A A

    2013-02-01

    The aim of this study was to analyze the effects of cryotherapy on the biochemical and morphological changes in ischemic and reperfused (I/R) gastrocnemius muscle of rats. Forty male Wistar rats were divided into control and I/R groups, and divided based on whether or not the rats were submitted to cryotherapy. Following the reperfusion period, biochemical and morphological analyses were performed. Following cryotherapy, a reduction in thiobarbituric acid-reactive substances and dichlorofluorescein oxidation levels were observed in I/R muscle. Cryotherapy in I/R muscle also minimized effects such as decreased cellular viability, levels of non-protein thiols and calcium ATPase activity as well as increased catalase activity. Cryotherapy also limited mitochondrial dysfunction and decreased the presence of neutrophils in I/R muscle, an effect that was corroborated by reduced myeloperoxidase activity in I/R muscle treated with cryotherapy. The effects of cryotherapy are associated with a reduction in the intensity of the inflammatory response and also with a decrease in mitochondrial dysfunction.

  4. Protective effect of hydrogen rich saline solution on experimental ovarian ischemia reperfusion model in rats.

    Science.gov (United States)

    Gokalp, Nurcan; Basaklar, Abdullah Can; Sonmez, Kaan; Turkyilmaz, Zafer; Karabulut, Ramazan; Poyraz, Aylar; Gulbahar, Ozlem

    2017-03-01

    The present study aimed to investigate the effects of hydrogen rich saline solution (HRSS) in a rat model of ovarian ischemia-reperfusion injury. Thirty-six female Wistar-albino rats were grouped randomly, into six groups of six rats. The groups were classified as: sham (S), hydrogen (H), torsion (T), torsion/detorsion (TD), hydrogen-torsion (HT), and hydrogen-torsion/detorsion (HTD). Bilateral adnexal torsion was performed for 3h in all torsion groups. HRSS was given 5ml/kg in hydrogen groups intraperitoneally. Malondialdehyde (MDA) and glutathione-S-transferase (GST) levels were measured in both the plasma and tissue samples. Tissue sections were evaluated histopathologically, and the apoptotic index was detected by TUNEL assay. The results were analyzed by Kruskal-Wallis and Pearson chi-square tests using computer software, SPSS Version 20.0 for Windows. The MDA levels were higher and GST levels were lower in the torsion and detorsion groups when compared to other groups, but the differences were insignificant (P>0.05). The MDA levels were lower and GST levels were higher in the HT and HTD groups compared with the T and TD groups (P>0.05). Follicular injury, edema, vascular congestion, loss of cohesion and apoptotic index were higher in the torsion groups but decreased in the groups that received HRSS. According to histopathological and biochemical examinations, HRSS is effective in attenuating ischemia-reperfusion induced ovary injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Time window characteristics of cultured rat hippocampal neurons subjected to ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    XU Zhong; XU Ru-xiang; LIU Bao-song; JIANG Xiao-dan; HUANG Tao; DING Lian-shu; YUAN Jun

    2005-01-01

    Objective: To explore cell death and apoptosis in rat hippocampal neurons at different time points after ischemia, hypoxia and reperfusion injury and to elucidate time window characteristics in ischemia neuronal injury.Methods: Hippocampal neurons were obtained from rat embryo and were cultured in vitro. The ischemia and reperfusion of cultured rat hippocampal neurons were simulated by oxygen-glucose deprivation (OGD) and recovery. OGD at different time points (0.25 h to 3.0 h) and then the same recovery (24 h) were prepared. Annexin V-PI staining and flow cytometry examined neuron death and apoptosis at different time after injury. Results: After OGD and recovery, both necrosis and apoptosis were observed. At different times after OGD, there were statistically significant differences in neuron necrosis rate (P0.05). At recovery, survival rate of hippocampal neurons further decreased while apoptosis rate increased. Furthermore, apoptosis rates of different time differed greatly (P<0.05). Apoptosis rate gradually increased with significant difference among those of different time points (P<0.05). However, 2 h after ischemia, apoptosis rate decreased markedly.Conclusions: Apoptosis is an important pathway of delayed neuron death. The therapeutic time window should be within 2 h after cerebral ischemia and hypoxia.

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

    Science.gov (United States)

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

    2015-01-01

    This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-α levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-α levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-α effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use. PMID:26885068

  7. The protective effects of pomegranate extracts against renal ischemia-reperfusion injury in male rats

    Directory of Open Access Journals (Sweden)

    Ahmet A Sancaktutar

    2014-01-01

    Full Text Available Aim: To evaluate the possible protective effect of pomegranate extract (PE on rats following renal ischemia-reperfusion (I/R injury. Materials and Methods: Twenty-four Wistar rats were divided into three groups. Sham group underwent laparotomy then waited for 45 minutes without ischemia. I/R group were subjected to left renal ischemia for 45 minutes followed by 60 minutes of reperfusion. I/R + PE group were subjected to the same renal I/R as the I/R group were also given 225 mg/kg PE peroral 30 minutes prior to the ischemia. Malondialdehyde (MDA, total antioxidant capacity (TAC, total oxidant status (TOS, and oxidative stress index (OSI were determined on the blood samples and kidney tissues. Histopathological analyses were conducted on the kidney tissues. Results: Serum TAC levels were significantly decreased in I/R group when compared with S group (P = 0.001. Serum MDA levels were increased in I/R group; however, it was not statistically significant. In rat kidney tissues, TOS levels and OSI index were significantly increased after I/R injury, while TAC levels were decreased. In I/R + PE group, PE reversed the negative effects of I/R injury. PE pretreatment was effective in decreasing tubular necrosis score. Conclusion: PE pretreatment ameliorated the oxidative damage and histopathological changes occurring following renal I/R injury.

  8. Protective Effects of N-acetylcysteine and a Prostaglandin E1 Analog, Alprostadil, Against Hepatic Ischemia: Reperfusion Injury in Rats

    OpenAIRE

    Hsieh, Cheng-Chu; Hsieh, Shu-Chen; Chiu, Jen-Hwey; Wu, Ying-Ling

    2014-01-01

    Ischemia–reperfusion (I/R) injury has a complex pathophysiology resulting from a number of contributing factors. Therefore, it is difficult to achieve effective treatment or protection by individually targeting the mediators or mechanisms. Our aim was to analyze the individual and combined effects of N-acetylcysteine (NAC) and the prostaglandin E1 (PGE1) analog alprostadil on hepatic I/R injury in rats. Thirty male Sprague-Dawley rats were randomly divided into five groups (six rats per group...

  9. Protective effects of honokiol on ischemia/reperfusion injury of rat ovary: an experimental study

    Science.gov (United States)

    Yaman Tunc, Senem; Agacayak, Elif; Goruk, Neval Yaman; Icen, Mehmet Sait; Turgut, Abdulkadir; Alabalik, Ulas; Togrul, Cihan; Ekinci, Cenap; Ekinci, Aysun; Gul, Talip

    2016-01-01

    Aim The purpose of this study was to investigate the protective effect of honokiol on experimental ischemia/reperfusion injury of rat ovary. Materials and methods A total of 40 female Wistar albino rats were used in this study. The rats were divided into five groups as follows: sham (Group I), torsion (Group II), torsion + detorsion (Group III), torsion + detorsion + saline (Group IV), and torsion + detorsion + honokiol (Group V). Bilateral adnexa in all the rats except for those in the sham group were exposed to torsion for 3 hours. The rats in Group IV were administered saline, whereas the rats in Group V were administered honokiol by intraperitoneal route 30 minutes before detorsion. Tissue and plasma concentrations of malondialdehyde and nitric oxide were determined. Ovarian tissue was histologically evaluated. Data analyses were performed by means of Kruskal–Wallis test and Mann–Whitney U-test (Bonferroni correction) in SPSS 15.0 (Statistical Package for Social Sciences; SPSS Inc., Chicago, IL, USA). Results The torsion and detorsion groups had higher scores in vascular congestion, hemorrhage, and inflammatory cell infiltration compared with the sham group (P<0.005). In addition, total histopathological scores were significantly higher in the torsion and detorsion groups compared with the sham group (P<0.005). A significant reduction was observed in hemorrhage, inflammatory cell infiltration, and cellular degeneration scores, of all histopathological scores, in the honokiol group (P<0.005). Ovarian tissue concentrations of malondialdehyde were significantly higher in the torsion and detorsion groups compared with the sham and honokiol groups (P<0.005). Ovarian tissue concentrations of nitric oxide, on the other hand, were significantly higher in the torsion group compared with the sham, saline, and honokiol groups (P<0.005). Conclusion Honokiol has a beneficial effect on ovarian torsion-related ischemia/reperfusion injury. PMID:27022246

  10. Effects of chromium picolinate on vascular reactivity and cardiac ischemia-reperfusion injury in spontaneously hypertensive rats.

    Science.gov (United States)

    Abebe, Worku; Liu, Jun Yao; Wimborne, Hereward; Mozaffari, Mahmood S

    2010-01-01

    Chromium picolinate [Cr(pic)(3)] is a nutritional supplement widely promoted to exert beneficial metabolic effects in patients with type 2 diabetes/impaired glucose tolerance. Frequent comorbidities in these individuals include systemic hypertension, abnormal vascular function and ischemic heart disease, but information on the effects of the supplement on these aspects is sparse. Utilizing male spontaneously hypertensive rats (SHR), we examined the potential impact of Cr(pic)(3) on blood pressure, vascular reactivity and myocardial ischemia-reperfusion injury (IRI). Dietary Cr(pic)(3) supplementation (as 10 mg chromium/kg diet for six weeks) did not affect blood pressure of the SHR. Also, neither norepinephrine (NE) and potassium chloride (KCl)-induced contractility nor sodium nitroprusside (SNP)-induced relaxation of aortic smooth muscle from the SHR was altered by Cr(pic)(3) treatment. However, Cr(pic)(3) augmented endothelium-dependent relaxation of aortas, produced by acetylcholine (ACh), and this effect was abolished by N-nitro-L-arginine methyl ester (L-NAME), suggesting induction of nitric oxide (NO) production/release. Treatment with Cr(pic)(3) did not affect baseline coronary flow rate and rate-pressure-product (RPP) or infarct size following regional IRI. Nonetheless, Cr(pic)(3) treatment was associated with improved coronary flow and recovery of myocardial contractility and relaxation following ischemia-reperfusion insult. In conclusion, dietary Cr(pic)(3) treatment of SHR alters neither blood pressure nor vascular smooth muscle reactivity but causes enhancement of endothelium-dependent vasorelaxation associated with NO production/release. Additionally, while the treatment does not affect infarct size, it improves functional recovery of the viable portion of the myocardium following IRI.

  11. Antioxidant and antiapoptotic effects of erdosteine in a rat model of ovarian ischemia-reperfusion injury

    OpenAIRE

    Ugurel, Vedat; Cicek, Ahmet Cagatay; Cemek, Mustafa; Demirtas, Selim; Kocaman, A Tuba; Karaca, Turan

    2017-01-01

    Objective(s): To evaluate the protective effect of erdosteine, an antiapoptotic and antioxidant agent, on torsion–detorsion evoked histopathological changes in experimental ovarian ischemia-reperfusion (IR) injury. Materials and Methods: Eighteen female Wistar albino rats were used in control, IR, and IR+Edosteine (IR-E) groups, (n=6 in each). The IR-E group received the erdosteine for seven days before the induction of torsion/retorsion, (10 mg/kg/days). The IR and IR-E groups were exposed t...

  12. Effects of Wy14643 on hepatic ischemia reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Si-Qi Xu; Yuan-Hai Li; Sheng-Hong Hu; Ke Chen; Liu-Yi Dong

    2008-01-01

    AIM: To investigate the effects and possible mechanisms of Wy14643 on hepatic ischemiareperfusion (I/R) injury in rats.METHODS: Thirty male Sprague-Dawley rats weighing 220-280 g were randomly divided into five experimental groups: sham group (G1, n = 6): a sham operation was performed (except for liver I/R);I/R-untreated group (G2, n = 6): rats underwent liver ischemia for 90 min followed by reperfusion for 4h; and I/R + Wy14643 groups (G3, G4, G5, n =6): after the same surgical procedure as in group 2,animals were pretreated with Wy14643 at the dose of 1, 5 and 10 mg/kg 1 h before ischemia, respectively.Hepatic ischemia-reperfusion (I/R) was induced by clamping blood supply to the left lateral and median lobes of the liver for 90 min, and atraumatic clamp was removed for 4 h reperfusion. Blood samples and liver tissues were obtained at the end of reperfusion to assess serum and hepatic tissue homogenate aminotransferase (ALT), aspartate aminotransferase (AST), myeloperoxidase (MPO), serum interleukin1β (IL-1β) and tumor necrosis factor alpha (TNF-α),as well as activity of superoxide dismutase (SOD)and content of malondialdehyde (MDA) in the hepatic tissue homogenate.RESULTS: Hepatic I/R induced a significant increase in the serum levels of ALT, AST, TNF-α, IL-1β and MPO, as well as the levels of ALT, AST and MDA in the liver tissue homogenate, which were reduced by pretreatment with Wy14643 at the dose of 1, 5 and 10 mg/kg, respectively. The activity of SOD in the liver tissue homogenate was decreased after hepatic I/R, which was enhanced by Wy14643 pretreatment.In addition, serum and liver tissue homogenate ALT and AST in the Wy14643 10 mg/kg group were lower than in the Wy14643 1 mg/kg and 5 mg/kg groups,respectively.CONCLUSION: Wy14643 pretreatment exerts significant protection against hepatic I/R injury in rats. The protective effects are possibly associated with enhancement of anti-oxidant and inhibition inflammation response.

  13. Cardioprotective effect of small nonerythropoietic helix B surface peptide on heart ischemia/reperfusion injury rats and expression effect of p44/42 MAPK%促红细胞生成素类似结构对大鼠心肌缺血损伤的保护作用及对心肌蛋白激酶丝氨酸/苏氨酸激酶表达的影响

    Institute of Scientific and Technical Information of China (English)

    王媛媛; 曹建; 邓莉; 陈勤; 欧阳先国

    2014-01-01

    Objective To investigate the protective effects of small nonerythropoietic helix B surface peptide (pHBP) based upon erythropoietin structure on heart ischemic myocardial damage (I/R) of rats, and the expression effect of p44/p42 MAPK. Methods 40 rats were randomly divided into 4 groups:sham-operated group (n=10), I/R group (n=10), I/R+rhE-PO group (n=10) and I/R+pHBP group (n=10). Experimental model was established by ligating the left anterior descend-ing coronary artery, I/R+rhEPO group and I/R+pHBP group were treated with rhEPO (3000 U/kg), pHBP (1 μg/kg) re-spectively after ischemia reperfusion 5 min, and the sham operation group and I/R group were given saline instead. Serum LDH,CK-MB were assessed, myocardial infarct areas were measured by TCC dyeing. After 3, 24 h of treatment, the expression of p44/p42 MAPK was analysized through Westen blot. Results he myocardial infarct size of I/R+rhEPO group [(12.32±1.27)%] and I/R+pHBP group [(11.64±2.32)%] were decreased than that of I/R group [(18.45±1.24)%], the differences were statistically significant (P 0.05)。结论 pHBP在大鼠心肌缺血损伤中具有心脏保护作用,其保护机制可能与其抑制心肌细胞凋亡有关。

  14. PI3K/Akt/GSK-3β信号通路在二氮嗪后处理减轻大鼠心肌缺血再灌注损伤中的作用:离体实验%Role of PI3K/Akt/GSK-3β signaling pathway in mitigation of ischemia-reperfusion injury by diazoxide postconditioning in isolated rat hearts

    Institute of Scientific and Technical Information of China (English)

    王英; 谢平; 张琳; 刘兴奎; 喻田

    2014-01-01

    diazoxide postconditioning in isolated rat hearts.Methods Pathogen-free Sprague-Dawley rats were used in the study.Thirty hearts were excised and passively perfused in a Langendorff apparatus with oxygenated K-H solution at 37 ℃.The hearts were randomly divided into 5 groups (n =6 each) using a random number table:control group (group C),I/R group,diazoxide postconditioning group (group DZ),PI3K inhibitor LY294002 group (group LY),and diazoxide postconditioning + LY294002 group (group DZ + LY).In group C,the hearts were continuously perfused with K-H solution for 70 min.In group I/R,the hearts were perfused with cardioplegic solution 4 ℃ ST-Thomas 10 ml/kg,the perfusion pump was then stopped to induce global ischemia,and 40 min later the hearts were perfused with K-H solution for 30 min.In DZ group,5 min of retrograde perfusion with diazoxide 50μmol/L was performed through the aorta starting from the onset of reperfusion.In LY group,5 min of retrograde perfusion with LY294002 15 μnol/L was performed through the aorta starting from the onset of reperfusion.In LY + DZ group,5 min of retrograde perfusion with LY294002 15 μmol/L was performed through the aorta starting from the onset of reperfusion,followed by 5 min of retrograde perfusion with diazoxide 50 μmol/L.At 20 min of stabilization (T1) and 30 min of reperfusion (T2),heart rate (HR),coronary flow (CF),left ventricular developed pressure (LVDP),left ventricular developed pressure (LVEDP) and ± dp/dtmax were measured.The expression of total Akt (t-Akt) and total GSK-3β (t-GSK-3β) and phosphorylation of Akt and GSK-3β in myocardial tissues were determined by Western blot.Results Compared with C group,HR,LVDP and ± dp/dtmax were significantly decreased,and LVEDP was increased at T2 in the other four groups,CF was decreased in I/R,LY and DZ + LY groups,and the phosphorylation of Akt and GSK-3β in myocardial tissues was increased in DZ group.Compared with I/R group,HR,CF,LVDP and ± dp/dtmax were significantly

  15. Ultrastructural changes of rat cortical neurons following ligustrazine intervention for cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Hui Zhang; Jianfeng Dong; Qiuzhen Zhao; Wen Song; Aihua Bo

    2008-01-01

    BACKGROUND: Ligustrazine can reduce the production of free radicals and the content of malonaldehyde, and improve the enzymatic activity of adenosine-triphosphate in cerebral anoxia. It also can increase the expression of heat shock protein-70 and Bcl-2, thus alleviating brain tissue injury caused by cerebral ischemia/reperfusion. This study aimed to address the question of whether ligustrazine can protect the membrane structure of neurons.OBJECTIVE: To establish rat models of cerebral ischemia/reperfusion, observe the membrane structure and main organelles of neurons with electron microscope after ligustrazine intervention, and to analyze the dose-dependent effects of ligustrazine on neuronal changes.DESIGN: Arandomized controlled study.SETTING: Department of Anatomy Research and Electron Microscopy, Hebei North University. MATERIALS: Forty Wistar rats of SPS grade, weighing 180–250 g and equal proportion of female and male, were provided by Hebei Medical University Animal Center (No. 060126). The ligustrazine injection (40 g/L, No. 05012) was produced by Beijing Yongkang Yaoye. LKB4 Ultramicrotome was purchased from LKB Company in Sweden. JEM100CXII electron microscope was purchased from JEOL in Japan.METHODS: The experiment was performed in the Laboratory of the Department of Anatomy and Electron Microscopy, Hebei North University from June to August 2006. ① Wistar rats were allowed to adapt for 3 days, and were then randomly divided into four groups, according to the numeration table method: normal group, model group, low-dose ligustrazine group, and high-dose ligustrazine group. There were 10 rats in each group. ②Rats in the model group, low-dose ligustrazine group, and high-dose ligustrazine group un-derwent cerebral ischemia/reperfusion model, according to Bannister's method. The carotid artery was opened for reperfusion after 90 minutes of cerebral ischemia. Samples were collected from the cerebral cor-tex after 24 hours. Animals from the ligustrazine

  16. Activation and subcellular distribution of ERK1/2 following cerebral ischemia/reperfusion in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    WANG Rui-min; ZHANG Guang-yi; ZHANG Quan-guang; YANG Fang; MA Wen-dong; LI Qi-jia

    2006-01-01

    Objective:To investigate the activation (phosphorylation) and subcellular localization of extracellular signal-regulated kinase(ERK1/2), as well as the possible mechanism, following cerebral ischemia and ischemia/reperfusion in rat hippocampus. Methods: Transient brain ischemia was induced by the four-vessel occlusion method in Sprague-Dawley rats. Western blot analysis. Results: During cerebral ischemia without reperfusion ERK1/2 activation immediately increased with a peak at 5 min and then decreased in the cytosol fraction, which was paralleled by the increase of ERK1/2 activation in the nucleus fraction. During reperfusion, ERK1/2 was activated with peaks occurring at 10 min in the cytosol and at 30 min in the nucleus, respectively. Under those conditions, the protein expressions had no significant change. In order to clarify the possible mechanism of ERK1/2 activation, the rats were intraperitoneally administrated with N-methyl D aspartate (NMDA) receptor antagonist dextromethorphan(DM), L-type voltage-gated Ca2+ channel (L-VGCC) antagonist nifedipine (ND) 20 min before ischemia, finding that DM and ND markedly prevented ERK1/2 activation of nucleus fraction induced by reperfusion, not by ischemia. Conclusion: These results suggested that the nuclear translocation mainly occurred during is chemia, while ischemia-reperfusion induced ERK1/2 activation both in the cytosol and the nucleus. Two type calcium channels contributed, at least partially, to the activation of ERK1/2.

  17. Dose-dependent effects of procyanidin on nerve growth factor expression following cerebral ischemia/ reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Feng Li; Hai Xie; Ying Gao; Tongxia Zhan

    2008-01-01

    BACKGROUND: Recently, grape seed procyanidin (GSP) has been shown to be exhibit antioxidant effects, effectively reducing ischemia/reperfusion injury and inhibiting brain cell apoptosis.OBJECTIVE: To study the effects of GSP on nerve growth factor (NGF) expression and neurological function following cerebral ischemia/reperfusion injury in rats.DESIGN: Randomized controlled study based on SD rats.SETTING: Weifang Municipal People's Hospital. MATERIALS: Forty-eight healthy adult SD rats weighing 280-330 g and irrespective of gender were provided by the Experimental Animal Center of Shandong University. GSP derived from grape seed was a new high-effective antioxidant provided by Tianjin Jianfeng Natural Product Researching Company (batch number: 20060107). Rabbit-anti-rat NGF monoclonal antibody was provided by Beijing Zhongshan Biotechnology Co., Ltd., and SABC immunohistochemical staining kit by Wuhan Boster Bioengineering Co., Ltd. METHODS: The present study was performed in the Functional Laboratory of Weifang Medical College from April 2006 to January 2007. Forty-eight SD rats were randomly divided into the sham operation group, ischemia/reperfusion group, high-dose GSP (40 mg/kg) group, or low-dose GSP (10 mg/kg) group (n = 12 per group). Ischemia/reperfusion injury was established using the threading embolism method of the middle cerebral artery. Rats in the ischemia/reperfusion model group were given saline injection (2 mL/kg i.p.) once daily for seven days pre-ischemia/reperfusion, and once more at 15 minutes before reperfusion. Rats in the high-dose and low-dose GSP groups were injected with GSP (20 or 5 mg/mL i.p., respectively, 2 mL/kg) with the same regime as the ischemia/reperfusion model group. The surgical procedures in the sham operation group were as the same as those in the ischemia/reperfusion model group, but the thread was approximately 10 mm long, thus, the middle cerebral artery was not blocked. MAIN OUTCOME MEASURES: NGF expression in the

  18. Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

    Science.gov (United States)

    Kip, Gülay; Çelik, Ali; Bilge, Mustafa; Alkan, Metin; Kiraz, Hasan Ali; Özer, Abdullah; Şıvgın, Volkan; Erdem, Özlem; Arslan, Mustafa; Kavutçu, Mustafa

    2015-01-01

    Objective Diabetic complications and lipid peroxidation are known to have a close association. Lipid peroxidation commonly occurs at sites exposed to ischaemia, but distant organs and tissues also get damaged during ischaemia/reperfusion (I/R). Some of these targets are vital organs, such as the lung, liver, and kidney; the lung is the most frequently affected. The aim of our study was to investigate the effects of dexmedetomidine on I/R damage in lung tissue and on the oxidant/anti-oxidant system in diabetic rats. Material and methods Diabetes was induced with streptozotocin (55 mg/kg) in 18 Wistar Albino rats, which were then randomly divided into three groups (diabetes control (DC), diabetes plus ischaemia-reperfusion (DIR), and diabetes plus dexmedetomidine-ischaemia/reperfusion (DIRD)) after the effects of diabetes were clearly evident. The rats underwent a left thoracotomy and then ischaemia was produced in the myocardium muscle by a left anterior descending artery ligation for 30 min in the DIR and DIRD groups. I/R was performed for 120 min. The DIRD group received a single intraperitoneal dose of dexmedetomidine (100 µg/kg); the DIR group received no dexmedetomidine. Group DC was evaluated as the diabetic control group and also included six rats (C group) in which diabetes was not induced. These mice underwent only left thoracotomy and were closed without undergoing myocardial ischaemia. Histopathological changes, activities of catalase (CAT) and glutathione-S-transferase anti-oxidant enzymes, and malondialdehyde (MDA) levels were evaluated in the lung tissues of all rats. Results Neutrophil infiltration/aggregation was higher in the DIR group than in the C, DC, and DIRD groups (p=0.001, p=0.013, and p=0.042, respectively). The lung injury score was significantly higher in the DIR group than in the C and DC groups (p<0.0001 and p=0.024, respectively). The levels of MDA were significantly higher in the DIR group than in the C and DIRD groups. CAT activity

  19. Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

    Directory of Open Access Journals (Sweden)

    Gülay Kip

    2015-09-01

    Full Text Available Objective: Diabetic complications and lipid peroxidation are known to have a close association. Lipid peroxidation commonly occurs at sites exposed to ischaemia, but distant organs and tissues also get damaged during ischaemia/reperfusion (I/R. Some of these targets are vital organs, such as the lung, liver, and kidney; the lung is the most frequently affected. The aim of our study was to investigate the effects of dexmedetomidine on I/R damage in lung tissue and on the oxidant/anti-oxidant system in diabetic rats. Material and methods: Diabetes was induced with streptozotocin (55 mg/kg in 18 Wistar Albino rats, which were then randomly divided into three groups (diabetes control (DC, diabetes plus ischaemia-reperfusion (DIR, and diabetes plus dexmedetomidine-ischaemia/reperfusion (DIRD after the effects of diabetes were clearly evident. The rats underwent a left thoracotomy and then ischaemia was produced in the myocardium muscle by a left anterior descending artery ligation for 30 min in the DIR and DIRD groups. I/R was performed for 120 min. The DIRD group received a single intraperitoneal dose of dexmedetomidine (100 µg/kg; the DIR group received no dexmedetomidine. Group DC was evaluated as the diabetic control group and also included six rats (C group in which diabetes was not induced. These mice underwent only left thoracotomy and were closed without undergoing myocardial ischaemia. Histopathological changes, activities of catalase (CAT and glutathione-S-transferase anti-oxidant enzymes, and malondialdehyde (MDA levels were evaluated in the lung tissues of all rats. Results: Neutrophil infiltration/aggregation was higher in the DIR group than in the C, DC, and DIRD groups (p=0.001, p=0.013, and p=0.042, respectively. The lung injury score was significantly higher in the DIR group than in the C and DC groups (p<0.0001 and p=0.024, respectively. The levels of MDA were significantly higher in the DIR group than in the C and DIRD groups. CAT

  20. Role of N-Nitro-L-Arginine-Methylester as anti-oxidant in transient cerebral ischemia and reperfusion in rats

    Directory of Open Access Journals (Sweden)

    Awooda Hiba A

    2013-01-01

    Full Text Available Abstract Background Previous reports assessing the neuroprotective role of nonselective Nitric Oxide synthase (NOS inhibitor N-nitro-L-arginine-methylester (L-NAME following cerebral ischemia/reperfusion are contradictory. The aim of this work was to examine the potential benefits of L-NAME on rats subjected to transient focal cerebral ischemia/reperfusion. Methods The study involved 30 adult male Wistar rats divided into three groups 10 rats in each: First group was sham-operated and served as a control, a ischemia/reperfusion (I/R group of rats infused with 0.9% normal saline intraperitoneally 15 minutes prior to 30 minutes of left common carotid artery (CCA occlusion and a test group infused with L-NAME intraperitoneally 15 minutes prior to ischemia. Neurobehavioral assessments were evaluated and quantitative assessment of malondialdehyde (MDA, Nitric oxide (NO metabolites and total antioxidant capacity (TAC in both serum and the affected cerebral hemisphere were achieved. Results Rats’ neurological deficit and TAC were significantly decreased while NO and MDA were significantly increased in the I/R compared with the control group (P Conclusions L-NAME pretreatment for rats undergoing cerebral ischemia/reperfusion significantly improves neurological deficit while reducing oxidative stress biomarkers in the affected cerebral hemisphere.

  1. Postextrasystolic potentiation in the isolated rat heart

    NARCIS (Netherlands)

    Meijler, F.L.; Boogaard, F. van de; Tweel, H. van der; Durrer, D.

    1962-01-01

    “Postextrasystolic potentiation" of isotonic contractions of the intact isolated rat heart was studied. It was found that the Frank-Starling mechanism does not participate in the increase of the contraction following a premature beat and a compensatory pause. A linear relationship could be demonstra

  2. Pretreatment with mangafodipir improves liver graft tolerance to ischemia/reperfusion injury in rat.

    Directory of Open Access Journals (Sweden)

    Ismail Ben Mosbah

    Full Text Available Ischemia/reperfusion injury occurring during liver transplantation is mainly due to the generation of reactive oxygen species (ROS upon revascularization. Thus, delivery of antioxidant enzymes might reduce the deleterious effects of ROS and improve liver graft initial function. Mangafodipir trisodium (MnDPDP, a contrast agent currently used in magnetic resonance imaging of the liver, has been shown to be endowed with powerful antioxidant properties. We hypothesized that MnDPDP could have a protective effect against liver ischemia reperfusion injury when administrated to the donor prior to harvesting. Livers from Sprague Dawley rats pretreated or not with MnDPDP were harvested and subsequently preserved for 24 h in Celsior® solution at 4°C. Organs were then perfused ex vivo for 120 min at 37°C with Krebs Henseleit solution. In MnDPDP (5 µmol/kg group, we observed that ATP content was significantly higher at the end of the cold preservation period relative to untreated group. After reperfusion, livers from MnDPDP-treated rats showed better tissue integrity, less hepatocellular and endothelial cell injury. This was accompanied by larger amounts of bile production and higher ATP recovery as compared to untreated livers. The protective effect of MnDPDP was associated with a significant decrease of lipid peroxidation, mitochondrial damage, and apoptosis. Interestingly, MnDPDP-pretreated livers exhibited activation of Nfr2 and HIF-1α pathways resulting in a higher catalase and HO-1 activities. MnDPDP also increased total nitric oxide (NO production which derived from higher expression of constitutive NO synthase and lower expression of inducible NO synthase. In conclusion, our results show that donor pretreatment with MnDPDP protects the rat liver graft from cold ischemia/reperfusion injury and demonstrate for the first time the potential interest of this molecule in the field of organ preservation. Since MnDPDP is safely used in liver imaging

  3. Effect of monoamine nervous transmitter and neuropeptide Y in the aged rats with myocardial injury after brain ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the mechanism of myocardial injury after brain ischemia-reperfusion in aged rats from the changes in Dopamine (DA), Noradrenalin (NE), Epinephrine(E) and Neuropeptide Y(NPY).METHODS: Young (5 months) and aged (20 months or more) rats were divided into model groups and normal control groups, respectively. We observed the following items in rats with 60 minute reperfusion after 30 minute brain ischemia: the pathological changed of myocardium, the activities of lactic dehydrrogenase(LDH), creatine phosphokinase(CPK), the contents of NE, DA, E, NPY. RESULTS:The CPK and LDH activities in the young model rats were higher than those in the young control rats was higher than that in the young control rats (P<0.05). The serum CPK activity in the aged control rats was higher than that in the young control rats (P<0.05). The myocardial CPK activity was higher in the aged model rats compared with the young molel rats (P<0.05) and was higher in aged control rats compared with the young control rats (P<0.01). The myocardial LDH activity was lower in the aged control rats than that in the young control rats (P<0.05) and aged model rats (P<0.01). The serum NE level, the level of NE and DA in the hypothalamus were higher obviously than those in the young control rats. The serum NE contents in the two model groups (young and aged) were higher respectively than the two control rats (young and aged). The following items’ contents were higher in the aged model rats than in the young model rats: serum NE, serum E, hypothalamus NE. The hypothalamus NE and E content was lower in the aged model rats than in te aged control rats. NPY level in the brain tissue was lower in the aged control rats than that in the young control rats and aged model rats (P<0.05).CONCLUSION: The myocardial injury after brain ischemia-reperfusion was concerned with the enhanced excitability of sympathetic-adrenal system, espectially in the aged rats. However, the change in myocardial

  4. Effects of Metallothionein on Isolated Rat Heart

    Institute of Scientific and Technical Information of China (English)

    SUN Zhongdong; XIA Jiahong; DONG Nianguo; DU Xinling; CHI Yifan; YANG Tienan; YANG Chenyuan

    2007-01-01

    To investigate the effects of metallothionein (MT) on isolated rat heart, 16 Wistar rats were randomly divided into 2 groups. In control group (group C), distilled water was injected intraperitoneally and 24 h later isolated hearts were perfused with Langendorff and stored at 4℃ for 3 h with histidine-tryptophan-ketoglutarate (HTK) solutions, and then isolated hearts were perfused for 2 h by Langendorff. In experimental group (group E), 3.6% ZnSO4 was injected intraperitoneally, 24 h later isolated hearts were perfused by Langendorff and stored at 4℃ for 3 h with HTK solutions, and then the isolated herts were perfused for 2 h with Langendorff. MT content, the recovery of hemodynamics, myocardial water content (MWC), lactate dehydrogenase (LDH) and creatine kinase (CK) leakage, adenosine triphosphate (ATP) and malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, myocardial cell Ca2+ content, Ca2+-ATPase activity of mitochondria ([Ca2+-ATPase]m) and its Ca2+ content ([Ca2+]m), synthesizing ATP activity of mitochondria ([ATP]m), and the ultrastructure of cells were examined. There were a significant increase in group E in hemodynamic recovery, ATP content, SOD activity, [Ca2+-ATPase]m activity, [ATP]m activity, and substantial reduction in MWC, LDH and CK leakage, MDA content, myocardial cell Ca2+ content, [Ca2+]m content,and the ultrastructural injury were obviously milder than that of group C. This study demonstrated that MT has protective effects on isolated rat heart.

  5. Protective effects of Guizhi-Fuling-Capsules on rat brain ischemia/reperfusion injury.

    Science.gov (United States)

    Li, Tie-Jun; Qiu, Yan; Mao, Jun-Qin; Yang, Peng-Yuan; Rui, Yao-Cheng; Chen, Wan-Sheng

    2007-09-01

    Previous studies revealed that Guizhi-Fuling-Capsules (GZFLC), a traditional Chinese medical (Kampo) formulation composed of five kinds of medicinal plants, Cinnamomum cassia BLUME (Cinnamomi Cortex), Paeonia lactiflora PALL. (Peonies Radix), Paeonia suffruticosa ANDREWS (Moutan Cortex), Prunus persica BATSCH (Persicae Semen), and Poria cocos WOLF (Hoelen), exerts a protective effect against vascular injury and has a protective effect against glutamate- or nitro oxide-mediated neuronal damage. In the present study, the effect of GZFLC in a rat in vivo model of focal cerebral ischemia and reperfusion was investigated. Administration of GZFLC (0.3 and 0.9 g/kg, p.o.) after focal cerebral ischemia significantly decreased brain infarction and water contents in rats subjected to 2-h ischemia followed by 24-h reperfusion from 31.72 +/- 2.49%, 84.76 +/- 1.63% in the model group to 17.31 +/- 3.66%, 82.51 +/- 1.36% and 8.30 +/- 3.73%, 81.35 +/- 1.73%, respectively. Furthermore, analysis of inflammatory cytokines in ischemic brain showed that GZFLC treatment significantly down-regulated expressions of pro-inflammatory cytokines including interleukin (IL)-1beta and tissue necrosis factor-alpha and markedly up-regulated expressions of anti-inflammatory cytokines IL-10 and IL-10R both in mRNA and protein levels. The serum levels of these inflammatory cytokines were also regulated the same way. These results suggested that GZFLC may be beneficial for the treatment of brain ischemia-reperfusion injury partly due to its anti-inflammatory properties.

  6. Protective effect of nitric oxide induced by ischemic preconditioning on reperfusion injury of rat liver graft

    Institute of Scientific and Technical Information of China (English)

    Jian-Ping Gong; Bing Tu; Wei Wang; Yong Peng; Shou-Bai Li; Lu-Nan Yan

    2004-01-01

    AIM: Ischemic preconditioning (IP) is a brief ischemic episode,which confers a state of protection against the subsequent long-term ischemia-reperfusion injuries. However, little is known regarding the use of IP before the sustained cold storage and liver transplantation. The present study was designed to evaluate the protective effect of IP on the long-term preservation of liver graft and the prolonged anhepatic-phase injury.METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation. All livers underwent 10 min of ischemia followed by 10 min of reperfusion before harvest. Rat liver transplantation was performed with the portal vein clamped for 25 min. Tolerance of transplanted liver to the reperfusion injury and liverdamage were investigated. The changes in adenosineconcentration in hepatic tissue and those of nitric oxide (NO)and tumor necrosis factor (TNF) in serum were also assessed.RESULTS: Recipients with IP significantly improved theirone-week survival rate and liver function, they had increasedlevels of circulating NO and hepatic adenosine, and a reducedlevel of serum TNF, as compared to controls. Histologicalchanges indicating hepatic injuries appeared improved in theIP group compared with those in control group. The protectiveeffect of IP was also obtained by administration of adenosine,while blockage of the NO pathway using Nω-nitro-L-argininemethyl ester abolished the protective effect of IRCONCLUSION: IP appears to have a protective effect onthe long-term preservation of liver graft and the prolongedanhepatic-phase injuries. NO may be involved in this process.

  7. Intermedin protects against myocardial ischemia-reperfusion injury in hyperlipidemia rats.

    Science.gov (United States)

    Yang, S M; Liu, J; Li, C X

    2014-10-20

    Hyperlipidemia is a well-established risk factor for the development of coronary atherosclerosis, while intermedin (IMD) has been identified as a novel calcitonin/calcitonin gene-related peptide family member involved in cardiovascular protection. However, whether IMD protects against hyperlipidemia-associated myocardial ischemia/reperfusion (MI/R) injury is unknown. We established a hyperlipidemia model using Sprague-Dawley rats, and created a MI/R condition by ligating the cardiac left circumflex artery. The possible pathophysiological role of IMD and its physiological function in MI/R was further studied. The level of IMD significantly decreased in hyperlipidemia rats (P hyperlipidemia rats compared to the sham-operated rats (P hyperlipidemia rats (P hyperlipidemia-associated MI/R injury. Additional IMD could protect cardiac myocytes against MI/R injury via reduction of apoptosis and inflammation in the hyperlipidemia rat model, and thus, it may play a potential role as a novel therapeutic target for cardiac ischemic injury in hyperlipidemic patients.

  8. Butyrate protects rat liver against total hepatic ischemia reperfusion injury with bowel congestion.

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    Bin Liu

    Full Text Available Hepatic ischemia/reperfusion (I/R injury is an unavoidable consequence of major liver surgery, especially in liver transplantation with bowel congestion, during which endotoxemia is often evident. The inflammatory response aggravated by endotoxin after I/R contributes to liver dysfunction and failure. The purpose of the present study was to investigate the protective effect of butyrate, a naturally occurring four-carbon fatty acid in the body and a dietary component of foods such as cheese and butter, on hepatic injury complicated by enterogenous endotoxin, as well as to examine the underlying mechanisms involved. SD rats were subjected to a total hepatic ischemia for 30 min after pretreatment with either vehicle or butyrate, followed by 6 h and 24 h of reperfusion. Butyrate preconditioning markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathological changes. The inflammatory factors levels, macrophages activation, TLR4 expression, and neutrophil infiltration in live were attenuated by butyrate. Butyrate also maintained the intestinal barrier structures, reversed the aberrant expression of ZO-1, and decreased the endotoxin translocation. We conclude that butyrate inhibition of endotoxin translocation, macrophages activation, inflammatory factors production, and neutrophil infiltration is involved in the alleviation of total hepatic I/R liver injury in rats. This suggests that butyrate should potentially be utilized in liver transplantation.

  9. Induction of chagasic-like arrhythmias in the isolated beating hearts of healthy rats perfused with Trypanosoma cruzi-conditioned medium

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    H. Rodriguez-Angulo

    2013-01-01

    Full Text Available Chagas' myocardiopathy, caused by the intracellular protozoan Trypanosoma cruzi, is characterized by microvascular alterations, heart failure and arrhythmias. Ischemia and arrythmogenesis have been attributed to proteins shed by the parasite, although this has not been fully demonstrated. The aim of the present investigation was to study the effect of substances shed by T. cruzi on ischemia/reperfusion-induced arrhythmias. We performed a triple ischemia-reperfusion (I/R protocol whereby the isolated beating rat hearts were perfused with either Vero-control or Vero T. cruzi-infected conditioned medium during the different stages of ischemia and subsequently reperfused with Tyrode's solution. ECG and heart rate were recorded during the entire experiment. We observed that triple I/R-induced bradycardia was associated with the generation of auricular-ventricular blockade during ischemia and non-sustained nodal and ventricular tachycardia during reperfusion. Interestingly, perfusion with Vero-infected medium produced a delay in the reperfusion-induced recovery of heart rate, increased the frequency of tachycardic events and induced ventricular fibrillation. These results suggest that the presence of parasite-shed substances in conditioned media enhances the arrhythmogenic effects that occur during the I/R protocol.

  10. A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo.

    Science.gov (United States)

    Tang, Yao Liang; Qian, Keping; Zhang, Y Clare; Shen, Leping; Phillips, M Ian

    2005-12-01

    The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed. When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy "vigilant vector'' system that amplifies cardioprotective gene expression. Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed. Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling. The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.

  11. Changes in corticocerebral morphology in a rat model of focal cerebral ischemia/reperfusion injury following"Xingnao Kaiqiao" acupuncture

    Institute of Scientific and Technical Information of China (English)

    Shu Wang; Zhankui Wang; Guangxia Ni

    2008-01-01

    BACKGROUND: Cerebral ischemia/reperfusion injury has been shown to induce inflammatory reactions,including white blood cell activation and adhesion molecule expression. These reactions often lead to aggravated neuronal injury.OBJECTIVE: To observe corticocerebral pathology, as well as ultrastructural changes, in a rat model of focal cerebral ischemia/reperfusion injury through optical and electron microscopy, and to investigate interventional effects of "Xingnao Kaiqiao" acupuncture (a brain-activating and orifice-opening acupuncture method).DESIGN, TIME AND SETTING: A randomized, controlled, neuropathology, animal experiment was performed at the Laboratory of Molecular Biology, First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine between April and June 2004.MATERIALS: A total of 50 healthy, male, Wistar rats were randomized into 5 groups, with 10 rats per group: control, sham-operated, model, non-acupoint, and "Xingnao Kaiqiao". Transmission electron microscope (TEM 400ST) was provided by Philips, Netherlands. Electro-acupuncture treatment apparatus (KWD-8082) was provided by Changzhou Wujin Great Wall Medical Instrument, China.METHODS: Focal cerebral ischemia/reperfusion injury was induced by occlusion of the middle cerebral artery in the model, non-acupoint, and "Xingnao Kaiqiao" groups. Rats from the control group did not undergo any treatment. The sham-operated group received identical experimental procedures as the model group, except that the nylon suture was not inserted into the right internal carotid artery. At 1, 3, 6, and 12 hours following focal cerebral ischemia/dreperfusion injury induction, rats from the Xingnao Kaiqiao group underwent l-minute acupuncture at the bilateral "Neiguan" (PC 6) acupoint, using a reducing method of lifting-thrusting and twirling-rotating. Subsequently, the rats were subjected to acupuncture at the "Renzhong" (DU26) acupoint 10 times by a heavy bird-pecking method. The non-acupoint group received

  12. TNF-α and plasma D(-)-lactate levels in rats after intestinal ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Yongming YAO; Ailan REN; Shengli DONG; Ning DONG; Yan YU; Zhiyong SHENG

    2004-01-01

    Objective To study the potential role of tumor necrosis factor-α (TNF-α) induction in the development of mucosal barrier dysfunction in rats caused by acute intestinal ischemia-reperfusion injury, and to examine whether pretreatment with monoclonal antibody against TNF-α (TNF-α MoAb) would affect the release of D(-)-lactate after local gut ischemia followed by reperfusion. Methods Anesthetized Sprague-Dawley rats underwent superior mesenteric artery occlusion for 75 min followed by reperfusion for 6 hr. The rats were treated intravenously with either TNF-α MoAb (20 mg/kg) or albumin (20 mg/kg) 30 min prior to the onset of ischemia. Plasma D(-)-lactate levels were measured in both the portal and systemic blood by an enzymatic spectrophotometric assay. Intestinal TNF-αmRNA expression as well as protein levels were also measured at various intervals. In addition, a postmortem examination was performed together with a macropathological evaluation based on a four-grade scoring system.Results Intestinal ischemia resulted in a significant elevation in D(-)-lactate levels in the portal vein blood in both the control and treatment groups ( P <0.05). However, animals pretreated with TNF-α MoAb at 6 hr after reperfusion showed significant attenuation of an increase in both portal and systemic D(-)-lactate levels when compared with those only receiving albumin (P < 0.05). In the control animals, a remarkable rise in intestinal TNF-α level was measured at 0.5 hr after clamp release ( P < 0.01); however, prophylactic treatment with TNF-α MoAb completely annulled the increase of local TNF-α levels seen in the control animals. Similarly, after anti-TNF-α MoAb administration, intestinal TNF-α mRNA expression was markedly inhibited, which showed significant differences when compared with the control group at 0.5 hr, 2 hr and 6 hr after the release of occlusion ( P < 0.05-0.01 ). In addition, the pathological examination showed marked intestinal lesions that

  13. Glutamine supplemented parenteral nutrition prevents intestinal ischemia- reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Guo-Hao Wu; Hao Wang; Yan-Wei Zhang; Zhao-Han Wu; Zhao-Guang Wu

    2004-01-01

    AIM: To examine whether glutamine prevents the injury to the intestinal mucosa after intestinal ischemia-reperfusion (I/R) in rats.METHODS: Thirty male Sprague-Dawley rats were randomly divided into 3 groups: a standard parenteral nutrition (PN)group (n = 10); an I/R-PN group (n = 10); an I/R-glutamine enriched PN (I/R-Gln) group (n = 10). The superior mesenteric artery (SMA) was clamped. After 60 min of ischemia, reperfusion was initiated and infusion was started. All rats received isocaloric and isonitrogenous nutritional support for 48 h. Spleen, liver, mesenteric lymph nodes (MLN), and intestinal segments were removed for morphological and biochemical analyses, and blood samples were collected for bacterial culture and measurement of endotoxin levels.The permeability of intestinnal mucosa was assayed by measurement of D-(-)-lactate levels in plasma.RESULTS: In I/R-PN group, extensive epithelial atrophy was observed, mucosal thickness, villous height, crypt depth and villous surface area were decreased significantly compared with PN group, whereas these findings did not occur in the I/R-Gln group. The incidence of intestinal bacterial translocation to spleen, liver, MLN, and blood was significantly higher in I/R-PN group than that in other groups.Plasma endotoxin levels significantly increased in the I/R-PN group compared with the I/R-Gln group. Remarkably higher values of D-(-)-lactate were also detected in PN group compared with that in I/R-Gln group.CONCLUSION: Glutamine protects the morphology and function of intestinal mucosa from injury after I/R in rats.

  14. Protective Effects of Hydrocortisone, Vitamin C and E Alone or in Combination against Renal Ischemia-Reperfusion Injury in Rat

    Science.gov (United States)

    Azari, Omid; Kheirandish, Reza; Azizi, Shahrzad; Farajli Abbasi, Mohammad; Ghahramani Gareh Chaman, Shahin; Bidi, Masoud

    2015-01-01

    Background: Renal ischemia reperfusion injury may occur in a variety of clinical situations, following a transient drop in total or regional blood flow to the kidney. This study was performed to investigate the protective effects of different antioxidants such as vitamin C, vitamin E, hydrocortisone and combination of these agents against experimental renal ischemia-reperfusion injury. Method: Thirty male rats were divided into six groups. Group Sham, Group I/R: (45 min of ischemia followed by 1h of reperfusion), Group I/R+Vit C: (50 mg/kg Vit C, IV, immediately after reperfusion), Group I/R+Vit E: (20 mg/kg Vit E, IM, 15 min before reperfusion), Group I/R+Hydrocortisone: (50 mg/kg, IV, immediately after reperfusion), and Group Combination: Ischemia-reperfusion plus combination of Vit C, E and hydrocortisone. After the experiments, the left kidney was removed and the tissues were processed for histopathological examination. Result: Severe injuries such as necrosis of tubules, atrophy of glomerulus, and hemorrhage were observed in group I/R. Histological scores indicating tissue injury significantly decreased in all treatment groups compared to the group I/R. The renal tissue in group treatment was preserved in comparison with the group I/R. Comparison between the treatment groups showed that group combination was more effective and group vit E was less effective in protecting of renal tissue against I/R injuries. Conclusion: The results demonstrated simultaneous administration of combination of Vit C, E and hydrocortisone before reperfusion of blood flow to the ischemic tissue could show a synergy against deleterious effects of I/R injuries in kidney. PMID:26351497

  15. The study of protective effects and mechanisms of rofecoxib on focal cerebral ischemia- reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    YUJuan; ZHOUYu; QIULi-Ying; CHENBai-Ling; CHENChong-Hong

    2004-01-01

    AIM : To study the protective effects and the mechanisms of rofecoxib as a specific type 2 cyclooxygenase (COX- 2 inhibitor on focal cerebral ischemia reperfusion injury ( CIRI in rats. METHODS : The model of focal CIRI was induced by reversible middle cerebral artery occlusion ( MCAO with inserting a thread through internal carotid artery, 2 h occlusion followed

  16. Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries in the rat liver.

    Science.gov (United States)

    Møller, Lin Nanna Okholm; Knudsen, Anders Riegels; Andersen, Kasper Jarlhelt; Nyengaard, Jens Randel; Hamilton-Dutoit, Stephen; Okholm Møller, Elise Marie; Svendsen, Pia; Møller, Holger Jon; Moestrup, Søren Kragh; Graversen, Jonas Heilskov; Mortensen, Frank Viborg

    2015-12-01

    The Pringle maneuver is a way to reduce blood loss during liver surgery. However, this may result in ischemia/reperfusion injury in the development of which Kupffer cells play a central role. Corticosteroids are known to have anti-inflammatory effects. Our aim was to investigate whether a conjugate of dexamethasone and antibody against the CD163 macrophage cell surface receptor could reduce ischemia/reperfusion injury in the rat liver. Thirty-six male Wistar rats were used for the experiments. Animals were randomly divided into four groups of eight receiving anti-CD163-dexamethasone, high dose dexamethasone, low dose dexamethasone or placebo intravenously 18 h before laparotomy with subsequent 60 min of liver ischemia. After reperfusion for 24 h the animals had their liver removed. Bloods were drawn 30 min and 24 h post ischemia induction. Liver cell apoptosis and necrosis were analyzed by stereological quantification. After 24 h' reperfusion, the fraction of cell in non-necrotic tissues exhibiting apoptotic profiles was significantly lower in the high dose dexamethasone (p = 0.03) and anti-CD163-dex (p = 0.03) groups compared with the low dose dexamethasone and placebo groups. There was no difference in necrotic cell volume between groups. After 30 min of reperfusion, levels of haptoglobin were significantly higher in the anti-CD163-dex and high dose dexamethasone groups. Alanine aminotransferase and alkaline phosphatase were significantly higher in the high dose dexamethasone group compared to controls after 24 h' reperfusion. We show that pharmacological preconditioning with anti-CD163-dex and high dose dexamethasone reduces the number of apoptotic cells following ischemia/reperfusion injury.

  17. Combination Anti-Apoptotic Effect of Erythropoietin and Melatonin on Ischemia Reperfusion-Induced Renal Injury in Rats

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    Shokofeh Banaei

    2016-11-01

    Full Text Available Renal ischemia-reperfusion (IR contributes to the development of acute renal failure (ARF. Oxygen free radicals are considered to be principal components involved in the pathophysiological tissue alterations observed during renal IR. The purpose of this study was to investigate the combination effect of melatonin (MEL and erythropoietin (EPO, which are a potent antioxidant and anti-apoptotic agents, in IR-induced renal injury in rats. Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. MEL (10 mg/kg, i.p and EPO (5000 U/kg, i.p were administered prior to ischemia. After 24 h reperfusion, following decapitation, blood samples were collected for the determination of superoxide dismutase (SOD, glutathione peroxidase (GPx, and malondialdehyde (MDA levels. Also, renal samples were taken for histological evaluation and apoptosis assay. Ischemia-reperfusion increased SOD, GPx, MDA levels, and TUNEL positive cells. Histopathological findings of the IR group confirmed that there was renal impairment in the tubular epithelium. Treatment with EPO and MEL decreased SOD, GPx, and MDA levels, histopathological changes, and TUNEL positive cells. These results indicated that the combination of MEL and EPO could not exert more nephroprotective and anti-apoptotic effects than MEL treatment in renal ischemia-reperfusion injury.

  18. A deficiency of apoptosis inducing factor (AIF in Harlequin mouse heart mitochondria paradoxically reduces ROS generation during ischemia-reperfusion

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    Qun eChen

    2014-07-01

    Full Text Available Background and Aims: AIF (apoptosis inducing factor is a flavin and NADH containing protein located within mitochondria required for optimal function of the respiratory chain. AIF may function as an antioxidant within mitochondria, yet when released from mitochondria it activates caspase-independent cell death. The Harlequin (Hq mouse has a markedly reduced content of AIF, providing an experimental model to query if the main role of AIF in the exacerbation of cell death is enhanced mitochondrial generation of reactive oxygen species (ROS or the activation of cell death programs. We asked if the ROS generation is altered in Hq heart mitochondria at baseline or following ischemia-reperfusion (IR.Methods: Buffer perfused mouse hearts underwent 30 min ischemia and 30 min reperfusion. Mitochondrial function including oxidative phosphorylation and H2O2 generation was measured. Immunoblotting was used to determine the contents of AIF and PAR [poly(ADP-ribose] in cell fractions.Results: There were no differences in the release of H2O2 between wild type (WT and Hq heart mitochondria at baseline. IR increased H2O2 generation from WT but not from Hq mitochondria compared to corresponding time controls. The complex I activity was decreased in WT but not in Hq mice following IR. The relocation of AIF from mitochondria to nucleus was increased in WT but not in Hq mice. IR activated PARP-1 only in WT mice. Cell injury was decreased in Hq mouse heart following in vitro IR.Conclusion: A deficiency of AIF within mitochondria does not increase ROS production during IR, indicating that AIF functions less as an antioxidant within mitochondria. The decreased cardiac injury in Hq mouse heart accompanied by less AIF translocation to the nucleus suggests that AIF relocation, rather than the AIF content within mitochondria, contributes to cardiac injury during IR.

  19. The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

    Science.gov (United States)

    Kiraz, Hasan Ali; Poyraz, Fatih; Kip, Gülay; Erdem, Özlem; Alkan, Metin; Arslan, Mustafa; Özer, Abdullah; Şivgin, Volkan; Çomu, Faruk Metin

    2015-01-01

    Objective Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results Myonecrosis findings were significantly different among groups (p=0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001). Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively). Also, myocardial tissue edema was significantly different among groups (p=0.006). The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively). Conclusion Taken together, our data indicate that

  20. The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

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    Hasan Ali Kiraz

    2015-12-01

    Full Text Available Objective: Ischemia/reperfusion (I/R injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods: A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg were randomly divided into three equal groups as follows: the diabetic I/R group (DIR in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL, which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC which underwent sham operations without tightening of the coronary sutures. As a control group (C, six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results: Myonecrosis findings were significantly different among groups (p=0.008. Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively. Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001. Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively. Also, myocardial tissue edema was significantly different among groups (p=0.006. The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively. Conclusion: Taken together, our data

  1. Cardioprotection by remote ischemic preconditioning of the rat heart is mediated by extracellular vesicles.

    Science.gov (United States)

    Giricz, Zoltán; Varga, Zoltán V; Baranyai, Tamás; Sipos, Péter; Pálóczi, Krisztina; Kittel, Ágnes; Buzás, Edit I; Ferdinandy, Péter

    2014-03-01

    Remote ischemic preconditioning (RIPC) of the heart is exerted by brief ischemic insults affected on a remote organ or a remote area of the heart before a sustained cardiac ischemia. To date, little is known about the inter-organ transfer mechanisms of cardioprotection by RIPC. Exosomes and microvesicles/microparticles are vesicles of 30-100 nm and 100-1000 nm in diameter, respectively (collectively termed extracellular vesicles [EVs]). Their content of proteins, mRNAs and microRNAs, renders EV ideal conveyors of inter-organ communication. However, whether EVs are involved in RIPC, is unknown. Therefore, here we investigated whether (1) IPC induces release of EVs from the heart, and (2) EVs are necessary for cardioprotection by RIPC. Hearts of male Wistar rats were isolated and perfused in Langendorff mode. A group of donor hearts was exposed to 3 × 5-5 min global ischemia and reperfusion (IPC) or 30 min aerobic perfusion, while coronary perfusates were collected. Coronary perfusates of these hearts were given to another set of recipient isolated hearts. A group of recipient hearts received IPC effluent depleted of EVs by differential ultracentrifugation. Infarct size was determined after 30 min global ischemia and 120 min reperfusion. The presence or absence of EVs in perfusates was confirmed by dynamic light scattering, the EV marker HSP60 Western blot, and electron microscopy. IPC markedly increased EV release from the heart as assessed by HSP60. Administration of coronary perfusate from IPC donor hearts attenuated infarct size in non-preconditioned recipient hearts (12.9 ± 1.6% vs. 25.0 ± 2.7%), similarly to cardioprotection afforded by IPC (7.3 ± 2.7% vs. 22.1 ± 2.9%) on the donor hearts. Perfusates of IPC hearts depleted of EVs failed to exert cardioprotection in recipient hearts (22.0 ± 2.3%). This is the first demonstration that EVs released from the heart after IPC are necessary for cardioprotection by RIPC, evidencing the importance of vesicular

  2. Hypercholesterolemia downregulates autophagy in the rat heart.

    Science.gov (United States)

    Giricz, Zoltán; Koncsos, Gábor; Rajtík, Tomáš; Varga, Zoltán V; Baranyai, Tamás; Csonka, Csaba; Szobi, Adrián; Adameová, Adriana; Gottlieb, Roberta A; Ferdinandy, Péter

    2017-03-23

    We have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathways. Therefore, we investigated whether isolated hypercholesterolemia modulates cardiac autophagy-related pathways or programmed cell death mechanisms such as apoptosis and necroptosis in rat heart. Male Wistar rats were fed either normal chow (NORM; n = 9) or with 2% cholesterol and 0.25% cholic acid-enriched diet (CHOL; n = 9) for 12 weeks. CHOL rats exhibited a 41% increase in plasma total cholesterol level over that of NORM rats (4.09 mmol/L vs. 2.89 mmol/L) at the end of diet period. Animals were sacrificed, hearts were excised and briefly washed out. Left ventricles were snap-frozen for determination of markers of autophagy, mTOR pathway, apoptosis, and necroptosis by Western blot. Isolated hypercholesterolemia was associated with a significant reduction in expression of cardiac autophagy markers such as LC3-II, Beclin-1, Rubicon and RAB7 as compared to controls. Phosphorylation of ribosomal S6, a surrogate marker for mTOR activity, was increased in CHOL samples. Cleaved caspase-3, a marker of apoptosis, increased in CHOL hearts, while no difference in the expression of necroptotic marker RIP1, RIP3 and MLKL was detected between treatments. This is the first comprehensive analysis of autophagy and programmed cell death pathways of apoptosis and necroptosis in hearts of hypercholesterolemic rats. Our data show that isolated hypercholesterolemia suppresses basal cardiac autophagy and that the decrease in autophagy may be a result of an activated mTOR pathway. Reduced autophagy was accompanied by increased apoptosis, while cardiac necroptosis was not modulated by isolated hypercholesterolemia. Decreased basal autophagy and elevated apoptosis may be responsible for the

  3. Protective role of adiponectin in a rat model of intestinal ischemia reperfusion injury

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    Liu, Xu-Hui; Yang, Yue-Wu; Dai, Hai-Tao; Cai, Song-Wang; Chen, Rui-Han; Ye, Zhi-Qiang

    2015-01-01

    AIM: To determine the potential protective role of adiponectin in intestinal ischemia reperfusion (I/R) injury. METHODS: A rat model of intestinal I/R injury was established. The serum level of adiponectin in rats with intestinal I/R injury was determined by enzyme-linked immunosorbent assay (ELISA). The serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured by ELISA. Apoptosis of intestinal cells was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The production of malondialdehyde (MDA) and superoxide dismutase (SOD) and villous injury scores were also measured. RESULTS: Adiponectin was downregulated in the serum of rats with intestinal I/R injury compared with sham rats. No significant changes in the expression of adiponectin receptor 1 and adiponectin receptor 2 were found between sham and I/R rats. Pre-treatment with recombinant adiponectin attenuated intestinal I/R injury. The production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, in rats with intestinal I/R injury was reduced by adiponectin pre-treatment. The production of MDA was inhibited, and the release of SOD was restored by adiponectin pre-treatment in rats with intestinal I/R injury. Adiponectin pre-treatment also inhibited cell apoptosis in these rats. Treatment with the AMP-activated protein kinase (AMPK) signaling pathway inhibitor, compound C, or the heme oxygenase 1 (HO-1) inhibitor, Snpp, attenuated the protective effects of adiponectin against intestinal I/R injury. CONCLUSION: Adiponectin exhibits protective effects against intestinal I/R injury, which may involve the AMPK/HO-1 pathway. PMID:26715807

  4. Effect of sildenafil in renal ischemia/reperfusion injury in rats Efeito do sildenafil na lesão renal por isquemia/reperfusão em ratos

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    Paulo José de Medeiros

    2010-12-01

    Full Text Available PURPOSE: To evaluate the effect of sildenafil, administered prior to renal ischemia/reperfusion (I/R, by scintigraphy and histopathological evaluation in rats. METHODS: Twenty-four rats were divided randomly into two groups. They received 0.1 ml of 99mTechnetium-etilenodicisteine intravenous, and a baseline (initial renal scintigraphy was performed. The rats underwent 60 minutes of ischemia by left renal artery clamping. The right kidney was not manipulated. The sildenafil group (n=12 received orally 1 mg/kg of sildenafil suspension 60 minutes before ischemia. Treatment with saline 0.9% in the control group (n=12. Half of the rats was assessed after 24 hours and half after seven days I/R, with new renal scintigraphy to study differential function. After euthanasia, kidneys were removed and subjected to histopathological examination. For statistical evaluation, Student t and Mann-Whitney tests were used. RESULTS: In the control group rats, the left kidneys had significant functional deficit, seven days after I/R, whose scintigraphic pattern was consistent with acute tubular necrosis, compared with the initial scintigraphy (pOBJETIVO: Estudar o efeito do sildenafil, administrado previamente à isquemia/reperfusão (I/R renal, em avaliações cintilográficas e histopatológicas em ratos. MÉTODOS: Vinte e quatro ratos Wistar foram aleatoriamente distribuídos em dois grupos. Os animais receberam 0,1 ml IV de 99mTecnécio-Etilenodicisteína, foram submetidos à cintilografia renal inicial e em seguida submetidos a isquemia no rim esquerdo, com oclusão da artéria renal, durante 60 minutos, com posterior reperfusão. O grupo sildenafil (n=12 recebeu previamente 1mg/kg de sildenafil em suspensão 60 minutos antes da isquemia. Solução salina 0,9% foi administrada no grupo controle (n=12. Metade dos animais de cada grupo foi avaliada após 24 horas e a outra metade após sete dias de reperfusão, com nova cintilografia renal. Após eutanásia, os

  5. Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats

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    Edip Gonullu

    2014-06-01

    Full Text Available Background and objectives: We investigated the effect of dexmedetomidine on ischemic renal failure in rats. Methods: In the present study, 26 male adult Wistar albino rats weighting 230-300 g were randomly separated into four groups: sham-operated (n = 5, ischemia reperfusion (IR (IR group, n = 7, IR/reperfusion treatment with dexmedetomidine (Dex. R group, n = 7 and IR/pre-ischemic treatment with dexmedetomidine (Dex. I group, n = 7. In the first group, sham operation was achieved and renal clamps were not applied. For the IR group, renal ischemia was induced by occlusion of the bilateral renal arteries and veins for 60 min followed by reperfusion for 24 h. For the Dex. R and Dex. I groups, the same surgical procedure as in the IR group was performed, and dexmedetomidine (100 mcg/kg intraperitoneal was administrated at the 5th min after reperfusion and before ischemia. At the end of reperfusion, blood samples were drawn, the rats were sacrificed, and the left kidney was processed for histopathology. Results: The blood urea nitrogen (BUN levels in groups Dex. R and Dex. I were significantly lower than in the IR group (p = 0.015, p = 0.043, although urine flow was significantly higher in group Dex. R (p = 0.003. The renal histopathological score in the IR group was significantly higher than in the other groups. There was no significant difference between the Dex. R and Dex. I groups. Conclusions: The results were shown that administration of dexmedetomidine reduced the renal IR injury histomorphologically. Administration of dexmedetomidine in the reperfusion period was considered as more effective due to increase in urinary output and decrease in BUN levels.

  6. The ethanolic extract of Kaempferia parviflora reduces ischaemic injury in rat isolated hearts.

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    Malakul, Wachirawadee; Ingkaninan, Kornkanok; Sawasdee, Pattara; Woodman, Owen L

    2011-09-01

    The ethanolic extract of Kaempferia parviflora (KPE) has been reported to contain a range of flavonoids and to enhance endothelial synthesis of NO. We investigated the vascular relaxant, antioxidant and cardioprotective activities of KPE. Vascular function was assessed in rat aortic rings and superoxide generation determined using lucigenin enhanced chemiluminescence. Ischaemia and reperfusion were induced in rat isolated, perfused hearts. KPE caused vasorelaxation (R(max) 102 ± 2%), which was partly inhibited by removal of the endothelium (R(max) 91 ± 1%) or by N(G)-nitro-l-arginine (L-NNA, R(max) 83 ± 3%) or 1H-[1,2,4] oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, R(max) 80 ± 2%). In addition KPE caused concentration-dependent inhibition of the contractile response to exogenous Ca(2+). KPE (10(-3)M) also significantly inhibited superoxide radical generation induced by of xanthine/xanthine oxidase (2.3 ± 0.4% of control) to a similar extent to the xanthine oxidase inhibitor allopurinol (10(-4)M, 1.6 ± 0.5%) or by rat isolated aorta in the presence of NADPH (30.0 ± 6.3% of control) similarly to the NADPH oxidase inhibitor diphenyliodonium (5 × 10(-6)M, 23.1 ± 5.6%). In the presence of oxidant stress generated by pyrogallol endothelium-dependent relaxation of rat aortic rings was impaired (ACh R(max) control 99 ± 1%; pyrogallol 44 ± 5%), an effect that was significantly reduced by KPE (10(-4)M, ACh R(max) 82 ± 4%). In addition, KPE was found to attenuate the ventricular dysfunction caused by 20 min global ischaemia and 30 min reperfusion (I/R) in rat isolated hearts (dP/dt IR 1016 ± 242, IR+KPE 2238±233 mm Hg/s). KPE is an effective vasodilator and antioxidant that is able to prevent myocardial ischaemia-reperfusion injury. We suggest that KPE may be useful as an adjunct to thrombolytic therapy in the management of reperfusion injury. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. EFFECT OF CANNABINOIDS ON TESTICULAR ISCHEMIA-REPERFUSION INJURY IN RAT

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    H. Sepehri

    2006-11-01

    Full Text Available Anandamide is an endogenous ligand for cannabinoid receptors and has endothelial protective effect against ischemic preconditioning. The purpose of this study was to investigate the effects of cannabinoids on reperfusion injury due to testicular torsion-detorsion (T/D. A total of 36 adult male Sprague-Dawley rats were divided into 6 groups. Testicular ischemia was achieved by twisting the right testes 720◦ counters clockwise for 1 hour and reperfusion was allowed for 4 hours after detorsion. In baseline (normal group, bilateral orchiectomies performed after anesthesia. Sham operated group was served as a control group. Torsion/detorsion group underwent 1 hour testicular torsion and 4 hours of detorsion. Anandamide (cannabinoid agonist group received pretreatment with intraperitoneally anandamide 30 min before torsion. AM251 (CB1 antagonist group, received intraperitoneally injection of AM251 45 min before torsion. Anandamid/AM251 (An/AM group received administrations of AM251 45 min before torsion and anandamide 30 min before torsion. The ipsilateral malondialdehyde (MDA level in T/D group were significantly higher versus control and base line groups. Ipsilateral MDA values in anandamid group were significantly lower than T/D and An/AM groups. There were also significant decreases in catalase activity in T/D group compared with control and base line groups. These values were significantly higher in cannabinoid group versus T/D and An/AM groups. Anandamide increased ipsilateral intratesticular antioxidative markers and decreased free radicals formation during reperfusion phase after unilateral testicular torsion, which was reflected in lesser testicular MDA level. Furthermore, the effects of anandamide were mediated via cannabinoid receptors, since AM251 could abolish these effects.

  8. Interacting Network of the Gap Junction (GJ) Protein Connexin43 (Cx43) is Modulated by Ischemia and Reperfusion in the Heart.

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    Martins-Marques, Tania; Anjo, Sandra Isabel; Pereira, Paulo; Manadas, Bruno; Girão, Henrique

    2015-11-01

    The coordinated and synchronized cardiac muscle contraction relies on an efficient gap junction-mediated intercellular communication (GJIC) between cardiomyocytes, which involves the rapid anisotropic impulse propagation through connexin (Cx)-containing channels, namely of Cx43, the most abundant Cx in the heart. Expectedly, disturbing mechanisms that affect channel activity, localization and turnover of Cx43 have been implicated in several cardiomyopathies, such as myocardial ischemia. Besides gap junction-mediated intercellular communication, Cx43 has been associated with channel-independent functions, including modulation of cell adhesion, differentiation, proliferation and gene transcription. It has been suggested that the role played by Cx43 is dictated by the nature of the proteins that interact with Cx43. Therefore, the characterization of the Cx43-interacting network and its dynamics is vital to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication, but also to unveil novel and unanticipated biological functions of Cx43. In the present report, we applied a quantitative SWATH-MS approach to characterize the Cx43 interactome in rat hearts subjected to ischemia and ischemia-reperfusion. Our results demonstrate that, in the heart, Cx43 interacts with proteins related with various biological processes such as metabolism, signaling and trafficking. The interaction of Cx43 with proteins involved in gene transcription strengthens the emerging concept that Cx43 has a role in gene expression regulation. Importantly, our data shows that the interactome of Cx43 (Connexome) is differentially modulated in diseased hearts. Overall, the characterization of Cx43-interacting network may contribute to the establishment of new therapeutic targets to modulate cardiac function in physiological and pathological conditions. Data are available via ProteomeXchange with identifier PXD002331.

  9. Minocycline inhibits neuroinflammation and enhances vascular endothelial growth factor expression in a cerebral ischemia/reperfusion rat model

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    Zhiyou Cai; Yong Yan; Changyin Yu; Jun Zhang

    2008-01-01

    BACKGROUND: Brain ischemia involves secondary inflammation, which significantly contributes to the outcome of ischemic insults. Vascular endothelial growth factor (VEGF) may play an important role in the vascular response to cerebral ischemia, because ischemia stimulates VEGF expression in the brain, and VEGF promotes formation of new cerebral blood vessels. Minocyclinc, a tetracycline derivative, protects against cerebral ischemia and reduces inflammation, oxidative stress, and apoptosis.OBJECTIVE: To observe the influence of minocycline on VEGE interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) expression in Wistar rats with focal cerebral ischemia/rcperfusion injury, and to study the neuroproteetion mechanism of minocycline against focal cerebral ischemia/rcpeffusion injury.DESIGN, TIME AND SETTING: Randomized, controlled experiment, which was performed in the Chongqing Key Laboratory of Neurology between March 2007 and March 2008.MATERIALS: A total of 36 female, Wistar rats underwent surgery to insert a thread into the left middle cerebral artery. Animals were randomly divided into sham-operation, minocyclinc treatment, and ischemia/reperfusion groups, with 12 rats in each group. Minocycline (Huishi Pharmaceutical Limited Company, China) was dissolved to 0.5 g/L in normal saline.METHODS: A 0.5- 1.0 cm thread was inserted into rats from the sham-operation group. Rats in the ischemia/reperfusion group underwent ischemia and reperfusion. The minocycline group received minocycline (50 mg/kg) 12 and 24 hours following ischemia and reperfusion, whereas the other groups received saline at the corresponding time points.MAIN OUTCOME MEASURES: mRNA and protein expression of IL-1β and TNF-α was measured by reverse transcriptase-polymerasc chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. VEGF mRNA and protein expression was examined by RT-PCR, Western blot, and ELISA.RESULTS: Minocycline decreased the focal infarct

  10. Mechanism of cardioprotective effect of erythropoietin-induced preconditioning in rat heart

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    Garg Kavita

    2010-01-01

    Full Text Available Objective : The cardioprotective potential of human recombinant erythropoietin (alpha (Epo against ischemia-reperfusion-induced injury is well known. But, the underlying mechanisms are not well elucidated. The aim of this study was to characterize the mechanism involved in the cardioprotective effect of Epo-induced preconditioning in isolated rat heart. Materials and Methods : The heart was mounted on a Langendorff apparatus. After 10 min of stabilization, four cycles of ischemic preconditioning (IPC were given followed by 30 min of global ischemia and 120 min of reperfusion. Epo preconditioning was induced by four cycles of 5-min perfusion of K-H solution containing Epo (1.0 U/ml followed by 5 min perfusion with K-H solution. Myocardial infarct size was estimated macroscopically using the triphenyltetrazolium chloride staining technique. The extent of myocardial injury was measured by release of lactate dehydrogenase and creatine kinase-MB in the coronary effluent. Results : The present study demonstrates that Epo preconditioning was almost as effective as IPC. Administration of Wortmannin (100 nM, a PI-3K inhibitor, or Chelerythrine (1 μM, a protein kinase-C (PKC inhibitor, or AG490 (5 μM, a JAK-2 inhibitor, significantly attenuated the cardioprotective effects of Epo-induced preconditioning. Conclusion : Our result suggest that the cardioprotective potential of Epo-induced preconditioning in isolated rat heart was due to an interplay of the JAK-2, PI-3K and PKC pathways. Inhibition of any one of the three pathways was sufficient to block the cardioprotective effect of Epo-induced preconditioning in isolated rat heart.

  11. JNK/PI3K/Akt signaling pathway is involved in myocardial ischemia/reperfusion injury in diabetic rats: effects of salvianolic acid A intervention.

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    Chen, Qiuping; Xu, Tongda; Li, Dongye; Pan, Defeng; Wu, Pei; Luo, Yuanyuan; Ma, Yanfeng; Liu, Yang

    2016-01-01

    Recent studies have demonstrated that diabetes impairs the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway, while insulin resistance syndrome has been associated with alterations of this pathway in diabetic rats after ischemia/reperfusion (I/R), and activation of C-jun N-terminal kinase (JNK) is involved. The present study was designed to investigate whether inhibiting JNK activity would partially restore the PI3K/Akt signaling pathway and protect against myocardial I/R injury in diabetic rats, and to explore the effect of intervention with salvianolic acid A (Sal A). The inhibitor of JNK (SP600125) and Sal A were used in type 2 diabetic (T2D) rats, outcome measures included heart hemodynamic data, myocardial infarct size, the release of lactate dehydrogenase (LDH), SERCA2a activity, cardiomyocyte apotosis, expression levels of Bcl-2, Bax and cleaved caspase-3, and the phosphorylation status of Akt and JNK. The p-Akt levels were increased after myocardial I/R in non-diabetic rats, while there was no change in diabetic rats. Pretreatment with the SP600125 and Sal A decreased the p-JNK levels and increased the p-Akt levels in diabetic rats with I/R, and heart hemodynamic data improved, infarct size and LDH release decreased, SERCA2a activity increased, Bax and cleaved caspase-3 expression levels decreased, and the expression of Bcl-2 and the Bcl-2/Bax ratio increased. Our results suggest that the JNK/PI3K/Akt signaling pathway is involved in myocardial I/R injury in diabetic rats and Sal A exerts an anti-apoptotic effect and improves cardiac function following I/R injury through the JNK/PI3K/Akt signaling pathway in this model.

  12. The effects of gallic acid on pain and memory following transient global ischemia/reperfusion in Wistar rats

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    Yaghoob Farbood

    2013-07-01

    Full Text Available Objective: It is generally agreed that most of the phenomena observed during brain ischemia and reperfusion can be explained by the damage to membrane structure. Oxidative stress is resulted in an imbalance between high consumption of oxygen and low levels of endogenous antioxidants. It is known that gallic acid (GA is a strong antioxidant. The present study was carried out to evaluate the effect of GA on ischemia/reperfusion (I/R-induced brain injury in rats.  Materials and Methods: Wistar adult male rats weighing 200–250 g were divided into six groups as sham operated (Sh, ischemia/reperfusion (I/R received normal saline (I+Veh, I/R groups treated with gallic acid (I+GA, 50, 100, or 200 mg/kg, orally, respectively, or with 100 mg /kg phenytoin (I+Phen. The global cerebral I/R injury was induced by occluding bilateral common carotid arteries (BCCA for 20 min, followed by 5 days reperfusion in adult male rats. Results: It was found that administration of 100 mg/kg GA for 5 days before and 5 days after I/R induction reversed gait performance, sensorimotor disorders (p

  13. Effects of isoflurane on ICAM-1 expression and neutrophils infiltration in rats with liver ischemia and reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Xu Guangmin; Tao Guocai

    2009-01-01

    Objective: To establish a rat model of warm partial hepatic ischemia-reperfusion (IR), and investigate the protective and anti-inflammatory effects of isoflurane on warm hepatic ischemia-reperfusion injury (IRI) in rats. Methods: Thirty-two female Sprague-Dawley rots were divided equally into 4 groups (n=8): PB-Sham group in which the rats were anesthetized by intraperitoneal injection of pentobarbital sodium (1.0%, 40 mg/kg, PB) and received a sham operation without occlusion of liver blood flow; PB-IR group whose rats underwent partial hepatic IR after anesthesia; Iso-Sham group in which inhalation of 1.0 MAC isoflurane and sham operation was performed; Iso-IR group in which 1.0 MAC isoflurane was inhaled for 4 h and IR was performed. Rat model of warm partial hepatic IR was established by clamping the hepatic arteries and hilar vessels distributing to the left and median lobes to induce partial hepatic ischemia (70%) for 60 min followed by reperfusion for 3 h. The rats were killed 3 h after declamping, and specimens of liver tissue and blood were obtained. The serum ALT and AST were detected as liver damage markers. Viability of myeloperoxidase (MPO) in liver was measured. The protein level of ICAM-1 in the liver was detected by immunohistochemistry and Western blotting. Results: Rats treated with 1.0 MAC isoflurane during warm partial (70%) hepatic ischemia 60 min and 3 h reperfusion had significantly lower serum ALT and AST compared with rats anesthetized with pentobarbital sodium subjected to hepatic IRI. The expression of ICAM-1 in hepatic tissue was significantly increased by hepatic IRI after pentobarbital sodium anesthesia. Isoflurane significantly inhibited protein expression of ICAM-1 in hepatic IR injury compared with pentobarbital sodium anesthesia. Viability of liver MPO was significantly increased by hepatic IRI after pentobarbital sodium anesthesia; Isoflurane can significantly inhibit MPO alteration in rat liver ischemia-reperfusion injury

  14. Spironolactone Effect in Hepatic Ischemia/Reperfusion Injury in Wistar Rats

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    Julio César Jiménez Pérez

    2016-01-01

    Full Text Available Introduction. Ischemia/reperfusion (IR injury, often associated with liver surgery, is an unresolved problem in the clinical practice. Spironolactone is an antagonist of aldosterone that has shown benefits over IR injury in several tissues, but its effects in hepatic IR are unknown. Objective. To evaluate the effect of spironolactone on IR-induced damage in liver. Materials and Methods. Total hepatic ischemia was induced in rats for 20 min followed by 60 min of reperfusion. Spironolactone was administered and hepatic injury, cytokine production, and oxidative stress were assessed. Results. After IR, increased transaminases levels and widespread acute inflammatory infiltrate, disorganization of hepatic hemorrhage trabeculae, and presence of apoptotic bodies were observed. Administration of SPI reduced biochemical and histological parameters of liver injury. SPI treatment increased IL-6 levels when compared with IR group but did not modify either IL-1β or TNF-α with respect to IR group. Regarding oxidative stress, increased levels of catalase activity were recorded in IR + SPI group in comparison with group without treatment, whereas MDA levels were similar in IR + SPI and IR groups. Conclusions. Spironolactone reduced the liver damage induced by IR, and this was associated with an increase in IL-6 production and catalase activity.

  15. Effect of iloprost on erythrocyte deformability in rat's lower extremity undergoing an ischemia reperfusion injury.

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    Arslan, M; Donmez, T; Erer, D; Tatar, T; Comu, F M; Alkan, M

    2013-01-01

    Ischemia reperfusion injury (I/R) in lower extremity is a frequent and important clinical phenomenon. The protective effect of iloprost on local and distant organ injury due to I/R has been well documented but its effect on erythrocyte deformability needs further investigation. Our aim was to investigate the effect of iloprost on erythrocyte deformability in the infrarenal aorta of rats undergoing I/R. Our study was conducted with 18 Wistar albino rats. Rats were divided into the 3 groups; the randomized control group (group C; n=6), I/R group without iloprost (group I/R; n=6) and I/R group with iloprost - 10 mcg.kg-1, 30 min infusion (group I/R-I; n=6). Packs of erythrocytes were prepared from heparinized blood samples and deformability measurements were done. The comparisons of the control and I/R-I groups revealed similar results (p=0.951). The values of the IR group were significantly higher than those of the control and IR-I groups (p=0.006, p=0.011, respectively). In our study, we detected the unfavourable effects of I/R on erythrocyte deformability, which may lead to disturbance in blood flow and hence tissue perfusion in the infrarenal rat aorta. We also found that Iloprost had beneficial effects by reversing the undesirable effects of I/R (Fig. 1, Ref. 15).

  16. Short-term melatonin consumption protects the heart of obese rats independent of body weight change and visceral adiposity.

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    Nduhirabandi, Frederic; Huisamen, Barbara; Strijdom, Hans; Blackhurst, Dee; Lochner, Amanda

    2014-10-01

    Chronic melatonin treatment has been shown to prevent the harmful effects of diet-induced obesity and reduce myocardial susceptibility to ischaemia-reperfusion injury (IRI). However, the exact mechanism whereby it exerts its beneficial actions on the heart in obesity/insulin resistance remains unknown. Herein, we investigated the effects of relatively short-term melatonin treatment on the heart in a rat model of diet-induced obesity. Control and diet-induced obese Wistar rats (fed a high calorie diet for 20 wk) were each subdivided into three groups receiving drinking water with or without melatonin (4 mg/kg/day) for the last 6 or 3 wk of experimentation. A number of isolated hearts were perfused in the working mode, subjected to regional or global ischaemia-reperfusion; others were nonperfused. Metabolic parameters, myocardial infarct sizes (IFS), baseline and postischaemic activation of PKB/Akt, ERK42/44, GSK-3β and STAT-3 were determined. Diet-induced obesity caused increases in body weight gain, visceral adiposity, fasting blood glucose, serum insulin and triglyceride (TG) levels with a concomitant cardiac hypertrophy, large postischaemic myocardial IFSs and a reduced cardiac output. Melatonin treatment (3 and 6 wk) decreased serum insulin levels and the HOMA index (P melatonin administration to obese/insulin resistant rats reduced insulin resistance and protected the heart against ex vivo myocardial IRI independently of body weight change and visceral adiposity.

  17. Protective Effect of N-Acetylcystein and Resveratrol on Ischemia-Reperfusion Injury in Rat Ovary

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    Avni Kılıç

    2016-06-01

    Full Text Available Objective: The aim of this study is evaluating the protective activity of N-acetyl cysteine and resveratrol treatment against ischemia - reperfusion damage created experimentally in rat ovaries. Methods: 42 female Wistar rats were used in our study. Rats were separated randomly into six groups consisting of seven rats as sham, torsion, torsion- detorsion, torsion-detorsion+saline, torsion-detorsion+resveretrol (20 mg/kg and torsion- detorsion+N-acetyl cysteine (150 mg/kg. Except Sham, ovarian torsion procedure was implemented to all other groups for 2 hours. Detorsion procedure was implemented to other groups for 2 hours, except the torsion group. Medications were given through intraperitoneal way half an hour before the detorsion procedure in saline (two milliliter, resveratrol (20 mg/kg and N-acetyl cysteine (150 mg/kg groups. Then, 2 ml of blood samples were drawn for markers of oxidative stress and tumour necrosis factor-alpha (TNF-α work and the ovaries, which were torsioned for the histologic examination, were ex­tracted from all rats. Edema, congestion, hemorrhage, leuko­cyte infiltration and degeneration of follicles were evaluated by histopathological examination. Results: According to histopathologic damage scores, the least damage was seen in sham group and the most damage was seen T-DT group (1.00±0.81 vs. 11.00±1.15, respectively; p<0.001. It was seen that resveratrol and N-acetyl cysteine treatments were effective in decreasing tissue damage (total damage score average 83.85±0.89 vs. 3.85±0.89, respec­tively; p<0.001, and on the other hand there was not any dif­ference between resveratrol and N-acetyl cysteine treatments (p=0.966. Besides, it was determined that oxidative stress levels were higher in torsion - detorsion group and the resve­ratrol and N-acetyl cysteine treatment caused a significant de­crease in oxidative stress levels. In additionally, the reductions of TNF-α levels were found to be equally effective in

  18. Effect of recombinant erythropoietin on ischemia-reperfusion-induced apoptosis in rat liver.

    Science.gov (United States)

    Shawky, Heba M; Younan, Sandra M; Rashed, Leila A; Shoukry, Heba

    2012-03-01

    Ischemia-reperfusion (I/R) cannot be avoided in liver transplantation procedures, and apoptosis is a central mechanism of cell death after liver reperfusion. Protective effect of recombinant erythropoietin (rhEPO) on liver apoptosis has not been clearly investigated. This work investigated intraportal (IP) rhEPO-protective effect in a rat model of hepatic I/R-induced apoptosis and its appropriated time and dose of administration. Eight groups were included (n = 10/group): sham-operated, I/R (45 min ischemia and 2 h reperfusion), preconditioned rhEPO I/R (24 h or 30 min before ischemia), and postconditioned rhEPO I/R (before reperfusion) using two different rhEPO doses (1,000 and 5,000 IU/kg). When compared with the sham-operated group, the I/R group showed significant increase of serum levels of aspartate and alanine aminotransferases (AST, ALT), hepatic caspase-9 activity(894.99 ± 176.90 relative fluorescence units (RFU)/mg/min versus 458.48 ± 82.96 RFU/mg/min), and Fas ligand (FasL) expression, histopathological damages, and significant decrease in the antiapoptotic Bcl-xL/apoptotic Bax ratio(0.38 ± 0.21 versus 3.35 ± 0.77) rhEPO-improved ALT and AST but failed to reduce FasL expression in all groups compared with the I/R group. Thirty minutes and 24 h preconditioning with rhEPO (1,000 IU/kg) increased Bcl-xL/Bax ratio and reduced caspase-9 activity, and the same effect was observed when higher dose was given 24 h before ischemia. Preconditioning was more effective than postconditioning in improving caspase-9 activity, and no dose-dependent effect was observed. In conclusion, single IP rhEPO injection 30 min before ischemia has an advantage over rhEPO postconditioning in improving post-hepatic I/R-induced apoptosis with no additional time- and dose-dependent effects which may provide potentially useful guide in liver transplantation procedures.

  19. Pretreatment with adenosine and adenosine A1 receptor agonist protects against intestinal ischemia-reperfusion injury in rat

    Institute of Scientific and Technical Information of China (English)

    V Haktan Ozacmak; Hale Sayan

    2007-01-01

    AIM: To examine the effects of adenosine and A1 receptor activation on reperfusion-induced small intestinal injury.METHODS: Rats were randomized into groups with sham operation, ischemia and reperfusion, and systemic treatments with either adenosine or 2-chloro-N6-cyclopentyladenosine, A1 receptor agonist or 8-cyclopentyl-1,3-dipropylxanthine, A1 receptor antagonist, plus adenosine before ischemia. Following reperfusion, contractions of ileum segments in response to KCl, carbachol and substance P were recorded. Tissue myeloperoxidase,malondialdehyde, and reduced glutathione levels were measured.RESULTS: Ischemia significantly decreased both contraction and reduced glutathione level which were ameliorated by adenosine and agonist administration. Treatment also decreased neutrophil infiltration and membrane lipid peroxidation. Beneficial effects of adenosine were abolished by pretreatment with A1 receptor antagonist.CONCLUSION: The data suggest that adenosine and A1 receptor stimulation attenuate ischemic intestinal injury via decreasing oxidative stress, lowering neutrophil infiltration, and increasing reduced glutathione content.

  20. Effects of melatonin on liver function and lipid peroxidation in a rat model of hepatic ischemia/reperfusion injury.

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    Deng, Wen-Sheng; Xu, Qing; Liu, Y E; Jiang, Chun-Hui; Zhou, Hong; Gu, Lei

    2016-05-01

    The present study aimed to investigate the effects of melatonin (MT) on liver function and lipid peroxidation following hepatic ischemia-reperfusion injury (IRI). A total of 66 male Sprague-Dawley rats were randomly assigned into three groups: Normal control (N) group, ischemia-reperfusion (IR) group and the MT-treated group. A hepatic IRI model was developed by blocking the first porta hepatis, and subsequently restoring hepatic blood inflow after 35 min. Following reperfusion, changes in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were detected by a chemical method at various time points. In the MT group, the MDA levels were significantly reduced (PLDH were significantly reduced in the MT group at each time point, as compared with that of the IR group (Pfunction following IRI.

  1. The Protection of Salidroside of the Heart against Acute Exhaustive Injury and Molecular Mechanism in Rat

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    Wang, Yunru; Xu, Peng; Wang, Yang; Liu, Haiyan; Zhou, Yuwen; Cao, Xuebin

    2013-01-01

    Objective. To investigate the protection of salidroside of the heart against acute exhaustive injury and its mechanism of antioxidative stress and MAPKs signal transduction. Method. Adult male SD rats were divided into four groups randomly. Cardiomyocytes ultrastructure was observed by optical microscopy and transmission electron microscopy. The contents of CK, CK-MB, LDH, MDA, and SOD were determined by ELISA method, and the phosphorylation degrees of ERK and p38 MAPK were assayed by Western blotting. Cardiac function of isolated rat heart ischemia/reperfusion was detected by Langendorff technique. Results. Salidroside reduced the myocardium ultrastructure injury caused by exhaustive swimming, decreased the contents of CK, CK-MB, and LDH, improved the LVDP, ±LV dp/dt max under the basic condition, reduced the content of MDA and the phosphorylation degree of p38 MAPK, and increased the content of SOD and the phosphorylation degree of ERK in acute exhaustive rats. Conclusion. Salidroside has the protection of the heart against acute exhaustive injury. The cardioprotection is mainly mediated by antioxidative stress and MAPKs signal transduction through reducing the content of MDA, increasing the content of SOD, and increasing p-ERK and decreasing p-p38 protein expressions in rat myocardium, which might be the mechanisms of the cardioprotective effect of salidroside. PMID:24454984

  2. The Protection of Salidroside of the Heart against Acute Exhaustive Injury and Molecular Mechanism in Rat

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    Yunru Wang

    2013-01-01

    Full Text Available Objective. To investigate the protection of salidroside of the heart against acute exhaustive injury and its mechanism of antioxidative stress and MAPKs signal transduction. Method. Adult male SD rats were divided into four groups randomly. Cardiomyocytes ultrastructure was observed by optical microscopy and transmission electron microscopy. The contents of CK, CK-MB, LDH, MDA, and SOD were determined by ELISA method, and the phosphorylation degrees of ERK and p38 MAPK were assayed by Western blotting. Cardiac function of isolated rat heart ischemia/reperfusion was detected by Langendorff technique. Results. Salidroside reduced the myocardium ultrastructure injury caused by exhaustive swimming, decreased the contents of CK, CK-MB, and LDH, improved the LVDP, ±LV dp/dtmax under the basic condition, reduced the content of MDA and the phosphorylation degree of p38 MAPK, and increased the content of SOD and the phosphorylation degree of ERK in acute exhaustive rats. Conclusion. Salidroside has the protection of the heart against acute exhaustive injury. The cardioprotection is mainly mediated by antioxidative stress and MAPKs signal transduction through reducing the content of MDA, increasing the content of SOD, and increasing p-ERK and decreasing p-p38 protein expressions in rat myocardium, which might be the mechanisms of the cardioprotective effect of salidroside.

  3. Olmesartan restores the protective effect of remote ischemic perconditioning against myocardial ischemia/reperfusion injury in spontaneously hypertensive rats.

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    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

  4. Olmesartan restores the protective effect of remote ischemic perconditioning against myocardial ischemia/reperfusion injury in spontaneously hypertensive rats

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    Xin Lu

    2015-07-01

    Full Text Available OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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 mi

  5. Beneficial effects of n-acetyl cysteine on pancreas and kidney following experimental pancreatic ischemia-reperfusion in rats

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    Roberto Ferreira Meirelles Junior

    2010-01-01

    Full Text Available OBJECTIVE: To evaluate the protective effects of N-acetyl cysteine on the pancreas and kidney after pancreatic ischemia reperfusion injury in a rat model. METHODS AND MATERIALS: Pancreatic ischemia reperfusion was performed in Wistar rats for 1 hour. Revascularization was achieved followed by 4 h of reperfusion. A total of 24 animals were divided into four groups: Group 1: sham; Group 2: pancreatic ischemia reperfusion without treatment; Group 3: pancreatic ischemia reperfusion plus N-acetyl cysteine intravenously; and Group 4: pancreatic ischemia reperfusion plus N-acetyl cysteine per os. Blood and tissue samples were collected after reperfusion. RESULTS: There were significant differences in amylase levels between Group 1 (6.11±0.55 and Group 2 (10.30±0.50 [p=0.0002] as well as between Group 2 (10.30±0.50 and Group 4 (7.82±0.38 [p=0.003]; creatinine levels between Group 1 (0.52 ± 0.07 and Group 2 (0.77±0.18 [p=0.035] as well as between Group 2 (0.77±0.18 and Group 3 (0.48±0.13 [p=0.012]; and pancreatic tissue thiobarbituric acid reactive substance levels between Group 1 (1.27±0.96 and Group 2 (2.60±3.01 [p=0.026] as well as between Group 2 (2.60±3.01 and Group 4 (0.52±0.56 [p=0.002]. A decrease in pancreatic tissue GST-α3 gene expression was observed in Group 2 in comparison to Group 1 (p =0.006, and an increase was observed in Groups 3 and 4 when compared to Group 2 (p= 0.025 and p=0.010, respectively. CONCLUSION: This study provides evidence that N-acetyl cysteine has a beneficial effect on pancreatic ischemia reperfusion injury and renal function in a rat model.

  6. Role of Centella asiatica on cerebral post-ischemic reperfusion and long-term hypoperfusion in rats

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    Raghavendra M

    2009-01-01

    Full Text Available Centella asiatica (CA, a well known adaptogenic agent in Indian system of Medicine (Ayurveda, is believed to have beneficial effects in improving memory, treating anxiety and eczema. It also possesses antioxidant, cognitive enhancing and antiepileptic properties. Acute ischemia followed by reperfusion is known to bring about biochemical and histopathological alterations. In the present study the effect of Centella asiatica on acute cerebral reperfusion and long-term cerebral hypoperfusion in rats was investigated. Transient cerebral ischemia was induced under Ketamine anaesthesia by blocking bilateral common carotid arteries (BCCAO for 30 min and then reperfusion was allowed for 45 min by releasing the block. Lipid peroxidation, superoxide dismutase (SOD and brain protein were estimated, behavioral and histopathological studies were done for both acute ischemia-reperfusion and chronic hypoperfusion studies. One way ANOVA followed by post hoc Tukey test was used. In the present study, acute ischemia-reperfusion induced increases in lipid peroxidation and superoxide SOD activity. CA pre-treatment (100 mg/kg p.o. for 5 days attenuated the reperfusion induced biochemical alterations. Long-term cerebral hypoperfusion in rats caused a propensity towards anxiety and listlessness (open field paradigm and elevated plus maze test accompanied by deficits in learning and memory (Morris′ water maze testing and tendency towards depression (Porsolts swim test. Additionally, histopathological observations in forebrain revealed changes like gliosis, astrocytosis, cellular edema and inflammatory changes. CA treatment (100 mg/kg p.o. for 28 days alleviated these behavioral, cognitive and histopathological changes. The results suggest that CA may be useful in cerebrovascular insufficiency conditions.

  7. Effects of FK506 on Hippocampal CA1 Cells Following Transient Global Ischemia/Reperfusion in Wistar Rat

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    Zahra-Nadia Sharifi

    2012-01-01

    Full Text Available Transient global cerebral ischemia causes loss of pyramidal cells in CA1 region of hippocampus. In this study, we investigated the neurotrophic effect of the immunosuppressant agent FK506 in rat after global cerebral ischemia. Both common carotid arteries were occluded for 20 minutes followed by reperfusion. In experimental group 1, FK506 (6 mg/kg was given as a single dose exactly at the time of reperfusion. In the second group, FK506 was administered at the beginning of reperfusion, followed by its administration intraperitoneally (IP 6, 24, 48, and 72 hours after reperfusion. FK506 failed to show neurotrophic effects on CA1 region when applied as a single dose of 6 mg/kg. The cell number and size of the CA1 pyramidal cells were increased, also the number of cell death decreased in this region when FK506 was administrated 48 h after reperfusion. This work supports the possible use of FK506 in treatment of ischemic brain damage.

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

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    Nicolosi Alfred C

    2009-12-01

    Full Text Available Abstract Background The lanthanide cation, gadolinium (GdCl3 protects the myocardium against infarction following ischemia and reperfusion. Neutrophils and macrophages are the main leukocytes responsible for infarct expansion after reperfusion. GdCl3 interferes with macrophage and neutrophil function in the liver by decreasing macrophage secretion of inflammatory cytokines and neutrophil infiltration. We hypothesized that GdCl3 protects against ischemia and reperfusion injury by decreasing inflammation. We determined the impact of GdCl3 treatment for reperfusion injury on 1 circulating monoctye and neutrophil counts, 2 secretion of inflammatory cytokines, and 3 influx of monocytes and neutrophils into the myocardium. Methods Rats (n = 3-6/gp were treated with saline or GdCl3 (20 μmol/kg 15 min prior to a 30 min period of regional ischemia and 120 min reperfusion. Sham rats were not subject to ischemia. Blood was collected either after 30 min ischemia or 120 min reperfusion and hearts were harvested at 120 min reperfusion for tissue analysis. Blood was analyzed for leukocytes counts and cytokines. Tissue was analyzed for cytokines and markers of neutrophil and monocyte infiltration by measuring myeloperoxidase (MPO and α-naphthyl acetate esterase (ANAE. Results GdCl3 did not affect the number of circulating neutrophils prior to ischemia. Two hours reperfusion resulted in a 2- and 3- fold increase in circulating monocytes and neutrophils, respectively. GdCl3 decreased the number of circulating monocytes and neutrophils during reperfusion to levels below those present prior to ischemia. Furthermore, after 120 min of reperfusion, GdCl3 decreased ANAE and MPO activity in the myocardium by 1.9-fold and 6.5-fold respectively. GdCl3 decreased MPO activity to levels below those measured in the Sham group. Serum levels of the major neutrophil chemoattractant cytokine, IL-8 were increased from pre-ischemic levels during ischemia and reperfusion in both

  9. Effect of picroside II on hind limb ischemia reperfusion injury in rats

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    Kılıç Y

    2017-06-01

    Full Text Available Yiğit Kılıç,1 Abdullah Özer,1 Tolga Tatar,1 Mustafa Hakan Zor,1 Mehmet Kirişçi,2 Hakan Kartal,3 Ali Doğan Dursun,4 Deniz Billur,5 Mustafa Arslan,6 Ayşegül Küçük7 1Department of Cardiovascular Surgery, Gazi University Medical Faculty, Ankara, 2Department of Cardiovascular Surgery, Kahramanmaras Sutcu Imam Medical Faculty, Kahramanmaras, 3Department of Cardiovascular Surgery, Ardahan State Hospital, Ardahan, 4Department of Physiology, Ankara University Medical Faculty, 5Department of Histology and Embryology, Ankara University Medical Faculty, 6Department of Anaesthesiology and Reanimation, Gazi University Medical Faculty, Ankara, 7Department of Physiology, Dumlupinar University Medical Faculty, Kütahya, Turkey Introduction: Many structural and functional damages are observed in cells and tissues after reperfusion of previously viable ischemic tissues. Acute ischemia reperfusion (I/R injury of lower extremities occurs especially when a temporary cross-clamp is applied to the abdominal aorta during aortic surgery. Research regarding the treatment of I/R injury has been increasing day-by-day. In this study, we aimed to investigate the effect of picroside II on skeletal muscle of rats experiencing simulated I/R.Materials and methods: Twenty-four male Wistar albino rats weighing between 210 and 300 g were used in this study. Rats were randomly divided into 4 groups of 6 rats each (control, I/R, control + picroside II, and I/R + picroside II. The infrarenal section of the abdominal aorta was occluded with an atraumatic microvascular clamp in I/R group. The clamp was removed after 120 minutes and reperfusion was provided for a further 120 minutes. Picroside II (10 mg kg–1 was administered intraperitoneally to the animals in control + picroside II and I/R + picroside II groups. At the end of the study, skeletal muscle tissue was obtained for the determination of total oxidant status (TOS and total antioxidant status (TAS levels

  10. Study of L-arginine-nitric oxide pathway in ischemia-reperfusion injured limbs in rats

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    朱立军; 黄耀添; 裴国献

    2002-01-01

    Objective: To observe the change of nitric oxide (NO) levels in the blood and the morphological change of the muscles in the limbs of rats during the (IR) injury and after being intervened by L-arginine (L-Arg) and L-nitroarginine (L-NNA).   Methods: Sixty-six male Sprague-Dawley (SD) rats were used and grouped into the normal controls, the sham injury controls, the IR injury group and the intervention groups (L-Arg group and L-NNA group). After 6 hours of ischemia, followed by reperfusion for 3, 12 or 24 hours, the samples in the IR injury group were obtained. The rats in the intervention groups were given L-Arg (100 mmol/L) and L-NNA (10 mmol/L), respectively, through the abdominal cavity. Then the anterior tibial muscle in the right limb was obtained for histological examination, the anterior tibial muscle in the left limb for ultrastructure observation and the blood for assay of NO in all the rats. NO was assayed by indirect measurement of NO2/NO3 with Griess method.   Results: There was no significant difference of NO between the normal controls and the sham injury controls (P>0.05). But NO significantly decreased in the IR injury group (P0.05). In the L-NNA group, NO decreased to the undetectable level (P<0.01). Histological examination and ultrastructure observation showed the muscles were normal in the control groups. After 6 hours of ischemia, the skeletal muscles displayed injuries, and they were most severely injured after 12 hours of reperfusion. In the L-Arg group, the skeletal muscles were less injured, while in the L-NNA group, the injury was similar to that in the IR injury group.   Conclusions: When the limbs of the rats sustain IR, NO in the blood decreases. Meanwhile, the muscles in the limbs are injured. When L-Arg is given, NO in the blood is restored and the muscles are protected. When L-NNA completely inhibits NO, no protection of the muscles is shown.

  11. Identification of differentially expressed genes after partial rat liver ischemia/reperfusion by suppression subtractive hybridization

    Institute of Scientific and Technical Information of China (English)

    Christine Fallsehr; Christina Zapletal; Michael Kremer; Resit Demir; Magnus von Knebel Doeberitz; Ernst Klar

    2005-01-01

    AIM: To identify potential diagnostic target genes in early reperfusion periods following warm liver ischemia before irreversible liver damage occurs.METHODS: We used two strategies (SSH suppression subtractive hybridization and hybridization of cDNA arrays)to determine early changes in gene expression profiles in a rat model of partial WI/R, comparing postischemic and adjacent nonischemic liver lobes. Differential gene expression was verified (WT/R; 1 h/2 h) and analyzed in more detail after warm ischemia (1 h) in a reperfusion time kinetics (0, 1, 2 and 6 h) and compared to untreated livers by Northern blot hybridizations. Protein expression was examined on Western blots and by immunohistochemistry for four differentially expressed target genes (Hsp70,Hsp27, Gadd45a and IL-1rl).RESULTS: Thirty-two individual WI/R target genes showing altered RNA levels after confirmation by Northern blot analyzes were identified. Among them, six functionally uncharacteristic expressed sequences and 26 known genes (12 induced in postischemic liver lobes, 14 with higher transcriptional expression in adjacent nonischemic liver lobes). Functional categories of the verified marker genes indicate on the one hand cellular stress and tissue damage but otherwise activation of protective cellular reactions (AP-1 transcription factors, apoptosis related genes, heat shock genes). In order to assign the transcriptional status to the biological relevant protein level we demonstrated that Hsp70, Hsp27, Gadd45a and IL-1rI were clearly up-regulated comparing postischemic and untreated rat livers, suggesting their involvement in the WI/R context.CONCLUSION: This study unveils a WI/R response gene set that will help to explore molecular pathways involved in the tissue damage after WI/R. In addition, these genes especially Hsp70and Gadd45a might represent promising new candidates indicating WI/R liver damage.

  12. Vagus nerve stimulation attenuates cerebral ischemia and reperfusion injury via endogenous cholinergic pathway in rat.

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    Ying Jiang

    Full Text Available Inflammation and apoptosis play critical roles in the acute progression of ischemic injury pathology. Emerging evidence indicates that vagus nerve stimulation (VNS following focal cerebral ischemia and reperfusion (I/R may be neuroprotective by limiting infarct size. However, the underlying molecular mechanisms remain unclear. In this study, we investigated whether the protective effects of VNS in acute cerebral I/R injury were associated with anti-inflammatory and anti-apoptotic processes. Male Sprague-Dawley (SD rats underwent VNS at 30 min after focal cerebral I/R surgery. Twenty-four h after reperfusion, neurological deficit scores, infarct volume, and neuronal apoptosis were evaluated. In addition, the levels of pro-inflammatory cytokines were detected using enzyme-linked immune sorbent assay (ELISA, and immunofluorescence staining for the endogenous "cholinergic anti-inflammatory pathway" was also performed. The protein expression of a7 nicotinic acetylcholine receptor (a7nAchR, phosphorylated Akt (p-Akt, and cleaved caspase 3 in ischemic penumbra were determined with Western blot analysis. I/R rats treated with VNS (I/R+VNS had significantly better neurological deficit scores, reduced cerebral infarct volume, and decreased number of TdT mediated dUTP nick end labeling (TUNEL positive cells. Furthermore, in the ischemic penumbra of the I/R+VNS group, the levels of pro-inflammatory cytokines and cleaved caspase 3 protein were significantly decreased, and the levels of a7nAchR and phosphorylated Akt were significantly increased relative to the I/R alone group. These results indicate that VNS is neuroprotective in acute cerebral I/R injury by suppressing inflammation and apoptosis via activation of cholinergic and a7nAchR/Akt pathways.

  13. The Effects of Apelin on Mesenteric Ischemia and Reperfusion Damage in an Experimental Rat Model

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    Mustafa Burak Sayhan

    2012-06-01

    Full Text Available Objective: Intestinal ischemia-reperfusion (I/R injury is associated with high morbidity and mortality rates. There is ongoing research to find an effective preventive or treatment agent. We aimed to evaluate the effects of apelin 13 (AP on intestinal I/R injury in a rat model. Material and Methods: Twenty-four male Sprague-Dawley rats aged 6-8 weeks and weighing 280±20 g were equally divided into three groups (control, I/R and I/R+AP. The control group underwent superior mesenteric artery (SMA mobilization alone without any clamping. In the I/R and I/R+AP groups, an atraumatic microvascular bulldog clamp was placed across the SMA at its point of origin from the aorta. In the I/R+AP group, 2 µg/kg/d apelin was administered intraperitoneally. After 60 minutes of ischemia, relaparotomy was performed to remove the microvascular clamp on the SMA for 3 hours of reperfusion. After 3 hours, tissue samples were obtained for biochemical [malondialdehyde (MDA and glutathione (GSH levels] and histopathological analyses.Results: MDA levels were significantly higher in the I/R group compared to the control group. Although MDA levels were lower in the I/R+AP group compared tothe I/R group, the difference was not statistically significant. There was also no significant difference between the I/R+AP and I/R groups regarding GSH levels. The median histopathological grade was significantly lower in the I/R+AP group compared to the I/R group (p=0.001.Conclusion: Apelin appeared to have a positive effect on oxidative injury; this did not reach statistical significance. Thus, the role of apelin and associated findings in the initial treatment of intestinal ischemia needs further large-scale animal studies before human use.

  14. Hyperglycemia raises the threshold of levosimendan- but not milrinone-induced postconditioning in rat hearts

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    Matsumoto Shuhei

    2012-01-01

    Full Text Available Abstract Background The authors examined whether milrinone and levosimendan could exert cardiac postconditioning effects in rats under normoglycemia and hyperglycemia, and whether the effects could be mediated by mitochondrial permeability transition pore (mPTP. Methods Wistar rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received milrinone or levosimendan just before reperfusion under normoglycemic or hyperglycemic conditions with or without atractyloside, an mPTP opener. Results Under normoglycemia, both 30 μg/kg milrinone (29 ± 12% and 10 μg/kg levosimendan (33 ± 13% reduced infarct size compared with that in the control (58 ± 7%. Under hyperglycemia, milrinone (34 ± 13% reduced infarct size at the same dose as under normoglycemia. In contrast, neither 10 nor 30 μg/kg levosimendan protected hyperglycemic hearts, and only 100 μg/kg levosimendan (32 ± 9% reduced infarct size compared with that in the hyperglycemic control (58 ± 13%. All of these cardioprotective effects under normoglycemia and hyperglycemia are abolished by atractyloside. Conclusion Milrinone and levosimendan exert postconditioning effects via inhibition of mPTP opening. Hyperglycemia raises the threshold of levosimendan-induced postconditioning, while milrinone-induced postconditioning is not influenced by hyperglycemia.

  15. Improved cardiac protection with Sabax cardioplegia in Langendorff isolated rat hearts

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    Perian M.

    2014-12-01

    Full Text Available Objective: Cardioplegia is an important step to facilitate cardiac surgery while limiting intraoperative myocardial injury. Although recent advances in cardioplegic arrest methods have significantly contributed to better postoperative outcomes, there is still controversy regarding the optimal composition and temperature of the cardioplegic solution. Accordingly, we aimed to assess whether cold or lukewarm Sabax cardioplegia offer improved myocardial protection compared with the classical Krebs-Henseleit solution. Methods: The hearts of 40 male Wistar rats were isolated and submitted to constant-flow retrograde perfusion using a Langendorff perfusion apparatus. The hearts were randomly assigned to cold Krebs-Henseleit (K-H, cold Sabax, or lukewarm Sabax cardioplegia. The ECG, heart rates, and left ventricular systolic pressures (LVSP were recorded pre- and post-cardioplegia. The time needed for cardioplegia induction and post-cardioplegia recovery were also noted. Results: Both cold and lukewarm Sabax cardioplegia insured faster induction and faster recovery following isothermic reperfusion compared to the standard K-H solution (both p< 0.01. With K-H cardioplegia, the hearts presented a 21.7% force loss after reperfusion (p< 0.001, whilst Sabax cardioplegia was associated with a slight increase in ventricular mechanical activity (3% LVSP increase with lukewarm Sabax cardioplegia, p< 0.001 and 2% LVSP increase with cold Sabax cardioplegia, p = 0.02. With Sabax cardioplegia the hearts displayed considerably less major arrhythmic events and presented less significant bradycardia. Conclusions: The present data suggest that Sabax cardioplegia may be superior to the classical cold crystalloid K-H solution in preserving mechanical activity of the heart and may provide superior protection against major arrhythmias.

  16. 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.

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    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.

  17. Combined postconditioning with ischemia and α7nAChR agonist produces an enhanced protection against rat myocardial ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    XIONG Jun; YUAN Yu-jing; XUE Fu-shan; WANG Qiang; LI Shan; LIAO Xu; LIU Jian-hua; CHEN Yi; LI Rui-ping

    2012-01-01

    Background Inflammation is one of important mechanisms for myocardial ischemia reperfusion injury (IRI).Ischemia postconditioning (IPOC) can protect the heart against IRI by inhibiting inflammation,but its cardioprotection is weaker than that of ischemia preconditioning.Recently,the α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR) agonist has shown anti-infiammatory effects in many diseases related to inflammation.This randomized controlled experiment was designed to evaluate whether combined postconditioning with IPOC and the α7nAChR agonist could produce an enhanced cardioprotection in a rat in vivo model of acute myocardial IRI.Methods Fifty Sprague-Dawley rats were randomly divided into five equal groups:sham group,control group,IPOC group,α7nAChR agonist postconditioning group (APOC group) and combined postconditioning with IPOC and α7nAChR agonist group (combined group).Hemodynamic parameters were recorded during the periods of ischemia and reperfusion.Serum concentrations of troponin I (Tnl),tumor necrosis factor α (TNF-α) and high-mobility group box 1 (HMGB-1) at 180 minutes after reperfusion were assayed in all groups.At the end of the experiment,the infarct size was assessed from excised hearts by Evans blue and triphenyl tetrazolium chloride staining.Results As compared to the sham group,the infarct size in the other four groups was significantly increased,serum levels of Tnl,TNF-α and HMGB1 in the control group and TNF-α,HMGB1 in the IPOC group were significantly increased.The infarct size and serum concentrations of TNF-α,HMGB1 and Tnl in the IPOC,APOC and combined groups were significantly lower than those in the control group.As compared to the IPOC group,the infarct size in the combined group was significantly decreased,serum concentrations of Tnl,TNF-α and HMGB1 in the APOC and combined groups were significantly reduced.Although the infarct size was significantly smaller in the combined group than in the APOC group

  18. The influence of calcium antagonists on the adenine nucleotide metabolism in the guinea-pig working heart during ischaemia and reperfusion.

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    Hugtenburg, J G; Mathy, M J; de Haan, N; Beckeringh, J J; van Zwieten, P A

    1991-05-01

    With the aim of gaining more insight into the metabolism of adenine nucleotides in working normoxic guinea-pigs and in hearts subjected to 45 min of global ischaemia and subsequent reperfusion for 25 min, we evaluated the effect of nifedipine, verapamil, diltiazem, bepridil, CERM 11956, lidoflazine, mioflazine and dipyridamole on the adenine nucleotide catabolite levels in these hearts. The drugs were applied at the concentrations that reduced the aortic dP/dt of normoxic working hearts by 10% (EC10) and 30% (EC30). In globally ischaemic hearts there was a large accumulation of adenine nucleotide catabolites. Inosine proved to be the major catabolite. The drugs, with the exception of bepridil, CERM 11956 and dipyridamole (3 mumol/l), decreased the accumulation of catabolites. In hearts treated with mioflazine and dipyridamole the amount of adenosine increased. A deficit in the balance between adenine nucleotides and catabolites indicated that in globally ischaemic hearts there was a large accumulation of inosine monophosphate. Indeed, a substantial amount of inosine monophosphate was determined in untreated hearts, and hearts treated with nifedipine (EC30) and mioflazine (EC10). During the first 5 min of reperfusion a large quantity of catabolites, mainly inosine, was washed out. During 20 min of subsequent reperfusion in untreated hearts and in nifedipine and mioflazine-treated hearts the efflux of catabolites returned to normoxic values. Similar to the effect in ischaemic hearts, in early perfusate from lidoflazine, mioflazine and dipyridamole-treated hearts the adenosine/inosine ratio was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Arctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammation.

    Science.gov (United States)

    Fan, Tao; Jiang, Wei Long; Zhu, Jian; Feng Zhang, Yu

    2012-01-01

    Stroke is the third leading cause of death in industrialized countries and the most important cause of acquired adult disability. Many evidences suggest that inflammation accounts for the progression of cerebral ischemic injury. Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignin isolated from certain plants, has shown anti-inflammatory activity against diabetes and Alzheimer's disease. In this study, we tested whether arctigenin can protect middle cerebral artery occluded (MCAO) rats. Male Sprague-Dawley rats were pretreated with arctigenin or vehicle for 7 d before being subjected to transient occlusion of middle cerebral artery and reperfusion. Rats were evaluated at 24 h after MCAO for neurological deficit scoring. Furthermore, the mechanism of the anti-inflammatory effect of arctigenin was investigated with a focus on inflammatory cells, proinflammatory cytokines, and transcriptional factors. Arctigenin significantly reduced cerebral infarction and improved neurological outcome. Arctigenin suppressed the activation of microglia and decreased the expression of interleukin (IL)- 1β and tumor necrosis factor (TNF)-α. These results revealed that arctigenin has a promising therapeutic effect in ischemic stroke treatment through an anti-inflammatory mechanism.

  20. Erdosteine improves oxidative damage in a rat model of renal ischemia-reperfusion injury.

    Science.gov (United States)

    Gurel, A; Armutcu, F; Cihan, A; Numanoglu, K V; Unalacak, M

    2004-01-01

    The aim of the present study was to determine the effects of erdosteine, a new antioxidant and anti-inflammatory agent, on lipid peroxidation, neutrophil infiltration, and antioxidant enzyme activities in a rat model of renal ischemia-reperfusion (I/R) injury. Twenty-eight rats were divided into three groups: sham operation, I/R, and I/R plus erdosteine groups. After the experimental procedure, rats were sacrificed and kidneys were removed and prepared for malondialdehyde (MDA) levels, myeloperoxidase (MPO), xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) activities. MDA level, MPO and XO activities were significantly increased in the I/R group. On the other hand, SOD and CAT activities were found to be decreased in the I/R group compared to the sham group. Pretreatment with erdosteine significantly diminished tissue MDA level, MPO and XO activities. Our data support a role for erdosteine in attenuation in renal damage after I/R injury of the kidney, in part at least by inhibition of neutrophil sequestration and XO activity.

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

    Science.gov (United States)

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

    2015-05-01

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

  2. Ginsenoside Rb1 Preconditioning Enhances eNOS Expression and Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Rui Xia

    2011-01-01

    Full Text Available Diabetes mellitus is associated with decreased NO bioavailability in the myocardium. Ginsenoside Rb1 has been shown to confer cardioprotection against ischemia reperfusion injury. The aim of this study was to investigate whether Ginsenoside Rb1 exerts cardioprotective effects during myocardial ischemia-reperfusion in diabetic rats and whether this effect is related to increase the production of NO via enhancing eNOS expression in the myocardium. The myocardial I/R injury were induced by occluding the left anterior descending artery for 30 min followed by 120 min reperfusion. An eNOS inhibitor L-NAME or Rb1 were respectively administered 25 min or 10 min before inducing ischemia. Ginsenoside Rb1 preconditioning reduced myocardial infarct size when compared with I/R group. Ginsenoside Rb1 induced myocardial protection was accompanied with increased eNOS expression and NO concentration and reduced plasma CK and LDH (P<0.05. Moreover, the myocardial oxidative stress and tissue histological damage was attenuated by Ginsenoside Rb1 (P<0.05. L-NAME abolished the protective effects of Ginsenoside Rb1. It is concluded that Ginsenoside Rb1 protects against myocardium ischemia/reperfusion injury in diabetic rat by enhancing the expression of eNOS and increasing the content of NO as well as inhibiting oxidative stress.

  3. Hippophae salicifolia D.Don berries attenuate cerebral ischemia reperfusion injury in a rat model of middle cerebral artery occlusion

    Institute of Scientific and Technical Information of China (English)

    Santhrani Thakur; Pradeepthi Chilikuri; Bindu Pulugurtha; Lavanya Yaidikar

    2015-01-01

    Objective: To investigate the protective effect of Hippophae salicifolia D.Don (H. salicifolia) berries extract against cerebral reperfusion injury induced neurobehavioral and neurochemical changes in a rat model of middle cerebral artery occlusion (MCAO). Methods: Rats were pretreated with alcoholic extract of H. salicifolia (250 and 500 mg/kg) for 14 d and focal cerebral ischemia was induced by MCAO. After 60 min of MCAO, reperfused for 24 h, a battery of behavioral tests were assessed the extent of neurological deficits. Infarct volume and brain edema were measured in 2,3,5-triphenyltetrazolium chloride stained brain sections. TNF-α, oxidative stress parameters like reduced glutathione, calcium, glutamate, malondialdehyde and apoptotic parameters like caspase-3, and caspase-9 were estimated in the brain homogenates. Results:Pretreatment with alcoholic extract of H. salicifolia at doses of 250 and 500 mg/kg significantly improved the neurobehavioral alterations and reduced the infarct volume, edema induced by ischemia reperfusion injury. H. salicifolia significantly prevented ischemia induced increase in malondialdehyde, glutamate, calcium, caspase-3, caspase-9 and TNF-αlevels as compared to ischemic animals. Conclusions: Our results indicate that H. salicifolia mitigated the ischemia reperfusion induced neuronal damage.

  4. Effects of the mitochondrial calcium uniporter on cerebral edema in a rat model of cerebral ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Linlin Li; Shilei Wang; Haihong Luan

    2011-01-01

    The present study investigated the effects of the mitochondrial calcium uniporter inhibitor ruthenium red and the agonist spermine on cerebral edema in rats with cerebral ischemia reperfusion injury.Left middle cerebral artery occlusion (MCAO) was induced in rats using the suture method.Following 24 hours of ischemic reperfusion, neurological function scores of rats with MCAO, and rats pretreated with ruthenium red and spermine were significantly lower, however, water content of brain tissue, aquaporin 4 expression and immunoglobulin G (IgG) exudation were significantly higher than those of sham-operated rats.Compared with MCAO rats and spermine-treated rats, neurological function scores were considerably higher, and brain tissue water content, aquaporin 4 expression and IgG exudation decreased in ruthenium red-treated rats.These findings suggest that preventive application of the mitochondrial calcium uniporter inhibitor ruthenium red can significantly decrease aquaporin 4 and IgG expression, influence the permeability of the blood brain barrier, and thereby decrease the extent of cerebral edema.

  5. Short-term sleep deprivation stimulates hippocampal neurogenesis in rats following global cerebral ischemia/reperfusion.

    Directory of Open Access Journals (Sweden)

    Oumei Cheng

    Full Text Available Sleep deprivation (SD plays a complex role in central nervous system (CNS diseases. Recent studies indicate that short-term SD can affect the extent of ischemic damage. The aim of this study was to investigate whether short-term SD could stimulate hippocampal neurogenesis in a rat model of global cerebral ischemia/reperfusion (GCIR.One hundred Sprague-Dawley rats were randomly divided into Sham, GCIR and short-term SD groups based on different durations of SD; the short-term SD group was randomly divided into three subgroups: the GCIR+6hSD*3d-treated, GCIR+12hSD-treated and GCIR+12hSD*3d-treated groups. The GCIR rat model was induced via the bilateral occlusion of the common carotid arteries and hemorrhagic hypotension. The rats were sleep-deprived starting at 48 h following GCIR. A Morris water maze test was used to assess learning and memory ability; cell proliferation and differentiation were analyzed via 5-bromodeoxyuridine (BrdU and neuron-specific enolase (NSE, respectively, at 14 and 28 d; the expression of hippocampal BDNF was measured after 7 d.The different durations of short-term SD designed in our experiment exhibited improvement in cognitive function as well as increased hippocampal BDNF expression. Additionally, the short-term SD groups also showed an increased number of BrdU- and BrdU/NSE-positive cells compared with the GCIR group. Of the three short-term SD groups, the GCIR+12hSD*3d-treated group experienced the most substantial beneficial effects.Short-term SD, especially the GCIR+12hSD*3d-treated method, stimulates neurogenesis in the hippocampal dentate gyrus (DG of rats that undergo GCIR, and BDNF may be an underlying mechanism in this process.