Effect of diazoxide postconditioning on cardiac function and mitochondrial cardiolipin in isolated rat heart

AIM: To investigate the effect of diazoxide (D) postconditioning on Cardiac function and mitochondrial cardiolipin in isolated rat heart and to explore the protective effect of ATP sensitive potassium channel on diazo-xide postconditioning myocardium. METHODS: The myocardial ischemia/reperfusion injury model in isolated rat hearts was established by Langendorff apparatus. The isolated rat hearts were randomized into 4 groups (n=8): control group (control), myocardial ischemia/reperfusion injury group (I/R), diazoxide postconditioning group (I/R+D), 5- hydroxy decanoic acid (5-HD) plus diazoxide postconditioning group (I/R+5-HD+D). The hearts in each group were started with 20 min perfusion for equilibration. The hearts in control group perfused for 70 min; The hearts in I/R group was global ischemia for 40 min after ischemia reperfusion at 4 ℃ ST. Thomas cardioplegia, then reperfusion for 30 min; The hearts in I/R+D group were treated with diazoxide (50 μmol/L) in K-H perfusion for 5 min after global ischemia for 40 min, then reperfusion for 25 min; The hearts in I/R+5-HD+D group were treated with 5-HD (100 μmol/L) in K-H perfusion for 5 min before diazoxide postconditioning, then reperfusion for 20 min. The heart rate, coronary outflow volume, heart function, myocardial enzymes and myocardial mitochondrial cardiolipin at the end of perfusion in each group were determined. RESULTS: Compared with control group and I/R+D group, the heart rate, the concentration of heart phospholipid and the coronary outflow volume were reduced, the heart function was significantly impaired the contents of myocardial enzymes were increased in I/R group. However, no significant difference between I/R group and I/R+5-HD+D group was observed. CONCLUSION: The diazoxide postconditioning protects the myocardium by increasing mitochondrial cardiolipin content, reducing the release of myocardial enzymes, improving heart function and reducing myocardial reperfusion injury. The myocardial protective effect of diazoxide is completely blocked by 5- hydroxy decanoic acid.     

Progress in brain protection with ischemic postconditioning

Cerebrocardiovascular diseases and stroke are serious threat to human health. More attentions focus on cerebral ischemia and the publications suggest that ischemic preconditioning prevents ischemic myocardium from ischemia/reperfusion injury, soon followed by preconditioning against cerebral ischemic injury. However, in clinical management, ischemia is often unpredictable. In recent years, researchers found that ischemic postconditioning and ischemic preconditioning obtained the similar effects on brain protection after cerebral ischemia. The endogenous protective mechanisms play a key role in protecting against brain ischemic injury. As a novel manner to protect against brain injury, postconditioning attenuates the infarct volume following brain ischemia/reperfusion and prompts the neurological recovery by prolonging the therapeutic time window. This article reviews the processes of ischemic, hypoxia, hypothermia and pharmacologic postconditioning, and the possible brain protection mechanisms activated by the signal transduction of serine/threonine kinase (Akt), phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), protein kinase C (PKC), and ATP-sensitive potassium channel (K_ATP) pathways.     

Role of calcium activated potassium channel in cardioprotection induced by anoxic postconditioning in isolated rat heart

AIM:To investigate whether calcium activated potassium channel (KCa) and mitochondrial permeability transition pore (mPTP) contribute to cardioprotective effect elicited by anoxic postconditioning.METHODS:The isolated perfused hearts of male Sprague-Dawley rats were subjected to 30 min global anoxic followed by 120 min reoxygenation. Formazan content of myocardium was measured at 490 nm spectrophotometrically,and the level of lactate dehydrogenase (LDH) in the coronary effluent was detected. The absorbance of isolated heart mitochondria at 520 nm was determined. RESULTS:Anoxic postconditioning increased formazan content,reduced LDH release,improved the hemodynamic parameters of the left ventricular developed pressure,maximal rise/fall rate of left ventricular pressure,left ventricular end-diastolic pressure and rate pressure product and attenuated the decrease of coronary flow during reperfusion. Pretreatment with paxilline (1 μmol/L) inhibited the effect of anoxic postconditioning. The opening of mPTP was suppressed in the mitochondria isolated from A/R hearts treated with anoxic postconditioning.CONCLUSION:The findings indicate that in the isolated rat heart,anoxic postconditioning protects myocardium against anoxic/reoxygenation injury via inhibiting KCa and the mPTP opening.     

Postconditioning of zacopride depresses ischemia/reperfusion-induced arrhythmias in rats

ATM: To investigate the effects of postconditioning of zacopride, a specific agonist of inwardly rectifying potassium channel (K_ir), on ischemia/reperfusion-induced arrhythmias and the involved electrophysiological mechanisms. METHODS: Langendorff-perfused SD rat hearts or anesthetized rats were subjected to coronary artery occlusion for 15 min followed by 15 min of reperfusion to induce ischemia/reperfusion arrhythmias. Zacopride was applied 3 min before reperfusion. Various arrhythmias were monitored and compared in different groups. The single rat ventricular myocyte was isolated by collagenase digestion. The effects of zacopride on hypoxia/reoxygenation-induced delayed afterdepolarizations (DADs) and ATP-sensitive potassium channel (K_ATP) were observed by the technique of whole-cell patch clamping. RESULTS: Post-conditioning of 0.1~10 μmol/L zacopride significantly prevented the hearts from reperfusion arrhythmias. During reperfusion, 0.1 μmol/L zacopride showed the maximum effect, with decreasing the number of premature ventricular beats (PVB), reducing the incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF), and shorte-ning the duration of VT and VF (P<0.01). The postconditioning effects were partly reversed by 1 μmol/L BaCl₂(P<0.01), suggesting that the antiarrhythmic effect of zacopride was mediated by K_ir. In the in vivo study, 1.5~5 μg/kg zacopride had positive effects on reperfusion-induced VT and VF and negative effect on PVB. At the dose of 1.5 μg/kg, zacopride showed the most potent antiarrhythmic effect, which compared favourably with that of a classical antiarrhythmic agent, lidocaine. Furthermore, zacopride significantly inhibited hypoxia/reoxygenation-induced DADs (P<0.01). Zacopride had no effect on K_ATP.CONCLUSION: The inhibitory effect of zacopride on ischemia/reperfusion-induced arrhythmias is mediated by the activation of K_ir. Augmentation of K_ir cuvrent, thus diminishing the DADs, might be the critical mechanisms underlying postconditioning of zacopride.     

Role of nitric oxide in ischemia/reperfusion injury and ischemic preconditioning

AIM: To clarify the role of nitric oxide(NO) in ischemic preconditioning(IP) and its effects on apoptosis. METHODS: Seventy-two male Wistar rats were divided into the following six groups:ischemia/reperfusion (IR) group,IP group,IR+L-arg group,IP+L-arg group,IR+L-NAME group and IP+L-NAME group,The following changes were measured:cardiac hemodynamic parameters,infarct size,PMNs counting myocardial MPO activity and TUNEL staining.RESULTS: ①L-arg significantly attenuated ischemia/reperfusion-induced heart injury,reduced PMNs infiltration and cardiomyocyte apoptosis.②L-NAME also significantly reduced infarct size,PMNs infiltration and cardiomyocyte apoptosis compared with IR group,however,L-NAME aggravated ischemia/reperfusions-induced cardiac functional injury.③L-arg or L-NAME did not significantly alter the protective effect of ischemic preconditioning. CONCLUSION: Increased production of endogenous NO before prolonged ischemic period can protect hearts and inhibit apoptosis.L-NAME can inhibit iNOS activity and ONOO^- production in reperfusion period to protect heart.     

Alteration of cardiac M3 receptor and its relationship with arrhythmias in drug-induced and ischemia-induced arrhythmic models

AIM: To investigate the alteration of cardiac M₃ receptor and its relationship with arrhythmias in various arrhythmic models. METHODS: Forty Wistar rats were randomly divided into 4 groups: control, aconitine, BaCl₂ and ischemia. In the later three groups, arrhythmias were induced by treatment with aconitine, BaCl₂ and coronary artery occlusion, respectively. The arrhythmias were recorded for 1 h. Western blotting was then used to detect M₃ receptor contents. RESULTS: Arrhythmias were all induced in each group. In aconitine-induced arrhythmias, duration of arrhythmias and arrhythmia score were significantly increased than those in other two model groups. Western blotting showed that the expression of M₃ receptor upregulated 2.3, 1.4 and 1.3 folds respectively, more abundant in various arrhythmic groups than that in the normal control. Moreover, M3 receptor expression in aconitine group increased significantly than that in BaCl₂ and ischemia group. The arrhythmias and M₃ receptor protein expressions in myocytes were positively correlated. CONCLUSION: Arrhythmias upregulate the expression of cardiac M₃ receptor. The upregulating levels of M₃ receptor proteins diverge strikingly in different arrhythmic models. It is probably that the diversity of increase in M₃ receptor is positive related to severity of ventricular arrhythmias.     

Impact of remote postconditioning on rabbit hearts with acute myocardial ischemia-reperfusion injury

AIM:In this study, we tested the hypothesis that remote postconditioning induced by a single 5-min episode of femoral artery occlusion and reperfusion applied immediately before the onset of coronary artery reperfusion protects the myocardium from reperfusion injury. METHODS:Thirty healthy New Zealand white rabbits were randomly divided into three groups (n=10 in each group):control, myocardial ischemic postconditioning (MIP) and Limb ischemic postconditioning (LIP). Myocardial infarct size and tissue myeloperoxidase (MPO) activity were determined at the end of the experiment. Plasma creatine kinase (CK) activity and malondialdehyde (MDA) levels were measured at baseline, the end of ischemia, and after 180 min of reperfusion, respectively. RESULTS:Myocardial infarct size was significantly reduced in MIP and LIP as compared to control (P<0.01), also was confirmed by plasma CK activity. Plasma MDA, a product of lipid peroxidation, was significantly lower at 180 min of reperfusion in MIP and LIP than that in control (P<0.01). Neutrophil accumulation (MPO activity) in the area at risk was lower in MIP and LIP than that in control (P<0.01). CONCLUSION:Limb postconditioning provides potent myocardial infarct size reduction. The potential mechanism of remote postconditioning might be associated with decreasing the injury caused by oxygen free radicals and strengthening the action of antioxidation.     

Inhibition of calcineurin is involved in cardioprotection induced by ischemic postconditioning in rats

AIM: To demonstrate the mechanisms underlying cardioprotection induced by ischemic postconditioning (I-postC) via studying the alteration of calreticulin (CRT)/calcineurin (CaN) signaling pathway in rat heart subjected to ischemia/reperfusion (I/R).METHODS: The model of myocardial I/R injury in vivo was made by occluding the left anterior descending artery for 45 min followed by 24 h of reperfusion in Wistar rats.Hemodynamics and activity of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in plasma were measured.Myocardial infarct size was measured by 2,3,5- triphenyltetrazolium chloride (TTC) staining and cardiomyocyte apoptosis was detected using in situ TDT-mediated dUTP nick end labeling (TUNEL).The activity of CaN,the expressions of CaN and CRT in myocardium were detected by enzyme reaction phosphorus measurement and Western blotting analysis,respectively.RESULTS: Cyclosporin A,the inhibitor of CaN,limited significantly myocardial infarct size and cardiomyocyte apoptosis induced by I/R,but had no significant effect on cardiac function.I-postC ameliorated significantly the cardiac dysfunction induced by I/R.Compared with those in I/R group,the myocardial infarct size,the LDH and CK-MB activities in plasma and the cardiomyocyte apoptotic index were significantly reduced in I-postC group.In addition,I/R-induced upregulation of CaN activity,CaN and CRT expression were relieved by I-postC.No significant difference was found between I-postC and ischemic preconditioning groups.I-postC had stronger protective effect on the reperfused heart compared with cyclosporin A.CONCLUSION: The findings indicate that I-postC protects myocardium against I/R injury,at least in part,via inhibiting the CRT/CaN signaling pathway.     

Proteomic study of myocardial mitochondria with ischemia/reperfusion injury and pinacidil postconditioning in isolated rat hearts

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 postconditioning 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 (50 μmol/L) for 2 min followed 58-min perfusion with regular K-H solution. Total proteins extracted from the mitochondria were applied to the two-dimensional gel electrophoresis (2-DE). The differentially expressed protein spots over 2 times were evaluated by a software. Then they were subjected to in-gel digestion, and analyzed by spectrometry. RESULTS: The expression levels of NDUFA10, NDUFS2 and NDUFV2 were elevated but those of IDHA and ECH1 were decreased in Pina group compared with I/R group. Interestingly, 2 spots in the 2-DE map were identified as ATPase subunit δ. The expression levels of one spot was elevated, while the other was decreased. CONCLUSION: Pinacidil postconditioning may decrease the degree of increased expression levels of NDUFA10, NDUFS2 and NDUFV2, promote the expression of IDHA and ECH1, and induce the phosphorylation of ATPase subunit δ, which may be related to the protective mechanism of pinacidil postconditioning.     

Extracellular signal regulatory kinases mediate the cardioprotection induced by monophosphoryl lipid A

AIM:To investigate the cardioprotective effects of monophosphoryl lipid A(MLA) and its molecular mechanisms.METHODS: In the ischemia/reperfusion(I/R) model of porcine hearts, the effect of MLA on myocardial infarct size was observed. The protein levels of extracellular signal regulatory kinases (ERKs) and heat shock protein (HSP) 86 were detected by using western blotting method. RESULTS: MLA pretreatment significantly limited the infarct size in the porcine hearts subjected to I/R. It is also found that MLA pretreatment upregulated the protein levels of HSP86 and ERKs. CONCLUSION: MLA pretreatment can attenuate I/R injury in porcine hearts. The protective mechanism might be associated with ERKs-induced upregulation of HSP86 synthesis.     

Role of cAMP signaling in cardioprotective mechanism of ischemic postconditioning

AIM: To assess the role of the cAMP signaling in cardioprotection by brief intermittent ischemia at the time of onset of reperfusion (i.e. postconditioning). METHODS: The model of rat myocardial ischemia/reperfusion (I/R) was used. The left ventricular functions were assessed by measuring the left ventricular developed pressure (LVDP) and the coronary flow (CF). The injury of myocardium was further confirmed by detecting the releases of lactate dehydrogenase(LDH) and creatine kinase(CK) in coronary effluent. The mRNA expression of caspase-3, bcl-2 and bax in myocardium was determined by real-time PCR. RESULTS: I/R treatment led to the decrease in LVDP and CF, and the increase in the releases of CK and LDH in coronary artery effluent. The mRNA expression of caspase-3 and bax/bcl-2 ratio was up-regulated simultaneously. Postconditioning treatment relieved the injury induced by I/R, which was enhanced by the specific phosphodiesterase 4(PDE4) inhibitor rolipram. On the other hand, the specific adenylyl cyclase inhibitor SQ22536 attenuated those protective effects of postconditioning. CONCLUSION: The cAMP signaling participates in the protective effect of postconditioning on heart from I/R injury, and the effect may be associated with the regulation of apoptosis.     

Effects of ischemic postconditioning on cerebral ischemia/reperfusion injury in rats

AIM: To study the effects of ischemic postconditioning on cerebral ischemia following middle cerebral artery occlusion in rats. METHODS: 21 rats were randomly divided into three groups: middle cerebral artery occlusion (MCAO), MCAO+transient unilateral common carotid artery occlusion (u-CCA-O), MCAO+transient bilateral common carotid artery occlusion (b-CCA-O)(n=7, respectively). u-CCA-O/b- CCA-O was generated by transient middle cerebral artery occlusion plus transient unilateral/bilateral common carotid artery (CCA) occlusion. After the suture was removed, ischemic postconditioning was performed by occluding CCA for 10s, reperfusion 10s, and then allowing for another 4 cycles of 10s of reperfusion and 10s of CCA occlusion. Rats were sacrificed 2 d later and infarct size was measured. Cerebral blood flow (CBF) was measured in different 15 time points: 0 min, 10 min, 1 h after MCA occlusion, 0 min after MCA reperfusion, 10s of CCA occlusion and 10s of CCA reperfusion in all five cycles, 30 min after MCA reperfusion. Functional neurological outcome was determined 1 h and 48 h after reperfusion. Infarct volume was measured 48 h after reperfusion. RESULTS: The infarct volumes in u-CCA-O group and b-CCA-O group diminished compared to the control group. The results of CBF demonstrated that b-CCA-O group diminished 9% compared with control and u-CCA-O group when 30 min after intervention. The rats in u-CCA-O and b-CCA-O group had better neurological performance at 1 h after reperfusion. CONCLUSION: Ischemic postconditioning reduces infarct size, improves functional neurological outcome, most plausibly by diminishing cerebral blood flow.     

COX-2 inhibitor protects rat heart against oxidative stress through a pathway independent of cyclooxygenase

AIM: To investigate whether nimesulide ［a selective cyclooxygenase 2 (COX-2) inhibitor］ and piroxicam (an inhibitor of COX-1) protect the rat hearts against oxidative stress induced by hydrogen peroxide,superoxide anion or hydroxyl free radical.METHODS: Cardiac contractility,lactate dehydrogenase (LDH) and malondialdehyde (MDA) were analyzed by the Langendorff method in isolated rat hearts.Production of 6-Keto-PGF1α,a marker of COX activity,was measured in isolated rat hearts.RESULTS: Rat hearts were exposed to hydrogen peroxide (H₂O₂),pyrogallol (which produced superoxide anion) or Vit C+Fe2+ (which produced hydroxyl free radical) for 10 min followed by reperfusion for 30 min.H₂O₂ decreased cardiac contractility and increased LDH release,which was inhibited by nimesulide (3 mg/kg) ［LVDP 72%±10% vs 61%±11%,LDH （5.5±2.5）U/L vs （8.0±2.1）U/L,P<0.05］.Piroxicam (3 mg/kg) increased systolic function (LVDP 73%±10% vs 61%±11%,P<0.05),but exacerbated diastolic function ［LVEDP （29.00±5.61）mmHg vs （23.16±3.57） mmHg,P<0.01］ in H₂O₂ treated rat hearts.Nimesulide also protected rat hearts against superoxide anion and hydroxyl free radical injury.Nimesulide and piroxicam had no effect on the content of 6-Keto-PGF_1α in rat hearts.Mitochondrial ATP sensitive potassium channel (mitoK_ATP) inhibitor 5-HD blocked the improvement of contractility (LVDP and ±dp/dt_max) induced by nimesulide in H₂O₂ treated rat hearts (53%±12% vs 69%±3%,58%±11% vs 72%±7% and 37%±8% vs 51%±4% respectively,P<0.01).CONCLUSION: The results suggests that COX-2 inhibitor nimesulide can protect rat hearts against oxidative injury.The protection is independent of COX activity.Activation of mitoK_ATP may be involved in nimsulide-induced cardioprotection in rat hearts.     

Blunted response of L-type calcium current to simulated ischemia and reperfusion in ventricular myocytes from diabetic rabbits

AIM: To evaluate the effects of simulated acute ischemia and reperfusion on L-type calcium current (I_{Ca, L}) in ventricular myocytes from diabetic and non-diabetic rabbits.METHODS: Using whole-cell patch clamp techniques, I_{Ca, L} was measured in left ventricular myocytes isolated from 6-week alloxan-induced diabetic rabbits and age-matched control ones at baseline, 5 min of simulated ischemia, and 5 min of reperfusion.RESULTS: There were no significant differences on baseline maximum I_{Ca, L} densities between diabetic and control ventricular myocytes. In control cells (n=11), maximal I_{Ca, L} densities of baseline, ischemia and reperfusion were (-8.36±1.63)pA/pF, (-5.90±1.75)pA/pF and (-4.22±1.02)pA/pF, respectively. The I_{Ca, L} of ischemia was less than that of baseline (P<0.01), while the I_{Ca, L} of reperfusion was less than those of baseline (P<0.01) and ischemia (P<0.05). In diabetic cells (n=9), the I_{Ca, L} of baseline, ischemia and reperfusion were (-7.55±1.62)pA/pF, (-6.05±1.58)pA/pF and (-5.12±1.13)pA/pF, respectively. Only I_{Ca, L} of reperfusion was less than that of baseline (P<0.01), while I_{Ca, L} of ischemia was not significantly different from that of baseline (P>0.05) or reperfusion (P>0.05).CONCLUSION: I_{Ca, L} in diabetic ventricular myocytes represents blunted response to acute ischemic injury, being decreased more slowly than that in control cells. Post-ischemic reperfusion is still a potent inhibitor against I_{Ca, L} in both diabetic and non-diabetic cells. This study may be indicative of the mechanism about ischemia-reperfusion injury to diabetic myocardium and the therapy for diabetic patients with ischemic heart disease.     

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会议由中国园艺学会主办 ,中国农业工程学会设施园艺工程专业委员会协办 ,沈阳农业大学园艺系承办 ,于 2 0 0 0年 4月 19日至 2 2日在沈阳农业大学召开。来自我国 13个省、自治区、直辖市的与会代表共 78人 ,会议论文 4 3篇 ,由沈阳农业大学学报专刊发表。经承办单位和与会者努力 ,会议圆满成功。开幕式由中国园艺学会副理事长李树德研究员主持 ,辽宁省科技厅、农业厅、沈阳市副食品局、沈阳农业大学的领导到会祝贺并发表讲话。会议就确定的主题进行了大会发言 ,小组讨论及现场考察。代表们欣喜地看到 ,近 2 0年来我国蔬菜设施生产迅猛发展 …     

Cardiac protective effect of granulocyte colony-stimulating factor combined with ischemic postconditioning on acute myocardial infarction in rabbits

AIM: To investigate the protective effect of granulocyte colony-stimulating factor (G-CSF) combined with ischemic postconditioning (IP) on acute myocardial infarction (AMI). METHODS: Male New Zealand rabbits were randomly divided into 4 groups (n=15) after 30 min of left ventricular artery (LVA) occlusion: the rabbits in ischemia-reperfusion (IR) group were directly given reperfusion|the rabbits in G-CSF group were subsequently treated with G-CSF (10 μg·kg^-1·d^-1) by subcutaneous injection after direct reperfusion|the rabbits in IP group received 4 episodes of 30 s reperfusion and 30 s occlusion before total reperfusion|the rabbits in IP combined with G-CSF (IP+G-CSF) group were treated with both IP and G-CSF. Electrocardiogram (ECG) monitoring was performed during the operation. Blood was drawn to evaluate white blood cell count (WBC) and cardiac troponin I (cTnI) before operation and 7 d later. Ultrasound cardiography was performed to evaluate left ventricular remodeling and functions 4 weeks after operation. The sizes of infarcted myocardium were determined by triphenyltetrazolium chloride (TTC) staining. Apoptosis of cardiomyocytes was measured by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) staining. RESULTS: ST-segment resolutions were significantly decreased in IP group and IP+G-CSF group compared with direct reperfusion groups (P<0.05). WBC significantly increased in the groups treated with G-CSF for 1 week. The values of cTnI after operation were significantly lowered in G-CSF group, IP group and IP+G-CSF group as compared with IR group (P<0.05). Left ventricular ejection fraction, the size of infarcted myocardium and apoptosis of cardiomyocytes were better in IP group, G-CSF group and IP+G-CSF group than those in IR group. CONCLUSION: G-CSF combined with IP is a promising strategy against cardiac reperfusion injury and accelerates cardiac repair in AMI.     

Effects of Shenmai injection on acute myocardial ischemia/reperfusion injury in rats

AIM: To observe the effect of Shenmai injection on the acute myocardial ischemia/ reperfusion injury in rats. METHODS: The left-anterior coronary artery was ligated for 10 minutes and then loosed for 15 minutes to establish the animal model of acute myocardial ischemia/reperfusion injury. During the process, electrocardiogram was traced continuously to observe the arrhythmia caused by reperfusion. The levels of SOD, MDA, Na⁺, K⁺-ATPase and Ca²⁺ -ATPase in ventricular myocardium were measured. The mitochondria was observed through electron microscope. RESULTS: Shenmai injection decreased the incidence of arrhythmia caused by reperfusion and shortened its duration. Shenmai injection improved the activity of SOD, Na⁺, K⁺-ATPase and Ca²⁺ -ATPase, decreased the content of MDA in myocardium and relieved the injury of mitochondria. CONCLUSION: Shenmai injection had a protective effect on acute myocardial ischemia/reperfusion injury in rats. The mechanism may be related to relieving the injury caused by oxygen free radical and calcium overload.     

Heptanol,a gap junction uncoupler,protects heart against ischemia-reperfusion injury in rats

AIM: To determine the effect of heptanol on the in vivo heart subjected to ischemia and reperfusion, on the whole-tissue resistance and electrical uncoupling in the isolated rat heart during prolonged ischemia. METHODS: The effect of heptanol at different doses (0.03, 0.06, 0.30, and 0.60 mg/kg) on the intact rat heart during 30 min ischemia (ligation of left anterior descending coronary artery) and 2 h of reperfusion was observed. The effect of heptanol on electrical uncoupling in the isolated rat heart was investigated by measuring the changes in whole-tissue resistance using the four-electrode method. RESULTS: Heptanol reduced infarct size and the severity of arrhythmia during ischemia and reperfusion within a range of doses (0.06-0.60 mg/kg). No effect was observed at dose of 0.03 mg/kg and the severity of arrhythmia during ischemia was increased at dose of 0.60 mg/kg. Heptanol at different concentrations (0.05-1.00 mmol/L) delayed the onset of electrical uncoupling and plateau time during prolonged ischemia, and reduced the maximal rate of uncoupling. CONCLUSION: Heptanol conferred cardioprotection on ischemia-reperfusion myocardium. The mechanism may be related to its uncoupling effect.     

Effects of ischemic postconditioning on sizes of myocardial infarction induced by ischemia/reperfusion and PKCα expression in rats

AIM: To observe the effects of ischemic postconditioning on the sizes of myocardial infarction induced by ischemia/reperfusion (I/R) and expression of protein kinase C-α (PKCα) in rats. METHODS: The infarction sizes (IS) were measured with Evan’s and TTC dye, and the expression of PKCα in myocardial tissue was investigated by immunohistochemistry. RESULTS: Compared with the I/R group, the IS was reduced significantly (P<0.01), and the expression of PKCα increased significantly in IPC and IPTC groups (P<0.01). There was no significant difference between IPC and IPTC groups. CONCLUSIONS: The postconditioning is as effective as preconditioning in reducing infarct size, and the expression of PKCα may be one of the potential mechanisms of reducing the infarction sizes.     

The relationship between delayed preconditioning mediated by R-PIA and myocardial nuclear factor-kappa B

AIM:To investigate the role of myocardial nuclear factor kappa B (NF-κB)and manganese superoxide dismutase (Mn-SOD) in the mechanism underlying cardioprotective effect of delayed preconditioning mediated by adenosine A₁ receptor agonist R-phenylisopropyladenosine ( R-PIA). METHODS:Male Wistar rats were randomly divided into three groups(n=12), Group normal saline, Group R-PIA and Group R-PIA plus DPCPX (an adenosine A₁ receptor antagonist). Twenty four hours after administration of above drug, left ventricular myocardial samples of 4 rats in each group were obtained for assessment of myocardial Mn-SOD content (ELISA) and NF-κB binding activity (EMSA). Eight rats in each group, 24 hours after pretreatment as above, were subjected to chest-open and subjected to 30 min of regional myocardial ischemia followed by 120 min of reperfusion, and then the hearts of the rats were isolated to determine the infarct size (TTC stain ). RESULTS: The infarct size in group R-PIA was significantly less than that in group normal saline (P＜0.01), and there was no significant difference between group R-PIA+DPCPX and group normal saline in infarct size (P＞0.05). Myocardial NF-kappa B binding activity and Mn-SOD content in group R-PIA were all higher than those in group normal saline. There was no significant difference between group R-PIA+DPCPX and group normal saline in NF-κB binding activity and Mn-SOD content (P＞0.05). CONCLUSIONS:This study suggested that there might be a close relationship between delayed preconditioning mediated by adenosine A₁ receptor agonist R-PIA and myocardial nuclear factor-kappa B binding activity and Mn-SOD protein expression.