Experimental Study On The Effect Of An Angiotensin Converting-Enzyme Inhibitor Fosinopril Delayed Precondition On Reperfusion Arrhythmias And Electrophysiology Mechanism

Murry et al. found episodes of sublethal ischemia in dog protected the heart and reduced the infarct size caused by a subsequent more sustained period of coronary artery occlusion in 1986. Since then, many researchers have been investigating into the protective effect and its mechanism of ischemic preconditioning (IPC) because of its widely prospect of clinical useness. But the mechanism responsible for this protection remains unresolved. Experimental studies have demonstrated that the mechanism of ischemic preconditioning involves many endogenous myocardial protective substnces such as adenosine, noradrenaline, bradykinin and angiotensin.After reperfusion the cardiac damage more than ischemia is called "reperfusion injury" involves: Calcium overload,ATP descrease and myocytes cell edema.Of all this reperfusion arrhythmia (RA) (ventricular fibrillation ventricular tachycardia or premature ventricular beats) is the acute coronary syndrome's complication. Because of it's cardiac sudden death, more studies have been carried on it. Experimental studies have demonstrated that the mechanism of reperfusion injury involves triggered activity ,the threshold of VF decrease ,reentry and excitation increase,and the biochemistry foundation is Calcium overload and free radical. And many experimental studies have demonstrated that KATP channel is important in the protective effect of reperfusion arrhythmia. Many scientists assumed that activation of KATP channel is a common pathway of the protective effect of ischemic preconditioning, but there is no evidiences in single on myocytes cell in perfusion period. And many studies have demonstrated that angiotensin converting –enzyme inhibitior have pharmacol precondition can decrease myocardial infraction size improvement of functional recovery and antiarrhythmic effects.So the purpose of the present study was to explore how KATP channel current of cardiomyocytes is changed after angiotensin-converting–enzyme inhibitor (Fosionopril) preconditioning in reperfusion period and whether its' opening during reperfusion period could protect the ischemic myocardium from reperfusion arrhythmia, then to make clear the protective effect and its importance of in the protection of reperfusion damage. This experiment consists of three parts: 1. Langendroff reperfusion experiment of isolated perfused rat heart 2. Floating microelectrode experiment of vivo heart 3. Whole cell clap configuration experiment of cultured rat cardiomyocytes cell. Statistical analysis All data were expressed as mean ±SD. One-way ANOVA and Student t-test were employed. P values＜0.05 were regarded as statistically significant difference. The results showed that: 1. Effect of Fosionopril(10mg/kg) preconditioning on the function of heart during the subsequent ischemia and／or reperfusion, ventricular fibrillation and ventricular tachycardia 's frequency and duration decreased during the subsequent sustained ischemia and reperfusion (P＜0.01 ) and heart function improved (P＜0.01 ) when compared with those in the rat hearts subjected to simple ischemia／reperfusion episode. The changes of blood pressure ±dP/dT and heart rate were significant improved(P<0.05 ). And the effect of Fosionopril can be blocked by glibenclamide.2. Effect of Fosionopril(10mg/kg) preconditioning on the parameters of action potential including APD50 APD90 and APA were significantly longer in the Fosionopril group when compared with those in the rat hearts subjected to simple ischemia in reperfusion episode. 3. Effect of Fosionopril(10mg/kg) preconditioning on KATP channel current of cultured cardiomyocytes. in normal condition KATP channel is closed.30min hypoxia and then 30min reoxygenation make KATP channel open. Fosionopril preconditioning induced a significant KATP current when compared with that in myocytes subjected to short-term hypoxia (p＜0.01). the effect of Fosionopril can be blocked by glibenclamide.The results presented in the present study suggest that 1. the angiotensin converting –enzyme inhibitor F...