Objective:To investigate the effect of dantrolene on myocardial ischemia-reperfusion(I/R) injury to isolated rat heart. Hemodynamics, lactate dehydrogenase (LDH) activity, myocardial infarct size, and activities of enzymes of glycometabolism were observed.Methods:Forty-eight healthy male Wistar rats were used in the Langendorff isolated heart perfusion system. The hearts were randomly divided into three groups:control group, ischemia-reperfusion (I/R) group and dantrolene-treated group, with sixteen rats in each. The hearts in control group were perfused 120 min.The hearts in ischemia-reperfusion (I/R) group were perfused 30 min, and then subjected to 30 min of global ischemia and 60 min of retrograde reperfusion. The hearts in dantrolene-treated group were perfused for 30 min in the working mode, in the presence of 5μM dantrolene, and then were perfused 30 min before subjected to 30 min of global ischemia and 60 min of reperfusion. Heart rate (HR), aortic flow (AF),coronary flow (CF), and cardiac output (CO) were determined at hearts working 5min, 10min,20min, and 30min.After the reperfusion, the myocardial infarct size was determined by the TTC staining method. The activities of Lactate dehydrogenase (LDH), phosphofructokinase-1(PFK), pyruvate kinase (PK), hexokinase (HK) and isocitrate dehydrogenase (IDH) were determined by ultraviolet spectrophotometry.Results:1. Effects of dantrolene on hemodynamics of isolated rat hearts. Compared to the ischemia-reperfusion (I/R) group, dantrolene group did not produce any hemodynamic effect, with the exception of a moderate increase in coronary flow (P<0.01).2. Effects of dantrolene on LDH activity and infarct size of rat hearts. The LDH activity in dantrolene group was lower than that in ischemia-reperfusion (I/R) group (P<0.01). And the myocardial infarct size in dantrolene group was less than that in ischemia-reperfusion (I/R) group.3. Effects of dantrolene on the activities of enzymes of glycometabolism. The activities of PFK,PK,HKand IDH in dantrolene group were lower than that in ischemia-reperfusion (I/R) group (P<0.05).Conclusions:1. Dantrolene can reduce the myocardial infarct size and the LDH release of myocardial cells. Consequently, dantrolene has a protective effect in myocardial ischemia-reperfusion.2. Dantrolene has a protective effect in myocardial ischemia-reperfusion by reducing the activities of enzymes of glycometabolism, therefore degrade the need in ischemia-reperfusion.3. The results of this study indicate that dantrolene can protect ischemia-reperfused myocardium. The findings might provide new basic information for further researches on the protective mechanisms of dantrolene on myocardial ischemia reperfusion injury as a new protect drug in clinical. |