| Objective:To investigate the effect of dantrolene on myocardial ischemia-reperfusion(I/R)injury to isolated rat heart. Hemodynamics (including heart rate, aortic flow, coronary flow and cardiac output), lactate dehydrogenase (LDH) activity, myocardial infarct size, and activities of mitochondrial respiratory chain complexⅠ,Ⅳas a starting point to study of dantrolene on myocardial ischemia-reperfusion specific mechanisms for protection were observed.Methods:Forty-eight male Wistar rats were randomly divided into three groups: control group, ischemia-reperfusion group and dantrolene-treated ischemia-reperfusion group. Isolated rat hearts were mounted on a Langendorff perfusion apparatus. They were first perfused with Krebs buffer for 30min. Pre-ischemic control continued to reperfuse for 90min; For ischemia-reperfusion, the hearts were subjected to global ischemia for 30min and reperfusion for 60min. The dantrolene-treated group was perfused in the presence of 5μmol/L dantrolene before ischemia. Heart rate (HR), aortic flow (AF), coronary fiow (CF), and cardiac output (CO) were determined of different concentrations of dantrolene.After the reperfusion, the myocardial infarct size was determined by the TTC staining method. The activities of Lactate dehydrogenase (LDH), mitochondrial respiratory chain complexⅠ,Ⅳ(CⅠI,CⅣ) was 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<0.05),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. The myocardial infarct size in dantrolene group was less than that in ischemia-reperfusion (I/R) group (P<0.01).3. Effects of dantrolene on the activities of mitochondrial respiratory chain complexⅠ,ⅣThe activities of mitochondrial respiratory chain complexⅠ,Ⅳin dantrolene group were higher than that in ischemia-reperfusion (I/R) group (P<0.05).Conclusion: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 increasing the activities of mitochondrial respiratory chain complexⅠ,Ⅳ.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. |
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