Abstract:ObjectiveIn order to evaluate the effect of diazoxide on myocardial inhibition of bupivacaine,observe the direct toxic effect of bupivacaine on myocardial cells,and whether the use of diazoxide can reduce or eliminate this toxic effect.MethodsFifty adult SD rats were selected and subjected to aortic retrograde perfusion enzymolysis for acute cardiomyocyte isolation.After the cells were successfully isolated,the cardiomyocytes with rod-shaped,clear stripes and regular edges were selected and divided into two groups by random number table method:bupivacaine group (Bup group) and diazoxide + bupivacaine group (Bup+D group).Both group were divided into 5 subgroups according to different bupivacaine concentrations（20.0,30.0,45.0,67.5,and 101.5 μmol/L）,respectively.Whether the cells stopped spontaneous beating before and after perfusion with different concentrations of bupivacaine,and whether the cells resumed spontaneous beating after changing the calcium Tyrode′s solution again were recorded.ResultsExcept for 20.0 μmol/L,after perfusion with diazoxide and bupivacaine at different concentrations,the rate of myocardial cell failure in each group was significantly lower than that given with bupivacaine perfusion alone (P<0.05).The EC50 and 95%CI diazoxide+bupivacaine-induced myocardial cell failure in rats was 64.6 (47.4-84.3)μmol/L,which was significantly higher than that induced by bupivacaine alone［44.9(33.9-55.4)μmol/L,P<0.05］.After the failed cells stopped perfusion of bupivacaine and diazoxide,the cells could return to normal contraction.ConclusionsThe cardiotoxicity of bupivacaine is related to its inhibition of mitochondrial ATP-sensitive potassium channel (mitoKATP),opening ATP-sensitive K channels can significantly improve the ability of rat myocardium to tolerate myocardial toxicity of bupivacaine.