Protective Effects Of Polarizing Cardioplegia With Sodium Channel Inhibitor On Ischemia/Reperfusion Myocardium Of Isolated Rat Hearts

Objective To investigate the protective effects of polarizing cardioplegia with sodium channel inhibitor tetrodotoxin(TTX) on ischemia/reperfusion myocardium of isolated rat hearts. The cooperative effects of Na+/H+ exchange inhibitor (Amiloride) and Na+/K+/2Cl- cotransport inhibitor (Furosemide) added in the polarizing cardioplegia solution were also studied. Methods Langendorff perfusion models and Neely working left ventricular perfusion models were sequentially created in 4 groups. The hearts in each group were arrested by different cardioplegia in GroupⅠ(TTX), Group Ⅱ(TTX+Amiloride) , Group Ⅲ(TTX+Amiloride+ Furosemide), GroupⅣ (control group, only STH-2). The arrested hearts were preserved in the corresponding cardioplegia solutionrespectively at 7℃ for 5 hours, and then reperfused. Pre-ischemic and post-ischemic indexes were studied including hemodynamic parameters, myocardial enzymology, ATP content, intracellular free calcium ion concentration [Ca2+]i ,and ultrastructural changes. Results There were no differences in four groups before myocardial ischemia. But the myocardial hemodynamic parameters during reperfusion in groups containing TTX(GroupⅠ,Ⅱ,Ⅲ) were respectively better than those in Group Ⅳ(P＜0.01). The releases of CPK and LDH in Group Ⅰ,Ⅱ, Ⅲ were less than those in Group Ⅳ(P＜0.05). The activities of Na+-K+-ATPase, Ca2+-ATPase, Ca2+-Mg2+-ATPase ; and contents of ATP in groups containing TTX kept relative higher level after reperfusion. Compared with depolarizing arrest group, [Ca2+]i in polarizing arrest group was relative lower. Myocardial ultrastructure was better protected in polarizing arrest group .Conclusion As a new and effective composition,sodium channel inhibitor TTX could prevent myocardial ischemia/reperfusion injuries caused by intracellular Na+-overload and Ca2+-overload , and reduce the consumption of energy by arresting heart under polarizing condition. Inhibitting Na+/H+ exchanger and Na+/K+/2Cl- cotransporter enhanced the protective effects of TTX. Therefore , compared with depolarizing arrest, polarizing arrest might be a more effective cardioplegia in myocardial protection and preservation .