Mitochondrial transplantation combined with coenzyme Q10 improves mitochondrial function and induces full cardioprotection in aged rats with myocardial ischemia/reperfusion injury

Abstract

Abstract Background: Ischemic heart diseases (IHD) are among the major causes of mortality in elderly population. Although timely reperfusion is a commen treatment for IHD, it also causes additional damage to the ischemic myocardium known as ischemia/reperfusion (IR) injury. Considering the importance of preventing reperfusion injuries, we aimed to examine the combination effect of mitochondrial transplantation and coenzyme Q10 (CoQ10) in myocardial IR injury of aged rats. Methods: Seventy-two aged male Wistar rats were randomly divided into 6 groups: Sham, IR, CoQ10, mitochondrial transplantation (MT), combination therapy (MT+CoQ10), and vehicle. Myocardial IR injury was established by occlusion of the left anterior descending coronary artery and re-opening. Young male Wistar rats were used as mitochondria donors. Isolated mitochondria were injected intraventricularly (500µl of the respiration buffer containing 6×106±5×105 mitochondria) in MT receiving groups at the onset of reperfusion. CoQ10 (10mg/kg/day) was injected intraperitoneally for two weeks before IR induction. Twenty-four hours after reperfusion, hemodynamic parameters, myocardial infarct size (IS), LDH level, and cardiac mitochondrial function (mitochondrial ROS generation and membrane potential) were measured. Result: Combination of mitochondrial transplantation and CoQ10 improved hemodynamic index changes and reduced IS and LDH level (P<.05). It also decreased mitochondrial ROS generation and increased membrane potential (P<.05). showed a significant cardioprotective effect. Combination therapy showed greater cardioprotective effects than single treatments. Conclusion: This study revealed that mitochondrial transplantation and CoQ10 combination treatment can be considered as a promising cardioprotective strategy to reduce myocardial IR injury in aging, in part by restoring mitochondrial function.