Evaluating the combinational effects of mitochondrial transplantation and co-enzyme Q10 on cardioprotection in aged rats with myocardial ischemia/reperfusion injur

Abstract

Ischemc heart disease, caused by coronary artery occlusion, is among the main causes of mortality in the elderly population. Although reperfusion is the most common treatment to prevent ischemic injury, this process itself leads to further damage to the myocardium, known as ischemia/reperfusion (IR) injury. Considering the importance of preventing IR injury, our aim was to investigate the effects of mitochondrial transplantation (MT) and coenzyme-Q10 (CoQ10), alone or in combination, on myocardial IR injury in aged male rats. Method: Seventy-five old male rats (aged 22-24 months) were randomly divided into five groups: sham, IR, CoQ10, MT and combined treatment (MT + CoQ10). Myocardial IR injury was induced by the left anterior descending coronary artery (LAD) occlusion for 30 minutes, followed by 24 hours reperfusion. In the CoQ10-receiving groups, 10 mg/kg of CoQ10 was injected intraperitoneally daily for two weeks before the induction of ischemia. Young male rats were used as mitochondrial donors. In the mitochondria-receiving groups, approximately 3 ± 0/25 x 106 isolated mitochondria were immediately injected intraventricularly at the onset of reperfusion. ECG was recorded during ischemia and the first 30 minutes of reperfusion to examine ventricular arrhythmias. After 24 hours reperfusion, arterial and cardiac hemodynamic parameters were measured and finally, serum samples were collected to measure cardiac damage indicators. four hearts were used to measure the infarct size by Evans Blue TTC staining, 3 hearts for histopathological changes using hematoxylin and eosin staining, and 8 hearts were used to assess other factors, including mitochondrial membrane potential and ROS production, the expression of mitochondrial dynamics related genes (Fis1, DRP-1, Mfn1 and Mfn2), oxidative stress markers and the amount of nitric oxide metabolites (NOx). Results: Single CoQ10 was able to exert significant cardioprotective effects, but MT alone did not demonstrate notable cardioprotective effects. However, the combined treatment indicated more robust cardioprotective effects than single CoQ10 (P <0.05). In the CoQ10 group, some variables did not show a significant improvement as compared with IR group, however in the combination therapy group, all the measured variables exhibited a positive trend. In general, combination therapy resulted in improvement in cardiac hemodynamic status (P <0.01 and P <0.001) as well as reduction in ventricular arrhythmias (P <0.01 and P <0.001), infarct size (P<0.001) and cardiac damage markers (P <0.001) in comparization to IR group. These effects were accompanied by a reduction in mitochondrial ROS production (P <0.001), an increase in mitochondrial membrane potential (P <0.001), an improvement in the expression of fission and fusion-related genes (P <0.01 and P <0.001), a reduction in oxidative stress (P <0.01 and P <0.001) and an elevation in NOx (P <0.01).