Diet-Induced Metabolic Syndrome Does Not Affect Postischemic Contractility of the Rat Myocardium

Highlights Diet-induced metabolic syndrome does not lead to mitochondrial respiration impairment and worsening of contractile dysfunction of the rat myocardium. Preservation of contractile function may be associated with substrate oxidation by complex II of the mitochondrial respiratory chain. It can be assumed that the initial metabolic changes of donors are not a significant obstacle to myocardial transplantation. Abstract Background. Tissue resistance to acute ischemia is an important problem of medical science in general and transplantology in particular. At the same time, carbohydrate and lipid metabolism disorders can cause a decrease in organ resistance to ischemia, and the high prevalence of such disorders in the population is an important problem for the preservation of the transplanted organ. Aim. To assess the effect of experimental metabolic syndrome (MS) on the severity of myocardial contractile dysfunction during reperfusion, and the relationship between myocardial contractility in MS and mitochondrial respiration. Methods. The study was performed on Wistar rats. Metabolic syndrome (MS) was modeled by feeding rats of a high-carbohydrate, high-fat diet for 12 weeks. Post-ischemic myocardial contractility was assessed using an in vivo model of acute coronary occlusion-reperfusion (ACR) echocardiography and an isolated heart ischemia-reperfusion model. Mitochondria were isolated by differential centrifugation from the ischemic zone after ACR. Mitochondrial respiration was assessed in the presence of malate, pyruvate, and succinate. Results. Keeping rats on a diet for 12 weeks led to the formation of obesity, hypertension, increased blood glucose, triglyceride, leptin, and adiponectin levels, i.e., to the metabolic syndrome formation. Myocardial contraction parameters before ischemia modeling both in vivo and in the isolated heart model did not differ. Mitochondria of rats with MS were distinguished by greater efficiency of ADP/O respiration on both NAD+ and FAD+-dependent substrates. ACR in vivo led to a decrease in the contractile and pumping function of the myocardium, suppression of mitochondrial respiration equally in the group of control animals and animals with MS. Similar data were obtained in the isolated heart model. An inverse correlation link was established between the efficiency of mitochondrial respiration in rats with MS in the presence of a FAD+-dependent substrate and the value of the end-systolic volume at late stages of reperfusion. Such a relationship was not observed in the control group rats. Conclusion. The obtained results suggest that diet-induced MS does not lead to mitochondrial respiration impairment and aggravation of myocardial contractile dysfunction. Preservation of contractile function may be associated with oxidation of substrates by complex II of the mitochondrial respiratory chain. It can be assumed that the initial metabolic changes in donors are not a significant obstacle to myocardial transplantation.