Exercise Training but Not Genetically Determined Exercise Capacity Reduces Cardiac Ischemia–Reperfusion Injury in Rats with High Intrinsic Aerobic Capacity

Background: Low aerobic exercise capacity is associated with high morbidity and mortality in healthy humans. Furthermore, low exercise capacity is associated with worse outcome in cardiac disease. However, exercise capacity is composed of an intrinsic (genetically determined) and an extrinsic (environmentally determined) component. The rat model of genetically determined high (HCR) and low (LCR) aerobic exercise capacity allows to disentangle these both components of exercise capacity. We aimed to assess the impact of genetically determined exercise capacity in combination with exercise training on cardiac function during ischemia-reperfusion of HCR and LCR.

Method: Female HCR and LCR at the age of ~15 weeks were kept sedentary or trained for 4 weeks with individually adapted aerobic interval training. Subsequently, cardiac mitochondrial function was assessed in isolated mitochondria prior to ischemia–reperfusion. Cardiac power and substrate oxidation were determined in the isolated working heart with ischemia–reperfusion.

Results: At baseline, cardiac power was comparable between HCR and LCR, whereas ischemia unexpectedly resulted in reduced recovery of HCR regarding cardiac power and number of recovering hearts (HCR: 57 vs. LCR: 83%). In addition, ATP production related to cardiac power was lower in HCR compared with LCR and worsened after ischemia. Exercise training increased individual running capacity in both HCR and LCR but was still significantly higher in HCR. Furthermore, exercise training increased maximal mitochondrial respiratory capacity (HCR control 706 ± 70 vs. HCR exercise 1,023 ± 159 natomsO/min/mg protein) and isolated complex activities in HCR only. Mitochondrial mass, however, was increased in both HCR and LCR. Following ischemia, all hearts of trained HCR and LCR recovered during reperfusion. Cardiac power in reperfusion was increased in trained versus untrained HCR, while recovery of trained LCR was similar to untrained LCR. Recovered hearts from trained HCR showed reduced glucose oxidation and increased efficacy at baseline and reperfusion compared with sedentary HCR.

Conclusion: Rats with high genetically determined aerobic capacity are not protected against ischemia-induced impairments of cardiac contractile function. However, exercise training significantly protected against ischemic injury in HCR. Such a strong protective effect cannot be seen with training in rats with low genetically determined aerobic capacity.

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Artikel online veröffentlicht:
28. Januar 2023