Key result
Rats selectively bred for low intrinsic aerobic capacity experienced acute cardiac pump failure significantly earlier during an acute hypoxic challenge compared to high capacity rats.
Low intrinsic aerobic capacity in a rat model is associated with altered sub-cellular calcium handling, myosin heavy chain isoform switching, and increased susceptibility to hypoxia-induced cardiac pump failure.
Low aerobic capacity may heighten hypoxic pump failure risk in rats; leaves open human translation and clinical relevance.
Oxygen metabolism is a strong predictor of the general health and fitness of an organism. In this study, we hypothesized that a divergence in intrinsic aerobic fitness would co-segregate with susceptibility for cardiovascular dysfunction. To test this hypothesis, cardiac function was assessed in rats specifically selected over nineteen generations for their low (LCR) and high (HCR) intrinsic aerobic running capacity. As an integrative marker of native aerobic capacity, run time to exhaustion between LCR and HCR rats had markedly diverged by 436% at generation nineteen of artificial selection. In vivo assessment of baseline cardiac function by echocardiography and catheter-based conductance micromanometry showed no marked difference in cardiac performance. However, when challenged by exposure to acute hypoxia, cardiac pump failure occurred significantly earlier in LCR rats compared to HCR animals. Acute cardiac decompensation in LCR rats was exclusively due to the development of intractable irregular ventricular contractions. Analysis of isolated cardiac myocytes showed significantly slower sarcomeric relaxation and delayed kinetics of calcium cycling in LCR myocytes compared to HCR myocytes. This study also revealed that artificial selection for low native aerobic capacity is a novel pathologic stimulus that results in myosin heavy chain isoform switching in the heart as shown by increased levels of beta-MHC in LCR rats. Together, these results provide evidence that alterations in sub-cellular calcium handling and MHC isoform composition are associated with susceptibility to compensatory cardiac remodeling and hypoxia induced pump failure in animals with low intrinsic aerobic capacity.
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Palpant et al. (2009) studied Hypoxia-induced cardiac pump failure. Low intrinsic aerobic capacity (LCR) vs. High intrinsic aerobic capacity (HCR) was evaluated on Acute cardiac pump failure during hypoxia (p=0.02). Rats selectively bred for low intrinsic aerobic capacity experienced acute cardiac pump failure significantly earlier during an acute hypoxic challenge compared to high capacity rats.
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