Strategies of hypoxia and anoxia tolerance in cardiomyocytes from the overwintering common frog, Rana temporaria.

Using ventricular cardiomyocytes of the common frog, Rana temporaria, we investigated the metabolic strategies employed by the heart to tolerate 4 mo of hypoxic submergence (overwintering) as well as acute bouts of anoxia. In contrast to what is observed for the whole animal, there was no change in oxygen consumption in cardiomyocytes isolated from normoxic frogs compared with those isolated from 4-mo hypoxic animals. Furthermore, cells from both normoxic and hypoxic frogs were able to completely recover oxygen consumption following 30 min of acute anoxia. From estimates of ATP turnover, it appears that frog cardiomyocytes are capable of a profound, completely reversible metabolic depression, such that ATP turnover is reduced by >90% of control levels during anoxia but completely recovers with reoxygenation. Moreover, this phenomenon is also observed in frogs that have been subjected to 4 mo of extended hypoxia. We found a significant increase in the stress protein, hsp70, after 1 mo of hypoxic submergence, which may contribute to the heart's remarkable hypoxia and anoxia tolerance and may act to defend metabolism during the overwintering period.