Studies of intact hearts suggest that cardiac myocytes may have the ability to reversibly suppress metabolic activity and energy demand in states of regional hypoperfusion. However, an ability to suppress respiration in response to
hypoxia has never been demonstrated in isolated myocytes. To test this, isolated embryonic chick cardiac myocytes were exposed to progressive
hypoxia while their rate of O2 uptake and concentrations of
lactate,
ATP,
ADP,
AMP, and
phosphocreatine were measured. Compared with the value obtained at an
oxygen tension (PO2) of 120 Torr, cellular O2 uptake decreased by 28 +/- 14% (SD) at PO2 = 50 Torr and by 64 +/- 25% at PO2 = 20 Torr (P < 0.05). This decrease was similar after 1 min or 2 h of
hypoxia, was sustained for 16 h, and was completely reversible within 2 min after reoxygenation. The reduction in O2 uptake was associated with a decrease in the rate of
ATP turnover, but no change in
adenine nucleotide or
phosphocreatine concentrations. In myocytes adherent to glass cover-slips, O2 uptake and contractile motion were decreased after 30-60 min at 50 and 20 Torr, compared with normoxic values. O2 uptake also was significantly decreased at 50 and 20 Torr in myocytes incubated with N,N,N',N'-
tetramethyl-p-phenylenediamine, which suggests that the catalytic activity of
cytochrome-c oxidase was partially inhibited during
hypoxia. In summary, these results demonstrate that embryonic chick cardiac myocytes can suppress their rates of
ATP demand,
ATP utilization, and O2 uptake during moderate
hypoxia through a mechanism that involves a reversible inhibition of
cytochrome-c oxidase. This mechanism may represent a protective response to cellular hypoxia.