Short-term hibernation in adult cardiomyocytes

Stumpe, Thomas, and Jürgen Schrader. Short-term hibernation in adult cardiomyocytes is PO2 dependent and Ca mediated. Am J Physiol Heart Circ Physiol 280: H42–H50, 2001.—The mechanism of myocardial hibernation, the reversible downregulation of contractile activity on reduction of coronary flow with unchanged cardiac energetics, is presently not understood. The oxygen consumption (V̇O2), shortening fraction (DL), energy status [phosphocreatine (PCr), ATP, and adenosine and lactate release], and free intracellular Ca concentration ([Ca]i) were measured in isolated rat cardiomyocytes at precisely controlled ambient PO2 (Oxystat). When PO2 was reduced from 25 to 6 mmHg, V̇O2 decreased by 50%, while DL was downregulated from 11.2 6 4.1 to 7.6 6 4.0%, and energy status was unchanged in the steady state (observation time 12 min). Only transiently PCr decreased, and lactate and adenosine release increased. Further reduction of PO2 (to 3 mmHg) reduced V̇O2 by 80%, decreased PCr by 35%, moderately increased adenosine and lactate release, and progressively reduced DL by 50% (to 5.6 6 3.3%). All parameters fully recovered during reoxygenation. PO2-dependent downregulation of DL was accompanied by a progressive reduction in systolic [Ca]i (from 512 6 110 to 357 6 91 nmol/l at 6 mmHg and to 251 6 69 nmol/l at 3 mmHg), whereas diastolic free [Ca]i remained unchanged. Therefore, the mechanism of the reversible, PO2-dependent downregulation of contractile activity (myocardial hibernation) involves a substantial reduction of systolic calcium.