REGULATION OF BIOENERGETICS IN O-2-LIMITED ISOLATED RAT HEARTS

Assessing the role of O-2 supply in the regulation of cardiac function in O-2-limited hearts is crucial to understanding myocardial ischemic preconditioning and adaptation to hypoxia. We exposed isolated Langen dorff-perfused rat hearts to either ischemia (low coronary flow) or hy poxemia (low PO2 in the perfusing medium) with matched O-2 supply (10% of baseline). Myocardial contractile work and ATP turnover were great er in hypoxemic than in ischemic hearts (P < 0.05; n = 12). Thus, the energy demand was higher during hypoxemia than during ischemia, sugges ting that ischemic hearts are more downregulated than hypoxemic hearts . Venous PO2 was 12 +/- 2 and 120 +/- 15 Torr (P < 0.0001) for ischemi c and hypoxemic hearts, respectively, but O-2 uptake was the same. Lac tate release was higher during hypoxemia than during ischemia (9.7 +/- 0.9 vs. 1.4 +/- 0.2 mu mol/min, respectively; P < 0.0001). Electrical stimulation (300 min(-1); to increase energy demand) increased perfor mance in ischemic (P < 0.005) but not in hypoxemic hearts without chan ges in venous PO2 or O-2 uptake. However, venous lactate concentration and lactate release increased in ischemic (P < 0.002) but not in hypo xemic hearts, suggesting that anaerobic glycolysis provides the energy necessary to meet the increased energy demand in ischemic hearts only . We conclude that high intracellular lactate or H+ concentration duri ng ischemia plays a major role as a downregulating factor. Downregulat ion disappears in hypoxemic hearts secondary to enhanced washout of la ctate or H+.