Regulation of bioenergetics in O2-limited isolated rat hearts.
Assessing the role of O2 supply in the regulation of cardiac function in O2-limited hearts is crucial to understanding myocardial ischemic preconditioning and adaptation to hypoxia. We exposed isolated Langendorff-perfused rat hearts to either ischemia (low coronary flow) or hypoxemia (low PO2 in the perfusing medium) with matched O2 supply (10% of baseline). Myocardial contractile work and ATP turnover were greater in hypoxemic than in ischemic hearts (P < 0.05; n = 12). Thus, the energy demand was higher during hypoxemia than during ischemia, suggesting that ischemic hearts are more downregulated than hypoxemic hearts. Venous PO2 was 12 +/- 2 and 120 +/- 15 Torr (P < 0.0001) for ischemic and hypoxemic hearts, respectively, but O2 uptake was the same. Lactate release was higher during hypoxemia than during ischemia (9.7 +/- 0.9 vs. 1.4 +/- 0.2 mumol/min, respectively; P < 0.0001). Electrical stimulation (300 min-1; to increase energy demand) increased performance in ischemic (P < 0.005) but not in hypoxemic hearts without changes in venous PO2 or O2 uptake. However, venous lactate concentration and lactate release increased in ischemic (P < 0.002) but not in hypoxemic 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 during ischemia plays a major role as a downregulating factor. Downregulation disappears in hypoxemic hearts secondary to enhanced washout of lactate or H+.
Samaja
M
M
Department of Biomedical Science and Technology, Scientific Institute San Raffaele, University of Milan, San Donato Hospital, Italy.
Casalini
S
S
Allibardi
S
S
Corno
A
A
Chierchia
S L
SL
D000818:Animals; D001158:Arteries; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation; D003971:Diastole; D004734:Energy Metabolism; D006339:Heart Rate; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left
D010100:Oxygen