[The reversal of the protective effects of intermittent perfusion on ischemic myocardium by hypoxic, no-substrates, zero-K+ perfusate].
Intermittent perfusion during ischemia protected ischemic myocardium and improved recovery of function. These protective effects were reversed when hearts were perfused intermittently with hypoxic, no-substrates, zero-K+ buffer instead of oxygenated standard buffer containing substrates. We investigated the mechanisms of this reversal in isolated rat hearts. After 40 mins of sustained global ischemia, intracellular Na (Nai) increased by 6 times along with decrease in ATP and accumulation of lactate. During 30 mins of reperfusion, 45Ca2+ uptake reached 10.0 mumol/g dry with reduced recovery of ventricular function (LVEDP from 1 to 48 mmHg). When the 40 min period of ischemia was interrupted at 10 min intervals by 3 mins of IP, Nai didn't increase and reperfusion resulted in no increase in 45Ca2+ uptake (0.5 mumol/g dry). Recovery of function was 100% of the preischemic value without elevation of LVEDP. When hypoxic buffer without substrate and K+ was used for IP, Nai increased more rapidly with less recovery of function and more increased 45Ca2+ uptake (8 times) than sustained ischemia. These results indicate that disappearance of prevention of an increase in Nai with increased Ca2+ overload in hypoxic, no-substrates, zero-K+ IP, which resulted from accelerated ATP depletion and inhibition of Na/K pump is probably the main cause of the reversal of the protective effects.
Tani
M
M
Department of Geriatrics, Keio University School of Medicine.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004734:Energy Metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D009926:Organ Preservation / Q000379:methods; D010100:Oxygen / Q000502:physiology*; D010477:Perfusion / Q000379:methods*; D051381:Rats; D011919:Rats, Inbred Strains
D007773:Lactates; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D010100:Oxygen; D002118:Calcium