Myocardial reoxygenation damage: can it be circumvented?
We investigated whether reoxygenation damage could be prevented by interventions directed towards reducing calcium influx only during the reoxygenation period. We measured reoxygenation contracture and recovery of contractile performance, using isolated papillary muscle preparations from cat and rabbit, pretreated with ouabain so as to exaggerate the phenomenon of reoxygenation contracture. Reoxygenation contracture was abolished and contractile recovery achieved by lowering extracellular calcium during early reoxygenation and then gradually replacing it. Gradual reoxygenation only postponed contracture and contractile failure. The slow channel blocker, diltiazem, but not verapamil or lidoflazine--in similarly negative inotropic concentrations of 10(-4) mol X litre-1, 10(-4) mol X litre-1 and 2 X 10(-5) mol X litre-1 respectively--reduced early reoxygenation contracture, as did Mg2+ (30 mmol X litre-1), Mn2+ (8 mmol X litre-1), or metabolic acidosis (pH 6.5), without in any case allowing contractile recovery. These observations indicate that reoxygenation damage is not an irrevocable consequence of the preceding hypoxic insult. They imply that calcium entry during early reoxygenation contributes both to contracture and contractile failure, that this occurs through paths other than the slow calcium channel, and that diltiazem may have properties additional to those of blocking the slow calcium channel.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002415:Cats; D004110:Diltiazem / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008013:Lidoflazine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010100:Oxygen / Q000009:adverse effects*; D010210:Papillary Muscles / Q000187:drug effects; D010477:Perfusion; D011817:Rabbits; D013268:Stimulation, Chemical; D014700:Verapamil / Q000494:pharmacology
D010042:Ouabain; D014700:Verapamil; D004110:Diltiazem; D008013:Lidoflazine; D010100:Oxygen; D002118:Calcium