Mechanism of enzyme release in the calcium paradox.
Calcium-free rat hearts develop separations of fascia adherens junctions of intercalated discs. Such hearts are susceptible to membrane injury and enzyme release during anoxic contracture. Anoxic enzyme release was exacerbated by distention of heart ventricles with a balloon. Dinitrophenol (DNP) and caffeine were used to induce contracture in calcium-free hearts. Both DNP and caffeine caused a massive enzyme release from calcium-free but not from control hearts. Caffeine-induced enzyme release occurred despite Amytal inhibition of mitochondrial respiration. These results demonstrate that in calcium-free hearts with contracture or ventricular distention, enzyme release occurred without calcium repletion, from hearts depleted of ATP and in the absence of mitochondrial function. A relationship between contracture-mediated enzyme release and the calcium paradox was suggested by studies of the effects of hypothermia on enzyme release. Hypothermia to 22 degrees C protects hearts against both the calcium paradox and anoxic, DNP and caffeine injury. The parallel temperature dependence of protection between contracture-mediated enzyme release and the calcium paradox is evidence that contracture may also be a mediator of sarcolemmal membrane injury and enzyme release in the calcium paradox.
D000818:Animals; D001696:Biomechanical Phenomena; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D003402:Creatine Kinase / Q000378:metabolism; D004140:Dinitrophenols / Q000494:pharmacology; D007035:Hypothermia / Q000201:enzymology; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology / Q000201:enzymology* / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains
D004140:Dinitrophenols; D002110:Caffeine; D003402:Creatine Kinase; D002118:Calcium