Dissociation of hypoxia-induced calcium gain and rise in resting tension in isolated rat hearts.
When isolated hearts are perfused with substrate-free hypoxic buffer for prolonged periods of time, resting tension and tissue Ca increase. These two events may be interrelated. Isolated rat hearts were used to establish whether the hypoxia-induced increase in tissue Ca can be dissociated from the rise in resting tension. Tension generation was inhibited at the start of hypoxic perfusion by adding 2,3-butanedione monoxime (BDM, 30 mM). In other experiments the Ca2+ in the hypoxic buffer was reduced from 1.3 to 0.1 mM. After 30-120 min of hypoxia, ventricular muscle was assayed for ATP, creatine phosphate, Ca, and Na, and the perfusion defect was established. Resting tension was recorded before and throughout the hypoxic perfusion. Sixty minutes of perfusion with 1.3 mM Ca2+ glucose-free hypoxic buffer caused the tissue Ca to increase (P less than 0.01). Resting tension increased by 7.9 +/- 0.6 g (P less than 0.01). Sixty minutes of perfusion with 0.1 mM Ca2+ glucose-free hypoxic buffer failed to cause an increase in tissue Ca, but resting tension increased (P less than 0.01). During perfusion with glucose-free hypoxic buffer containing 2.6 mM Ca2+ and 30 mM BDM, resting tension remained low for up to 120 min, but after 60 min Ca accumulation occurred. After 120 min of BDM-hypoxic perfusion, tissue Ca reached 11.8 +/- 0.9 mumol/g dry wt. With or without BDM, hypoxia caused an early increase in tissue Na ahead of any increase in tissue Ca.(ABSTRACT TRUNCATED AT 250 WORDS)
Nayler
W G
WG
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Elz
J S
JS
Buckley
D J
DJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D004852:Epoxy Compounds; D010725:Phosphocreatine; C007366:diepoxybutane; D000255:Adenosine Triphosphate; D012964:Sodium; D002118:Calcium