Normothermic ischaemic cardiac arrest and reperfusion of the isolated working heart: effect of chlorpromazine on functional, metabolic and morphological recovery.
The effects of chlorpromazine, an inhibitor of both Ca2+ flux and phospholipase activity, on myocardial ultrastructure, function and metabolism were assessed during normothermic ischaemic cardiac arrest and reperfusion of the isolated working rat heart. Normothermic ischaemic cardiac arrest produced significant changes in myocardial ultrastructure, high energy phosphate contents and mitochondrial oxidative phosphorylation within 20 min. Reperfusion of untreated hearts subjected to 20 and 25 min ischaemia failed to restore mitochondrial function, mechanical activity and ATP content to control, pre-ischaemic levels. Morphological signs of ischaemic injury regressed, especially in the subendocardial layer. Pretreatment of hearts with chlorpromazine did not prevent the ischaemia-induced changes in myocardial ultrastructure and mitochondrial function. However, during reperfusion the chlorpromazine-treated, totally ischaemic heats (20 to 25 min) exhibited improved coronary flow rates, and ultrastructural and mechanical recovery. The mitochondrial oxidative phosphorylation process and tissue high energy phosphate contents were not affected by the drug.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006324:Heart Arrest, Induced / Q000379:methods; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010085:Oxidative Phosphorylation; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D002746:Chlorpromazine