Normothermic ischaemic cardiac arrest and reperfusion of the isolated working heart: Effect of chlorpromazine on functional, metabolic and morphological recovery

• Published in: Journal of molecular and cellular cardiology Vol. 15; no. 9; pp. 603 - 620
• Main Authors: Edoute, Y., van der Merwe, E.L., Sanan, D., Kotzé, J.C.N., van Niekerk, I., Lochner, A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.1983
• Subjects: Adenosine Triphosphate - metabolism; Animals; Chlorpromazine - pharmacology; Heart - drug effects; Heart - physiopathology; Heart Arrest, Induced - methods; Male; Mitochondria, Heart - metabolism; Mitochondrial oxidative phosphorylation; Mitochondrial ultrastructure; Myocardium - metabolism; Myocardium - ultrastructure; Oxidative Phosphorylation; Perfusion; Phosphocreatine - metabolism; Rats; Rats, Inbred Strains; Tissue high energy phosphates; Mitochondrial ultrastructure; Tissue high energy phosphates; Mitochondrial oxidative phosphorylation
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/0022-2828(83)90270-5

The effects of chlorpromazine, an inhibitor of both Ca 2+ 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 hearts (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.