Trifluoperazine protection of hypoxic myocardium.
Effect of trifluoperazine (TFP) (2.5 X 10(-7) M and 2.5 X 10(-6)M)--an inhibitor of calmodulin, on Langendorff-perfused rabbit hearts was examined. In the normoxic hearts TFP increased coronary flow and reduced force of contraction and oxygen consumption. In the hearts subjected to 180 min hypoxia followed by 30 min reoxygenation TFP reduced hypoxic release of LDH by approx. 50% and improved recovery of coronary flow, oxygen consumption and force of contraction upon reoxygenation suggesting protection of the heart against hypoxic injury. Reoxygenation-induced release of LDH was blocked in the TFP-pretreated hearts. It was not affected when TFP was administered only during reoxygenation. This suggests that TFP does not prevent reoxygenation-induced damage as such but only some changes developing during hypoxia which make myocardium more vulnerable to the reoxygenation damage. The mechanism of the TFP-induced protection of hypoxic myocardium is not apparent from this study. One of the possibilities is anti-calmodulin action of the drug.
D000332:Aerobiosis; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D011817:Rabbits; D014268:Trifluoperazine / Q000494:pharmacology*
D007773:Lactates; D014268:Trifluoperazine; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D009638:Norepinephrine