The effects of large doses of dexamethasone on myocardial contractility and calcium metabolism in experimental myocardial infarction.
Metabolic effects of dexamethasone (DX) on the noninfarcted functioning myocardium were studied in rabbits with experimental coronary artery ligation to evaluate the usefulness of glucocorticoids in acute myocardial infarction. Maximum active tension of noninfarcted area of the isolated perfused hearts was markedly reduced 6 hr, 2 days, and 5 days after ligation, associated with significant decreases in norepinephrine (NE) and cAMP contents, but with no changes in adenylate cyclase (AC) and cAMP phosphodiesterase (PDE) activities. Calcium content of mitochondrial fraction was considerably increased in the peri- and noninfarcted area without any changes in microsomal CA2+ or myocardial total Ca2+. Ca2+ uptake rate and Ca2+-dependent ATPase activity of the sarcoplasmic reticulum fraction from the operated hearts were markedly reduced. Intramuscular administration of DX (3 mg/kg body wt/day) for 2 days after operation significantly improved these reductions in myocardial function and metabolism. In normal hearts from animals without infarction, DX caused 48% elevation in basal cAMP level, marked reductions in mitochondria and microsomal Ca2+, and 26% decrease in PDE activity, although no changes in myocardial total Ca2+ AC activity and myocardial contractility were observed. NE-induced inotropic effects were markedly enhanced in both control and operated groups with DX treatment. These results indicated that large doses of DX would improve the reduced myocardial function and metabolism in acute myocardial infarction by increasing basal cAMP level and by its influence on intracellular Ca2+ available for cellular activity.
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D008297:Male; D008929:Mitochondria, Heart / Q000032:analysis; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D013268:Stimulation, Chemical
D003907:Dexamethasone; D002118:Calcium