Influence of glucose metabolism on ouabain-induced changes in the transmembrane potential and contraction of human heart in vitro
Effects of glucose, anoxia, iodoacetate, and 2,4-dinitrophenol on the ouabin-induced changes in the simultaneously recorded transmembrane action potential and contraction of 72 human papillary muscle strips obtained from 36 patients undergoing corrective open heart surgery were investigated. Ouabain (10−8M, 10−9M, 10−10M) produced a shortening of the action potential duration (APD) and an increase in the force of contraction in the muscle. Non-oxygenated glucose-free solution, iodoacetate (10−5M), and 2,4-dinitrophenol (10−6M) produced partial to complete inhibition of the positive inotropic effects of ouabain (10−8M or 10−9M) in the papillary muscles. The shortening of the APD produced by ouabain was further enhanced in the presence of the above metabolic inhibitors. As the glucose level was raised (0, 5, 10, 20, 30 mM), anoxic papillary muscles responded to ouabain by a progressive increase in the force of contraction and a parallel increase in the APD. Glucose (30 mM) was effective in restoring the positive inotropic effects of ouabain in DNP-poisoned muscle while it was ineffective in doing so in the muscle poisoned with both IAA and DNP. These results indicate the requirement of energy for the positive inotropic effects of ouabain in cardiac muscle.