Economy of contraction of cardiomyocytes as influenced by different positive inotropic interventions

Abstract

In the present study the effects of the novel cardiotonic agent EMD-57033 on contraction and energetic demand of isolated, electrically stimulated cardiomyocytes were investigated and compared with the effects of enhancement of extracellular calcium and of the beta-mimetic isoproterenol. In a specially designed setup [H. Rose, K.H. Strotmann, S. Popping, Y. Fischer, D. Kulsch, and H. Kammermeier. Am. J. Physiol. 261 (Heart Circ. Physiol. 30): H1329-H1334, 1991] parameters of contractile behavior and metabolic demand (O2 consumption) of isolated cardiac myocytes were measured. For a given enhancement of contractile performance (cell shortening) the increase in energetic demand (VO2) after application of EMD-57033 were markedly lower than on treatment with elevated extracellular Ca2+ concentration or with isoproterenol. This economization of positive inotropic effects was proposed to be due to two factors. First, stimulation-related ion cycling was only slightly enhanced with marked increase in contraction amplitude after application of EMD-57033. Second, calcium sensitization reflected in a leftward shift of the calcium concentration needed for half-maximum force development could be interpreted to be mediated by modulation of the cross-bridge dynamics of the myofilaments, where reduction of the switch-off rate of the cross bridges and prolongation of their force-generating states were presumed to be involved. Lowered pH (7.0) decreased economy of contraction. EMD-57033 restored contraction amplitude and economy of contraction at lowered pH.