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

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 β-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 (O 2 consumption) of isolated cardiac myocytes were measured. For a given enhancement of contractile performance (cell shortening) the increase in energetic demand (VO 2 ) after application ofEMD-57033 were markedly lower than on treatment with elevated extracellular Ca 2+ 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 switchoff rate of the cross bridges and prolongation of their forcegenerating 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.