Effect of isomazole on the responsiveness to calcium of the contractile elements in skinned cardiac muscle fibres of various species

We report here that the new cardiotonic agent isomazole increases the Ca2+ responsiveness of skinned myocardial fibres from different species. Isomazole (0.01-1 mM) increased the half-maximal, Ca2+-activated force development in atrial fibres from humans and in ventricular fibres from pigs, monkeys, guinea-pigs and rats in a concentration-dependent manner. The maximal force development was also increased in fibres from all species except pig. Isomazole shifted force-calcium curves to the left and enhanced maximal force as demonstrated for guinea-pig and human fibres, indicating increases in both calcium sensitivity and maximum force-generating capability of the contractile apparatus. In guinea-pig tissue, the concentration dependence for the activation of skinned fibres was similar to that for the positive inotropic effect in papillary muscle. These results suggest a direct effect of isomazole on contractile proteins, but the degree to which this effect contributes to the overall positive inotropic action of isomazole remains to be determined.