The effects of EMD 57033 on rigor tension in porcine skinned cardiac trabecula.

5-[1-(3,4-Dimethoxybenzoyl)-1,2,3,4-tetrahydro-6-quinolyl]-6-methy l-3,6- dihydro-2H-1,3,4-thiadiazin-2-one (EMD 57033) is a cardiotonic agent which acts directly on the myofilaments, increasing their sensitivity to Ca2+. We studied the effects of EMD 57033 on porcine cardiac skinned fibres to investigate the roles of Ca2+ and crossbridges in its Ca2+ sensitisation. EMD 57033 potentiated resting and maximum tensions and caused a leftward shift of the force-Ca2+ relationship. Under rigor conditions, in which fibres developed Ca(2+)-independent force, EMD 57033 was still able to potentiate tension, provided the compound was added prior to rigor development. These results show that EMD 57033 increases force by a Ca(2+)-independent mechanism in the intact myofilament lattice and that the Ca2+ sensitiser acts during the transition of crossbridge state rather than on crossbridges that are fixed in the strongly attached state corresponding to rigor.