REDUCTION OF MYOCARDIAL CROSS-BRIDGE TURNOVER RATE IN PRESENCE OF EMD-53998, A NOVEL CA-2+-SENSITIZING AGENT

We have studied the effect of EMD 53998 (5-(1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydrochinolin-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one) on cross-bridge turnover rate at varying Ca2+ concentrations. Cross-bridge cycling rate was estimated both by adenosine triphosphatase measurements and determination of mechanical characteristics of constantly activated fibres, which is assumed to reflect cross-bridge kinetics. The results indicate that the turnover rate of myocardial cross-bridges was reduced in the presence of EMD 53998 at low Ca2+ concentrations (pCa greater-than-or-equal-to 6.25), but not at higher Ca2+ concentrations (pCa greater-than-or-equal-to 5.85).