Reduction of myocardial cross-bridge turnover rate in presence of EMD 53998, a novel Ca(2+)-sensitizing agent.

Abstract

We have studied the effect of EMD 53998 (5-(1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydrochinolin-6-yl)-6-me thyl-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 less than or equal to 5.85).