MCI-154, a novel cardiotonic agent, reverses the acidic pH-induced decrease in responses of cardiac myofilaments to Ca++: comparison with sulmazole and pimobendan.

摘要: In the present study, we have examined effects of decreasing pH from 7.0 to 6.6 on tension developed by direct activation myofilaments in chemically skinned fibers guinea pig papillary muscles. We then compared novel inotropic agents MCI-154, pimobendan and sulmazole, which action cardiac myofilaments, acidic pH-induced changes responses contractile system Ca++. The reduction 6.8 shifted pCa (-log[Ca++] M)-tension relation curve right with no change maximum tension. However, also depressed force development. These were reversible returning neutral (pH 7.0), but not overcome increasing free [Ca++] (decreasing 4.4 4.0). amplitude pMg-ATP (-log[MgATP]M)-tension absence Ca++ (Ca++ less than 1 nM, bell-shaped curve) was downward reducing 6.6. MCI-154 (1-100 microM) reversed decrease development activated 5.8 a concentration-dependent manner. Moreover, acidosis induced reductions (pCa, 4.4) pMgATP 6.0-activated nM) manner.(ABSTRACT TRUNCATED AT 250 WORDS)