Ishisu R, Abe Y, Onishi K, Sekioka K, Nakano T
First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
Am J Physiol. 1996 Jul;271(1 Pt 2):H311-9. doi: 10.1152/ajpheart.1996.271.1.H311.
We investigated the effects of EMD-53998 and digoxin on Ca2+ transients and left ventricular (LV) function in indo 1-loaded Langendorff guinea pig hearts. EMD-53998 (10(-9) to 10(-5) M) and digoxin (10(-10) to 10(-6) M) increased +dP/dt and Ca2+ transients in normal hearts. The relative increase in Ca2+ transients by EMD-53998 was similar to digoxin. At 10(-5) M, EMD-53998 increased LV end-diastolic pressure. Low-flow ischemia decreased +dP/dt by 50%, while indo 1 ratio increased by 10-25%. EMD-53998 (10(-9) to 10(-6) M) effectively restored the depressed +dP/dt with little effect on indo 1 ratio, but at 10(-5) M, it markedly elevated LV end-diastolic pressure and the beneficial effect on contractile dysfunction disappeared. Digoxin (10(-10) to 10(-7) M) failed to improve LV function, but at 10(-6) M, it restored contractile dysfunction with a large increase in indo 1 ratio. The relation between indo 1 ratio and +dP/dt clearly showed that EMD-53998 restored contractile dysfunction by Ca2+ sensitization. These findings suggest that Ca2+ sensitization by EMD-53998 is an advantageous approach for ischemic contractile failure but impairs diastolic function.
我们研究了EMD - 53998和地高辛对用indo 1负载的Langendorff豚鼠心脏中Ca2+瞬变和左心室（LV）功能的影响。EMD - 53998（10^(-9)至10^(-5) M）和地高辛（10^(-10)至10^(-6) M）可增加正常心脏中的 +dP/dt和Ca2+瞬变。EMD - 53998引起的Ca2+瞬变相对增加与地高辛相似。在10^(-5) M时，EMD - 53998增加了左心室舒张末期压力。低流量缺血使 +dP/dt降低50%，而indo 1比率增加10 - 25%。EMD - 53998（10^(-9)至10^(-6) M）有效恢复了降低的 +dP/dt，对indo 1比率影响很小，但在10^(-5) M时，它显著升高了左心室舒张末期压力，对收缩功能障碍的有益作用消失。地高辛（10^(-10)至10^(-7) M）未能改善左心室功能，但在10^(-6) M时，它恢复了收缩功能障碍，同时indo 1比率大幅增加。indo 1比率与 +dP/dt之间的关系清楚地表明，EMD - 53998通过Ca2+致敏恢复了收缩功能障碍。这些发现表明，EMD - 53998引起的Ca2+致敏是治疗缺血性收缩功能衰竭的一种有利方法，但会损害舒张功能。
