EMD 57033对离体兔心脏收缩和舒张的影响。

Effects of EMD 57033 on contraction and relaxation in isolated rabbit hearts.

作者信息

Hgashiyama A, Watkins M W, Chen Z, LeWinter M M

机构信息

Cardiology Unit, College of Medicine, University of Vermont, Burlington, USA.

出版信息

Circulation. 1995 Nov 15;92(10):3094-104. doi: 10.1161/01.cir.92.10.3094.

DOI:10.1161/01.cir.92.10.3094

PMID:7586281

Abstract

BACKGROUND

Ca2+ sensitizers are reported to enhance contractility with modest effects on energy utilization. In the present study we assessed the effects of the relatively "pure" Ca2+ sensitizer EMD 57033 on mechanical performance and energy consumption in the beating heart.

METHODS AND RESULTS

In 10 isolated, red blood cell-perfused rabbit hearts the effects of EMD 57033 (5.0 to 5.8 mumol/L) on left ventricular (LV) pressure and O2 consumption (VO2) were examined at heart rates of 100 and 150 beats per minute (bpm) and perfusate [Ca2+] ([Ca2+]o) of 2.5 and 1.0 mmol/L (isovolumic contractions). LV developed pressure and maximum dP/dt increased, but less so at 150 bpm or 1.0 mmol/L [Ca2+]. End-diastolic pressure also increased, more so at 150 bpm or 1.0 mmol/L [Ca2+]o. EMD 57033 decreased time to peak isovolumic pressure (Tmax) and prolonged time to 50% pressure decline (T1/2). These changes were greater at slower heart rate or lower [Ca2+]o. The magnitude of increased VO2 with EMD 57033 was greater at 100 bpm than 150 bpm but unaffected by [Ca2+]o. We then investigated the influence of ejection on the response to EMD 57033 (n = 7). The increase in developed pressure with EMD 57033 was greater for ejecting than isovolumic beats (25.5 +/- 10.2 versus 14.7 +/- 7.5 mm Hg at 100 bpm, P < .01), while the increase in end-diastolic pressure was less (P = NS). The increase in VO2 was significantly greater for ejecting than isovolumic beats (0.027 +/- 0.013 versus 0.020 +/- 0.009 mL O2/beat per 100 g at 100 bpm, P < .01).

CONCLUSIONS

EMD 57033 enhances contractility and prolongs relaxation. Its effects are modulated by heart rate, [Ca2+]o, and contraction mode, with positive inotropic effects being more prominent for ejecting beats.

摘要

背景

据报道，Ca2+ 增敏剂可增强心肌收缩力，且对能量利用影响较小。在本研究中，我们评估了相对 “纯” 的 Ca2+ 增敏剂 EMD 57033 对跳动心脏的机械性能和能量消耗的影响。

方法与结果

在 10 个离体的、用红细胞灌注的兔心脏中，研究了 EMD 57033（5.0 至 5.8 μmol/L）在心率为每分钟 100 次和 150 次（bpm）以及灌注液 [Ca2+]（[Ca2+]o）为 2.5 mmol/L 和 1.0 mmol/L（等容收缩）时对左心室（LV）压力和氧消耗（VO2）的影响。左心室舒张末压力和最大 dP/dt 增加，但在 150 bpm 或 1.0 mmol/L [Ca2+] 时增加幅度较小。舒张末压力也增加，在 150 bpm 或 1.0 mmol/L [Ca2+]o 时增加更明显。EMD 57033 缩短了等容压力峰值时间（Tmax），并延长了压力下降至 50% 的时间（T1/2）。这些变化在心率较慢或 [Ca2+]o 较低时更明显。EMD 57033 导致 VO2 增加的幅度在 100 bpm 时大于 150 bpm，但不受 [Ca2+]o 影响。然后我们研究了射血对 EMD 57033 反应的影响（n = 7）。与等容搏动相比，EMD 57033 使射血搏动的舒张末压力增加幅度更大（100 bpm 时为 25.5 ± 10.2 mmHg 对 14.7 ± 7.5 mmHg，P <.01），而舒张末压力增加幅度较小（P = 无显著性差异）。射血搏动时 VO2 的增加显著大于等容搏动（100 bpm 时为 0.027 ± 0.013 对 0.020 ± 0.009 mL O2/每 100 g 搏动，P <.01）。