Ruf T, Hebisch S, Gross R, Alpert N, Just H, Holubarsch C
Department of Cardiology and Angiology, University of Freiburg, Germany.
Cardiovasc Res. 1996 Dec;32(6):1047-55. doi: 10.1016/s0008-6363(96)00157-5.
We investigated the energy-metabolic consequences of positive inotropic stimulation by the calcium channel activator, BAY K 8644, in comparison with isoprenaline, focussing both on the economy of force development and the efficiency of external work.
In the first instance, heat liberation was measured in isometrically contracting right ventricular papillary muscles from guinea pigs by means of antimony-bismuth thermopiles; in the second instance, external work and myocardial oxygen consumption were analyzed in isolated failing and non-failing working rat hearts.
In the guinea pig muscle strip preparations BAY K 8644 (10(-5) M) and isoprenaline (10(-8 M) increased peak developed force from 13.7 +/- 2.7 to 37.6 +/- 14.9 mN/mm2 and from 13.6 +/- 5.2 to 38.8 +/- 3.3 mN/mm2, respectively (P < 0.01). Stress-time integral was increased from 10.3 +/- 3.0 to 34.7 +/- 19.2 mN.s/mm2 by BAY K 8644 and from 9.5 +/- 2.4 to 23.0 +/- 1.6 mN.s/mm2 by isoprenaline. Whereas a significant decrease in the ratio between stress-time integral and initial heat (integral of Pdt/IH) (i.e., economy contraction) was observed for isoprenaline (5.26 +/- 1.91 before and 3.11 +/- 0.72 N.m.s.J-1 after treatment (P < 0.01), BAY K 8644 did not significantly alter this index (5.26 +/- 2.39 before and 6.22 +/- 2.63 N.m.s.J-1 after treatment). Similar results were obtained for the ratio between stress-time integral and tension-dependent heat. Significantly more calcium ions were required for equieffective activation of the contractile proteins with isoprenaline as compared to BAY K 8644. In working preparations of sham-operated and infarcted rat hearts, the increase in myocardial oxygen consumption per minute (delta MVO2) for a given increase in external work per minute (delta P) was significantly higher with isoprenaline than with equipotent concentrations of BAY K 8644 or high calcium.
Inotropic mycardial stimulation by BAY K 8644 is associated with higher economy and efficiency than stimulation by isoprenaline when analyzed both by heat measurements in isometric preparations and by myocardial oxygen consumption in working heart preparations.
我们研究了钙通道激活剂BAY K 8644与异丙肾上腺素相比，正性肌力刺激对能量代谢的影响，重点关注力量产生的经济性和外部做功的效率。
首先，通过锑 - 铋热电堆测量豚鼠右心室乳头肌等长收缩时的热释放；其次，分析离体的衰竭和非衰竭工作大鼠心脏的外部做功和心肌氧消耗。
在豚鼠肌肉条制备中，BAY K 8644（10⁻⁵ M）和异丙肾上腺素（10⁻⁸ M）分别使最大发展力峰值从13.7±2.7增加到37.6±14.9 mN/mm²和从13.6±5.2增加到38.8±3.3 mN/mm²（P < 0.01）。BAY K 8644使应力 - 时间积分从10.3±3.0增加到34.7±19.2 mN·s/mm²，异丙肾上腺素使其从9.5±2.4增加到23.0±1.6 mN·s/mm²。异丙肾上腺素治疗后应力 - 时间积分与初始热（Pdt/IH积分）之比（即收缩经济性）显著降低（治疗前5.26±1.91，治疗后3.11±0.72 N·m·s·J⁻¹，P < 0.01），而BAY K 8644并未显著改变该指标（治疗前5.26±2.39，治疗后6.22±2.63 N·m·s·J⁻¹）。应力 - 时间积分与张力依赖性热之比也得到类似结果。与BAY K 8644相比，异丙肾上腺素使收缩蛋白达到等效激活需要更多的钙离子。在假手术和梗死大鼠心脏的工作制备中，对于每分钟给定的外部做功增加量（ΔP），异丙肾上腺素导致的每分钟心肌氧消耗增加量（ΔMVO₂）显著高于等效浓度的BAY K 8644或高钙。
当通过等长制备中的热测量和工作心脏制备中的心肌氧消耗进行分析时，BAY K 8644对心肌的正性肌力刺激比异丙肾上腺素刺激具有更高的经济性和效率。
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