Holubarsch C, Hasenfuss G, Just H, Alpert N R
Department of Physiology and Biophysics, University of Vermont, Burlington.
Cardiovasc Res. 1994 Jul;28(7):994-1002. doi: 10.1093/cvr/28.7.994.
The aim was to study the effect of three positive inotropic interventions on myocardial force development and heat production in guinea pig papillary muscles in order to investigate the energetic consequences.
The positive inotropic agents used were epinine (beta adrenoceptor stimulation), E-1020 (phosphodiesterase inhibition), and ouabain (sodium-potassium ATPase inhibition). Heat measurements were accomplished using antimony-bismuth thermopiles, and initial heat was separated into tension dependent and tension independent heat using the butanedione-monoxime (BDM) and the shortening methods.
Optimal concentrations of epinine, E-1020, and ouabain increased peak developed force from 20.0(SD 6.6) to 55.5(9.3) (n = 5; p < 0.01), from 20.9(9.1) to 27.2(7.2) (n = 6; p < 0.05), and from 23.4(9.2) to 44.9(18.0) mN.mm-2 (n = 6; p < 0.01), respectively. Epinine and E-1020 decreased the tension-time integral per unit initial heat, ie, the economy of isometric contraction, from 5.5(1.4) to 3.6(0.5) (p < 0.01) and from 5.5(1.4) to 3.1(0.9) N.m.s.J-1 (p < 0.01), respectively; no significant change was observed with ouabain [6.7(1.4) to 8.3(0.5) N.m.s.J-1]. The tension independent heat (calcium turnover) was measured in two different ways using BDM or shortening to abolish force production. It was increased significantly by epinine (by 141-243%), E-1020 (by 77-114%), and ouabain (by 23-38%). The first measurement in brackets is the BDM estimate, the second is the shortening estimate. From the tension-time integral and the tension dependent heat the crossbridge force-time integral was analysed: epinine and E-1020 decreased the crossbridge force-time integral from 0.46(0.16) to 0.31(0.06) pN.s (p < 0.01) and from 0.50(0.19) to 0.31(0.08) pN.s (p < 0.01), respectively, while ouabain left the force-time integral unchanged [0.59(0.27) to 0.63(0.20) pN.s].
(1) The inotropic effect of ouabain results from an increase in muscle activation with no change in crossbridge kinetics; (2) epinine and E-1020 increase the tension independent heat and decrease the crossbridge force-time integral, both effects reducing the overall economy; and (3) the shortening and BDM methods for measuring the tension independent heat give qualitatively similar but quantitatively different results.
研究三种正性肌力干预措施对豚鼠乳头肌心肌力量产生和热量产生的影响，以探讨其能量后果。
使用的正性肌力药物为依匹宁（β肾上腺素能受体刺激）、E - 1020（磷酸二酯酶抑制）和哇巴因（钠钾ATP酶抑制）。使用锑 - 铋热电堆进行热量测量，并使用丁二酮一肟（BDM）和缩短方法将初始热量分为张力依赖性热量和张力非依赖性热量。
依匹宁、E - 1020和哇巴因的最佳浓度分别使峰值发展力从20.0（标准差6.6）增加到55.5（9.3）（n = 5；p < 0.01），从20.9（9.1）增加到27.2（7.2）（n = 6；p < 0.05），以及从23.4（9.2）增加到44.9（18.0）mN·mm - 2（n = 6；p < 0.01）。依匹宁和E - 1020使每单位初始热量的张力 - 时间积分（即等长收缩的经济性）分别从5.5（1.4）降至3.6（0.5）（p < 0.01）和从5.5（1.4）降至3.1（0.9）N·m·s·J - 1（p < 0.01）；哇巴因未观察到显著变化[6.7（1.4）至8.3（0.5）N·m·s·J - ）。使用BDM或缩短方法消除力量产生，以两种不同方式测量张力非依赖性热量（钙周转）。依匹宁（增加141 - 243%）、E - 1020（增加77 - 114%）和哇巴因（增加23 - 38%）使其显著增加。括号中的第一个测量值是BDM估计值，第二个是缩短估计值。从张力 - 时间积分和张力依赖性热量分析横桥力 - 时间积分：依匹宁和E - 1020分别使横桥力 - 时间积分从0.46（0.16）降至0.31（0.06）pN·s（p < 0.01）和从0.50（0.19）降至0.31（（0.08）pN·s（p < 0.01），而哇巴因使力 - 时间积分保持不变[0.59（0.27）至0.63（0.20）pN·s]。
（1）哇巴因的正性肌力作用源于肌肉激活增加，横桥动力学无变化；（2）依匹宁和E - 1020增加张力非依赖性热量并降低横桥力 - 时间积分，这两种效应均降低了整体经济性；（3）测量张力非依赖性热量的缩短方法和BDM方法在定性上相似，但在定量上不同。
