Trines S A, Slager C J, Onderwater T A, Lamers J M, Verdouw P D, Krams R
Department of Cardiology, Thoraxcentre, Erasmus Medical Centre Rotterdam, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands.
Cardiovasc Res. 2001 Jul;51(1):122-30. doi: 10.1016/s0008-6363(01)00277-2.
We investigated whether an increased oxygen cost of contractility and/or a decreased myofibrillar efficiency contribute to oxygen wastage of stunned myocardium. Because Ca(2+)-sensitizers may increase myofibrillar Ca(2+)-sensitivity without increasing cross-bridge cycling, we also investigated whether EMD 60263 restores myofibrillar efficiency and/or the oxygen cost of contractility.
Regional fiber stress and strain were calculated from mesomyocardially implanted ultrasound crystals and left ventricular pressure in anesthetized pigs (n=18). Regional myocardial oxygen consumption (MVO(2)) was measured before contractility (end-systolic elastance, E(es)) and total myofibrillar work (stress-strain area, SSA) were determined from stress-strain relationships. Atrial pacing at three heart rates and two doses of dobutamine were used to vary SSA and E(es), respectively. After stunning (two times 10-min ischemia followed by 30-min reperfusion), measurements were repeated following infusion of saline (n=8) or EMD 60263 (1.5 mg.kg(-1) i.v., n=10). Linear regression was performed using: MVO(2)=alpha.SSA+beta.E(es)+gamma.HR(-1) (alpha(-1), myofibrillar efficiency; beta, oxygen cost of contractility; and gamma, basal metabolism/min).
Stunning decreased SSA by 57% and E(es) by 64%, without affecting MVO(2), while increasing alpha by 71% and beta by 134%, without affecting gamma. From the wasted oxygen, 72% was used for myofibrillar work and 18% for excitation-contraction coupling. EMD 60263 restored both alpha and beta.
Oxygen wastage in stunning is predominantly caused by a decreased myofibrillar efficiency and to a lesser extent by an increased oxygen cost of contractility. Considering that EMD 60263 reversed both causes of oxygen wastage, it is most likely that this drug increases myofibrillar Ca(2+)-sensitivity without increasing myofibrillar cross-bridge cycling.
我们研究了收缩性氧耗增加和/或肌原纤维效率降低是否导致顿抑心肌的氧浪费。由于钙敏化剂可增加肌原纤维对钙的敏感性而不增加横桥循环，我们还研究了EMD 60263是否能恢复肌原纤维效率和/或收缩性氧耗。
从麻醉猪（n = 18）心肌中层植入的超声晶体和左心室压力计算局部纤维应力和应变。在根据应力-应变关系确定收缩性（收缩末期弹性，E(es)）和总肌原纤维功（应力-应变面积，SSA）之前，测量局部心肌氧耗（MVO(2)）。分别通过三种心率的心房起搏和两种剂量的多巴酚丁胺来改变SSA和E(es)。在顿抑（两次10分钟缺血后30分钟再灌注）后，在输注生理盐水（n = 8）或EMD 60263（1.5 mg·kg(-1)静脉注射，n = 10）后重复测量。使用以下公式进行线性回归：MVO(2)=α·SSA + β·E(es) + γ·HR(-1)（α(-1)，肌原纤维效率；β，收缩性氧耗；γ，基础代谢/分钟）。
顿抑使SSA降低57%，E(es)降低64%，而不影响MVO(2)，同时使α增加71%，β增加134%，而不影响γ。在浪费的氧中，72%用于肌原纤维功，18%用于兴奋-收缩偶联。EMD 60263恢复了α和β两者。
顿抑中的氧浪费主要由肌原纤维效率降低引起，在较小程度上由收缩性氧耗增加引起。鉴于EMD 60263逆转了氧浪费的两个原因，很可能该药物增加了肌原纤维对钙的敏感性而不增加肌原纤维横桥循环。
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