Methods to improve cardiac efficiency and load matching.

心脏消耗氧气产生自由能，供机械泵工作使用。在正常负荷和收缩条件下，心脏的机械效率为10-20%。降低这一效率的因素有：1)基础代谢水平显著；2)收缩力增强的耗氧效应；3)总机械能转化为有效机械功的能量损失。我们认为可以通过1)提高心脏的收缩效率，2)改善心脏的负荷匹配来提高心脏的机械效率。在这个项目中，我们寻找可能的方法来提高心脏的机械效率。通过一系列适当设计的狗心脏实验，我们发现：1)各种急性正性肌力药物在不影响收缩效率的情况下，增加了激活（膜兴奋和兴奋-收缩耦合）的能量利用率。心肌冷却是迄今为止唯一不增加激活能量的正性肌力干预。3)收缩压-容积面积（PVA）作为心肌收缩产生的总机械能的度量指标，已被确立为心肌耗氧量（MVo_2）的可靠预测指标。4)心肌峰值力和力的时间积分（FTI）被认为是MVo_2的可靠预测因子，但结果表明其不可靠。5) FTI线性加入PVA无助于提高mvo2的可预测性（2.6）肾上腺素和钙具有相同的收缩氧耗，尽管它们的正性肌力的药理机制不同。这些发现共同给我们留下了深刻的印象，即在正常负荷条件下，心脏的机械效率通常是最大化的，要找到提高机械效率的方法并不容易。

The heart consumes oxygen to generate free energy for the mechanical pump performance. The mechanical efficiency of the heart is 10-20% under normal loading and contractile conditions. The factors which decrease this efficiency are 1) significant level of basal metabolism, 2) oxygen wasting effect of enhanced, contractility, and 3) loss in the energy conversion from total I mechanical energy to effective mechanical work. We considered that the mechanical efficiency of the heart could be improved by 1) increasing the contractile efficiency of the heart, and 2) improving the load matching of the heart. In this project, we searched for possible methods to improve the mechanical efficiency of the heart. Through a series of appropriately designed dog heart experiments, we have found the followings: 1) Various acute positive inotropic agents increases the energy utilization for activation (membrane excitation and excitation-contraction coupling) without affecting the contractile efficiency. 2) Myocardial cooling is so far the only positive inotropic intervention which does not increase energy for activation. 3) Systolic pressure-volume area (PVA) as a measure of the total mechanical energy generated by contraction has been established as a reliable predictor of myocardial oxygen consumption (MVo_2). 4) The peak myocardial force and the time integral of force (FTI) which have been recognized to be reliable predictors of MVo_2 were shown not to be go reliable as believed. 5) Linear addition of FTI to PVA does not help improving the predictability of MVo_2.6) Epinephrine and calcium have the same oxygen cost of contractility despite their different pharmacological mechanisms of positive inotropism. These findings together impress us that it would not be easy to find methods to improve mechanical efficiency of the heart which has been usually maximized under normal loading conditions.