Methods to improve cardiac efficiency and load matching.

心脏消耗氧气以产生用于机械泵性能的自由能。在正常负荷和收缩条件下，心脏的机械效率为10-20%。降低这种效率的因素是1）基础代谢的显著水平，2）增强的收缩性的耗氧效应，和3）从总I机械能到有效机械功的能量转换的损失。我们认为，心脏的机械效率可以通过1）增加心脏的收缩效率和2）改善心脏的负荷匹配来提高。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。通过一系列合理设计的狗心脏实验，我们发现：1）各种急性正性肌力药物增加了激活（膜兴奋和兴奋-收缩偶联）的能量利用，而不影响收缩效率。2)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）作为收缩产生的总机械能的量度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）是预测MVo_2的可靠指标，但其可靠性不高。5)FTI与PVA线性相加无助于改善MVo_2的可预测性。6）尽管正性肌力作用的药理机制不同，但肾上腺素和钙具有相同的收缩氧消耗。这些发现共同给我们留下了深刻的印象，这将是不容易找到的方法来提高机械效率的心脏，通常已在正常负荷条件下最大化。

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.