心機能の統合生理

抄録

I would like to review the four eurekas I have experienced in my cardiac function research over these 40 years. In 1966, the major concepts of cardiac pump function were Frank's ventricular pressure (P)-volume (V) relation, Starling's law of the heart, Sarnoff's ventricular function curve, and Sonnenblick's myocardial force-velocity relation. Since these could not persuade me, I started my own research, using canine in situ beating hearts. I obtained P-V loops of the left ventricle (LV) and their relations with LV contractility. My first eureka suggested in 1967 that the contracting LV could be modeled as a time-varying elastance E(t). I then found that its end-systolic peak (Emax) could serve as a reliable contractility index, later adopted as a core concept in cardiac physiology. My second eureka suggested in 1974 that the E(t) model could provide a specific P-V area (PVA) as a measure of the total mechanical energy generated by an LV contraction. Both Emax and PVA could reliably predict LV oxygen consumption (Suga: Ventricular energetics. Physiol Rev, 1990). My third eureka suggested in 1994 that the total amount of calcium recruited in the excitation-contraction coupling could be calculated from a set of Emax, PVA, and a decay time constant of the post-extrasystolic transient alternans. My forth eureka suggested in 2003 that the sliding length of a crossbridge per ATP could be calculated from a set of PVA and its oxygen cost to be variable up to more than 20 times unit step. These integrative physiological findings seem to have advanced a better integrative understanding of the pump function of a beating heart. [J Physiol Sci. 2006;56 Suppl:S4]