The development of increasing the energetic efficiency of failing heart : Application of Emax and PVA

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We found that all postextrasystolic contractile potentiation decayd in alternans with the exception of particular cases in excised cross-circulated canine left ventricles even under physiological conditions. Our analysis showed the transient alternans to consist of two comoponens, exponential and sinusoidal decay. So we hypothesized that the normalized pressure (y) of postextrasystolic beats (beat number x) could be expressed by the following equation.y=a ・ exp [- (x-1) /tau_e] +b ・ exp [- (x-1) /tau_s] Xcos [pi (x-1)] +1This equation very closely fitted the alternans data with a squared corelation coefficient of 0.9996 on average. Then, we speculated that the exponential component of this equation would be related to the intracellular Ca ^<2+> recirculation fraction (RF) and the sinusoidal component to Ca^<2+> handling by the sarcoplasmic reticulum.We investigated the effects of intracoronary Ca^<2+> and epinephrine on the intracellular Ca^<2+> RF and total Ca^<2+> handling in the lef … More t ventricle. RF was calculated from tau_s by exp (-1/tau_s). Ca^<2+> slightly increased RF but epinephrine scarcely affected it althoug both drugs enhanced Emax (an index of con) 2-3 times. We also obtained the total amount of Ca^2 handled in one cardiac cycle by combining these RF data with Ca^<2+> handling Vo_2 data.We observed disproportionately high E-C coupling Vo_2 and decreased RF when intracoronarily infused ryanodine (approximately 40nmol/l blood for 1h) decreased Emax. We considered that the decreased RF indicated wasteful myocardial Ca^<2+> handling for a greater fraction of transsarcolemmal Ca^<2+> handling which was half economical of intracellular Ca^<2+> handling via the sarcoplasmic reticulum.We conclude that analysis of postextrasystolic potentiation in various situation s enables us to better understand pathophysiology of failing hearts and to evaluate pharmacology of cardiotonic agents from anew stand point. No other methods can evaluate intracellular total Ca^<2+> handling in the whole heart like this method. Less