Heat, mechanics, and myosin ATPase in normal and hypertrophied heart muscle.

In this paper we review our previous work on the myothermic economy of isometric force production in compensated cardiac hypertrophy secondary to pulmonary artery constriction (pressure overload) and/or thyrotoxicosis (volume overload). Hypertrophy-induced changes in isotonic and isometric twitch mechanics are correlated with accompanying changes in actin-activated myosin ATPase and heat liberation. Heat measurements were made with rapid, high-sensitivity thermopiles on right ventricular papillary muscles from normal and hypertrophied rabbit hearts. Total activity-related heat was separated into initial and recovery heat. Initial heat was separated into a tension-dependent component (TDH) relating to cross-bridge activity, and a tension-independent component (TIH) relating to excitation-contraction coupling. There were oppositely directed changes in most parameters studied in pressure overload hypertrophy (P) as compared with thyrotoxic hypertrophy (T). Thus, in P there was depression (30-50% in the rate of isometric force production, mechanical Vmax, TDH and TDH rate, myosin ATPase, TIH, and prolongation in time-to-peak twitch tension, whereas in T all parameters were oppositely changed except for no change in TIH. Thyrotoxicosis following pressure overload reversed the P-induced changes in all parameters. There was a direct, linear relation between in vitro actin-activated myosin ATPase and in vivo TDH. However, TDH per unit twitch tension or tension-time integral varied inversely with ATPase, making force production more economical than normal in P muscles and less economical than normal in T muscles. These cellular changes beneficially equip P hearts for slow, high-pressure, economical pumping the T hearts for fast, high-volume, uneconomical pumping. The differences are similar to those between slow and fast skeletal muscle and between neonatal and adult skeletal muscle. The mechanism of these changes is discussed in terms of an enzyme kinetic scheme of chemomechanical coupling in actomyosin interaction.