We have developed precise methods, using rapid myothermal techniques, which provide measurements of the time course of tension dependent (TDH) and tension independent (TIH) heats in normal and hypertrophied heart muscle preparations. The TDH has been shown to be an accurate monitor of myosin crossbridge ATPase activity in vivo during a twitch contraction. This system has the potential advantage over other approaches by providing an instantaneous temporal correlation between myosin crossbridge cycles and functional parameters such as 1) the rate and extent of tension development, 2) shortening velocity, 3) power output, and 4) work output. The TIH is a reflection of excitation contraction coupling phenomena and provides a measure of the kinetics of calcium release and uptake. In various forms of hypertrophy (pressure overload, P; thyrotoxic, T) the TDH, measured in fixed-end isometrically contracting right ventricular papillary muscles, has been shown to correlate with the actin activated myosin ATPase activity. The present study is to extend these observation by testing the following hypotheses; 1) the ratio of myosin isoenzymes in the papillary muscles determine the in vivo crossbridge cycling rate and thus economy of isometric contractions and the efficiency of working contractions in the presence of absence of hypertrophy; 2) there is a """"""""matched"""""""" transformation of the kinetics of the contractile and EC coupling systems as the heart hypertrophies or atrophies in response to the various stresses. The measurements are made under improved conditions so that the uncontrolled internal shortening during isometric contractions and shortening deactivation during working contractions are eliminated or minimized. This should permit the demonstration of a tight correlation between V1/V3 isoenzyme ratios and economy or efficiency. It should also allow the demonstration that shortening energetics in heart muscle is similar to that in skeletal muscle. This is an observation which has not been previously made. This work is to be carried out on a various compensated hypertrophied and atrophied heart models in order to have preparations with a broad spectrum of V1/V3 myosin isoenzyme ratios and EC coupling kinetics. These experiments should provide information about the functional integration of mixtures of myosin isoenzymes and the enthalpic parameters within which molecular models of the myocardial contractile system must fit.
