Mechanics, energetics, and crossbridge kinetics of rabbit diaphragm during congestive heart failure

Crossbridge (CB) properties were investigated in isolated diaphragm of rabbits during congestive heart failure (CHF, n=9) induced by chronic volume and pressure overload. This model induced cardiac hypertrophy and heart failure. Controls (C) were prepared (n=14). Compared to C, peak tension in CHF fell by 57% in twitch and by 40% in tetanus; Vmax declined by 47% in twitch and by 48% in tetanus. Our study provided an analytical means of calculating from A. F. Huxley's equations the rate constants for CB attachment and detachment, CB single force (II), CB number per mm3 (m'), peak mechanical efficiency (Effmax), and turnover rate of myosin ATPase (kcat); m', II, and Effmax were lower in CHF than in C in both twitch and tetanus. The marked decline in m' and II accounted for the fall in diaphragm strength. In the overall population of C and CHF, Effmax was linearly related to II. Conversely, there was no relationship between Vmax and kcat. Dissociation between Vmax and kcat might be explained by the crucial role attributed to two apparently nonconserved surface 'loops' on the motor domain of myosin head.