Changes in muscle mechanics during chronic conditioning for cardiomyoplasty

Chronic repetitive stimulation of skeletal muscle causes significant changes in contractile mechanics and makes the muscle fatigue resistant. The purpose of this study was to quantify the magnitude and time course of these changes. One latissimus dorsi muscle from each of 28 mongrel dogs was stimulated in situ at 1 Hz for 0, 3, 7, 14, 21, 42, or 70 days. Changes in isometric and isotonic mechanical performance were measured as a function of conditioning time. Isotonic force and velocity data were fitted to the Hill equation to obtain Vmax. The most striking early change was a 30 and 26% decline in muscle mass and cross-sectional area, respectively. Coincident with this was an approximate 40% decline in tetanic and twitch tension. There was a similar decline in the rates of rise and fall of twitch and tetanus tensions (+dT/dt and -dT/dt). The decline in tetanus +dT/dt and -dT/dt followed a similar time course, suggesting that these muscle functions were under similar influences. Calculation of the isometric force data per unit of cross-sectional area minimized the effect of stimulation on isometrically measured muscle function but did not eliminate it. Fusion frequency declined 52% with conditioning. The increases in time-to-peak twitch tension and half-relaxation time were independent of cross-sectional area. Time-to-peak twitch tension and half-relaxation time increased after 7 days of stimulation and became maximal after 42 or 70 days, respectively. Time-to-peak tetanus tension was unchanged by muscle conditioning. Changes in the force-velocity relationship began after 3 days of stimulation, changed very little between 3 and 21 days of stimulation, and showed another change after 42 and 70 days of stimulation. It may be possible to better modify the muscle for dynamic cardiomyoplasty by pharmacological or stimulation regimens once the mechanism of fiber switching is better understood.