Clenbuterol increases stroke power and contractile speed of skeletal muscle for cardiac assist

Background-Skeletal muscle assist (SMA) may be limited by loss of power, sl owing of contraction and relaxation, and atrophy of the transformed latissi mus dorsi muscle (LD). Clenbuterol (clen), a beta(2)-adrenergic receptor ag onist, was used to improve the performance of trained skeletal muscle in sh eep. Methods and Results-The following 4 groups were used: A (n=6), untrained co ntrols; B (n=6), left LD progressively transformed toward a slow-twitch and fatigue-resistant phenotype by electrical stimulation over 12 weeks (2.5 t o 5 V, 240-mu sec pulse duration, 35 Hz, 3 to 6 pulses per burst, and up to 40 bursts per minute); C (n=6), clen-treated (0.5 mg/kg SC) for 12 weeks; and D (n=6), clen+trained. in a terminal experiment, the mobilized LD was w rapped around a rubber aorta of a mock circulation and stimulated to contra ct 40 times per minute. Group A had an initial mean pressure augmentation ( Delta P) of 24.6 mm Hg and stroke power of 2.28 W/kg, but both fell to <20% of their original values by 15 minutes because of fatigue (P<0.005). Group B was fatigue-resistant, with a Delta P and stroke power at 60 minutes of 13 mm Hg (70% of initial) and 0.34 W/kg (39% of initial), respectively. The performance of group C was similar to that of controls. In group D, howeve r, the muscles were stronger at all time points than in B, with a Delta P o f 23 mm Hg and stroke power of 2.66 W/kg at 60 minutes (P<0.01). The speeds of contraction (+dP/dt:Delta P) and relaxation (-dP/dt:Delta P) were signi ficantly greater in group D than B. Protein analyses showed group D to have only a trend toward greater abundance of the fast isoforms of myosin heavy chain and sarcoplasmic reticulum Ca2+-ATPase (P>0.1). Conclusions-Clen improves the performance of trained skeletal muscle in a m odel of aortomyoplasty by unknown mechanisms. These findings may have impor tant implications in SMA.