Clenbuterol Increases Stroke Power and Contractile Speed of Skeletal Muscle for Cardiac Assist
Abstract
Background—Skeletal muscle assist (SMA) may be limited by loss of power, slowing of contraction and relaxation, and atrophy of the transformed latissimus dorsi muscle (LD). Clenbuterol (clen), a β[SUB]2[/SUB]-adrenergic receptor agonist, was used to improve the performance of trained skeletal muscle in sheep.Methods and Results—The following 4 groups were used: A (n=6), untrained controls; B (n=6), left LD progressively transformed toward a slow-twitch and fatigue-resistant phenotype by electrical stimulation over 12 weeks (2.5 to 5 V, 240-μsec 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 wrapped around a rubber aorta of a mock circulation and stimulated to contract 40 times per minute. Group A had an initial mean pressure augmentation (ΔP) 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 ΔP 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, however, the muscles were stronger at all time points than in B, with a ΔP of 23 mm Hg and stroke power of 2.66 W/kg at 60 minutes (P<0.01). The speeds of contraction (+dP/dt:ΔP) and relaxation (−dP/dt:ΔP) were significantly 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 Ca[SUP]2+[/SUP]-ATPase (P>0.1)
.Conclusions—Clen improves the performance of trained skeletal muscle in a model of aortomyoplasty by unknown mechanisms. These findings may have important implications in SMA.
Key Words:
[*=left]M. Petrou, FRCS;
[*=left]S. Clarke, BSc;
[*=left]K. Morrison, PhD;
[*=left]C. Bowles, PhD;
[*=left]M. Dunn, PhD;
[*=left]M. Yacoub, FRCS
- <address style="margin: 0px; padding: 0px; border: 0px; outline-style: none; font-style: normal; font-size: inherit; font-family: inherit; line-height: inherit; text-align: inherit; vertical-align: baseline; display: inline; ">From Imperial College, National Heart and Lung Institute, London, UK.</address>
- Correspondence to Prof Sir Magdi Yacoub, Department of Cardiac Surgery, Royal Brompton Hospital, Sydney St, London SW3 6NP, UK.
Abstract
Background—Skeletal muscle assist (SMA) may be limited by loss of power, slowing of contraction and relaxation, and atrophy of the transformed latissimus dorsi muscle (LD). Clenbuterol (clen), a β[SUB]2[/SUB]-adrenergic receptor agonist, was used to improve the performance of trained skeletal muscle in sheep.Methods and Results—The following 4 groups were used: A (n=6), untrained controls; B (n=6), left LD progressively transformed toward a slow-twitch and fatigue-resistant phenotype by electrical stimulation over 12 weeks (2.5 to 5 V, 240-μsec 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 wrapped around a rubber aorta of a mock circulation and stimulated to contract 40 times per minute. Group A had an initial mean pressure augmentation (ΔP) 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 ΔP 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, however, the muscles were stronger at all time points than in B, with a ΔP of 23 mm Hg and stroke power of 2.66 W/kg at 60 minutes (P<0.01). The speeds of contraction (+dP/dt:ΔP) and relaxation (−dP/dt:ΔP) were significantly 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 Ca[SUP]2+[/SUP]-ATPase (P>0.1)
.Conclusions—Clen improves the performance of trained skeletal muscle in a model of aortomyoplasty by unknown mechanisms. These findings may have important implications in SMA.
Key Words:
[*=left]muscles
[*=left]circulation
[*=left]clenbuterol
