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 ␤ 2 -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 (nϭ6), untrained controls; B (nϭ6), left LD progressively transformed toward a slow-twitch and fatigue-resistant phenotype by electrical stimulation over 12 weeks (2.5 to 5 V, 240-sec pulse duration, 35 Hz, 3 to 6 pulses per burst, and up to 40 bursts per minute); C (nϭ6), clen-treated (0.5 mg/kg SC) for 12 weeks; and D (nϭ6), clenϩtrained. 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 (⌬P) of 24.6 mm Hg and stroke power of 2.28 W/kg, but both fell to Ͻ20% of their original values by 15 minutes because of fatigue (PϽ0.005). Group B was fatigue-resistant, with a ⌬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, however, the muscles were stronger at all time points than in B, with a ⌬P of 23 mm Hg and stroke power of 2.66 W/kg at 60 minutes (PϽ0.01). The speeds of contraction (ϩdP/dt:⌬P) and relaxation (ϪdP/dt:⌬P) 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

Role of Masseter Muscle β2-Adrenergic Signaling in Regulation of Muscle Activity, Myosin Heavy Chain Transition, and Hypertrophy

“…It is controversial whether CB-mediated skeletal muscle hypertrophy and slow-tofast MHC transition are beneficial changes in the physiological and biochemical characters of skeletal muscle. CB might attenuate the muscle atrophy and increase stroke power as well as contractile speed (35,36). On the other hand, CB has been reported to induce apoptosis and impair function of skeletal muscle, which are similar to the well-known toxic effects of catecholamine (37 -39).…”

Clenbuterol Increases Lean Muscle Mass but Not Endurance in Patients With Chronic Heart Failure

“…22,23 However, when clenbuterol is combined with electrical stimulation or low endurance training there is a reduction in the switch of slow to fast twitch muscle fibers and improvement in both strength and endurance that is not seen with clenbuterol treatment alone. 24,25 This strategy has been adopted by athletes who combine clenbuterol with an exercise training regimen to improve performance. 14,15 Our on-going protocols are testing the combination of clenbuterol with exercise training in patients with CHF.…”

β2-Adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle

“…These data show that, when administered in vivo, ␤2-AR stimulation by clenbuterol is detrimental to cardiac and skeletal muscles even at low doses, by inducing apoptosis through ␤1-and ␤2-AR, respectively. clenbuterol; caspase 3; skeletal muscle; myocardium; adrenergic receptor agonists/antagonists THE 〉 2 -ADRENERGIC RECEPTOR (AR) agonist clenbuterol can induce hypertrophy of striated muscles and may also lead to the development of a faster contracting muscle phenotype (34). Because of this, clenbuterol is used as an adjunct to ventricular assist devices (22) and has also been proposed as a possible anticachectic agent (2).…”

“…Apoptotic cell death can often be induced by lesser stimuli than required to induce necrosis (23). Whether the doses of clenbuterol administered differentiate between its well-known anabolic effects (34) and the more recently reported injurious effects (4,13,26,39) is unknown. But if it does, a rigorously investigated dose dependency is required to find the highest dose of clenbuterol that does not induce myocyte death and could therefore potentially be used as a therapeutic intervention for muscle wasting.…”