Petrou M, Clarke S, Morrison K, Bowles C, Dunn M, Yacoub M
Imperial College, National Heart and Lung Institute, London, UK.
Circulation. 1999 Feb 9;99(5):713-20. doi: 10.1161/01.cir.99.5.713.
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 beta2-adrenergic receptor agonist, was used to improve the performance of trained skeletal muscle in sheep.
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- microsec 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 (DeltaP) 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 DeltaP 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 DeltaP of 23 mm Hg and stroke power of 2.66 W/kg at 60 minutes (P<0.01). The speeds of contraction (+dP/dt:DeltaP) and relaxation (-dP/dt:DeltaP) 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 Ca2+-ATPase (P>0.1). CONCLUSIOINS: ++Clen improves the performance of trained skeletal muscle in a model of aortomyoplasty by unknown mechanisms. These findings may have important implications in SMA.
骨骼肌辅助（SMA）可能会受到力量丧失、收缩和舒张减慢以及转化的背阔肌（LD）萎缩的限制。克仑特罗（clen）是一种β2肾上腺素能受体激动剂，被用于改善绵羊训练有素的骨骼肌的性能。
使用了以下4组：A组（n = 6），未训练的对照组；B组（n = 6），通过12周的电刺激（2.5至5 V，240微秒脉冲持续时间，35 Hz，每次爆发3至6个脉冲，每分钟最多40次爆发）使左侧LD逐渐转变为慢肌纤维且抗疲劳表型；C组（n = 6），接受12周的克仑特罗治疗（0.5 mg/kg皮下注射）；D组（n = 6），克仑特罗+训练。在一项终末实验中，动员的LD被包裹在模拟循环的橡胶主动脉周围，并被刺激每分钟收缩40次。A组的初始平均压力增加（ΔP）为24.6 mmHg，每千克的搏出功率为2.28 W，但由于疲劳，两者在15分钟内均降至原始值的<20%（P<0.005）。B组具有抗疲劳能力，在60分钟时的ΔP和搏出功率分别为13 mmHg（初始值的70%）和0.34 W/kg（初始值的39%）。C组的性能与对照组相似。然而，在D组中，肌肉在所有时间点都比B组更强，在60分钟时的ΔP为23 mmHg，搏出功率为2.66 W/kg（P<0.01）。D组的收缩速度（+dP/dt:ΔP）和舒张速度（-dP/dt:ΔP）明显高于B组。蛋白质分析显示D组仅在肌球蛋白重链和肌浆网Ca2+-ATP酶的快速同工型丰度增加方面有趋势（P>0.1）。结论：克仑特罗通过未知机制改善了主动脉成形术模型中训练有素的骨骼肌的性能。这些发现可能对SMA具有重要意义。
