Ryall James G, Schertzer Jonathan D, Alabakis Tammy M, Gehrig Stefan M, Plant David R, Lynch Gordon S
Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria, 3010 Australia.
J Appl Physiol (1985). 2008 Jul;105(1):165-72. doi: 10.1152/japplphysiol.00317.2007. Epub 2008 Apr 24.
Systemic administration of beta(2)-adrenoceptor agonists (beta(2)-agonists) can improve skeletal muscle regeneration after injury. However, therapeutic application of beta(2)-agonists for muscle injury has been limited by detrimental cardiovascular side effects. Intramuscular administration may obviate some of these side effects. To test this hypothesis, the right extensor digitorum longus (EDL) muscle from rats was injected with bupivacaine hydrochloride to cause complete muscle fiber degeneration. Five days after injury, half of the injured muscles received an intramuscular injection of formoterol (100 mug). Muscle function was assessed at 7, 10, and 14 days after injury. A single intramuscular injection of formoterol increased muscle mass and force-producing capacity at day 7 by 17 and 91%, respectively, but this effect was transient because these values were not different from control levels at day 10. A second intramuscular injection of formoterol at day 7 prolonged the increase in muscle mass and force-producing capacity. Importantly, single or multiple intramuscular injections of formoterol did not elicit cardiac hypertrophy. To characterize any potential cardiovascular effects of intramuscular formoterol administration, we instrumented a separate group of rats with indwelling radio telemeters. Following an intramuscular injection of formoterol, heart rate increased by 18%, whereas systolic and diastolic blood pressure decreased by 31 and 44%, respectively. These results indicate that intramuscular injection can enhance functional muscle recovery after injury without causing cardiac hypertrophy. Therefore, if the transient cardiovascular effects associated with intramuscular formoterol administration can be minimized, this form of treatment may have significant therapeutic potential for muscle-wasting conditions.
全身性给予β₂肾上腺素能受体激动剂（β₂激动剂）可改善损伤后骨骼肌的再生。然而，β₂激动剂在肌肉损伤治疗中的应用一直受到有害心血管副作用的限制。肌肉内给药可能会避免其中一些副作用。为了验证这一假设，给大鼠右侧趾长伸肌（EDL）注射盐酸布比卡因，导致肌肉纤维完全变性。损伤后5天，一半受伤肌肉接受肌肉内注射福莫特罗（100μg）。在损伤后7天、10天和14天评估肌肉功能。单次肌肉内注射福莫特罗在第7天时使肌肉质量和力量产生能力分别增加了17%和91%，但这种效果是短暂的，因为在第10天时这些值与对照水平没有差异。在第7天第二次肌肉内注射福莫特罗延长了肌肉质量和力量产生能力的增加。重要的是，单次或多次肌肉内注射福莫特罗均未引起心脏肥大。为了表征肌肉内注射福莫特罗的任何潜在心血管效应，我们给另一组大鼠植入了植入式无线电遥测仪。肌肉内注射福莫特罗后，心率增加了18%，而收缩压和舒张压分别下降了31%和44%。这些结果表明，肌肉内注射可增强损伤后功能性肌肉恢复，而不会引起心脏肥大。因此，如果与肌肉内注射福莫特罗相关的短暂心血管效应能够最小化，这种治疗方式可能对肌肉萎缩病症具有显著的治疗潜力。
