Clenbuterol attenuates muscle atrophy and dysfunction in hindlimb-suspended rats.

BACKGROUND: Muscle wasting and dysfunction is a significant problem in prolonged exposure to microgravity. HYPOTHESIS: This study tested the hypothesis that a beta-adrenergic agonist (clenbuterol) could attenuate the effects of 14 d of unweighting on mixed fiber type skeletal muscle. METHODS: Female, Sprague-Dawley rats were maintained in cages as: 1. controls (C; n = 12); 2. hindlimb suspended via tail casting (HLU; n = 12); 3. clenbuterol injected daily (3 mg x kg(-1)) (CL; n = 10); or 4. hindlimb suspended and injected with clenbuterol daily (3 mg x kg(-1)) (HLU + CL; n = 12). RESULTS: At the end of the study, both CL and HLU + CL had higher body weights compared with HLU (p < 0.05). Gastrocnemius mass (wet weight and muscle weight/body weight) and maximal tetanic force were significantly decreased during HLU (p < 0.05) (mean +/- SE; mass: C = 1.6 +/- 0.04 g, HLU = 1.2 +/- 0.05 g force: C = 3483 +/- 113 g, HLU = 2765 +/- 52 g). Clenbuterol attenuated the decrease in both mass and force generation (mass: HLU + CL = 1.4 +/- 0.04 g; force: HLU + CL = 3162 +/- 135). Twitch tension during HLU (1057 +/- 72 g) was significantly less (p < 0.05) than during C (1362 +/- 61 g), and clenbuterol did not attenuate this loss. HLU caused a decrease (p < 0.05) in force at 30 Hz and decreased one-half relaxation time (1/2 RT) (p < 0.05) from 30 +/- 2 to 25 +/- 2 ms. Clenbuterol caused further decreases (p < 0.05) in both force (20 and 30 Hz) and 1/2 RT. CONCLUSIONS: These data suggest that a beta-adrenergic agonist may be of benefit in attenuating wasting and the reduced maximal force seen during periods of unweighting in mixed fiber type muscle.

Mechanical ventilation results in progressive contractile dysfunction in the diaphragm.

These experiments tested the hypothesis that a relatively short duration of controlled mechanical ventilation (MV) will impair diaphragmatic maximal specific force generation (specific P(o)) and that this force deficit will be exacerbated with increased time on the ventilator. To test this postulate, adult Sprague-Dawley rats were randomly divided into one of six experimental groups: 1) control (n = 12); 2) 12 h of MV (n = 4); 3) 18 h of MV (n = 4); 4) 18 h of anesthesia and spontaneous breathing (n = 4); 5) 24 h of MV (n = 7); and 6) 24 h of anesthesia and spontaneous breathing (n = 4). MV animals were anesthetized, tracheostomized, and ventilated with room air. Animals in the control group were acutely anesthetized but were not exposed to MV. Animals in two spontaneous breathing groups were anesthetized and breathed spontaneously for either 18 or 24 h. No differences (P > 0.05) existed in diaphragmatic specific P(o) between control and the two spontaneous breathing groups. In contrast, compared with control, all durations of MV resulted in a reduction (P < 0.05) in diaphragmatic specific tension at stimulation frequencies ranging from 15 to 160 Hz. Furthermore, the MV-induced decrease in diaphragmatic specific P(o) was time dependent, with specific P(o) being approximately 18 and approximately 46% lower (P < 0.05) in animals mechanically ventilated for 12 and 24 h, respectively. These data support the hypothesis that relatively short-term MV impairs diaphragmatic contractile function and that the magnitude of MV-induced force deficit increases with time on the ventilator.