CLENBUTEROL INDUCES HYPERTROPHY OF THE LATISSIMUS-DORSI MUSCLE AND HEART IN THE RAT WITH MOLECULAR AND PHENOTYPIC CHANGES

Background Skeletal muscle assistance of the circulation for patients in end-stage heart failure requires electrical training of the latissi mus dorsi flap to produce fatigue resistance. This process of electric al transformation and the development of postmobilization atrophy resu lts in a profound loss in peak power generated. The beta(2)-adrenocept or agonist clenbuterol was used to investigate its potential to select ively induce skeletal muscle hypertrophy, particularly the latissimus dorsi muscle (LDM), independent of adverse effects on cardiac muscle. Methods and Results Forty-one male Sprague-Dawley rats were divided in to four groups and used in this study. Clenbuterol 2 mu g . g body wt( -1) . d(-1) was administered subcutaneously for a period of either 5 w eeks (group A) or 2 weeks (group Al). Groups B and B1 (controls) were injected with 0.5 mL normal saline once daily. At the end of the exper imental period, all rats were weighed and terminally anesthetized for removal of the left LDM, left gastrocnemius-plantaris-soleus (GPS) mus cles, and heart. The results showed that the increase in body weight d id not differ significantly between the clenbuterol-treated and contro l groups (P>.5). The ratio of LDM to tibial length (hypertrophic index ) for groups A and Al was significantly greater than controls (P<.01), which represented a 20% to 29% increase. The hypertrophy was more pro nounced for hindlimb skeletal muscle (21% to 35% for GPS), and the eff ects of this relatively high dose of clenbuterol on the heart were les s marked (18% to 20% hypertrophy). RNA analyses indicate that ventricl es of clenbuterol-treated rats express elevated levels of mRNA to atri al natriuretic factor without a concomitant increase in skeletal alpha -actin and beta-myosin heavy chain, consistent with a ''physiological' ' form of cardiac hypertrophy. Conclusions Clenbuterol induces signifi cant hypertrophy of the LDM associated with specific changes in cardia c gene expression.