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(Circulation. 1995;92:483-489.)
© 1995 American Heart Association, Inc.

Articles

Clenbuterol Induces Hypertrophy of the Latissimus Dorsi Muscle and Heart in the Rat With Molecular and Phenotypic Changes

Mario Petrou, BSC, MBBS; Dylan G. Wynne, PHD; Kenneth R. Boheler, PHD; Magdi H. Yacoub, FRCS

From the Royal Brompton National Heart and Lung Institute, London, UK.

Correspondence to Prof Sir Magdi Yacoub, Professor in Cardiac Surgery, Royal Brompton Hospital, Sydney St, London SW3 6NP, UK.

Background Skeletal muscle assistance of the circulation for patients in end-stage heart failure requires electrical training of the latissimus dorsi flap to produce fatigue resistance. This process of electrical transformation and the development of postmobilization atrophy results in a profound loss in peak power generated. The ß₂-adrenoceptor agonist clenbuterol was used to investigate its potential to selectively 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 into four groups and used in this study. Clenbuterol 2 µg · g body wt^-1 · d^-1 was administered subcutaneously for a period of either 5 weeks (group A) or 2 weeks (group A1). Groups B and B1 (controls) were injected with 0.5 mL normal saline once daily. At the end of the experimental period, all rats were weighed and terminally anesthetized for removal of the left LDM, left gastrocnemius-plantaris-soleus (GPS) muscles, and heart. The results showed that the increase in body weight did not differ significantly between the clenbuterol-treated and control groups (P>.5). The ratio of LDM to tibial length (hypertrophic index) for groups A and A1 was significantly greater than controls (P<.01), which represented a 20% to 29% increase. The hypertrophy was more pronounced for hindlimb skeletal muscle (21% to 35% for GPS), and the effects of this relatively high dose of clenbuterol on the heart were less marked (18% to 20% hypertrophy). RNA analyses indicate that ventricles of clenbuterol-treated rats express elevated levels of mRNA to atrial natriuretic factor without a concomitant increase in skeletal -actin and ß-myosin heavy chain, consistent with a "physiological" form of cardiac hypertrophy.

Conclusions Clenbuterol induces significant hypertrophy of the LDM associated with specific changes in cardiac gene expression.

Key Words: clenbuterol • muscles • hypertrophy • rats

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