(Circulation. 2000;101:2213.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Clenbuterol-Supported Dynamic Training of Skeletal Muscle Ventricles Against Systemic Load
A Key for Powerful Circulatory Assist?
Presented in part at the 71st Scientific Sessions of the American Heart Association, Dallas, Tex, November 9–12, 1998, and published in abstract form (Circulation. 1998;98[suppl I]:I-751).
From the Clinic of Cardiac Surgery (N.W.G., P.K., M.S., H.-H.S.) and the Institutes of Anesthesiology (M.G.), Anatomy (E.R.), and Animal Care (R.N.), Medical University of Lübeck, Germany.
Correspondence to Priv Doz Dr med Norbert W. Guldner, Klinik für Herzchirurgie, Medizinische Universität zu Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. E-mail guldner{at}medinf.mu-luebeck.de
Background—The profound loss of power that occurs in skeletal muscle after electrical conditioning has been the major limiting factor in its clinical application. This study investigates a 3-fold approach for chronic conditioning of skeletal muscle ventricles (SMVs) combining electrical transformation, dynamic training against systemic load, and pharmacological support with clenbuterol.
Methods and Results—In 10 adult male goats, SMVs were constructed from latissimus dorsi muscle wrapped around an intrathoracic training device with windkessel characteristics. SMVs were stimulated electrically and trained dynamically by shifting volume against systemic load. Group 1 goats were controls (n=5), and group 2 goats (n=5) were supported with clenbuterol (150 µg 3 times a week). SMV dynamics were recorded weekly over 5 to 8 months: peak pressure (Pmax), stroke volume (SV), volume displacement per minute (VD), stroke work per day (SW/d), and maximum rates of pressure generation, +dP/dtmax, and decay, -dP/dtmax. In group 1, after 149.5±2.7 days (n=4), data were Pmax=70.8±4.7 mm Hg, SV=3.2±1.2 mL, VD=62.3±21.1 mL/min, SW/d=0.8±0.4 kJ, +dP/dtmax=64±13 mm Hg/s, and -dP/dtmax=156±32 mm Hg/s. These parameters were significantly improved (P<0.007) in the clenbuterol-treated group 2 after 151±2.7 days: Pmax=176.2±43.8 mm Hg, SV=23.3±6.1 mL, VD=568.2±186.1 mL/min, SW/d=9.1±2.2 kJ, +dP/dtmax=1134±267 mm Hg/s, and -dP/dtmax=1028±92 mm Hg/s. In 2 SMVs of group 2, VD increased to 1090 and 1235 mL/min after 202 and 246 days of training, respectively. At termination, myosin heavy chains were totally transformed into myosin heavy chain-1 in all SMVs.
Conclusions—This clenbuterol-supported dynamic training provides powerful SMVs that may have important clinical implications for the treatment of end-stage heart failure by muscular blood pumps.
Key Words: muscles • electrical stimulation • contraction • circulation • clenbuterol
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