Clenbuterol-supported dynamic training of skeletal muscle ventricles against systemic load - A key for powerful circulatory assist?

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 conditio ning of skeletal muscle ventricles (SMVs) combining electrical transformati on, dynamic training against systemic load, and pharmacological support wit h clenbuterol, Methods and Results-In 10 adult male goats, SMVs were constructed from lati ssimus dorsi muscle wrapped around an intrathoracic training device with wi ndkessel characteristics. SMVs were stimulated electrically and trained dyn amically by shifting volume against systemic load. Group 1 goats were contr ols (n=5), and group 2 goats (n=5) were supported with clenbuterol (150 mu g 3 times a week). SMV dynamics were recorded weekly over 5 to 8 months: pe ak pressure (P-max), stroke volume (SV), volume displacement per minute (VD ), stroke work per day (SW/d), and maximum rates of pressure generation, +d P/dt(max), and decay, -dP/df(max). In group 1, after 149.5 +/- 27 days (n=4 ), data were P-max = 70.8 +/- 4.7 mm Hg, SV=3.2 +/- 1.2 mt, VD=62.3 +/- 21. 1 mL/min, SW/d=0.8 +/- 0.4 kJ, dP/dt(max)= 64 +/- 13 mm Hg/s, and -dP/dt(ma x) = 156 +/- 32 mm Hg/s. These parameters were significantly improved (P<0. 007) in the clenbuterol-treated group 2 after 151 +/- 2.7 days: P-max=176.2 +/- 43.8 mmHg, SV=23.3 +/- 6.1 mt, VD=568.2 +/- 186.1 mL/min, SW/d=9.1 +/- 2.2 kJ, +dP/dt(max)=1134 +/- 267 mm Hg/s, and -dP/dt(max)=1028 +/- 92 mm H g/s. In 2 SMVs of group 2, VD increased to 1090 and 1235 mL/min after 202 a nd 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 S MVs that may have important clinical implications for the treatment of end- stage heart failure by muscular blood pumps.