Effect of clenbuterol on cardiac and skeletal muscle function during left ventricular assist device support.
BACKGROUND
High-dose clenbuterol (a selective beta2-adrenergic agonist) has been proposed to promote myocardial recovery during left ventricular assist device (LVAD) support, but its effects on cardiac and skeletal muscle are largely unknown.


METHODS
Seven subjects with heart failure (5 ischemic, 2 non-ischemic) were started on oral clenbuterol 5 to 46 weeks post-LVAD implantation and up-titrated to daily doses of 720 microg. The following procedures were performed at baseline and after 3 months of therapy: echocardiography at reduced support (4 liters/min); cardiopulmonary exercise testing; body composition analysis; and quadriceps maximal voluntary contraction (MVC). Myocardial histologic analysis was measured at device implantation and explantation.


RESULTS
There were no serious adverse events or arrhythmias. Creatine phosphokinase (CPK) was elevated in 4 subjects, with no clinical sequelae. No change in ejection fraction was seen. End-diastolic dimension increased significantly (4.73 +/- 0.67 vs 5.24 +/- 0.66; p < 0.01), despite a trend toward increased LV mass. Body weight and lean mass increased significantly (75.5 +/- 17.9 vs 79.2 +/- 25.1 kg, 21.1 +/- 8.9 vs 23.6 +/- 9.7 kg, respectively; both p < 0.05). Exercise capacity did not change, but MVC improved significantly from 37.0 +/- 15.7 to 45.8 +/- 20.6 kg (p < 0.05). No significant change in myocyte size or collagen deposition was seen.


CONCLUSIONS
Cardiac function did not improve in this cohort of LVAD patients treated with high-dose clenbuterol. However, clenbuterol therapy increased skeletal muscle mass and strength and prevented the expected decrease in myocyte size during LVAD support. Further study will clarify its potential for cardiac and skeletal muscle recovery.
George
Isaac
I
Department of Surgery, Division of Cardiothoracic Surgery, Columbia College of Physicians and Surgeons, New York, New York 10032, USA. isaacgeorge@hotmail.com
Xydas
Steve
S
Mancini
Donna M
DM
Lamanca
John
J
DiTullio
Marco
M
Marboe
Charles C
CC
Shane
Elizabeth
E
Schulman
Allison R
AR
Colley
Patrick M
PM
Petrilli
Christopher M
CM
Naka
Yoshifumi
Y
Oz
Mehmet C
MC
Maybaum
Simon
S
D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000494:pharmacology*; D001823:Body Composition; D002303:Cardiac Output, Low / Q000503:physiopathology / Q000628:therapy*; D002976:Clenbuterol / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D004562:Electrocardiography; D005080:Exercise Test; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006353:Heart-Assist Devices; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000628:therapy
D000318:Adrenergic beta-Agonists; D002976:Clenbuterol