title: Effect of clenbuterol on cardiac and skeletal muscle function during left ventricular assist device support.
abstract: 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.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Columbia College of Physicians and Surgeons, New York, New York 10032, USA. isaacgeorge@hotmail.com
authors.forename: Isaac
authors.initials: I
authors.lastname: George
authors.forename: Steve
authors.initials: S
authors.lastname: Xydas
authors.forename: Donna M
authors.initials: DM
authors.lastname: Mancini
authors.forename: John
authors.initials: J
authors.lastname: Lamanca
authors.forename: Marco
authors.initials: M
authors.lastname: DiTullio
authors.forename: Charles C
authors.initials: CC
authors.lastname: Marboe
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shane
authors.forename: Allison R
authors.initials: AR
authors.lastname: Schulman
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Colley
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Petrilli
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Naka
authors.forename: Mehmet C
authors.initials: MC
authors.lastname: Oz
authors.forename: Simon
authors.initials: S
authors.lastname: Maybaum
mesh_terms: 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
chemical_list: D000318:Adrenergic beta-Agonists; D002976:Clenbuterol