title: Treatment with a growth hormone secretagogue in a model of developing heart failure: effects on ventricular and myocyte function.
abstract: BACKGROUND
  Exogenous administration of growth hormone (GH) and subsequently increased production of insulin-like growth factor-1 can influence left ventricular (LV) myocardial growth and geometry in the setting of congestive heart failure (CHF). This study determined the effects of an orally active GH secretagogue (GHS) treatment that causes a release of endogenous GH on LV function and myocyte contractility in a model of developing CHF.
  
  
  RESULTS
  Pigs were randomly assigned to the following treatment groups: (1) chronic rapid pacing at 240 bpm for 3 weeks (n=11); (2) chronic rapid pacing and GHS (CP-424,391 at 10 mg x kg(-1) x d(-1), n=9); and (3) sham controls (n=8). In the untreated pacing CHF group, LV fractional shortening was reduced (21+/-2% versus 47+/-2%) and peak wall stress increased (364+/-21 versus 141+/-5 g/cm(2)) from normal control values (P:<0.05). In the GHS group, LV fractional shortening was higher (29+/-2%) and LV peak wall stress lower (187+/-126 g/cm(2)) than untreated CHF values (P:<0.05). With GHS treatment, the ratio of LV mass to body weight increased by 44% from untreated values. Steady-state myocyte velocity of shortening was reduced with pacing CHF compared with controls (38+/-1 versus 78+/-1 microm/s, P:<0.05) and was increased from pacing CHF values with GHS treatment (55+/-7 microm/s, P:<0.05).
  
  
  CONCLUSIONS
  The improved LV pump function that occurred with GHS treatment in this model of CHF was most likely a result of favorable effects on LV myocardial remodeling and contractile processes. On the basis of these results, further studies are warranted to determine the potential role of GH secretagogues in the treatment of CHF.
authors.affiliation: Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: King
authors.forename: D M
authors.initials: DM
authors.lastname: Gay
authors.forename: L C
authors.initials: LC
authors.lastname: Pan
authors.forename: J H
authors.initials: JH
authors.lastname: McElmurray
authors.forename: J W
authors.initials: JW
authors.lastname: Hendrick
authors.forename: C
authors.initials: C
authors.lastname: Pirie
authors.forename: A
authors.initials: A
authors.lastname: Morrison
authors.forename: C
authors.initials: C
authors.lastname: Ding
authors.forename: R
authors.initials: R
authors.lastname: Mukherjee
authors.forename: F G
authors.initials: FG
authors.lastname: Spinale
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial; D004452:Echocardiography; D013006:Growth Hormone / Q000378:metabolism*; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D013552:Swine; D016276:Ventricular Function / Q000187:drug effects*
chemical_list: C433143:CP 424391; D010880:Piperidines; D011720:Pyrazoles; D013006:Growth Hormone