Treatment with a growth hormone secretagogue in a model of developing heart failure - Effects on ventricular and myocyte function

Background-Exogenous administration of growth hormone (GH) and subsequently increased production of insulin-like growth factor-1 can influence left ve ntricular (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 L V function and myocyte contractility in a model of developing CHF, Methods and 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.kg(-1).d(-1), n=9); and (3) sham controls (n=8). In the untreated pacing CHF group, LV fractional shortenin g 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 GI -IS group, LV fractional shortening was higher (29+/-2%) and LV peak wall s tress lower (187+/-126 g/cm(2)) than untreated CHF values (P<0.05), With GH S treatment, the ratio of LV mass to body weight increased by 44% from untr eated values. Steady-state myocyte velocity of shortening was reduced with pacing CHF compared with controls (38+/-1 versus 78+/-1 mum/s, P<0.05) and was increased from pacing CHF values with GHS treatment (55+/-7 <mu>m/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 my ocardial remodeling and contractile processes. On the basis of these result s, further studies an warranted to determine the potential role of GH secre tagogues in the treatment of CHF.