Growth hormone prolongs survival in experimental postinfarction heart failure.
OBJECTIVE
We evaluated the effects of growth hormone (GH) on survival in experimental heart failure (HF).


BACKGROUND
Growth hormone has been beneficial in various models of experimental HF. Whether GH also affects HF progression and survival is not known.


METHODS
A total of 119 rats with moderate myocardial infarction were randomized to receive either GH (3.5 mg/kg every other day) or placebo for 28 days. Treatment was initiated one month after coronary ligation; the follow-up lasted 13 months. In the surviving animals, Doppler echocardiography and closed-chest Millar left ventricular (LV) catheterization were performed. Apoptosis, collagen volume fraction, and capillary density in the LV zone remote from infarction were measured. The early effects of GH on apoptosis were also assessed in a subgroup of eight infarcted rats, treated as specified earlier and euthanized at one month.


RESULTS
Survival rate was 68% in GH-treated rats and 48% in the placebo group (p = 0.0377). Growth hormone had no effect on myocardial architecture, systolic function, and sarcoplasmatic reticulum calcium ATPase-2 messenger ribonucleic acid. Growth hormone improved LV relaxation; this was associated with a 50% reduction in collagen volume fraction and a 27% increase in capillary density. Growth hormone reduced the apoptotic index by 50% at one month and by 33% at 13 months.


CONCLUSIONS
Growth hormone prolonged survival of rats with postinfarction HF. This effect was associated with marked attenuation of cardiomyocyte apoptosis and pathologic interstitial remodeling in the surviving myocardium and enhanced LV relaxation.
Cittadini
Antonio
A
Department of Internal Medicine and Cardiovascular Sciences, University Federico II, Naples, Italy.
Isgaard
Jörgen
J
Monti
Maria Gaia
MG
Casaburi
Cosma
C
Di Gianni
Angela
A
Serpico
Raffaella
R
Iaccarino
Guido
G
Saccà
Luigi
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004452:Echocardiography; D013006:Growth Hormone / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D032383:Myocytes, Cardiac / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D013006:Growth Hormone