title: GH replacement fails to improve ventricular function in hypophysectomized rats with myocardial infarction.
abstract: To determine whether growth hormone (GH) replacement improves cardiac function, GH-deficient hypophysectomized rats with moderate myocardial infarction (MI) were studied after 3 wk of treatment with either recombinant rat GH (3.2 mg.kg-1.day-1 sc) or vehicle. The serum insulin-like growth factor I level in rats after GH treatment was approximately 10-fold greater than in vehicle-treated rats. GH replacement prevented a decrease in body weight at 1 wk (+5 +/- 6 vs. -26 +/- 4 g in vehicle group, P < 0.01) and increased body weight at 3 wk (+40 +/- 5 vs. -30 +/- 4 g in vehicle group, P < 0.01) after MI. Infarct size, expressed as a percentage of left ventricular (LV) perimeter, was similar for GH-treated (21 +/- 3%) and vehicle-treated (23 +/- 3%) rats. Basal LV systolic pressure, LV end-diastolic pressure, LV dP/dt, mean arterial pressure and heart rate, and the changes in these parameters in response to isoproterenol and norepinephrine were similar for these two groups. Although GH replacement tended to prevent depression in myocardial contractility during the recovery period after maximal stimulation either by the largest dose of isoproterenol (0.8 microgram/kg iv) or by acute volume loading, differences between the two groups were not statistically significant. In addition, to determine the effects of excess GH treatment in a severe state of cardiac dysfunction, nonhypophysectomized rats with larger infarcts (i.e., > 45% of the LV) were studied after 4 wk of treatment. There were no differences either in hemodynamic indexes or in infarct size between the GH- and vehicle-treated groups, whereas body weight had increased (P < 0.01) in the GH-treated group. Thus, although GH treatment effectively prevents the loss of body weight after MI, neither GH replacement nor excess GH treatment plays an important role in preserving cardiac function in rats with moderate or large MI.
authors.affiliation: Department of Pharmacology and Clinical Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
authors.forename: Y T
authors.initials: YT
authors.lastname: Shen
authors.forename: R T
authors.initials: RT
authors.lastname: Wiedmann
authors.forename: J J
authors.initials: JJ
authors.lastname: Lynch
authors.forename: W
authors.initials: W
authors.lastname: Grossman
authors.forename: R G
authors.initials: RG
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007016:Hypophysectomy; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000502:physiology; D011994:Recombinant Proteins; D016276:Ventricular Function / Q000187:drug effects*
chemical_list: D011941:Receptors, Adrenergic; D011994:Recombinant Proteins; D013006:Growth Hormone