Growth hormone replacement fails to improve ventricular function in
hypophysectomized rats with myocardial infarction.
Shen, You-Tang, Richard T. Wiedmann, Joseph J. Lynch, William
Grossman, Robert G. Johnson.
Department of Pharmacology and Clinical Research, Merck Research
Laboratories, West Point, PA 19486
APStracts 3:0184H, 1996.
To determine whether or not growth hormone (GH) replacement improves
cardiac function, GH-deficient hypophysectomized rats with moderate
myocardial infarction were studied after 3 weeks of treatment with
either recombinant rat GH (3.2mg/kg/d, s.c.) or vehicle. The serum
IGF-1 level in the rats following GH treatment was about 10-fold
greater than in the 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 wks (+40+/-5 vs.
-30+/-4 g in vehicle group, p<0.01) after infarction. Infarct
size, expressed as a percentage of left ventricular (LV) perimeter,
was similar for the GH-treated (21+/-3%) and vehicle-treated (23+/
-3%) rats. The 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 the depression in myocardial contractility during the
recovery period following maximal stimulation either by the largest
dose of isoproterenol (0.8 [mu]g/kg, i.v) or by acute volume loading,
the 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, non
-hypophysectomized rats with larger infarcts (i.e., >45% of the
LV) were studied after 4 weeks of treatment. There were no
differences either in the hemodynamic indices or in the infarct size
between the GH- and vehicle-treated groups, whereas the body weight
had increased (p<0.01) in the GH-treated group. Thus, although
GH treatment effectively prevents the loss of body weight following
myocardial infarction, neither GH replacement nor excess GH treatment
plays an important role in preserving cardiac function in rats with
moderate or large myocardial infarction.
Received 6 November 1995; accepted in final form 8 April 1996.
APS Manuscript Number H1034-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96