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Departments of Pharmacology and Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486
The effects of chronic treatment with growth
hormone (porcine GH, 0.56 mg · kg
1 · day
1
sc) were examined in dogs with heart failure induced by rapid ventricular pacing (240 beats/min) for 4 wk. Fourteen conscious dogs
were studied 2-3 wk after surgical instrumentation with catheters in the descending aorta and left atrium, a pressure gauge in the left
ventricle (LV), a flow probe around the ascending aorta, pacing leads
on the ventricular free wall and left atrium, and ultrasonic crystals
on the opposing anterior and posterior endomyocardium of the LV. GH
treatment for 4 wk significantly increased both body weight and plasma
insulin-like growth factor 1 (IGF-1) compared with vehicle-treated dogs
(P < 0.01, +2.0 ± 0.5 vs. +0.3 ± 1.1 kg; 1,043 ± 218 vs. 241 ± 64 ng/ml, respectively).
However, the changes in resting LV systolic (i.e., both isovolumic and
ejection phases) and diastolic function (i.e., isovolumic relaxation
time constant
) and the systemic vascular resistance were similar for the GH- and vehicle-treated groups during the development of heart
failure. LV contractile reserve, assessed with step infusion of
isoproterenol or dobutamine challenge, was markedly attenuated after
heart failure, but there were no differences between the GH- and
vehicle-treated groups. During the progression of heart failure, the
increases in plasma atrial natriuretic peptide correlated (P < 0.01) directly with left atrial
pressure and inversely with LV circumferential fiber shortening.
However, GH treatment did not substantially modify these relationships.
In addition, renal function and myocardial ultrastructure at the
advanced stage of heart failure also showed similar changes for the GH-
and vehicle-treated groups. We conclude that in conscious dogs during
the development of congestive heart failure produced by rapid
ventricular pacing, GH at a dose that increases body weight and plasma
IGF-1 levels does not affect LV performance or systemic vascular
dynamics.
insulin-like growth factor 1; left ventricular dysfunction; renal function; myocardial contractile reserve; atrial natriuretic peptide
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