(Circulation. 1995;92:262-267.)
© 1995 American Heart Association, Inc.
Articles |
Growth Hormone Improves Cardiac Performance in Experimental Heart Failure
Presented in part at the 1994 Clinical Research Meeting, Baltimore, Md, April 29 to May 2, 1994.
From the Department of Cardiovascular Research, Pharmacology, and Endocrinology, Genentech, Inc, South San Francisco, Calif.
Correspondence to Hongkui Jin, MD, Mail Stop #42, Department of Cardiovascular Research, Genentech, Inc, 460 Point San Bruno Blvd, South San Francisco, CA 94080.
Background Growth hormone has been shown to increase maximum isometric active force of the left ventricular papillary muscle of rats in vitro. Administration of growth hormone causes an increase in myocardial contractility in normal humans. Our preliminary study suggests that treatment with growth hormone results in increased ventricular contractility in rats with left ventricular dysfunction. In the present study, the effects of growth hormone on cardiac function, including cardiac output, stroke volume, and peripheral vascular resistance, were determined in a rat model of heart failure.
Methods and Results Ligation of the left coronary artery or sham operation was performed; 4 weeks after surgery, recombinant human growth hormone (2 mg/kg per day SC) or vehicle then was administered for 15 days. The animals were catheterized after 13 days of the treatment. Cardiac output, measured by a thermodilution method, and other hemodynamic parameters were measured in the conscious animals 2 days after catheterization. The infarct sizes induced by left coronary ligation were comparable between growth hormone–treated and vehicle-treated rats. Six weeks after ligation, rats treated with vehicle exhibited significant decreases in cardiac index, stroke volume index, and left ventricular maximum dP/dt and increases in left ventricular end-diastolic pressure compared with sham rats. In the ligated rats, treatment with growth hormone increased cardiac index, stroke volume index, and left ventricular maximum dP/dt (P<.05) and reduced left ventricular end-diastolic pressure and systemic vascular resistance (P<.05). In sham rats, growth hormone slightly reduced arterial pressure but did not significantly alter cardiac performance. There was no significant difference in heart rate between the experimental groups.
Conclusions These results suggest that growth hormone treatment may improve cardiac function by both increased myocardial contractility and decreased peripheral vascular resistance in heart failure.
Key Words: heart failure • congestive • myocardial infarction • hemodynamics • stroke volume • cardiac output • catheterization
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