Published online before print August 16, 2004, doi: 10.1161/01.CIR.0000139339.85840.DD
(Circulation. 2004;110:955-961.)
© 2004 American Heart Association, Inc.
Original Articles |
Recombinant Glucagon-Like Peptide-1 Increases Myocardial Glucose Uptake and Improves Left Ventricular Performance in Conscious Dogs With Pacing-Induced Dilated Cardiomyopathy
From the Department of Medicine, Allegheny General Hospital, Pittsburgh, Pa (all authors); Drexel University College of Medicine, Philadelphia, Pa (all authors); and the Department of Surgery, University of Massachusetts School of Medicine, Worcester, Mass (D.E.).
Reprint requests to Richard P. Shannon, MD, Department of Medicine, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212. E-mail rshannon{at}wpahs.org
Received May 8, 2003; de novo received January 13, 2004; revision received March 25, 2004; accepted March 26, 2004.
Background— The failing heart demonstrates a preference for glucose as its metabolic substrate. Whether enhancing myocardial glucose uptake favorably influences left ventricular (LV) contractile performance in heart failure remains uncertain. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with potent insulinotropic effects the action of which is attenuated when glucose levels fall below 4 mmol. We examined the impact of recombinant GLP-1 (rGLP-1) on LV and systemic hemodynamics and myocardial substrate uptake in conscious dogs with advanced dilated cardiomyopathy (DCM) as a mechanism for overcoming myocardial insulin resistance and enhancing myocardial glucose uptake.
Methods and Results— Thirty-five dogs were instrumented and studied in the fully conscious state. Advanced DCM was induced by 28 days of rapid pacing. Sixteen dogs with advanced DCM received a 48-hour infusion of rGLP-1 (1.5 pmol · kg–1 · min–1). Eight dogs with DCM served as controls and received 48 hours of a saline infusion (3 mL/d). Infusion of rGLP-1 was associated with significant (P<0.02) increases in LV dP/dt (98%), stroke volume (102%), and cardiac output (57%) and significant decreases in LV end-diastolic pressure, heart rate, and systemic vascular resistance. rGLP-1 increased myocardial insulin sensitivity and myocardial glucose uptake. There were no significant changes in the saline control group.
Conclusions— rGLP-1 dramatically improved LV and systemic hemodynamics in conscious dogs with advanced DCM induced by rapid pacing. rGLP-1 has insulinomimetic and glucagonostatic properties, with resultant increases in myocardial glucose uptake. rGLP-1 may be a useful metabolic adjuvant in decompensated heart failure.
Key Words: cardiomyopathy • insulin • ventricles • glucose
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Circulation 2004 110: 894-896.
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