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Glucagon-like peptide-1 (7–36) but not (9–36) augments cardiac output during myocardial ischemia via a Frank–Starling mechanism

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Abstract

This study examined the cardiovascular effects of GLP-1 (7–36) or (9–36) on myocardial oxygen consumption, function and systemic hemodynamics in vivo during normal perfusion and during acute, regional myocardial ischemia. Lean Ossabaw swine received systemic infusions of saline vehicle or GLP-1 (7–36 or 9–36) at 1.5, 3.0, and 10.0 pmol/kg/min in sequence for 30 min at each dose, followed by ligation of the left circumflex artery during continued infusion at 10.0 pmol/kg/min. Systemic GLP-1 (9–36) had no effect on coronary flow, blood pressure, heart rate or indices of cardiac function before or during regional myocardial ischemia. Systemic GLP-1 (7–36) exerted no cardiometabolic or hemodynamic effects prior to ischemia. During ischemia, GLP-1 (7–36) increased cardiac output by approximately 2 L/min relative to vehicle-controls (p = 0.003). This response was not diminished by treatment with the non-depolarizing ganglionic blocker hexamethonium. Left ventricular pressure–volume loops measured during steady-state conditions with graded occlusion of the inferior vena cava to assess load-independent contractility revealed that GLP-1 (7–36) produced marked increases in end-diastolic volume (74 ± 1 to 92 ± 5 ml; p = 0.03) and volume axis intercept (8 ± 2 to 26 ± 8; p = 0.05), without any change in the slope of the end-systolic pressure–volume relationship vs. vehicle during regional ischemia. GLP-1 (9–36) produced no changes in any of these parameters compared to vehicle. These findings indicate that short-term systemic treatment with GLP-1 (7–36) but not GLP-1 (9–36) significantly augments cardiac output during regional myocardial ischemia, via increases in ventricular preload without changes in cardiac inotropy.

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Acknowledgments

The authors gratefully acknowledge financial support from multiple agencies. This work was supported by a National Institutes of Health grant, HL117620 (J. Tune and K. Mather, PI). Dr. Goodwill was supported by National Institutes of Health T32HL079995 (K. March, PI) and American Heart Association 13POST1681001813 (A. Goodwill, PI). Mr. Conteh was supported by National Institutes of Health HL117620-S1 (J. Tune and K. Mather, PI). Mr. Sassoon was supported by grant number TL1 TR000162 (A. Shekhar, PI) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202-5111, USA

    Adam G. Goodwill, Johnathan D. Tune, Jillian N. Noblet, Abass M. Conteh, Daniel Sassoon & Eli D. Casalini

  2. Department of Medicine, Indiana University of School of Medicine, Indianapolis, IN, USA

    Kieren J. Mather

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  1. Adam G. Goodwill
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Correspondence to Adam G. Goodwill.

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Goodwill, A.G., Tune, J.D., Noblet, J.N. et al. Glucagon-like peptide-1 (7–36) but not (9–36) augments cardiac output during myocardial ischemia via a Frank–Starling mechanism. Basic Res Cardiol 109, 426 (2014). https://doi.org/10.1007/s00395-014-0426-9

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