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

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

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish
JournalBasic Research in Cardiology
Volume109
Issue number5
DOIs
StatePublished - 10 Sep 2014

Keywords

  • Cardioprotection
  • Contractility
  • ESPVR
  • Glucagon-like peptide 1
  • Ischemic injury

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