title: Glucagon-like peptide-1 (7-36) but not (9-36) augments cardiac output during myocardial ischemia via a Frank-Starling mechanism.
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.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202-5111, USA, agoodwil@iu.edu.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Goodwill
authors.forename: Johnathan D
authors.initials: JD
authors.lastname: Tune
authors.forename: Jillian N
authors.initials: JN
authors.lastname: Noblet
authors.forename: Abass M
authors.initials: AM
authors.lastname: Conteh
authors.forename: Daniel
authors.initials: D
authors.lastname: Sassoon
authors.forename: Eli D
authors.initials: ED
authors.lastname: Casalini
authors.forename: Kieren J
authors.initials: KJ
authors.lastname: Mather
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000187:drug effects*; D004195:Disease Models, Animal; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D013552:Swine
chemical_list: D010446:Peptide Fragments; D010455:Peptides; C114437:glucagon-like peptide-1 (9-36)-amide; C055453:glucagon-like peptide 1 (7-36)amide; D052216:Glucagon-Like Peptide 1