title: Glucagon-like peptide-1 preserves coronary microvascular endothelial function after cardiac arrest and resuscitation: potential antioxidant effects.
abstract: Glucagon-like peptide-1 (GLP-1) has protective effects in the heart. We hypothesized that GLP-1 would mitigate coronary microvascular and left ventricular (LV) dysfunction if administered after cardiac arrest and resuscitation (CAR). Eighteen swine were subjected to ventricular fibrillation followed by resuscitation. Swine surviving to return of spontaneous circulation (ROSC) were randomized to receive an intravenous infusion of either human rGLP-1 (10 pmol·kg(-1)·min(-1); n = 8) or 0.9% saline (n = 8) for 4 h, beginning 1 min after ROSC. CAR caused a decline in coronary flow reserve (CFR) in control animals (pre-arrest, 1.86 ± 0.20; 1 h post-ROSC, 1.3 ± 0.05; 4 h post-ROSC, 1.25 ± 0.06; P < 0.05). GLP-1 preserved CFR for up to 4 h after ROSC (pre-arrest, 1.31 ± 0.17; 1 h post-ROSC, 1.5 ± 0.01; 4 h post-ROSC, 1.55 ± 0.22). Although there was a trend toward improvement in LV relaxation in the GLP-1-treated animals, overall LV function was not consistently different between groups. 8-iso-PGF(2α), a measure of reactive oxygen species load, was decreased in post-ROSC GLP-1-treated animals [placebo, control (NS): 38.1 ± 1.54 pg/ml; GLP-1: 26.59 ± 1.56 pg/ml; P < 0.05]. Infusion of GLP-1 after CAR preserved coronary microvascular and LV diastolic function. These effects may be mediated through a reduction in oxidative stress.
authors.affiliation: Department of Medicine, University of Arizona, Tucson, AZ, USA. bdokken@deptofmed.arizona.edu
authors.forename: Betsy B
authors.initials: BB
authors.lastname: Dokken
authors.forename: Charles V
authors.initials: CV
authors.lastname: Piermarini
authors.forename: Mary K
authors.initials: MK
authors.lastname: Teachey
authors.forename: Michael T
authors.initials: MT
authors.lastname: Gura
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Dameff
authors.forename: Brian D
authors.initials: BD
authors.lastname: Heller
authors.forename: Jonida
authors.initials: J
authors.lastname: Krate
authors.forename: Aeen M
authors.initials: AM
authors.lastname: Ashgar
authors.forename: Lauren
authors.initials: L
authors.lastname: Querin
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Mitchell
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Hilwig
authors.forename: Karl B
authors.initials: KB
authors.lastname: Kern
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D016887:Cardiopulmonary Resuscitation; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use*; D006323:Heart Arrest / Q000188:drug therapy* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008297:Male; D055806:Microvessels / Q000187:drug effects* / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; C075750:8-epi-prostaglandin F2alpha; D052216:Glucagon-Like Peptide 1; D015237:Dinoprost