Glucagon-like peptide-1 preserves coronary microvascular endothelial function after cardiac arrest and resuscitation: Potential antioxidant effects

Betsy B. Dokken, Charles V. Piermarini, Mary K. Teachey, Michael T. Gura, Christian J. Dameff, Brian D. Heller, Jonida Krate, Aeen M. Ashgar, Lauren Querin, Jennifer L. Mitchell, Ronald W. Hilwig, Karl B. Kern

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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, 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.

Original languageEnglish (US)
Pages (from-to)H538-H546
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume304
Issue number4
DOIs
StatePublished - Feb 15 2013

Keywords

  • Coronary flow reserve
  • Endothelium
  • Incretin
  • Microcirculation
  • Swine

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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