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Horm Metab Res 2011; 43(5): 300-305
DOI: 10.1055/s-0031-1271777
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Glucagon-like Peptide-1 (GLP-1), Immediately Prior to Reperfusion, Decreases Neutrophil Activation and Reduces Myocardial Infarct Size in Rodents

B. B. Dokken1 , 2 , 3 , L. R. La Bonte3 , 4 , G. Davis-Gorman2 , 5 , M. K. Teachey1 , 2 , N. Seaver2 , P. F. McDonagh2 , 3 , 5
  • 1Department of Medicine, University of Arizona, Tuscon, AZ, USA
  • 2Sarver Heart Center, University of Arizona, Tuscon, AZ, USA
  • 3Physiological Sciences Graduate Interdisciplinary Program, University of Arizona, Tuscon, AZ, USA
  • 4Department of Anesthesiology, Harvard Medical School, Boston, MA, USA
  • 5Department of Surgery, University of Arizona, Tuscon, AZ, USA
Further Information

Publication History

received 09.09.2010

accepted 26.01.2011

Publication Date:
28 February 2011 (online)

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Abstract

Glucagon-like peptide-1 (GLP-1) is an incretin that has glucoregulatory effects as well as protective effects in a variety of tissues, including the heart. We hypothesized that GLP-1 may have a direct effect on neutrophils (PMNs) after myocardial ischemia, to ameliorate reperfusion injury. Deeply anesthetized Sprague-Dawley rats underwent 30 min of left coronary artery occlusion followed by 120 min of reperfusion. Immediately prior to reperfusion, rats were treated with either GLP-1 (human rGLP-1, 30 pM/kg/min) or PBS as placebo. GLP-1 significantly decreased myocardial infarct size [73.2±11.7% INF/AAR in PBS (n=4) vs. 15.7 ±5.52% INF/AAR in GLP-1-treated animals (n=5),  p<0.05], PMN activation in blood in vivo (fMLP-stimulated CD11b surface expression: PBS 2.78±1.14 vs. GLP-1 1.7±0.21, TFI, p<0.05), and accumulation in myocardium (PBS: 6.52±0.31 vs. GLP-1: 4.78±0.90, n=4–6 animals/group, p<0.05). In addition, we found that GLP-1 mitigated PMN CD11b surface expression in whole rat blood in vitro, an effect that was abolished by GLP-1 receptor blockade (PBS 6.52±0.31 vs. GLP-1 4.78±0.90, TFI, p<0.05). These findings suggest that one mechanism by which GLP-1 decreases reperfusion injury may be the attenuation of PMN-mediated reperfusion injury.

Key words

myocardial infarction - ischemia-reperfusion injury - PMN - GLP-1 - CD11b

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Correspondence

B. B. Dokken

Department of Medicine

University of Arizona

1656 E. Mabel Street

PO Box 245218

AZ 85724-5218

Tucson

USA

Phone: +1/520/626 8515

Fax: +1/520/626 3644

Email: bdokken@deptofmed.arizona.edu

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