Glucagon-like peptide-1 (GLP-1) attenuates post-resuscitation myocardial microcirculatory dysfunction

Betsy B Dokken, W. Ronald Hilwig, Mary K. Teachey, R. Ashish Panchal, Karl Hubner, Daniel Allen, David C. Rogers, Karl B Kern

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Aim of the study: Post-resuscitation syndrome leads to death in approximately 2 out of every 3 successfully resuscitated victims, and myocardial microcirculatory dysfunction is a major component of this syndrome. The aim of this study was to determine if glucagon-like peptide-1 (GLP-1) improves post-resuscitation myocardial microcirculatory function. Methods: Ventricular fibrillation (VF) was induced electrically in 20 anesthetized domestic swine (30-35 kg). Following 8 min of untreated VF, animals were resuscitated with aggressive advanced cardiac life support (ACLS). Animals were blindly randomized to receive a continuous infusion of either GLP-1 (10 pM/kg/min) or equal volume saline as placebo (PBO) for 4 h, beginning 1 min after return of spontaneous circulation (ROSC). Left ventricular (LV) haemodynamics, LV ejection fraction, cardiac output, and coronary flow reserve (CFR) [using a standard technique of intracoronary Doppler flow measurements before and after intracoronary administration of 60 μg adenosine] were performed pre-arrest and at 1 and 4 h post-resuscitation. In the present study, CFR is a measure of myocardial microcirculatory function since these swine had no obstructive coronary artery disease. Twenty-four hour post-resuscitation survival and neurological functional scores were also determined. Results: CFR was significantly increased in GLP-1-treated animals, 1 h (1.79 ± 0.13 in control animals vs. 2.05 ± 0.12 in GLP-1-treated animals, P=< 0.05) and 4 h (1.82 ± 0.16 in control animals vs. 2.31 ± 0.13 in GLP-1-treated animals, P=< 0.05) after ROSC. In addition, compared to PBO-treated animals, GLP-1 increased cardiac output 1 h after ROSC (2.1 ± 0.1 in control animals vs. 2.7 ± 0.2 in GLP-1-treated animals, P=< 0.05). There was no statistically significant difference in survival between GLP-1-treated (100%) and PBO-treated animals (78%). Conclusions: In this swine model of prolonged VF followed by successful resuscitation, myocardial microcirculatory function was enhanced with administration of GLP-1. However, GLP-1 treatment was not associated with a clinically significant improvement in post-resuscitation myocardial function.

Original languageEnglish (US)
Pages (from-to)755-760
Number of pages6
JournalResuscitation
Volume81
Issue number6
DOIs
StatePublished - Jun 2010

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Glucagon-Like Peptide 1
Resuscitation
Ventricular Fibrillation
Swine
Placebos
Cardiac Output
Advanced Cardiac Life Support
Stroke Volume
Adenosine
Coronary Artery Disease
Hemodynamics

Keywords

  • Coronary flow reserve
  • GLP-1
  • Microcirculation
  • Resuscitation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Emergency
  • Emergency Medicine

Cite this

Glucagon-like peptide-1 (GLP-1) attenuates post-resuscitation myocardial microcirculatory dysfunction. / Dokken, Betsy B; Hilwig, W. Ronald; Teachey, Mary K.; Panchal, R. Ashish; Hubner, Karl; Allen, Daniel; Rogers, David C.; Kern, Karl B.

In: Resuscitation, Vol. 81, No. 6, 06.2010, p. 755-760.

Research output: Contribution to journalArticle

Dokken, Betsy B ; Hilwig, W. Ronald ; Teachey, Mary K. ; Panchal, R. Ashish ; Hubner, Karl ; Allen, Daniel ; Rogers, David C. ; Kern, Karl B. / Glucagon-like peptide-1 (GLP-1) attenuates post-resuscitation myocardial microcirculatory dysfunction. In: Resuscitation. 2010 ; Vol. 81, No. 6. pp. 755-760.
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AU - Panchal, R. Ashish

AU - Hubner, Karl

AU - Allen, Daniel

AU - Rogers, David C.

AU - Kern, Karl B

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N2 - Aim of the study: Post-resuscitation syndrome leads to death in approximately 2 out of every 3 successfully resuscitated victims, and myocardial microcirculatory dysfunction is a major component of this syndrome. The aim of this study was to determine if glucagon-like peptide-1 (GLP-1) improves post-resuscitation myocardial microcirculatory function. Methods: Ventricular fibrillation (VF) was induced electrically in 20 anesthetized domestic swine (30-35 kg). Following 8 min of untreated VF, animals were resuscitated with aggressive advanced cardiac life support (ACLS). Animals were blindly randomized to receive a continuous infusion of either GLP-1 (10 pM/kg/min) or equal volume saline as placebo (PBO) for 4 h, beginning 1 min after return of spontaneous circulation (ROSC). Left ventricular (LV) haemodynamics, LV ejection fraction, cardiac output, and coronary flow reserve (CFR) [using a standard technique of intracoronary Doppler flow measurements before and after intracoronary administration of 60 μg adenosine] were performed pre-arrest and at 1 and 4 h post-resuscitation. In the present study, CFR is a measure of myocardial microcirculatory function since these swine had no obstructive coronary artery disease. Twenty-four hour post-resuscitation survival and neurological functional scores were also determined. Results: CFR was significantly increased in GLP-1-treated animals, 1 h (1.79 ± 0.13 in control animals vs. 2.05 ± 0.12 in GLP-1-treated animals, P=< 0.05) and 4 h (1.82 ± 0.16 in control animals vs. 2.31 ± 0.13 in GLP-1-treated animals, P=< 0.05) after ROSC. In addition, compared to PBO-treated animals, GLP-1 increased cardiac output 1 h after ROSC (2.1 ± 0.1 in control animals vs. 2.7 ± 0.2 in GLP-1-treated animals, P=< 0.05). There was no statistically significant difference in survival between GLP-1-treated (100%) and PBO-treated animals (78%). Conclusions: In this swine model of prolonged VF followed by successful resuscitation, myocardial microcirculatory function was enhanced with administration of GLP-1. However, GLP-1 treatment was not associated with a clinically significant improvement in post-resuscitation myocardial function.

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