Glucagon-like peptide-1 (GLP-1) attenuates post-resuscitation myocardial microcirculatory dysfunction
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Published on: May 28, 2019
Betsy B Dokken1, W Ronald Hilwig, Mary K Teachey
1Department of Medicine, University of Arizona, Tucson, AZ, USA. bdokken@deptofmed.arizona.edu
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 4h, 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 microg adenosine] were performed pre-arrest and at 1 and 4h 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, 1h (1.79+/-0.13 in control animals vs. 2.05+/-0.12 in GLP-1-treated animals, P = <0.05) and 4h (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 1h 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.
Insights
Glucagon-like peptide-1 (GLP-1) improved myocardial microcirculation after cardiac arrest in swine. However, this enhancement did not translate to significant improvements in overall post-resuscitation function or survival.
Area of Science:
- Cardiology
- Critical Care Medicine
- Endocrinology
Background:
- Post-resuscitation syndrome is a leading cause of death after successful resuscitation.
- Myocardial microcirculatory dysfunction is a critical component of post-resuscitation syndrome.
- Investigating novel therapeutic targets to improve outcomes is crucial.
Purpose of the Study:
- To evaluate the effect of glucagon-like peptide-1 (GLP-1) on myocardial microcirculatory function post-resuscitation.
- To determine if GLP-1 administration improves cardiac output and coronary flow reserve (CFR) after cardiac arrest and resuscitation.
Main Methods:
- Ventricular fibrillation (VF) was induced in swine, followed by 8 minutes of untreated VF.
- Animals received advanced cardiac life support (ACLS) and were randomized to GLP-1 or placebo infusion post-return of spontaneous circulation (ROSC).
- Left ventricular hemodynamics, ejection fraction, cardiac output, and CFR were measured pre-arrest and at 1 and 4 hours post-ROSC.
Main Results:
- GLP-1 significantly increased coronary flow reserve (CFR) at 1 and 4 hours post-ROSC compared to placebo.
- GLP-1 administration led to a significant increase in cardiac output at 1 hour post-ROSC.
- Survival rates were high in both GLP-1 (100%) and placebo (78%) groups, with no statistically significant difference.
Conclusions:
- GLP-1 administration enhances myocardial microcirculatory function in a swine model of cardiac arrest and resuscitation.
- Despite improved microcirculation, GLP-1 did not demonstrate a clinically significant improvement in overall post-resuscitation myocardial function.
- Further research is needed to explore the therapeutic potential of GLP-1 in post-cardiac arrest care.
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