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

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.