Glucagon-Like Peptide-1 Attenuates Post-Resuscitation Myocardial Microcirculatory Dysfunction In A Swine Model Of Prolonged Ventricular Fibrillation

Background : In humans, there is a significant decrease in myocardial contractile function post arrest evidenced by decreased cardiac output and ejection fraction. This decreased function is also associated with impaired myocardial microcirculatory function in swine. In ischemic models, the endogenous incretin hormone glucagon-like peptide-1 (GLP-1) has demonstrated benefits in myocardial infarct size reduction and improvement of left ventricular (LV) function, however treatment with this agent has not been evaluated following resuscitation from cardiac arrest. We hypothesized that post resuscitation administration of GLP-1 would improve myocardial microcirculatory function. Methods : Domestic swine (n=20; 30–35 kg) were electrically fibrillated and left untreated for 8 minutes. Aggressive ACLS was performed to restore spontaneous circulation. Animals were then blindly randomized to post resuscitation infusions of either human rGLP-1 (American Peptide, 10 pM/kg/min) or equal volume saline for 4 hrs. LV hemodynamics, 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 mcg adenosine] were performed pre-arrest and at 1 and 4 Hr post resuscitation. In the present study, low CFR indicates abnormal myocardial microcirculatory function since these swine had no obstructive coronary artery disease. Results : Post resuscitation, CFR was significantly increased compared to placebo-treated animals (p Conclusion : In this swine model of prolonged VF followed by successful resuscitation, myocardial microcirculatory function was enhanced with administration of GLP-1.