Glucagon‐like peptide‐1 (GLP‐1) improves coronary microvascular endothelial function after cardiac arrest and resuscitation and prevents anoxia‐induced coronary microvascular endothelial cell death

Abstract

Cardiac arrest and resuscitation cause dysfunction of the coronary microcirculation. The aims of this study were to determine: 1) effects of GLP‐1 on coronary endothelial microvascular function after cardiac arrest and resuscitation, and 2) effects of GLP‐1 on coronary endothelial cell viability after anoxia and reoxygenation in vitro. Ventricular fibrillation (VF) was induced electrically in 20 anesthetized domestic swine (30–35 Kg). Following 8 min of untreated VF, animals were resuscitated and randomized to receive either GLP‐1 (10 pM/Kg/min) or saline as placebo (PBO) for 4 hr. Coronary flow reserve (CFR) was measured before and after intracoronary administration of Substance‐P (0.2 nG/2 min) pre‐arrest, 1 and 4 hr post‐resuscitation. In addition, human microvascular coronary endothelial cells (HCMVECs) were subjected to 1 hr of anoxia after pre‐incubation with GLP‐1 (0.3 nM) followed by reoxygenation for 72 hr.ResultsCFR was increased in those treated with GLP‐1 (1 Hr: PBO group 0.8 ± 0.1, GLP‐1 group 1.3 ± 0.1; 4 Hr: PBO group 0.8 ± 0.1, GLP‐1 group 1.1 ± 0.1, p< 0.05). Viability of ECs decreased by 77% in untreated cells; GLP‐1 prevented anoxia‐induced cell death (untreated group 23% viable/total, GLP‐1 group 94% viable/total, p< 0.01).ConclusionsGLP‐1 attenuates post‐resuscitation coronary microvascular endothelial dysfunction in vivo, and prevents anoxia‐induced HCMVEC cell death in vitro.