Polyethylene glycol-20k reduces post-resuscitation cerebral dysfunction in a rat model of cardiac arrest and resuscitation: A potential mechanism

Abstract

Out-of-hospital cardiac arrest (CA) is a leading cause of death in the United States. Severe post-resuscitation cerebral dysfunction is a primary cause of poor outcome. Therefore, we investigate the effects of polyethylene glycol-20k (PEG-20k), a cell impermeant, on post-resuscitation cerebral function. Thirty-two male Sprague-Dawley rats were randomized into four groups: 1) Control; 2) PEG-20k; 3) Sham control; 4) Sham with PEG-20k. To investigate blood brain barrier (BBB) permeability, ten additional rats were randomized into two groups: 1) CPR+Evans Blue (EB); 2) Sham+EB. Ventricular fibrillation was induced and untreated for 8 min, followed by 8 min of CPR, and resuscitation was attempted by defibrillation. Cerebral microcirculation was visualized at baseline, 2, 4 and 6 h after return of spontaneous circulation (ROSC). Brain edema was assessed by comparing wet-to-dry weight ratios after 6 h. S-100β, NSE and EB concentrations were analyzed to determine BBB permeability damage. For results, Post-resuscitation cerebral microcirculation was impaired compared to baseline and sham control (p < 0.05). However, dysfunction was reduced in animals treated with PEG-20k compared to control (p < 0.05). Post-resuscitation cerebral edema as measured by wet-to-dry weight ratio was lower in PEG-20k compared to control (3.23 ± 0.5 vs. 3.36 ± 0.4, p < 0.05). CA and CPR increased BBB permeability and damaged neuronal cell with associated elevation of S-100β sand NSE serum levels. PEG-20k administered during CPR improved cerebral microcirculation and reducing brain edema and injury.

Keywords: Blood brain barrier; Cardiopulmonary resuscitation (CPR); Cerebral edema; Microvascular flow index (MFI); Perfused vessel density (PVD); Polyethylene glycol-20k.