title: Extracorporeal versus conventional cardiopulmonary resuscitation after ventricular fibrillation cardiac arrest in rats: a feasibility trial.
abstract: OBJECTIVE
  Extracorporeal cardiopulmonary resuscitation with cardiopulmonary bypass potentially provides cerebral reperfusion, cardiovascular support, and temperature control for resuscitation from cardiac arrest. We hypothesized that extracorporeal cardiopulmonary resuscitation is feasible after ventricular fibrillation cardiac arrest in rats and improves outcome versus conventional cardiopulmonary resuscitation.
  
  
  METHODS
  Prospective randomized study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Adult male Sprague-Dawley rats.
  
  
  METHODS
  None.
  
  
  RESULTS
  Rats (intubated, instrumented with arterial and venous catheters and cardiopulmonary bypass cannulae) were randomized to conventional cardiopulmonary resuscitation, extracorporeal cardiopulmonary resuscitation with/without therapeutic hypothermia, or sham groups. After 6 minutes of ventricular fibrillation cardiac arrest, resuscitation was performed with drugs (epinephrine, sodium bicarbonate, and heparin), ventilation, either cardiopulmonary resuscitation or extracorporeal cardiopulmonary resuscitation, and defibrillation. Temperature was maintained at 37.0°C or 33.0°C for 12 hours after restoration of spontaneous circulation. Neurologic deficit scores, overall performance category, histological damage scores (viable neuron counts in CA1 hippocampus at 14 days; % of sham), and microglia proliferation and activation (Iba-1 immunohistochemistry) were assessed.
  
  
  RESULTS
  Extracorporeal cardiopulmonary resuscitation induced hypothermia more rapidly than surface cooling (p<0.05), although heart rate was lowest in the extracorporeal cardiopulmonary resuscitation hypothermia group (p<0.05). Survival, neurologic deficit scores, overall performance category, and surviving neurons in CA1 did not differ between groups. Hypothermia significantly reduced neuronal damage in subiculum and thalamus and increased the microglial response in CA1 at 14 days (all p<0.05). There was no benefit from extracorporeal cardiopulmonary resuscitation versus cardiopulmonary resuscitation on damage in any brain region and no synergistic benefit from extracorporeal cardiopulmonary resuscitation with hypothermia.
  
  
  CONCLUSIONS
  In a rat model of 6-minute ventricular fibrillation cardiac arrest, cardiopulmonary resuscitation or extracorporeal cardiopulmonary resuscitation leads to survival with intact neurologic outcomes. Twelve hours of mild hypothermia attenuated neuronal death in subiculum and thalamus but not CA1 and, surprisingly, increased the microglial response. Resuscitation from ventricular fibrillation cardiac arrest and rigorous temperature control with extracorporeal cardiopulmonary resuscitation in a rat model is feasible, regionally neuroprotective, and alters neuroinflammation versus standard resuscitation. The use of experimental extracorporeal cardiopulmonary resuscitation should be explored using longer insult durations.
authors.affiliation: Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Janata
authors.forename: Tomas
authors.initials: T
authors.lastname: Drabek
authors.forename: Ingrid A M
authors.initials: IA
authors.lastname: Magnet
authors.forename: Jason P
authors.initials: JP
authors.lastname: Stezoski
authors.forename: Keri
authors.initials: K
authors.lastname: Janesko-Feldman
authors.forename: Erik
authors.initials: E
authors.lastname: Popp
authors.forename: Robert H
authors.initials: RH
authors.lastname: Garman
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Tisherman
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology; D016887:Cardiopulmonary Resuscitation; D015199:Extracorporeal Membrane Oxygenation; D005240:Feasibility Studies; D006323:Heart Arrest / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000150:complications*