Abstract
OBJECTIVES: 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. DESIGN: Prospective randomized study. SETTING: University laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: None. MEASUREMENTS AND MAIN 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.