Abstract 17496: The Influence of Arrest Duration in a Conventional CPR Rat Model for Prolonged Cardiac Arrest on Graded Neurological and Neuropathologic Damage
Introduction: Rodent models of ventricular fibrillation (VF) cardiac arrest (CA) allow the investigation of pathophysiologic mechanisms and development of novel treatment strategies.
Hypothesis: Different CA durations produce graded neurological and neuropathologic damage. In this study two different CA durations were assessed to produce consistent neurologic and neuropathologic damage as therapeutic target.
Materials and Methods: CA was induced in 21 male Sprague-Dawley rats via 2 min intracardial electrical current application. Following 6 (n=10) or 8 min (n=11) of CA, resuscitation was started with chest compressions, ventilations and drugs. After successful defibrillation and return of spontaneous circulation (ROSC) the animals were temperature monitored for 24 hours and sacrificed on day 14. Sham animals (n=4) underwent the same procedure except for CA. Outcome parameters included resuscitability, neurologic deficit scores (NDS; 0%=normal, 100%=dead) and overall performance category (OPC; 1=normal, 5=dead) assessed daily. For the histological evaluation the presence of hypereosinophilic degenerated neurons (DN) in eleven brain regions was rated in a semi-quantitative matter. Data are presented as mean and standard deviation.
Results: ROSC was achieved in 7/10 animals in the 6 min group and 6/11 in the 8 min group. All rats survived to 14 days with favourable neurologic outcome - all OPC 1, NDS 0±0 in 6 min CA versus 5 rats OPC 1, 1 rat OPC 2, NDS 0.83±2.4 in 8 min CA. Both OPC and NDS were significantly different between 6 and 8 min CA during the first 7 days post ROSC (OPC: p=0.03 NDS: p=0.02), but equalized until day 14 (OPC: p=0.28 NDS: p=0.30). All animals after CA showed consistent lesions in the hippocampal CA1 region (DN 6min: 2.0±1.0; 8min: 3.2±0.4) while sham animals showed no damage. Significantly more severe lesions were found in the hippocampal CA1 region in the 8 min group compared to the 6 min group (p=0.011).
Conclusions: Both CA durations caused graded cognitive and neuropathologic damage with detectable differences between the groups. This dynamic ischemia model offers the possibility to evaluate further cognitive testing after CA, test novel neuroprotective therapies as well as further studies with cardiopulmonary bypass.
- © 2013 by American Heart Association, Inc.