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Emergency preservation and delayed resuscitation allows normal recovery after exsanguination cardiac arrest in rats: A feasibility trial*

Drabek, Tomas MD; Stezoski, Jason; Garman, Robert H. DVM, DACVP; Wu, Xianren MD; Tisherman, Samuel A. MD, FACS, FCCM; Stezoski, S William; Fisk, Jesse A. MS; Jenkins, Larry PhD; Kochanek, Patrick M. MD, FCCM

doi: 10.1097/01.CCM.0000253398.61666.0D
Laboratory Investigations

Objective: Emergency preservation and resuscitation (EPR) comprise a novel approach for resuscitation of exsanguination cardiac arrest victims. EPR uses a cold aortic flush to induce deep hypothermic preservation, followed by resuscitation with cardiopulmonary bypass. Development of a rat EPR model would enable study of the molecular mechanisms of neuronal injury and the screening of novel agents for emergency preservation.

Design: A prospective, randomized study.

Setting: University research facility.

Subjects: Adult male Sprague-Dawley rats.

Interventions: Isoflurane-anesthetized rats were subjected to lethal hemorrhage (12.5 mL for 5 mins), followed by KCl-induced cardiac arrest and 1 min of no flow. Three groups (n = 6) were studied: hypothermic EPR (H-EPR; 0°C flush; target temperature, 15°C); normothermic EPR (N-EPR; 38°C flush); and controls. After 20 mins of H-EPR or N-EPR, resuscitation was initiated with cardiopulmonary bypass for 60 mins and mechanical ventilation. Controls were subjected to complete experimental preparation and anesthesia without cardiac arrest, followed by 60 mins of cardiopulmonary bypass and mechanical ventilation. Surviving rats were extubated 2 hrs later. Survival, Overall Performance Category (1, normal; 5, death), Neurologic Deficit Score, Histologic Damage Score, and biochemistry were assessed in survivors on day 7.

Measurements and Main Results: All rats in H-EPR and control groups survived, whereas none of the rats in the N-EPR group had restoration of spontaneous circulation. All rats in the H-EPR and control groups achieved Overall Performance Category 1, normal Neurologic Damage Score, and normal or near normal Histologic Damage Score and biochemical markers of organ injury.

Conclusions: We have established an EPR model in rats showing no neurologic injury, despite an exsanguination cardiac arrest, followed by 20 mins of EPR using miniaturized cardiopulmonary bypass. Establishment of this model should facilitate application of molecular tools to study the effects of hypothermic preservation and reperfusion and to screen novel pharmacologic adjuncts.

From the Safar Center for Resuscitation Research (TD, JS, XW, SAT, SWS, JAF, LJ, PMK) and the Departments of Anesthesiology (TD, XW), Critical Care Medicine (JS, XW, SAT, SWS, PMK), Surgery (SAT), and Neurological Surgery (LJ), University of Pittsburgh School of Medicine, Pittsburgh, PA; and Charles River Laboratories Pathology Associates, Murrysville, PA (RHG).

Supported, in part, by the United States Army Medical Research and Materiel Command, Telemedicine and Advanced Technology Research Center, Ft. Detrick, MD (DAMD 17-01-2-0038) (to PMK) and The Laerdal Foundation for Acute Medicine (to TD).

Drs. Wu, Tisherman, and Kochanek and Mr. Stezoski are co-inventors and have a U.S. Provisional Patent on the emergency preservation and resuscitation method.

Address requests for reprints to: Patrick M. Kochanek, MD, Safar Center for Resuscitation Research, 3434 Fifth Avenue, Pittsburgh, PA 15260. E-mail:

© 2007 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins