Antioxidant Tempol Enhances Hypothermic Cerebral Preservation during Prolonged Cardiac Arrest in Dogs

Author:

Behringer Wilhelm12,Safar Peter12,Kentner Rainer12,Wu Xianren12,Kagan Valerian E.3,Radovsky Ann12,Clark Robert S. B.124,Kochanek Patrick M.124,Subramanian Murugan12,Tyurin Vladimir A.3,Tyurina Yulia Y.3,Tisherman Samuel A.125

Affiliation:

1. Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.

2. Department of Anesthesiology/Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.

3. Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.

4. Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.

5. Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.

Abstract

The authors are systematically exploring pharmacologic preservation for temporarily unresuscitable exsanguination cardiac arrest in dogs. They hypothesized that the antioxidant Tempol improves cerebral outcome when added to aortic saline flush at the start of cardiac arrest. In study A, no drug (n = 8), Tempol 150 mg/kg (n = 4), or Tempol 300 mg/kg (n = 4) was added to 25 mL/kg saline flush at 24°C (achieving mild cerebral hypothermia) at the start of 20-minute cardiac arrest. In study B, no drug (n = 8) or Tempol 300 mg/kg (n = 7) was added to 50 mL/kg saline flush at 2°C (achieving moderate cerebral hypothermia) at the start of 40-minute cardiac arrest. Cardiac arrest was reversed with cardiopulmonary bypass. Mild hypothermia lasted for 12 hours, controlled ventilation was sustained to 24 hours, and intensive care was provided for up to 72 hours. In study A, overall performance category 1 or 2 (good outcome) was achieved in all eight dogs treated with Tempol compared with three of eight dogs in the control group ( P = 0.03). In study B, good outcome was achieved in all seven dogs treated with Tempol versus only two of 8 dogs in the control group ( P = 0.007). In both studies, neurologic deficit scores were significantly better in the Tempol group, but not total histologic damage scores. At 72 hours, electron paramagnetic resonance spectroscopy of Tempol revealed direct evidence for its presence in the brain. Single- and double-strand DNA damage, nitrotyrosine immunostaining, total antioxidant reserve, and ascorbate acid levels were similar between groups, and thiol levels were decreased after Tempol in study B. The authors conclude that when added to aortic saline flush at the start of prolonged cardiac arrest, the antioxidant Tempol can enhance mild or moderate hypothermic cerebral preservation in terms of improved functional outcome. The mechanisms involved in this beneficial effect need further clarification.

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine,Clinical Neurology,Neurology

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