Effects of heme oxygenase 1 on brain edema and neurologic outcome after cardiopulmonary resuscitation in rats

Abstract

Background: Heme oxygenase 1 (HO-1) has been shown to attenuate neuronal injury. Therefore, the authors examined whether HO-1 would reduce the brain damage caused by cardiac arrest. Methods: Rats anesthetized with halothane were subjected to 8 min of cardiac arrest by asphyxia without any pretreatment (control group) or pretreated with an inducer of HO-1 (hemin group) or with an inhibitor of HO-1 (tin protoporphyrin group). Then, the animals were resuscitated with a standardized method. Brain water content (1 and 6 h after resuscitation), neurologic deficit score, viable neuronal counts, and caspase-3 immunostaining in the hippocampus (4 and 14 days) were evaluated. Results: Water content in the hemin group was significantly reduced (mean ± SD: 83.1 ± 1.9% for 1 h after resuscitation; P = 0.03) and significantly greater in the tin protoporphyrin group (91.1 ± 2.0% for 1 h after resuscitation; P = 0.035) when compared with the control group (88.2 ± 2.4%). Water content of the cortex was nearly the same as that of the hippocampus. Neurologic deficit scores and neuronal survival were significantly better in the hemin group than in the control group on the 4th and 14th days. In rats that survived for 4 days, the amount of caspase 3-positive neurons was 27 ± 7 in the control group, whereas the value was 14 ± 6 in the hemin group (P < 0.05). Conclusions: In rats resuscitated from cardiac arrest, induction of HO-1 by hemin reduced brain edema, improved neurologic outcome, and protected neurons against apoptosis. Copyright © 2008 The American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.