Effect of mild hypothermia combined with hydrogen-rich saline on cerebral injury after cardiac arrest and resuscitation in rats

Abstract

Objective To evaluate the effect of mild hypothermia combined with hydrogen-rich saline on cerebral injury after cardiac arrest and resuscitation in rats. Methods Healthy male Sprague-Dawley rats, aged 7-8 weeks, weighing 280-320 g, were divided into 5 groups (n=33 each) using a random number table method: sham operation group (group S), cardiac arrest and resuscitation group(group CA-R), hydrogen-rich saline group (group H2), mild hypothermia group (group MH), and mild hypothermia plus hydrogen-rich saline group (group MH+ H2). Cardiac arrest was induced with transoesophageal cardiac pacing followed by cardiopulmonary resuscitation to establish the cerebral injury model.Hydrogen-rich saline 5 ml/kg was intraperitoneally injected immediately after return of spontaneous circulation (ROSC) in H2 and MH+ H2 groups, while the equal volume of normal saline was given instead in the other groups.The body temperature of rats was cooled down to 32-34℃ within 15 min starting from the time point immediately after ROSC and maintained for 4 h in MH and MH+ H2 groups.Fifteen rats were selected at 24 h after ROSC to assess the neurological function score (NDS). Eighteen rats in each group were sacrificed at 24 h after ROSC, and brains were removed for microscopic examination of the pathological changes in hippocampal CA1 region after hematoxylin and eosin staining and for determination of pyramidal cell count and expression of glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP), caspase-12, caspase-3, Bcl-2 and Bax in hippocampal CA1 region (by Western blot). Results Compared with group S, the NDS was significantly decreased, the pyramidal cell count was reduced, the expression of GRP78, CHOP, caspase-12, caspase-3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in the other four groups (P 0.05). Conclusion Combination of mild hypothermia and hydrogen-rich saline offers enhanced efficacy in reducing cerebral injury after cardiac arrest and resuscitation over mild hypothermia or hydrogen-rich saline alone in rats. Key words: Hypothermia, induced; Hydrogen; Heart arrest; Cardiopulmonary resuscitation; Reperfusion injury; Brain