Efficacy of sodium hydrosulfide for improvement of cerebral protection provided by mild hypothermia in a rat model of cardiac arrest and resuscitation

Abstract

Objective To evaluate the efficacy of sodium hydrosulfide for improvement of cerebral protection provided by mild hypothermia in a rat model of cardiac arrest and resuscitation. Methods One hundred and forty pathogen-free healthy male Sprague-Dawley rats, weighing 280-320 g, aged 7-8 weeks, were randomly divided into 5 groups using a random number table: sham operation group (group S, n=20), cardiac arrest and resuscitation group (group CAR, n=30), sodium hydrosulfide group (group SH, n=30), mild hypothermia group (group MH, n=30) and sodium hydrosulfide plus mild hypothermia group (group SH+ MH, n=30). Cardiac arrest was induced by transesophageal cardiac pacing, and cardiopulmonary resuscitation was started after 4 min untreated arrest.The administration regimen for sodium hydrosulfide was as follows: sodium hydrosulfide was intravenously injected as a bolus of 0.5 mg/kg immediately after restoration of spontaneous circulation followed by an infusion of 1.5 mg·kg-1·h-1 for 3 h. Mild hypothermia was performed as follows: the rectal temperature was cooled down to 32-34 ℃ by rubbing the body surface with ethanol within 15 min starting from the time point immediately after restoration of spontaneous circulation and maintained at this level for 4 h, and then increased to 38-39 ℃ within 2 h. The animals were observed for 7 consecutive days after resuscitation, the survival rate was recorded, and the neurological function was evaluated by the tape removal test.At 24 h after resuscitation, brain tissues were harvested for determination of brain water content, permeability of blood brain barrier, expression of occludin in hippocampi (by Western blot), and expression of matrix metalloproteinase-9 (MMP-9) in hippocampi (by immunohistochemical staining). Results Compared with group S, the survival rate was significantly decreased, the tape removal time was significantly prolonged, the brain water content and permeability of blood brain barrier were significantly increased, the expression of occludin was significantly down-regulated, and the expression of MMP-9 was significantly up-regulated in CAR, SH, MH and SH+ MH groups (P<0.05). Compared with group CAR, the survival rate was significantly increased, the tape removal time was significantly shortened, the brain water content and permeability of blood brain barrier were significantly decreased, the expression of occludin was significantly up-regulated, and the expression of MMP-9 was significantly down-regulated in SH, MH and SH+ MH groups, and the changes in the parameters mentioned above were more obvious in group SH+ MH (P<0.05). Conclusion Sodium hydrosulfide significantly improves cerebral protection provided by mild hypothermia in a rat model of cardiac arrest and resuscitation, and the mechanism is related to reduction of occludin degradation, down-regulation of MMP-9 expression and decrease in the permeability of blood brain barrier. Key words: Hydrogen sulfide; Hypothermia, induced; Heart arrest; Cardiopulmonary resuscitation; Brain injuries; Reperfusion injury