Effect of protease inhibitor on brain energy metabolism in rats at the early stage of cardiopulmonary resuscitation

Abstract

Objective To explore the effect of protease inhibitor ulinastatin (UTI) on brain energy metabolism and cerebral protection after rats' respiratory and cardiac arrest with early cardiopulmonary resuscitation.Methods Thirty adult male SD rats were divided into three groups accroding to the table of random numbers (n=10):control group (group C),normal saline cardiopulmonary resuscitation group (group NS) and ulinastatin cardiopulmonary resuscitation group (group UTI).Anaesthesia,tracheotomy and carotid artery cannulation were performed in all groups.Asphyxial cardiac arrest and resuscitation model performed in group NS and group UTI expect group C.105 U/kg ulinastatin and the same amount of saline were injected via arteria carotis within 2 min after restoration of spontaneous circulation (ROSC) in group UTI and group NS.Time periods from asphyxiation to cardiac arrest(CA) and from cardiopulmonary resuscitation(CPR) performing to ROSC were recorded,the mean arterial pressure(MAP) was monitored within 1 h after ROSC.One hour after tracheostomy and vascular centesis in group C and 1 h after ROSC in group NS and group UTI,rats were sacrificed to get blood samples from carotid arteries and decapitated to get brain tissue samples.Adenosine triphosphate (ATP) content and lactic acid (LA) content of brain tissue were tested.Pathological changes of hippocampus were observed with light microscope and transmission electron microscope (TEM).Results ① The baseline of MAP were no statistical significance among three groups (P＞0.05).There were no statistical significance of MAP between group NS and group UTI when 2,5 min and 30 min after ROSC (P＞0.05).MAP of 2 min after ROSC in group NS and group UTI were higher than those of baseline [group NS:(166±11) mmHg vs (143±12) mmHg,P＜0.01,group UTI:(170±11) mmHg vs (141±16) mmHg,1 mmHg=0.133 kPa,P＜0.01],however,MAP of 5 min after ROSC in group NS (91±9) mmHg and group UTI (96±10) mmHg showed downtrend,which were lower than those ofbaseline (P＜0.01).Thirty minutes after ROSC,MAP in group NS (125 ±12) mmHg and group UTI (122±13) mmHg recovered but still lower than those of the baseline (P＜0.05).② Comparing to group C,the contents of LA in brain samples of the other two groups were increased significantly at 1 h after ROSC [group C ∶ group NS ∶ group UTI,(0.29±0.13) mmol/g prot vs (0.69±0.14) mmol/g prot vs (0.53±0.08) mmol/g prot,P＜0.01],however,the content of LA was lower in group UTI than that in group NS (P＜0.05).Comparing to group C,the contents of ATP in brain samples of the other two groups were decreased significantly at 1 h after ROSC[group C ∶ group NS,(26±6) μmol/g prot vs (12±5) μmol/g prot,P＜0.01,group C ∶ group UTI,(26±6) μmol/g prot vs (19±8) μmol/g prot,P＜0.05],the content of ATP were higher in group UTI than that in group NS(P＜0.05).③ Observations by light microscope with hematoxylin-eosin(HE) staining and nissl staining and by transmission electron microscope revealed that the pathological changes in group NS were more serious than that of group UTI,and the pathological changes in group UTI were nearly to those of group UTI.Conclusions To some extent,the improving of brain energy metabolism,the decrease of lactic acidosis and amelioration of the brain pathological changes one hour after CPR may contribute to the effects of UTI. Key words: Protease inhibitor; Ulinastatin ; Cardiopulmonary resuscitation; Cerebral; Energy metabolism