ABSTRACT
Objective To investigate the effects of mild hypothermia on post-resuscitation neurological outcome after ventricular fibrillation (VF) in rabbits.Methods Forty-five adult New Zealand rabbits were induced VF by direct current of electricity.The rabbits were randomly(random number) divided into following groups:normothermic resuscitation group (NR),mild hypothermia prearrest group (HP),mild hypothermia resuscitation 30 min group (HRe30),mild hypothermia resuscitation 90 min group (HRe90),normothermic sham group (NS),and hypothermia sham group (HS).The rabbits of NR group were observed for 600 min in room temperature after restoration of spontaneous circulation (ROSC).The mild hypothermia was induced by surface cooling,and maintained for 600 min after the aimed low temperature reached.The arterial blood samples were collected for determining neuron-specific enolase (NSE) and thioredoxin (Trx) and the mean arterial pressure (MAP),left ventricular end-diastolic pressure (LVEDP) and left ventricular pressure raise and fall rate (±dp/dtmax) were observed at 15 min before CA,and 30 min,60 min,120 min,360 min and 600 min after ROSC.After the animals were sacrificed at 600 min after ROSC,the whole brain of animals was harvested and observed under light microscope to calculate the apoptotic index of the hippocampal CA1 neurons by using TUNEL method.One-way ANOVA was used to determine the statistical significance between two groups,a two-tailed value of P＜0.05 was considered statistically significant.Results (1) Hemodynamically compared with normal temperature groups,HR was lower in hypothermia groups.Compared with NR,HRe30,and HRe90 group,LVEDP was higher in HP group at 30 min after ROSC(3.4±0.8 vs.4.6±1.0,4.1±0.5,4.3±0.2,F=9.85,P=0.019).In Hp group,the level of +dp/dtmax was higher than that in NR,HRe30 and HRe90 groups at 30 min and 120 min after ROSC.In HP group,the level of-dp/dtmax was higher than that of NR group at 30 min,60 min,120 min,360 min and 600 min after ROSC.(2) Serologically compared with HP,HRe30 and HRe90 group,NSE levels were higher in NR group at 60 min,120 min and 360 min after ROSC.Compared with NR,HRe30,and HRe90 group,Trx levels in NR group were lower at 60 min,120 min,360 min and 600 min after ROSC.Compared with HP group,Trx levels in HRe30 and HRe90 groups were higher at 60 min,120 min,360 min and 600 min after ROSC.(3) Pathologically compared with NR group,histopathological changes in hippocampus CA1 area were milder found in HP,HRe30 and HRe90 groups.AI (％) was lower in HP,HRe30 and HRe90 groups than that in NR group[(62.25±10.43)％ vs.(20.61±5.02)％,(25.08±3.92)％,(30.33±7.15)％,P=0.001].Concusions This study shows that hypothermia should be initiated as soon as possible,and especially early intra-arrest cooling appears to be significantly better than post-ROSC cooling and normothermia.
ABSTRACT
Objective To evaluate the effect and mechanism of rt-PA combined with high pressure oxygen (HPO)on cerebral ischemia-reperfusion injury in rats.Methods The model of cerebral ischemia-reperfusion injury was constructed by using middle cerebral artery occlusion.The neurological function score;brain index,water content and infarction volume;SOD;LDH;NOS;MDA;LD;NO and NOS were measured.The protein and mRNA expressions of iNOS,BDNF,p75NTR and TrkB were also detected by RT-PCR and Western blot to evaluate and compare the protective effect of rt-PA combined HPO therapy. Results rt-PA combined HPO could significantly decrease the neurological function score;brain index,water content,and infarction volume;SOD;NOS;MDA;LD;NO and NOS but increase LDH content and the weight of rats,compared with rt-PA.In addition,rt-PA combined HPO could increase BNDF and TrKB expressions and downregulate the expressions of iNOS and p75NTR,compared with rt-PA (P<0.05).Conclusion The rt-PA combined HPO therapy has a greater protective effect than rt-PA therapy and its mechanism might be related to having antioxidant effects, increasing the expressions of BDNF and TrKB,and decreasing the expressions of iNOS and p75NTR.
ABSTRACT
Objective To explore the effects of intraventricular administration of insulin on the expressions of Bcl-2,Bax mRNA and neuronal hippocampus apoptosis in rats after cardiopulmonary resuscitation (CPR).Methods This experiment was implemented in the animal Laboratory center of Xuanwu Hospital of Capital Medical University.Thirty male SD rats were randomly (random number)divided into three groups:control group (n=6),CPR group (n=12),insulin treated group ( n =12).CPR was performed at 6 minutes after ventricular fibrillation induced by transesophageal overdrive pacing.Resuscitation procedures lasted until restoration of spontaneous circulation (ROSC).ROSC was defined as the recovery of the supraventricular heart rates and the increase of mean arterial pressure (MAP) ＞ 60mmHg for more than 10 minutes.Ten minutes after ROSC in rats,12.5 μL ( 1 U) regular insulin was injected into the left ventricle in the insulin group,and 12.5 μL isotonic saline was injected the control and CPR groups at least 10 minutes.Real-time PCR was used to observe the expressions of Bcl-2,Bax mRNA in hippocampus CAI after reperfusion 24 h and 72 h.TUNEL staining was used to observe the neuronal apoptosis in all groups after reperfusion 7 days.Blood glucose was monitored in rats before and after CPR.Results ① The Bcl-2mRNA in insulin groups were significantly higher than those in the CPR group after 24 h and 72 h (P ＜0.01 ).The expression of Bcl-2 mRNA in 24 h insulin group were significantly higher than those in 72 h insulin group ( P ＜ 0.01 ) ; There were no significantly different in the Bax mRNA between insulin groups and the CPR and the control group after 24 h and 72 h ( P ＞ 0.05 ) ; ②After CPR 7 d,the apoptotic neurons of hippocampal CA1 area in the CPR group ( 124.75 ± 17.35 ) were significantly higher than those in the control group (5.12 ± 3.26) ( P ＜ 0.01 ) and the insulin group (92.79 ± 7.35 )(P ＜0.01 ); the apoptotic neurons in the insulin group were higher than those in the control group (P ＜0.0l ),and the differences were statistically significant.③There were no significant difference in venous blood glucose in the CPR and insulin groups (P ＞ 0.05).Conclusions Insulin may regulate Bcl-2mRNA expression in hippocampus,inhibit neuronal apoptosis and protect neurons after CPR in rats.