高渗氯化钠右旋糖酐对大鼠心博骤停脑复苏作用的研究
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摘要
目的探讨高渗氯化钠右旋糖酐(hypertonic saline dextran,HSD)对心肺复苏(cardiopulmonary resuscitation,CPR)后脑组织的作用,寻找治疗心博骤停(sudden cardiac arrest, SCA)脑复苏的有效方法。
方法40只雄性SD大鼠随机分为4组(各组10只):正常组(A组)、假手术组(B组)、复苏对照组(C组)、HSD干预组(D组)。制作窒息致大鼠SCA模型。复苏即刻,C组予以4ml/kg生理盐水静脉注射,D组予以4ml/kg的HSD静脉注射。记录各组SCA时间、自主循环恢复(restoration of spontaneous circulation,ROSC)时间,监测各组ROSC后1h内的平均动脉压(mean arterial pressure, MAP)及心电图的变化,测定ROSC后1h各组大鼠血清尿素氮、血糖、电解质,并计算出各组血浆渗透压值。记录ROSC后24h内的神经功能缺损评分(neurodeficit score, NDS)。ROSC后24h时采静脉血检测各组血清神经元特异性烯醇化酶(neurone specific enolase, NSE)浓度,处死大鼠取脑组织进行海马S100表达、脑组织含水量和海马组织病理学损伤的检测。
结果D组与C组的SCA时间和ROSC时间差异无显著性(P<0.05)。D组与C组ROSC后心电图的变化基本相似。与B组相比,D组大鼠ROSC后1min的MAP升高(P<0.05),但明显低于C组(P<0.05);其他时间点D、C两组MAP无显著差异(P>0.05),且均低于B组(P<0.05)。各组大鼠血清尿素氮、电解质和渗透压比差异无显著性(P>0.05)。D组ROSC后1h血糖与A、B两组比无显著性差异(P>0.05),而C组ROSC后1h血糖却明显高于其它三组(P<0.01)。ROSC后24h的血清NSE水平,D组与A、B组比无显著性差异(P>0.05), C组较A、B组均显著升高(P<0.01),D组显著低于C组(P<0.01)。ROSC后24h脑组织S100表达,D组较A、B组增多(P<0.01),C组较A、B组均显著增多(P<0.01),D组明显少于C组(P<0.01)。A、B、D组脑组织含水量无显著性差异(P>0.05),且均明显低于C组。D组脑组织病理学损伤较C组轻,NDS评分较C组提高(P<0.01),但C组和D组ROSC后任一时间点的NDS均较A组、B组明显降低(P<0.01)。
结论HSD对CPR后的血电解质、渗透压和ROSC时间无明显影响,但SCA实验中应用HSD的确能稳定自主循环恢复后的血压,维持血糖平衡,保持内环境平衡,减少脑组织S100的表达,降低血清NSE水平,减轻脑水肿及脑组织病理学损伤,改善脑功能,进而对CPR后的脑组织起到保护作用。
Object To explore the effect of Hypertonic saline dextran on brain tissue after cardiopulmonary resuscitation(CPR) and seek for the modus operandi of cerebral resuscitation.
Method 40 Sprague-Dawley male rats were randomly divided into four groups (10 for each group) as normal group (group A), shame-operated group (group B), CPR control group (group C) and HSD-treated group (group D).Sudden cardiac arrest was induced on rats by asphyxia. At the onset of CPR, 4ml/kg HSD was injected intravenously in the rats of group D and 4ml/kg normal saline was injected intravenously in the rats of group C. The time for both sudden cardiac arrest and restoration of spontaneous circulation (ROSC) were recorded, and a continuous monitoring on the change of mean arterial pressure(MAP)and electrocardiogram was held in 1h after ROSC. Blood urea nitrogen, blood glucose and serum electrolyte of the rats in each group at 1h after ROSC were determined, and then the plasma osmotic pressure in each group was calculated. Neurodeficit score (NDS) was also recorded in 24h after ROSC. At 24h after ROSC, the venous blood was got to detcect the concentration of serum neurone specific enolase (NSE) in each group, and the rats were sacrificed to get the brain tissue and compare the expression of S100 in hippocampus, brain water content and the hippocampus histopathological damages of the rats in each group.
Result The difference in the time for SCA and ROSC between group D and C was not significant (P>0.05). The change of electrocardiogram after ROSC between group D and C were similar. MAP in group D at 1min after ROSC increased (P<0.05) compared with group B, but much lower than those in group C (P<0.05), and MAP at the other time points in group D and C were both lower than those in group B (P<0.05),with no significant difference between group D and C(P>0.05). There was no significant difference in the serum urea nitrogen, electrolyte and osmotic pressure among all the groups (P>0.05). Blood glucose at 1h after ROSC in group D was not obviously different with group A and B(P>0.05), but that in group C was much higher than those in all the other groups (P<0.01). Serum NSE level at 24h after ROSC in group D was not significantly different with group C and D, which in group C was elevated obviously contrasted to group A and B (P<0.01), and that in group D was much lower than in group C (P<0.01). The expression of S100 in hippocampus at 24h after ROSC was higher in group D (P<0.01) and much higher in group C (P<0.01) than both in group A and B, and that in group D was extremely higher than the one in group C (P<0.01).There was no significant difference among group A,group B and group D in the brain water content (P>0.05),which were all much lower than that in group C (P<0.01). There were less severe cerebral histopathological damages and higher NDS (P<0.01) in group D compared with group C, but NDS at any time point after ROSC in both group C and D were significantly lower than those in group A and B(P<0.01).
Conclusion HSD has no significant effect on serum electrolyte and osmotic pressure as well as the time for ROSC after CPR. But indeed, the use of HSD in experimental sudden cardiac arrest is associated with more stable MAP,better balance of blood glucose, better homeostatic equilibrium, lower expression of S100 in hippocampus, lower serum NSE level, less cerebral edema, less histopathological damages and better neurologic recovery after ROSC, and therefor play a role in protection of brain tissue after CPR.
方法40只雄性SD大鼠随机分为4组(各组10只):正常组(A组)、假手术组(B组)、复苏对照组(C组)、HSD干预组(D组)。制作窒息致大鼠SCA模型。复苏即刻,C组予以4ml/kg生理盐水静脉注射,D组予以4ml/kg的HSD静脉注射。记录各组SCA时间、自主循环恢复(restoration of spontaneous circulation,ROSC)时间,监测各组ROSC后1h内的平均动脉压(mean arterial pressure, MAP)及心电图的变化,测定ROSC后1h各组大鼠血清尿素氮、血糖、电解质,并计算出各组血浆渗透压值。记录ROSC后24h内的神经功能缺损评分(neurodeficit score, NDS)。ROSC后24h时采静脉血检测各组血清神经元特异性烯醇化酶(neurone specific enolase, NSE)浓度,处死大鼠取脑组织进行海马S100表达、脑组织含水量和海马组织病理学损伤的检测。
结果D组与C组的SCA时间和ROSC时间差异无显著性(P<0.05)。D组与C组ROSC后心电图的变化基本相似。与B组相比,D组大鼠ROSC后1min的MAP升高(P<0.05),但明显低于C组(P<0.05);其他时间点D、C两组MAP无显著差异(P>0.05),且均低于B组(P<0.05)。各组大鼠血清尿素氮、电解质和渗透压比差异无显著性(P>0.05)。D组ROSC后1h血糖与A、B两组比无显著性差异(P>0.05),而C组ROSC后1h血糖却明显高于其它三组(P<0.01)。ROSC后24h的血清NSE水平,D组与A、B组比无显著性差异(P>0.05), C组较A、B组均显著升高(P<0.01),D组显著低于C组(P<0.01)。ROSC后24h脑组织S100表达,D组较A、B组增多(P<0.01),C组较A、B组均显著增多(P<0.01),D组明显少于C组(P<0.01)。A、B、D组脑组织含水量无显著性差异(P>0.05),且均明显低于C组。D组脑组织病理学损伤较C组轻,NDS评分较C组提高(P<0.01),但C组和D组ROSC后任一时间点的NDS均较A组、B组明显降低(P<0.01)。
结论HSD对CPR后的血电解质、渗透压和ROSC时间无明显影响,但SCA实验中应用HSD的确能稳定自主循环恢复后的血压,维持血糖平衡,保持内环境平衡,减少脑组织S100的表达,降低血清NSE水平,减轻脑水肿及脑组织病理学损伤,改善脑功能,进而对CPR后的脑组织起到保护作用。
Object To explore the effect of Hypertonic saline dextran on brain tissue after cardiopulmonary resuscitation(CPR) and seek for the modus operandi of cerebral resuscitation.
Method 40 Sprague-Dawley male rats were randomly divided into four groups (10 for each group) as normal group (group A), shame-operated group (group B), CPR control group (group C) and HSD-treated group (group D).Sudden cardiac arrest was induced on rats by asphyxia. At the onset of CPR, 4ml/kg HSD was injected intravenously in the rats of group D and 4ml/kg normal saline was injected intravenously in the rats of group C. The time for both sudden cardiac arrest and restoration of spontaneous circulation (ROSC) were recorded, and a continuous monitoring on the change of mean arterial pressure(MAP)and electrocardiogram was held in 1h after ROSC. Blood urea nitrogen, blood glucose and serum electrolyte of the rats in each group at 1h after ROSC were determined, and then the plasma osmotic pressure in each group was calculated. Neurodeficit score (NDS) was also recorded in 24h after ROSC. At 24h after ROSC, the venous blood was got to detcect the concentration of serum neurone specific enolase (NSE) in each group, and the rats were sacrificed to get the brain tissue and compare the expression of S100 in hippocampus, brain water content and the hippocampus histopathological damages of the rats in each group.
Result The difference in the time for SCA and ROSC between group D and C was not significant (P>0.05). The change of electrocardiogram after ROSC between group D and C were similar. MAP in group D at 1min after ROSC increased (P<0.05) compared with group B, but much lower than those in group C (P<0.05), and MAP at the other time points in group D and C were both lower than those in group B (P<0.05),with no significant difference between group D and C(P>0.05). There was no significant difference in the serum urea nitrogen, electrolyte and osmotic pressure among all the groups (P>0.05). Blood glucose at 1h after ROSC in group D was not obviously different with group A and B(P>0.05), but that in group C was much higher than those in all the other groups (P<0.01). Serum NSE level at 24h after ROSC in group D was not significantly different with group C and D, which in group C was elevated obviously contrasted to group A and B (P<0.01), and that in group D was much lower than in group C (P<0.01). The expression of S100 in hippocampus at 24h after ROSC was higher in group D (P<0.01) and much higher in group C (P<0.01) than both in group A and B, and that in group D was extremely higher than the one in group C (P<0.01).There was no significant difference among group A,group B and group D in the brain water content (P>0.05),which were all much lower than that in group C (P<0.01). There were less severe cerebral histopathological damages and higher NDS (P<0.01) in group D compared with group C, but NDS at any time point after ROSC in both group C and D were significantly lower than those in group A and B(P<0.01).
Conclusion HSD has no significant effect on serum electrolyte and osmotic pressure as well as the time for ROSC after CPR. But indeed, the use of HSD in experimental sudden cardiac arrest is associated with more stable MAP,better balance of blood glucose, better homeostatic equilibrium, lower expression of S100 in hippocampus, lower serum NSE level, less cerebral edema, less histopathological damages and better neurologic recovery after ROSC, and therefor play a role in protection of brain tissue after CPR.
引文
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[2] Prohl J,R?ther J,Kluge S,et al.Prediction of short-term and long-term outcomes after cardiacarrest:A prospective multivariate approach combining biochemical, clinical, electro-physiological, and neuropsychological investigations[J].Crit Care Med, 2007,35(5):1230- 1237.
[3] Rech TH, Vieira SR, Nagel F,et al.Serum neuron-specific enolase as early predictor of outcome after in-hospital cardiac arrest:a cohort study[J].Crit Care,2006, 10(6):133-138.
[4] Zingler VC, Krumm B, Bertsch T,et al.Early prediction of neurological outcome after cardiopulmonary resuscitation: a multimodal approach combining neurobiochemical and electrophysiological investigations may provide high prognostic certainty in patients after cardiac arrest[J].Eur Neurol,2003,49(2): 79-84.
[5] Reisinger J, H?llinger K, Lang W,et al.Prediction of neurological outcome after cardio- pulmonary resuscitation by serial determination of serum neuron-specific enolase [J].Eur.Heart J,2007,28(1):52-58.
[6] Rosén H, Sunnerhagen KS, Herlitz J,et al.Serum levels of the brain-derived proteins S-100 and NSE predict long-term outcome after cardiac arrest[J].Resuscitation, 2001,49(2):183-191.
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[1] Pfeifer R,B?rnerb A,Krack A,et al.Outcome after cardiac arrest: predictive values and limitations of the neuroproteins neuron-specific enolase and protein S-100 and the Glasgow Coma Scale[J].Resuscitation,2005,65(1):49-55.
[2] Prohl J,R?ther J,Kluge S,et al.Prediction of short-term and long-term outcomes after cardiacarrest:A prospective multivariate approach combining biochemical, clinical, electro-physiological, and neuropsychological investigations[J].Crit Care Med, 2007,35(5):1230- 1237.
[3] Rech TH, Vieira SR, Nagel F,et al.Serum neuron-specific enolase as early predictor of outcome after in-hospital cardiac arrest:a cohort study[J].Crit Care,2006, 10(6):133-138.
[4] Zingler VC, Krumm B, Bertsch T,et al.Early prediction of neurological outcome after cardiopulmonary resuscitation: a multimodal approach combining neurobiochemical and electrophysiological investigations may provide high prognostic certainty in patients after cardiac arrest[J].Eur Neurol,2003,49(2): 79-84.
[5] Reisinger J, H?llinger K, Lang W,et al.Prediction of neurological outcome after cardio- pulmonary resuscitation by serial determination of serum neuron-specific enolase [J].Eur.Heart J,2007,28(1):52-58.
[6] Rosén H, Sunnerhagen KS, Herlitz J,et al.Serum levels of the brain-derived proteins S-100 and NSE predict long-term outcome after cardiac arrest[J].Resuscitation, 2001,49(2):183-191.
[7] Topjian A,lin R,Morris M,et al.Neuron specific enolase predicts neurologic outcome after pediatric cardiac arrest[J].Pediatr Crit Care Med,2006,7(5): 517-522.
[8] Zhang M,Ma YF,Gan JX,et al.Basic fibroblast growth factor alleviates brain injury following global ischemia reperfusion in rabbits[J].J Zhejiang Univ Sci B,2005,6(7):637-643.
[9] Zandbergen EG,Hijdra A,Koelman JH,et al.Prediction of poor outcome within the first 3 days of postanoxic coma[J].Neurology,2006,66(1):62-68.
[10] Zingler VC,Pohlman-Eden B.Diagnostic pitfalls in patients with hypoxic brain damage:three case reports[J].Resuscitation,2005,65(1):107-110.
[11] Wijdicks EF,Hijdra A,Young GB,et al. Practice Parameter: Prediction of outcome in comatose survivors after cardiopulmonary resuscitation(an evidence-based review)[J]. Neurology, 2006,67(2):203-210.
[12] Grubb NR, Simpson C, Sherwood RA,et al. Prediction of cognitive dysfunction after resuscitation from out-of-hospital cardiac arrest using serum neuron-specific enolase and protein S-100[J].Heart,2007 May 13[Epub ahead of print].
[13] Auer J,Berent R,Weber T,et al. Ability of neuron-specific enolase to predict survival to hospital discharge after successful cardiopulmonary resuscitation [J]. CJEM,2006,8(1): 13-18.
[14] Tiainen M,Roine RO,Pettil? V,et al. Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia[J].Stroke,2003, 34(12):2881-2886.