亚低温对心脏骤停大鼠复苏后内毒素受体的影响
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摘要
第一部分人工气道建立方式对心脏骤停模型复苏的影响
目的:观察不同人工气道建立方式对大鼠心脏骤停模型自主循环恢复后呼吸功能、存活情况的影响;以及改良后经口气管插管法的可行性。
方法:建立窒息法大鼠心脏骤停模型;30只雄性Sprague-Dawley(SD)大鼠随机分成2组,经口气管插管组(n = 15)、气管切开插管组(n =15)。观察复苏后大鼠在机械通气与自主呼吸状况下动脉血气值变化,比较复苏后6h、24h、72h存活情况。
结果:经口气管插管组大鼠,在心脏骤停复苏后机械通气状态下血气pH值与拔管后半小时自主呼吸状态下比较,差异无统计学意义(P>0.05);而比较气管切开组两种呼吸状态下pH(7.40±0.03 vs 7.31±0.02, P <0.001)、PaCO_2(40.32±2.43mmHg vs 49.56±3.35mmHg, P <0.001),差异均有统计学意义。同期两组间比较pH(7.40±0.02 vs 7.31±0.02,)、PaCO2(42.03±2.01mmHg vs 49.56±3.35mmHg)、PaO2(95.43±2.36mmHg vs 71.29±9.51mmHg),差异均有显著统计学意义(P分别<0.001);比较经口气管插管组与气管切开组大鼠复苏后6h生存率(92.9% vs 78.6%)、24h存活率(85.7% vs 57.1%),气管切开组有明显下降趋势,但是差异无统计学意义(P>0.05);72h存活率(85.7% vs 50%)比较差异有统计学意义(P<0.05)。
结论:对于需要撤除人工气道、实验观察时间长的大鼠心脏骤停模型,经口气管插管法建立人工气道优于气管切开插管法;且改良后经口气管插管法是值得推荐的一种大鼠气管插管方法。
第二部分亚低温对心脏骤停大鼠复苏后内毒素受体的影响
目的:研究心肺复苏后大鼠血清内毒素可溶性受体的变化特点及亚低温对其影响。
方法:采有改良后窒息致大鼠心脏骤停动物模型,实验设计和记录按照Utstein模式。雄性Sprague-Dawley大鼠24只,随机分为3组:对照组(假手术组)、常规心肺复苏组、亚低温心肺复苏组,每组8只;对照组大鼠在手术后24h静脉注射3mg/Kg脂多糖(Lipopolysaccharide,LPS),并于手术后6h、12h、24h,及注射LPS后1.5h、3h、6h静脉取血;常规心肺复苏组与亚低温心肺复苏组大鼠在复苏后24h静脉注射3mg/Kg脂多糖,于复苏后6h、12h、24h,及注射LPS后1.5h、3h、6h静脉取血;采用ELISA法,测定各组大鼠不同时段血浆可溶性内毒素受体CD14(sCD14)、肿瘤坏死因子α(TNF-α)含量;采用免疫组织化学法测定注射LPS后6h左肺肺泡及肺间质巨噬细胞表面内毒素受体CD14(mCD14)蛋白表达;观察右肺组织病理改变。
结果:与对照组比较,常规复苏组和亚低温组大鼠在复苏后和注射LPS后各时间点血浆sCD14水平都明显升高,复苏后24小时仍维持在高水平,但亚低温组复苏后6h、24h sCD14水平与与常规复苏组比较(0.35±0.09ug/ml vs 0.54±0.16 ug/ml、0.84±0.13ug/ml vs 1.02±0.19 ug/ml),两组间比较差异有统计学意义(P均<0.05);在注射LPS后,亚低温组sCD14上升水平明显低于常规复苏组,与常规复苏组在1.5h、3h、6h比较(1.82±0.21ug/ml vs 2.84±0.33ug/ml、2.76±0.21ug/ml vs 3.23±0.28ug/ml、2.72±0.29 ug/ml vs 3.16±0.43ug/ml),差异均有统计学意义(P均<0.05)。对于TNF-α,注射LPS前对照组未能测出其浓度,常规复苏组与亚低温组之间差异无统计学意义;注射LPS后,各组TNF-α水平均增高,但亚低温组在1.5h、3h、6h明显低于常规复苏组,两组间比较差异均有统计学意义(P均<0.01);且TNF-α与sCD14水平成正相关(r=0.92,P<0.01)。注射LPS后,常规复苏组和亚低温组大鼠的肺泡巨噬细胞(alveolar macrophage, AM)mCD14表达与对照组比较明显增强,亚低温组与常规复苏组比较(△OD 0.25±0.04 vs△OD 0.37±0.05),差异有统计学意义(P<0.01);但肺间质巨噬细胞mCD14表达在两组之间无统计学意义(P=0.42)。常规组肺损伤评分与亚低温组比较(9.65±1.65 vs 8.04±0.81),差异有统计学意义(P<0.05)。
结论:对于心脏骤停及心肺复苏这一全身性缺血再灌注过程,存在着内毒素受体的上调,伴随着对内毒素敏感性的增强;而亚低温对这种上调有一定的抑制作用,从而减轻复苏后内毒素引起的炎症介质释放和对肺的损害。
Part-I Effect of the type of advanced airway on cardiopulmonary resuscitation in a model of cardiac arrest
Objective: To investigate the influence of the type of artificial airway on the respiratory function and the survival rate after return of spontaneous circulation in a rat model of asphyxial cardiac arrest(CA).
Methods: The rat model of asphyxial CA was made by clamping endotracheal tube at expiration. Thirty male SD rats were randomly divided into two groups: orotracheal intubation group (n=15) and tracheotomy group (n=15). To observe the changes of blood gas during mechanical ventilation and spontaneously breathing, and to compare the 6-hour、24-hour and 72-hour survival rate between two groups.
Results: The pH of orotracheal intubation group was not statistically different during mechanical ventilation and spontaneously breathing(7.41±0.02 versus 7.40±0.02) (P>0.05), but in tracheotomy group , the pH(7.40±0.03 versus 7.31±0.02, P<0.001) and PaCO2(40.32±2.43mmHg versus 49.56±3.35mmHg, P<0.001) were statistically different. Between two groups, the synchronous pH(7.40±0.02 versus 7.31±0.02, P<0.001)、 PaCO2(42.03±2.01mmHg versus 49.56±3.35mmHg, P<0.001) and PaO2(95.43±2.36mmHg versus 71.29±9.51mmHg, P<0.001) were statistically different. 6-hour、24-hour survival rates between two groups were not statistically different(P>0.05), but declined apparently in tracheotomy group. 72-hour survival rate between orotracheal intubation group and tracheotomy group was statistically different(85.7% versus 50%, P<0.05).
Conclusion: For the rat model of CA , which needs a long time observation, to stop mechanical ventilation or to remove the artificial airway, orotracheal intubation should be selected with priority. And the orotracheal intubation, we have improved, is more practical and feasible in the rat.
Part-II Effect of mild hypothermia on endotoxin receptor expression after cardiopulmonary resuscitation in cardiac arrest rats
Objective:To investigate the change of endotoxin receptor in cardiac arrest rat and the effect of mild hypothermia on the change.
Methods:After setting up cardiac arrest model in rats, 24 animals were randomly divided into control group(S group), routine resuscitation group(C group) and mild hypothermia resuscitation group(M group), (n=8, per group). All animals were injected 3mg/kg LPS at 24h after operation or after CPR. In three groups, the contents of sCD14 and TNF-αin the plasma were determined by enzyme immunoassay method at 6 h, 12 h, 24 h after CPR or operation, and then at 1.5 h, 3 h, 6 h after injection of LPS. The expression of mCD14 protein in alveolar macrophage(AM) and interstitial macrophage were determined by immunohistochemistry. Pathological observation were observed in the right lung.
Results:Contrast to S group, the contents of sCD14 in other groups increased after CPR and injection of LPS, but M group was less than C group at 6h(0.35±0.09ug/ml versus 0.54±0.16 ug/ml, P<0.05) and 24h(0.84±0.13ug/ml versus 1.02±0.19 ug/ml, P<0.05) after CPR. After injection of LPS, the contents of sCD14 in M group were compared with C group at 1.5h、3h、6h(1.82±0.21ug/ml versus 2.84±0.33ug/ml、2.76±0.21ug/ml versus 3.23±0.28ug/ml、2.72±0.29ug/ml versus 3.16±0.43ug/ml), two groups were statistically different(P<0.05). After injection of LPS, the contents of TNF-αin all the groups increased, M group was less than C group at 1.5h、3h、6h, two groups were statistically different(P<0.01). Furthermore, it was direct correlation between the contents of TNF-αand sCD14(r=0.92,P<0.01). The expression of AM mCD14 in C group was more than in M group (△OD 0.37±0.05 versus△OD 0.25±0.04, P<0.01). The ALI score in M group was lower in C group(8.04±0.81 versus 9.65±1.65, P<0.05).
Conclusion:The expression of endotoxin receptor in cardiac arrest rat increased after CPR, meanwhile, enhanced sensitivity to the subsequent LPS challenge. But mild hypothermia could inhibit the increase, and mitigate the lung injury of LPS after CPR.
目的:观察不同人工气道建立方式对大鼠心脏骤停模型自主循环恢复后呼吸功能、存活情况的影响;以及改良后经口气管插管法的可行性。
方法:建立窒息法大鼠心脏骤停模型;30只雄性Sprague-Dawley(SD)大鼠随机分成2组,经口气管插管组(n = 15)、气管切开插管组(n =15)。观察复苏后大鼠在机械通气与自主呼吸状况下动脉血气值变化,比较复苏后6h、24h、72h存活情况。
结果:经口气管插管组大鼠,在心脏骤停复苏后机械通气状态下血气pH值与拔管后半小时自主呼吸状态下比较,差异无统计学意义(P>0.05);而比较气管切开组两种呼吸状态下pH(7.40±0.03 vs 7.31±0.02, P <0.001)、PaCO_2(40.32±2.43mmHg vs 49.56±3.35mmHg, P <0.001),差异均有统计学意义。同期两组间比较pH(7.40±0.02 vs 7.31±0.02,)、PaCO2(42.03±2.01mmHg vs 49.56±3.35mmHg)、PaO2(95.43±2.36mmHg vs 71.29±9.51mmHg),差异均有显著统计学意义(P分别<0.001);比较经口气管插管组与气管切开组大鼠复苏后6h生存率(92.9% vs 78.6%)、24h存活率(85.7% vs 57.1%),气管切开组有明显下降趋势,但是差异无统计学意义(P>0.05);72h存活率(85.7% vs 50%)比较差异有统计学意义(P<0.05)。
结论:对于需要撤除人工气道、实验观察时间长的大鼠心脏骤停模型,经口气管插管法建立人工气道优于气管切开插管法;且改良后经口气管插管法是值得推荐的一种大鼠气管插管方法。
第二部分亚低温对心脏骤停大鼠复苏后内毒素受体的影响
目的:研究心肺复苏后大鼠血清内毒素可溶性受体的变化特点及亚低温对其影响。
方法:采有改良后窒息致大鼠心脏骤停动物模型,实验设计和记录按照Utstein模式。雄性Sprague-Dawley大鼠24只,随机分为3组:对照组(假手术组)、常规心肺复苏组、亚低温心肺复苏组,每组8只;对照组大鼠在手术后24h静脉注射3mg/Kg脂多糖(Lipopolysaccharide,LPS),并于手术后6h、12h、24h,及注射LPS后1.5h、3h、6h静脉取血;常规心肺复苏组与亚低温心肺复苏组大鼠在复苏后24h静脉注射3mg/Kg脂多糖,于复苏后6h、12h、24h,及注射LPS后1.5h、3h、6h静脉取血;采用ELISA法,测定各组大鼠不同时段血浆可溶性内毒素受体CD14(sCD14)、肿瘤坏死因子α(TNF-α)含量;采用免疫组织化学法测定注射LPS后6h左肺肺泡及肺间质巨噬细胞表面内毒素受体CD14(mCD14)蛋白表达;观察右肺组织病理改变。
结果:与对照组比较,常规复苏组和亚低温组大鼠在复苏后和注射LPS后各时间点血浆sCD14水平都明显升高,复苏后24小时仍维持在高水平,但亚低温组复苏后6h、24h sCD14水平与与常规复苏组比较(0.35±0.09ug/ml vs 0.54±0.16 ug/ml、0.84±0.13ug/ml vs 1.02±0.19 ug/ml),两组间比较差异有统计学意义(P均<0.05);在注射LPS后,亚低温组sCD14上升水平明显低于常规复苏组,与常规复苏组在1.5h、3h、6h比较(1.82±0.21ug/ml vs 2.84±0.33ug/ml、2.76±0.21ug/ml vs 3.23±0.28ug/ml、2.72±0.29 ug/ml vs 3.16±0.43ug/ml),差异均有统计学意义(P均<0.05)。对于TNF-α,注射LPS前对照组未能测出其浓度,常规复苏组与亚低温组之间差异无统计学意义;注射LPS后,各组TNF-α水平均增高,但亚低温组在1.5h、3h、6h明显低于常规复苏组,两组间比较差异均有统计学意义(P均<0.01);且TNF-α与sCD14水平成正相关(r=0.92,P<0.01)。注射LPS后,常规复苏组和亚低温组大鼠的肺泡巨噬细胞(alveolar macrophage, AM)mCD14表达与对照组比较明显增强,亚低温组与常规复苏组比较(△OD 0.25±0.04 vs△OD 0.37±0.05),差异有统计学意义(P<0.01);但肺间质巨噬细胞mCD14表达在两组之间无统计学意义(P=0.42)。常规组肺损伤评分与亚低温组比较(9.65±1.65 vs 8.04±0.81),差异有统计学意义(P<0.05)。
结论:对于心脏骤停及心肺复苏这一全身性缺血再灌注过程,存在着内毒素受体的上调,伴随着对内毒素敏感性的增强;而亚低温对这种上调有一定的抑制作用,从而减轻复苏后内毒素引起的炎症介质释放和对肺的损害。
Part-I Effect of the type of advanced airway on cardiopulmonary resuscitation in a model of cardiac arrest
Objective: To investigate the influence of the type of artificial airway on the respiratory function and the survival rate after return of spontaneous circulation in a rat model of asphyxial cardiac arrest(CA).
Methods: The rat model of asphyxial CA was made by clamping endotracheal tube at expiration. Thirty male SD rats were randomly divided into two groups: orotracheal intubation group (n=15) and tracheotomy group (n=15). To observe the changes of blood gas during mechanical ventilation and spontaneously breathing, and to compare the 6-hour、24-hour and 72-hour survival rate between two groups.
Results: The pH of orotracheal intubation group was not statistically different during mechanical ventilation and spontaneously breathing(7.41±0.02 versus 7.40±0.02) (P>0.05), but in tracheotomy group , the pH(7.40±0.03 versus 7.31±0.02, P<0.001) and PaCO2(40.32±2.43mmHg versus 49.56±3.35mmHg, P<0.001) were statistically different. Between two groups, the synchronous pH(7.40±0.02 versus 7.31±0.02, P<0.001)、 PaCO2(42.03±2.01mmHg versus 49.56±3.35mmHg, P<0.001) and PaO2(95.43±2.36mmHg versus 71.29±9.51mmHg, P<0.001) were statistically different. 6-hour、24-hour survival rates between two groups were not statistically different(P>0.05), but declined apparently in tracheotomy group. 72-hour survival rate between orotracheal intubation group and tracheotomy group was statistically different(85.7% versus 50%, P<0.05).
Conclusion: For the rat model of CA , which needs a long time observation, to stop mechanical ventilation or to remove the artificial airway, orotracheal intubation should be selected with priority. And the orotracheal intubation, we have improved, is more practical and feasible in the rat.
Part-II Effect of mild hypothermia on endotoxin receptor expression after cardiopulmonary resuscitation in cardiac arrest rats
Objective:To investigate the change of endotoxin receptor in cardiac arrest rat and the effect of mild hypothermia on the change.
Methods:After setting up cardiac arrest model in rats, 24 animals were randomly divided into control group(S group), routine resuscitation group(C group) and mild hypothermia resuscitation group(M group), (n=8, per group). All animals were injected 3mg/kg LPS at 24h after operation or after CPR. In three groups, the contents of sCD14 and TNF-αin the plasma were determined by enzyme immunoassay method at 6 h, 12 h, 24 h after CPR or operation, and then at 1.5 h, 3 h, 6 h after injection of LPS. The expression of mCD14 protein in alveolar macrophage(AM) and interstitial macrophage were determined by immunohistochemistry. Pathological observation were observed in the right lung.
Results:Contrast to S group, the contents of sCD14 in other groups increased after CPR and injection of LPS, but M group was less than C group at 6h(0.35±0.09ug/ml versus 0.54±0.16 ug/ml, P<0.05) and 24h(0.84±0.13ug/ml versus 1.02±0.19 ug/ml, P<0.05) after CPR. After injection of LPS, the contents of sCD14 in M group were compared with C group at 1.5h、3h、6h(1.82±0.21ug/ml versus 2.84±0.33ug/ml、2.76±0.21ug/ml versus 3.23±0.28ug/ml、2.72±0.29ug/ml versus 3.16±0.43ug/ml), two groups were statistically different(P<0.05). After injection of LPS, the contents of TNF-αin all the groups increased, M group was less than C group at 1.5h、3h、6h, two groups were statistically different(P<0.01). Furthermore, it was direct correlation between the contents of TNF-αand sCD14(r=0.92,P<0.01). The expression of AM mCD14 in C group was more than in M group (△OD 0.37±0.05 versus△OD 0.25±0.04, P<0.01). The ALI score in M group was lower in C group(8.04±0.81 versus 9.65±1.65, P<0.05).
Conclusion:The expression of endotoxin receptor in cardiac arrest rat increased after CPR, meanwhile, enhanced sensitivity to the subsequent LPS challenge. But mild hypothermia could inhibit the increase, and mitigate the lung injury of LPS after CPR.
引文
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6.陈尔真,蒋健.复苏实验研究Utstein模式[J].中国急救医学,1999,19(2):70-73.
7. Chin JY, Koh Y, Kim MJ, et al. The Effects of Hypothermia on Endotoxin-Primed Lung[J]. Critical Care and Trauma, 2007, 104(5): 1171-1178.
8. Adrie C, Adib-Conquy M, Laurent I, et al. Successful Cardiopulmonary Resuscitation After Cardiac Arrest as a“Sepsis-Like”Syndrome[J]. Circulation, 2002, 106:562-568.
9. Landmann R, Zimmerli W, Sansano S, et al. Increased circulating soluble CD14 is associated with high mortality in gram-negative septic shock[J]. The Journal of Infectious Disease, 1995, 171:639-644.
10. Aalto H, Takala A, Kautiainen H, et al. Monocyte CD14 and soluble CD14 in predicting mortality of patients with severe community acquired infection[J]. Scandinavian Journal of Infectious Disease, 2007, 39:596-603.
11. Marion DW. Cytokines and therapeutic hypothermia[J]. Crit Care Med, 2002, 30(7):1666-1667.
12. Torossian A, Ruehlmann S, Middeke M, et al. Mild preseptic hypothermia isdetrimental in rats [J]. Crit Care Med, 2004, 32:1899-1930.
13. Kawamura N, Schmeichel AM, Wang Y, et al. Multiple effects of hypothermia on inflammatory response following ischemia– reperfusion injury in experimental ischemic neuropathy[J]. Experimental Neurology, 2006, 203:487-496.
1. Caffrey SL, Willoughby PJ, Pepe PE, et al. Public use of automated external defibrillators[J]. N Engl J Med, 2002,347:1242-7.
2. Fredriksson M, Herlitz J, Nichol G. Variation in outcome in studies of out-of-hospital cardiac arrest: a review of studies conforming to the Utstein guidelinesV. Am J Emerg Med, 2003, 21:276-81.
3. Eckstein M, Stratton SJ, Chan LS. Cardiac arrest resuscitation evaluation in Los Angeles: CARE-LA[J]. Ann Emerg Med, 2005, 45:504-9.
4. Meyers A, Bernard SA, Smith KL, et al. Asystolic cardiac arrest in Melbourne, Australia[J]. Emerg Med, 2001,13:186-9.
5. Bunch TJ, White RD, Gersh BJ, et al. Long term outcomes of out-of-hospital cardiac arrest after successful early defibrillation [J]. N Engl J Med, 2003, 348:2626-33.
6. Bernard SA, Gray T, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia [J]. N Engl J Med, 2002, 346:557-63.
7. The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurological outcome after cardiac arrest [J]. N Engl J Med, 2002, 346:549-56.
8. Marion DW, Leonov Y, Ginsberg M, et al. Resuscitative hypothermia [J]. Crit Care Med, 1996, 24:S81-S89
9. Sterz F, Safar P, Tisherman SA, et al. Mild hypothermic cardiopulmonary resuscitation improves outcome after cardiac arrest in dogs[J]. Crit Care Med 1991, 19:379-89.
10. Bernard SA, Jones BM, Horne MK. A clinical trial of induced hypothermia in comatose survivors of prehospital cardiac arrest[J]. Ann Emerg Med, 1997, 30:146-53.
11. Nolan JP, Morley PT, Hoek TL, et al. Therapeutic hypothermia after cardiac arrest: anadvisory statement by the Advancement Life Support Task Force of the International Liaison Committee on Resuscitation[J]. Resuscitation, 2003, 57:231-235
12. 2005 American Heart Association Guidelines For Cardiopulmonary Resuscitation And Emergency Cardiovascular Care: Part 7.5: Postresuscitation Support[J]. Circulation, 2005, 112: IV-84 - IV-88.
13. Takata K, Takeda Y, Sato T, et al. Effects of hypothermia for a short period on histologic outcome and glutamate concentration during and after cardiac arrest in rats[J]. Crit Care Med, 2005, 33:1340-5.
14. Yenari MA, Wijman CA. Effects of hypothermia on cerebral metabolism, blood flow, and autoregulation. In: Mayer SA, Sessler D, eds. Therapeutic hypothermia. New York, NY: Marcel Dekker, 2005, 141-178
15. Alzaga AG, Cerdan M, Varon J. Therapeutic hypothermia[J]. Resuscitation, 2006, 70:369-380
16. Bernard SA, Buist M. Induced hypothermia in critical care medicine: a review[J]. Crit Care Med, 2003, 31:2041-2051
17. Bernard SA, Jones BM, Buist M. Experience with prolonged induced hypothermia in patients with severe head injury[J]. Crit Care, 1999, 3:167-72.
18. Polderman KH: Induced hypothermia and fever control for prevention and treatment of neurological injuries[J]. Lancet 2008, 371: 1955-1969
19. Polderman KH, Herold I. Therapeutic hypothermia and controlled normothermia in the intensive care unit: Practical considerations, side effects, and cooling methods[J]. Crit Care Med, 2009, 37:1101-1120
20. Laurent I, Monchi M, Chiche JD, et al. Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest[J]. J Am Coll Cardiol, 2002, 40:2110-2116.
21. Boddicker KA, Zhang Y, Zimmerman MB, et al: Hypothermia improves defibrillation success and resuscitation outcomes from ventricular fibrillation[J]. Circulation 2005, 111:3195-3201
22. Zeiner A, Sunder-Plassmann G, Sterz F, et al. The effect of mild therapeutichypothermia on renal function after cardiopulmonary resuscitation in men[J]. Resuscitation, 2004, 60:253-261
23. Polderman KH, Zanten ARH van, Girbes ARJ: The importance of magnesium in critically ill patients: A role in mitigating neurological injury and in the prevention of vasospasms[J]. Intensive Care Med 2003, 29: 1202-1203
24. Altman D, Carroli G, Duley L, et al: Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: A randomised placebocontrolled Trial[J]. Lancet 2002, 359: 1877-1890
25. Soliman HM, Mercan D, Lobo SS, et al: Development of ionized hypomagnesemia is associated with higher mortality rates[J]. Crit Care Med 2003, 31:1082-1087
26. Temkin NR, Anderson GD, Winn HR, et al: Magnesium sulfate for neuroprotection after traumatic brain injury: A randomized controlled trial[J]. Lancet Neurol 2007, 6:29-38
27. Zeiner A, Plassmann GS, Sterz F, et al. The effect of mild therapeutic hypothermia on renal function after cardiopulmonary resuscitation in men[J]. Resuscitation, 2004, 60:253-261.
28. Rundgren M, Engstrom M. A Thromboelastometric Evaluation of the Effects of Hypothermia on the Coagulation System[J]. Anesth Analg, 2008, 107:1465-8.
29. Dirkmann D, Hanke AA, Gorlinger K, et al. Hypothermia and Acidosis Synergistically Impair Coagulation in Human Whole Blood[J]. Anesth Analg, 2008, 106:1627-32.
30. Polderman KH: Induced hypothermia and fever control for prevention and treatment of neurological injuries[J]. Lancet 2008, 371: 1955-1969
31. Polderman KH: Application of therapeutic hypothermia in the ICU: Opportunities and pitfalls of a promising treatment modality, Part 1. Indications and evidence[J]. Intensive Care Med 2004, 30:556-575
32. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients[J]. N Engl J Med, 2001, 345:1359-1367
33. Diringer MN. Treatment of fever in the neurologic intensive care unit with a catheter-based heat exchange system[J]. Crit Care Med, 2004, 32:559-564
34. Sterz F, Holzer M, Roine R, et al. Hypothermia after cardiac arrest: a treatment that worksV. Curr Opin Crit Care, 2003, 9:205-210
35. Zviman MM, Roguin A, Jacobs A, et al. A new method for inducing hypothermia during cardiac arrest[J]. Crit Care Med, 2004, 32:S369-S373
36. Ryan M, Beattie TF, Husselbee K, et al. Use of the infant transwarmer mattress as an external warming modality in resuscitation from hypothermia[J]. Emerg Med J, 2003, 20:487-488
37. Bell DD, Brindley PG, Forrest D, et al. Management following resuscitation from cardiac arrest: recommendations from the 2003 Rocky Mountain Critical Care Conference[J]. Can J Anaesth, 2005, 52:309-322
38. Mayer S. Surface cooling for fever control in brain-injured patients[J]. Crit Care Med , 2005, 33:1891-5.
39. Mayer SA, Kowalski RG, Presciutti M, et al. Clinical trial of a novel surface cooling system for fever control in neurocritical care patients[J]. Crit Care Med, 2004, 32:2508-2515
40. Haugk M, Sterz F, Grassberger M, et al. Feasibility and efficacy of a new non-invasive surface cooling device in post-resuscitation intensive care medicine[J]. Resuscitation, 2007, 75:76-81
41. Janata A, Weihs W, Bayegan K, et al. Therapeutic hypothermia with a novel surface cooling device improves neurologic outcome after prolonged cardiac arrest in swine[J]. Crit Care Med ,2008, 36:895-902.
42. Konstas AA, Neimark MA, Laine AF, et al. A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain[J]. J Appl Physiol, 2007, 102:1329-1340
43. Al-Senani FM, Graffagnino C, Grotta JC, et al. A prospective, multicenter pilot study to evaluate the feasibility and safety of using the CoolGard System and Icy catheterfollowing cardiac arrest[J]. Resuscitation 2004, 62:143-150
44. Kliegel A, Losert H, Sterz F, et al. Cold simple intravenous infusions preceding special endovascular cooling for faster induction of mild hypothermia after cardiac arrest: a feasibility study[J]. Resuscitation, 2005, 64:347-351
45. Bernard S, Buist M, Monteiro O, et al. Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out-of-hospital cardiac arrest: a preliminary report[J]. Resuscitation, 2003, 56:9-13
46. Virkkunen I, Yli-Hankala A, Silfvast T. Induction of therapeutic hypothermia after cardiac arrest in prehospital patients using ice-cold Ringer’s solution: a pilot study[J]. Resuscitation, 2004, 62:299-302
47. Kim F, Olsufka M, Carlbom D, et al. Pilot study of rapid infusion of 2 L of 4 degrees C normal saline for induction of mild hypothermia in hospitalized, comatose survivors of out-of-hospital cardiac arrest[J]. Circulation, 2005, 112:715-719.
48. Georgiadis D, Schwarz S, Kollmar R, et al. Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach [J]. Stroke , 2001, 32: 2550-2553.
49. Piepgras A, Roth H, Schurer L, et al. Rapid active internal core cooling for induction of moderate hypothermia in head injury by use of an extracorporeal heat exchanger [J]. Neurosurgery, 1998, 42:317-8.
50. Holzer M, Behringer W, Janata A, et al. Extracorporeal venovenous cooling for induction of mild hypothermia in human-sized swine[J]. Crit Care Med, 2005, 33:1346-50.
51. Mori K, Itoh Y, Saito J, et al. Post-resuscitative hypothermic bypass reduces ischemic brain injury in swine[J]. Acad Emerg Med, 2001, 8:937-945
52. Wen YS, Huang MS, Lin MT, et al. Rapid brain cooling by hypothermic retrograde jugular vein flush[J]. J Trauma 2005, 58:577-581
53. Covaciu L, Allers M, Enblad P, et al. Intranasal selectivebrain cooling in pigs[J]. Resuscitation 2008, 76:83-88
54. Zweifler RM, Voorhees ME, Mahmood MA, et al. Rectal temperature reflects tympanic temperature during mild induced hypothermia in nonintubated subjects[J]. J Neurosurg Anesthesiol, 2004, 16:232-235
55. Akata T, Setoguchi H, Shirozu K, et al: Reliability of temperatures measured at standard monitoring sites as an index of brain temperature during deep hypothermic cardiopulmonary bypass conducted for thoracic aortic reconstruction[J]. J Thorac Cardiovasc Surg 2007, 133:1559-1565
56. Crowder CM, Tempelhoff R, Theard MA, et al. Jugular bulb temperature: comparison with brain surface and core temperatures in neurosurgical patients during mild hypothermia[J]. J Neurosurg, 1996, 85:98-103
57. McIlvoy L. Comparison of brain temperature to core temperature: a review of the literature[J]. J Neurosci Nurs, 2004, 36:23-31
58. Silfvast T, Tiainen M, Poutiainen E, et al. Therapeutic hypothermia after prolonged cardiac arrest due to noncoronary causes[J]. Resuscitation, 2003, 57:109-112
59. Katz LM, Young A, Frank JE, et al. Neurotensin-induced hypothermia improves neurologic outcome after hypoxic-ischemia[J]. Crit Care Med 2004, 32:806-10.
60. Ueda Y, Suehiro E, Wei EP, et al. Uncomplicated rapid posthypothermic rewarming alters cerebrovascular responsiveness[J]. Stroke, 2004, 35:601-6.
2. Hendrickx HH, Rao GR, Safar P, et al. Asphyxia, cardiac arrest and resuscitation in rats. I. Short term recovery [J]. Resuscitation, 1984, 12(2): 97-116.
3.符岳,方向韶,罗志刚,等.大鼠电刺激诱发心室颤动和机械性心肺复苏模型的建立[J].岭南急诊医学杂志, 2007, 12(1): 1-6.
4.黄唯佳,李章平,陈寿权.心肺脑复苏动物模型[J].中华急诊医学杂志, 2002, 11(6): 419-420.
5.涂建锋,蒋国平,江观玉.心脏骤停动物模型的动物和实验方法选择[J].中国病理生理杂志, 2006, 22(4): 830-832.
6.邱永明,田鑫.大鼠简易的气管插管方法[J].上海第二医科大学学报, 2001, 21(6): 576.
7.陈尔真,蒋健.复苏实验研究Utstein模式[J].中国急救医学, 1999, 19(2): 70-73.
8.陈寿权,李章平,王姗姗,等.窒息法致大鼠心脏骤停模型复苏的影响因素[J].中华急诊医学杂志, 2005, 14(10): 814-817.
9.马勇,孟庆义,王志忠,等.氨茶碱与肾上腺素合用在大鼠心脏停搏中的疗效[J].中华老年心脑血管病杂志, 2004, 6(11): 41-43.
10. Shinichi Kono, Suzuki A, Obata Y, et al. Vasopressin with delayed combination of nitroglycerin increases survival rate in asphyxia rat model[J]. Resuscitation, 2002, 54(3): 297-301.
11. Pena H, Cabrera C. Improved endotracheal intubation technique in the rat[J]. Lab Anim Sci, 1980, 30(4): 712-713 .
12. Vergari A, Polito A, Musumeci M, et al. Video-assisted orotracheal intubation in mice[J]. Laboratory Animals, 2003, 37(3): 204-206 .
13. Fuentes JM, Hanly EJ, Bachman LS, et al. Videoendoscopic endotracheal intubation in the rat: a comprehensive rodent model of laparoscopic surgery[J]. Journal of Surgical Research, 2004, 122(2): 240-248.
14.李娜,王焱林,王成夭,等. 3种大鼠气管插管方法的比较[J].医学新知杂志, 2005, 15(4): 20-22.
15.陶运明,莫绪明,戚继荣,等.一种新的大鼠气管插管方法[J].中华实验外科杂志, 2004, 21(4): 504.
1. Claridage JA, Schulman AM, Young JS. Improved resuscitation minimizes respiratory dysfunction and blunts interleukin-6 and nuclear factor-kappa B activation after traumatic hemorrhage [J]. Crit Care Med, 2002, 30(8):1815-1819.
2. Weisfeldt ML,Becker LB.Resuscitation after cardiac arrest: a 3-phasetime-sensitive model[J]. JAMA, 2002, 288(23): 3035-3038.
3.姚咏明,盛志勇.脓毒症防治学.第一版.北京:科学技术文献出版社,2008;26-32.
4. Catherine w,Yong-Ming Yao,Zhi-Guo Shi,et al.Lipopolysaccharide -Binding Protein and Lipopolysaccharide Receptor CD14 Gene Expression after Thermal Injury and its Potential Mechanism(s) [J]. J Trauma, 2001, 50:810-816.
5.张伟,蒋耀光,谢志坚,等.急性肺损伤肺间质巨噬细胞TLR4的表达及意义[J].中国危重病急救医学,2004,16(10):622-625.
6.陈尔真,蒋健.复苏实验研究Utstein模式[J].中国急救医学,1999,19(2):70-73.
7. Chin JY, Koh Y, Kim MJ, et al. The Effects of Hypothermia on Endotoxin-Primed Lung[J]. Critical Care and Trauma, 2007, 104(5): 1171-1178.
8. Adrie C, Adib-Conquy M, Laurent I, et al. Successful Cardiopulmonary Resuscitation After Cardiac Arrest as a“Sepsis-Like”Syndrome[J]. Circulation, 2002, 106:562-568.
9. Landmann R, Zimmerli W, Sansano S, et al. Increased circulating soluble CD14 is associated with high mortality in gram-negative septic shock[J]. The Journal of Infectious Disease, 1995, 171:639-644.
10. Aalto H, Takala A, Kautiainen H, et al. Monocyte CD14 and soluble CD14 in predicting mortality of patients with severe community acquired infection[J]. Scandinavian Journal of Infectious Disease, 2007, 39:596-603.
11. Marion DW. Cytokines and therapeutic hypothermia[J]. Crit Care Med, 2002, 30(7):1666-1667.
12. Torossian A, Ruehlmann S, Middeke M, et al. Mild preseptic hypothermia isdetrimental in rats [J]. Crit Care Med, 2004, 32:1899-1930.
13. Kawamura N, Schmeichel AM, Wang Y, et al. Multiple effects of hypothermia on inflammatory response following ischemia– reperfusion injury in experimental ischemic neuropathy[J]. Experimental Neurology, 2006, 203:487-496.
1. Caffrey SL, Willoughby PJ, Pepe PE, et al. Public use of automated external defibrillators[J]. N Engl J Med, 2002,347:1242-7.
2. Fredriksson M, Herlitz J, Nichol G. Variation in outcome in studies of out-of-hospital cardiac arrest: a review of studies conforming to the Utstein guidelinesV. Am J Emerg Med, 2003, 21:276-81.
3. Eckstein M, Stratton SJ, Chan LS. Cardiac arrest resuscitation evaluation in Los Angeles: CARE-LA[J]. Ann Emerg Med, 2005, 45:504-9.
4. Meyers A, Bernard SA, Smith KL, et al. Asystolic cardiac arrest in Melbourne, Australia[J]. Emerg Med, 2001,13:186-9.
5. Bunch TJ, White RD, Gersh BJ, et al. Long term outcomes of out-of-hospital cardiac arrest after successful early defibrillation [J]. N Engl J Med, 2003, 348:2626-33.
6. Bernard SA, Gray T, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia [J]. N Engl J Med, 2002, 346:557-63.
7. The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurological outcome after cardiac arrest [J]. N Engl J Med, 2002, 346:549-56.
8. Marion DW, Leonov Y, Ginsberg M, et al. Resuscitative hypothermia [J]. Crit Care Med, 1996, 24:S81-S89
9. Sterz F, Safar P, Tisherman SA, et al. Mild hypothermic cardiopulmonary resuscitation improves outcome after cardiac arrest in dogs[J]. Crit Care Med 1991, 19:379-89.
10. Bernard SA, Jones BM, Horne MK. A clinical trial of induced hypothermia in comatose survivors of prehospital cardiac arrest[J]. Ann Emerg Med, 1997, 30:146-53.
11. Nolan JP, Morley PT, Hoek TL, et al. Therapeutic hypothermia after cardiac arrest: anadvisory statement by the Advancement Life Support Task Force of the International Liaison Committee on Resuscitation[J]. Resuscitation, 2003, 57:231-235
12. 2005 American Heart Association Guidelines For Cardiopulmonary Resuscitation And Emergency Cardiovascular Care: Part 7.5: Postresuscitation Support[J]. Circulation, 2005, 112: IV-84 - IV-88.
13. Takata K, Takeda Y, Sato T, et al. Effects of hypothermia for a short period on histologic outcome and glutamate concentration during and after cardiac arrest in rats[J]. Crit Care Med, 2005, 33:1340-5.
14. Yenari MA, Wijman CA. Effects of hypothermia on cerebral metabolism, blood flow, and autoregulation. In: Mayer SA, Sessler D, eds. Therapeutic hypothermia. New York, NY: Marcel Dekker, 2005, 141-178
15. Alzaga AG, Cerdan M, Varon J. Therapeutic hypothermia[J]. Resuscitation, 2006, 70:369-380
16. Bernard SA, Buist M. Induced hypothermia in critical care medicine: a review[J]. Crit Care Med, 2003, 31:2041-2051
17. Bernard SA, Jones BM, Buist M. Experience with prolonged induced hypothermia in patients with severe head injury[J]. Crit Care, 1999, 3:167-72.
18. Polderman KH: Induced hypothermia and fever control for prevention and treatment of neurological injuries[J]. Lancet 2008, 371: 1955-1969
19. Polderman KH, Herold I. Therapeutic hypothermia and controlled normothermia in the intensive care unit: Practical considerations, side effects, and cooling methods[J]. Crit Care Med, 2009, 37:1101-1120
20. Laurent I, Monchi M, Chiche JD, et al. Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest[J]. J Am Coll Cardiol, 2002, 40:2110-2116.
21. Boddicker KA, Zhang Y, Zimmerman MB, et al: Hypothermia improves defibrillation success and resuscitation outcomes from ventricular fibrillation[J]. Circulation 2005, 111:3195-3201
22. Zeiner A, Sunder-Plassmann G, Sterz F, et al. The effect of mild therapeutichypothermia on renal function after cardiopulmonary resuscitation in men[J]. Resuscitation, 2004, 60:253-261
23. Polderman KH, Zanten ARH van, Girbes ARJ: The importance of magnesium in critically ill patients: A role in mitigating neurological injury and in the prevention of vasospasms[J]. Intensive Care Med 2003, 29: 1202-1203
24. Altman D, Carroli G, Duley L, et al: Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: A randomised placebocontrolled Trial[J]. Lancet 2002, 359: 1877-1890
25. Soliman HM, Mercan D, Lobo SS, et al: Development of ionized hypomagnesemia is associated with higher mortality rates[J]. Crit Care Med 2003, 31:1082-1087
26. Temkin NR, Anderson GD, Winn HR, et al: Magnesium sulfate for neuroprotection after traumatic brain injury: A randomized controlled trial[J]. Lancet Neurol 2007, 6:29-38
27. Zeiner A, Plassmann GS, Sterz F, et al. The effect of mild therapeutic hypothermia on renal function after cardiopulmonary resuscitation in men[J]. Resuscitation, 2004, 60:253-261.
28. Rundgren M, Engstrom M. A Thromboelastometric Evaluation of the Effects of Hypothermia on the Coagulation System[J]. Anesth Analg, 2008, 107:1465-8.
29. Dirkmann D, Hanke AA, Gorlinger K, et al. Hypothermia and Acidosis Synergistically Impair Coagulation in Human Whole Blood[J]. Anesth Analg, 2008, 106:1627-32.
30. Polderman KH: Induced hypothermia and fever control for prevention and treatment of neurological injuries[J]. Lancet 2008, 371: 1955-1969
31. Polderman KH: Application of therapeutic hypothermia in the ICU: Opportunities and pitfalls of a promising treatment modality, Part 1. Indications and evidence[J]. Intensive Care Med 2004, 30:556-575
32. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients[J]. N Engl J Med, 2001, 345:1359-1367
33. Diringer MN. Treatment of fever in the neurologic intensive care unit with a catheter-based heat exchange system[J]. Crit Care Med, 2004, 32:559-564
34. Sterz F, Holzer M, Roine R, et al. Hypothermia after cardiac arrest: a treatment that worksV. Curr Opin Crit Care, 2003, 9:205-210
35. Zviman MM, Roguin A, Jacobs A, et al. A new method for inducing hypothermia during cardiac arrest[J]. Crit Care Med, 2004, 32:S369-S373
36. Ryan M, Beattie TF, Husselbee K, et al. Use of the infant transwarmer mattress as an external warming modality in resuscitation from hypothermia[J]. Emerg Med J, 2003, 20:487-488
37. Bell DD, Brindley PG, Forrest D, et al. Management following resuscitation from cardiac arrest: recommendations from the 2003 Rocky Mountain Critical Care Conference[J]. Can J Anaesth, 2005, 52:309-322
38. Mayer S. Surface cooling for fever control in brain-injured patients[J]. Crit Care Med , 2005, 33:1891-5.
39. Mayer SA, Kowalski RG, Presciutti M, et al. Clinical trial of a novel surface cooling system for fever control in neurocritical care patients[J]. Crit Care Med, 2004, 32:2508-2515
40. Haugk M, Sterz F, Grassberger M, et al. Feasibility and efficacy of a new non-invasive surface cooling device in post-resuscitation intensive care medicine[J]. Resuscitation, 2007, 75:76-81
41. Janata A, Weihs W, Bayegan K, et al. Therapeutic hypothermia with a novel surface cooling device improves neurologic outcome after prolonged cardiac arrest in swine[J]. Crit Care Med ,2008, 36:895-902.
42. Konstas AA, Neimark MA, Laine AF, et al. A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain[J]. J Appl Physiol, 2007, 102:1329-1340
43. Al-Senani FM, Graffagnino C, Grotta JC, et al. A prospective, multicenter pilot study to evaluate the feasibility and safety of using the CoolGard System and Icy catheterfollowing cardiac arrest[J]. Resuscitation 2004, 62:143-150
44. Kliegel A, Losert H, Sterz F, et al. Cold simple intravenous infusions preceding special endovascular cooling for faster induction of mild hypothermia after cardiac arrest: a feasibility study[J]. Resuscitation, 2005, 64:347-351
45. Bernard S, Buist M, Monteiro O, et al. Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out-of-hospital cardiac arrest: a preliminary report[J]. Resuscitation, 2003, 56:9-13
46. Virkkunen I, Yli-Hankala A, Silfvast T. Induction of therapeutic hypothermia after cardiac arrest in prehospital patients using ice-cold Ringer’s solution: a pilot study[J]. Resuscitation, 2004, 62:299-302
47. Kim F, Olsufka M, Carlbom D, et al. Pilot study of rapid infusion of 2 L of 4 degrees C normal saline for induction of mild hypothermia in hospitalized, comatose survivors of out-of-hospital cardiac arrest[J]. Circulation, 2005, 112:715-719.
48. Georgiadis D, Schwarz S, Kollmar R, et al. Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach [J]. Stroke , 2001, 32: 2550-2553.
49. Piepgras A, Roth H, Schurer L, et al. Rapid active internal core cooling for induction of moderate hypothermia in head injury by use of an extracorporeal heat exchanger [J]. Neurosurgery, 1998, 42:317-8.
50. Holzer M, Behringer W, Janata A, et al. Extracorporeal venovenous cooling for induction of mild hypothermia in human-sized swine[J]. Crit Care Med, 2005, 33:1346-50.
51. Mori K, Itoh Y, Saito J, et al. Post-resuscitative hypothermic bypass reduces ischemic brain injury in swine[J]. Acad Emerg Med, 2001, 8:937-945
52. Wen YS, Huang MS, Lin MT, et al. Rapid brain cooling by hypothermic retrograde jugular vein flush[J]. J Trauma 2005, 58:577-581
53. Covaciu L, Allers M, Enblad P, et al. Intranasal selectivebrain cooling in pigs[J]. Resuscitation 2008, 76:83-88
54. Zweifler RM, Voorhees ME, Mahmood MA, et al. Rectal temperature reflects tympanic temperature during mild induced hypothermia in nonintubated subjects[J]. J Neurosurg Anesthesiol, 2004, 16:232-235
55. Akata T, Setoguchi H, Shirozu K, et al: Reliability of temperatures measured at standard monitoring sites as an index of brain temperature during deep hypothermic cardiopulmonary bypass conducted for thoracic aortic reconstruction[J]. J Thorac Cardiovasc Surg 2007, 133:1559-1565
56. Crowder CM, Tempelhoff R, Theard MA, et al. Jugular bulb temperature: comparison with brain surface and core temperatures in neurosurgical patients during mild hypothermia[J]. J Neurosurg, 1996, 85:98-103
57. McIlvoy L. Comparison of brain temperature to core temperature: a review of the literature[J]. J Neurosci Nurs, 2004, 36:23-31
58. Silfvast T, Tiainen M, Poutiainen E, et al. Therapeutic hypothermia after prolonged cardiac arrest due to noncoronary causes[J]. Resuscitation, 2003, 57:109-112
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