缺血后适应用于深低温停循环的神经系统保护效应
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摘要
目的探索缺血后适应(IPOC)对于深低温停循环(DHCA)相关神经功能损伤的保护效应。方法健康成年巴马香猪12只,随机分为A组(DHCA组)和B组(DHCA IPOC组),每组6只。两组均经颈总动脉和颈内静脉插管建立体外循环,转流并降温至直肠温度15℃,暂停循环90 min后恢复体外循环并复温,先后脱离体外循环、呼吸机辅助,并观察神经系统功能状况至术后7天。B组在停循环后恢复体外循环之初,进行3个轮回的灌注/阻断操作,每个轮回时间为30 s/30 s。结果术后近期两组动物均有一定程度神经系统功能障碍,术后第一天,B组神经系统功能评级明显低于A组,而评分明显高于A组(P <0.05);术后3～7 d,B组神经系统功能评分仍稍高于A组,但无明显统计学差异。至第七天两组动物神经功能状况均渐接近正常。结论 IPOC有助于改善DHCA术后第一天神经系统功能,术后第三天及一周则未见其神经保护效应。进一步评估需假以更大样本量、更长的观测时间及组织病理学等微观分析。
Objective To evaluate the neuroprotective effect of ischemic postconditioning( IPOC) after deep hypothermia circulatory arrest( DHCA) in swines. Methods Twelve healthy adult swines were randomly assigned to group A( control group) or group B( experiment group). Animals were placed on cardiopulmonary bypass by intubation in the common carotid artery and the internal jugular vein,cooled to 15℃,subjected to 90 minutes of DHCA,rewarmed,weaned from CPB and ventilator in sequence. Neurological function was observed for 7 days after the operation. Results After operation,both two groups of animals had a certain degree of neurocognitive dysfunction. On the first day after operation,the neurological function rating of group B was significantly lower than that in group A,and the score was significantly higher than that in group A( P <0.05). The neurological function score of group B was still higher than that of group A at 3-7 days after operation,but there was no significant difference. On the seventh day,neurological function of the two groups was almost back to normal. Conclusion IPOC improves neurocognitive function in pig model on the first day after DHCA,but neuroprotective effect was no longer observed on the third day through to the seventh day.
Objective To evaluate the neuroprotective effect of ischemic postconditioning( IPOC) after deep hypothermia circulatory arrest( DHCA) in swines. Methods Twelve healthy adult swines were randomly assigned to group A( control group) or group B( experiment group). Animals were placed on cardiopulmonary bypass by intubation in the common carotid artery and the internal jugular vein,cooled to 15℃,subjected to 90 minutes of DHCA,rewarmed,weaned from CPB and ventilator in sequence. Neurological function was observed for 7 days after the operation. Results After operation,both two groups of animals had a certain degree of neurocognitive dysfunction. On the first day after operation,the neurological function rating of group B was significantly lower than that in group A,and the score was significantly higher than that in group A( P <0.05). The neurological function score of group B was still higher than that of group A at 3-7 days after operation,but there was no significant difference. On the seventh day,neurological function of the two groups was almost back to normal. Conclusion IPOC improves neurocognitive function in pig model on the first day after DHCA,but neuroprotective effect was no longer observed on the third day through to the seventh day.
引文
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[14] Bellinger DC,Wypij D,duplessis AJ,et al. Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries:the boston circulatory arrest trial[J]. J Thorac Cardiovasc Surg,2003,126(6):1385-1396.
[15] Wypij D,Newburger JW,Rappaport LA,et al. The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment:the boston circulatory arrest trial[J]. J Thorac Cardiovasc Surg,2003,126(5):1397-1403.
[16] Pastuszko P,Schears GJ,Greeley WJ,et al. Granulocyte colony stimulating factor reduces brain injury in a cardiopulmonary bypass-circulatory arrest model of ischemia in a newborn piglet[J]. Neurochem Res,2014,39(11):2085-2092.
[17] Garcia S,Rector TS,Zakharova M,et al. Cardiac remote ischemic preconditioning prior to elective vascular surgery(CRIPES):a prospective,randomized,sham-controlled phaseⅡclinical trial[J]. J Am Heart Assoc,2016,5(10):e003916.
[18] Zhao H,Sapolsky RM,Steinberg GK. Interrupting reperfusion as a stroke therapy:ischemic postconditioning reduces infarct size after focal ischemia in rats[J]. J Cereb Blood Flow Metab,2006,26(9):1114-1121.
[19] Wu H,Yang SF,Dai J,et al. Combination of early and delayed ischemic postconditioning enhances brain-derived neurotrophic factor production by upregulating the ERK-CREB pathway in rats with focal ischemia[J]. Mol Med Rep,2015,12(5):6427-6434.
[20] Gao L,Jiang T,Guo J,et al. Inhibition of autophagy contributes to ischemic postconditioning-induced neuroprotection against focal cerebral ischemia in rats[J]. PLoS One,2012,7(9):e46092.
[21] Gao X,Ren C,Zhao H. Protective effects of ischemic postconditioning compared with gradual reperfusion or preconditioning[J]. J Neurosci Res,2008,86(11):2505-2511.
[22] Rezazadeh H,Kahnuee MH,Roohbakhsh A,et al. Neuroprotective consequences of postconditioning on embolic model of cerebral ischemia in rat[J]. Iran J Basic Med Sci,2013,16(2):144-149.
[2] Le Maire SA,Carter SA,Coselli JS. The elephant trunk technique for staged repair of complex aneurysms of the entire thoracic aorta[J]. Ann Thorac Surg,2006,81(5):1561-1569.
[3] Alam HB,Duggan M,Li Y,et al. Putting life on hold-for how long? profound hypothermic cardiopulmonary bypass in a swine model of complex vascular injuries[J]. J Trauma,2008,64(4):912-922.
[4] Staat P,Rioufol G,Piot C,et al. Postconditioning the human heart[J]. Circulation,2005,112(14):2143-2148.
[5] Taylor MJ,Bailes JE,Elrifai AM,et al. A new solution for life without blood. asanguineous low-flow perfusion of a whole-body perfusate during 3 hours of cardiac arrest and profound hypothermia[J]. Circulation,1995,91(2):431-444.
[6] Neumar RW,Bircher NG,Sim KM,et al. Epinephrine and sodium bicarbonate during CPR following asphyxial cardiac arrest in rats[J]. Resuscitation,1995,29(3):249-263.
[7] Rhee P,Talon E,Eifert S,et al. Induced hypothermia during emergency department thoracotomy:an animal model[J]. J Trauma,2000,48(3):439-447.
[8] Tseng EE,Brock MV,ange ML,et al. Glutamate excitotoxicity mediates neuronal apoptosis after hypothermic circulatory arrest[J]. Ann Thorac Surg,2010,89(2):440-445.
[9] Penna C,Rastaldo R,Mancardi D,et al. Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism,mitochondrial ATP-sensitive K+channel and protein kinase c activation[J]. Basic Res Cardiol,2006,101(2):180-189.
[10] Tsutsumi YM,Yokoyama T,Horikawa Y,et al. Reactive oxygen species trigger ischemic and pharmacological postconditioning:in vivo and in vitro characterization[J]. Life Sci,2007,81(15):1223-1227.
[11] Banasiak KJ,Xia Y,Haddad GG. Mechanisms underlying hypoxia-induced neuronal apoptosis[J]. Prog Neurobiol,2000,62(3):215-249.
[12] Snider BJ,Gottron FJ,Choi DW. Apoptosis and necrosis in cerebrovascular disease[J]. Ann N Y Acad Sci,1999,893:243-253.
[13] Bellinger DC,Jonas RA,Rappaport LA,et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass[J]. N Engl J Med,1995,332(9):549-555.
[14] Bellinger DC,Wypij D,duplessis AJ,et al. Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries:the boston circulatory arrest trial[J]. J Thorac Cardiovasc Surg,2003,126(6):1385-1396.
[15] Wypij D,Newburger JW,Rappaport LA,et al. The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment:the boston circulatory arrest trial[J]. J Thorac Cardiovasc Surg,2003,126(5):1397-1403.
[16] Pastuszko P,Schears GJ,Greeley WJ,et al. Granulocyte colony stimulating factor reduces brain injury in a cardiopulmonary bypass-circulatory arrest model of ischemia in a newborn piglet[J]. Neurochem Res,2014,39(11):2085-2092.
[17] Garcia S,Rector TS,Zakharova M,et al. Cardiac remote ischemic preconditioning prior to elective vascular surgery(CRIPES):a prospective,randomized,sham-controlled phaseⅡclinical trial[J]. J Am Heart Assoc,2016,5(10):e003916.
[18] Zhao H,Sapolsky RM,Steinberg GK. Interrupting reperfusion as a stroke therapy:ischemic postconditioning reduces infarct size after focal ischemia in rats[J]. J Cereb Blood Flow Metab,2006,26(9):1114-1121.
[19] Wu H,Yang SF,Dai J,et al. Combination of early and delayed ischemic postconditioning enhances brain-derived neurotrophic factor production by upregulating the ERK-CREB pathway in rats with focal ischemia[J]. Mol Med Rep,2015,12(5):6427-6434.
[20] Gao L,Jiang T,Guo J,et al. Inhibition of autophagy contributes to ischemic postconditioning-induced neuroprotection against focal cerebral ischemia in rats[J]. PLoS One,2012,7(9):e46092.
[21] Gao X,Ren C,Zhao H. Protective effects of ischemic postconditioning compared with gradual reperfusion or preconditioning[J]. J Neurosci Res,2008,86(11):2505-2511.
[22] Rezazadeh H,Kahnuee MH,Roohbakhsh A,et al. Neuroprotective consequences of postconditioning on embolic model of cerebral ischemia in rat[J]. Iran J Basic Med Sci,2013,16(2):144-149.