Studies of isolated global brain ischaemia: I. A new large animal model of global brain ischaemia and its baseline perfusion studies
Studies of isolated global brain ischaemia: I. A new large animal model of global brain ischaemia and its baseline perfusion studies
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DOI：
10.1093/ejcts/ezr316
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发表时间：
2012-05-01
影响因子：
3.4
通讯作者：
Tan, Zhong
中科院分区：
文献类型：
--
作者：
Allen, Bradley S.;Ko, Yoshihiro;Tan, Zhong
全脑缺血（即猝死）后的神经损伤仍然是个问题，尽管可以改善心脏存活率。不幸的是，由于多器官损伤，猝死模型为研究大脑引入了不必要的变量。为了避免这一点，一个新的微创大动物模型孤立的全球脑缺血，连同基线灌注studies描述，该模型采用颈部和小（3-4英寸）胸骨上切口，以阻止流入从颈动脉和椎动脉30分钟的常温缺血。24 h后，将6只猪的神经学变化与6只Sham猪进行比较，通过2，3，5-三苯基氯化四氮唑（TTC）染色评估神经功能缺损评分（NDS，0 =正常，500 =脑死亡）、脑水肿和脑梗死。在颈动脉流量为750、550和450 cc/min的新模型中，其他6只猪具有基线灌注特征，脑灌注压、脑血氧饱和度[体内光学光谱（INVOS）]和经颅O-2摄取测量结果表明，该模型从未改变心脏或肺功能，6只Sham猪的神经功能恢复正常（NDS = 0），无脑损伤。相反，24小时分析表明，30分钟的全球常温脑缺血引起多次再灌注后癫痫发作（P < 0.001 vs Sham），NDS升高（231 +/- 16; P < 0.001，与假手术组相比），并引起明显的脑水肿（P < 0.001相对于Sham）和广泛脑梗死（TTC染色; P < 0.001相对于Sham）。基线灌注显示750 cc/min流速在平均90-100 mmHg颈动脉压下产生正常INVOS水平和O-2消耗。颈动脉压和INVOS在中、低流速时下降。虽然INVOS没有改变，但450 cc/min的流量降低了整体O-2消耗，在短暂缺血（30 s）和再灌注5 min后进一步降低。750 cc/min的流量维持正常的平均全身动脉压（90-100 mmHg）、INVOS水平和O-2消耗。在中低流量研究中，脑压和INVOS下降。在短暂性缺血后，在450 cc/min的较低流速下，INVOS氧饱和度和总体O-2消耗量之间存在差异，表明表面氧饱和度测量值不能反映总体脑O-2消耗量。
Neurological injury after global brain ischaemia (i.e. sudden death) remains problematic, despite improving cardiac survival. Unfortunately, sudden death models introduce unwanted variables for studying the brain because of multiple organ injury. To circumvent this, a new minimally invasive large animal model of isolated global brain ischaemia, together with baseline perfusion studies is described.The model employs neck and small (3-4 inches) supra-sternal incisions to block inflow from carotid and vertebral arteries for 30 min of normothermic ischaemia. Neurological changes after 24 h in six pigs was compared with six Sham pigs assessing neurological deficit score (NDS, 0 = normal, 500 = brain death), brain oedema and cerebral infarction by 2,3,5-triphenyltetrazolium chloride (TTC) stain. Six other pigs had baseline perfusion characteristics in this new model evaluated at carotid flows of 750, 550 and 450 cc/min, with cerebral perfusion pressure, cerebral oximeter saturation [IN Vivo Optical Spectroscopy (INVOS)] and transcranial O-2 uptake measurements.The model never altered cardiac or pulmonary function, and six Sham pigs had normal (NDS = 0) neurological recovery without brain injury. Conversely, 24 h analysis showed that 30 min of global normothermic brain ischaemia caused multiple post-reperfusion seizures (P < 0.001 versus Sham), raised NDS (231 +/- 16; P < 0.001 versus Sham) in four of six survivors and caused marked post-brain oedema (P < 0.001 versus Sham) and extensive cerebral infarctions (TTC stain; P < 0.001 versus Sham). Baseline perfusion showed 750 cc/min flow rate produced normal INVOS levels and O-2 consumption at mean 90-100 mmHg carotid pressure. Carotid pressure and INVOS fell at mid- and low-flow rates. Although INVOS did not change, 450 cc/min flow lowered global O-2 consumption, which further decreased after transient ischaemia (30 s) and 5 min of reperfusion.This new isolated global brain model consistently caused anatomic, biochemical and functional neurological damage in pigs after 30 min of ischaemia. Flows of 750 cc/min maintained normal mean systemic arterial (90-100 mmHg) pressure, INVOS levels and O-2 consumption. Cerebral pressure and INVOS fell in mid- and low-flow studies. A disparity existed between INVOS oxygen saturation and global O-2 consumption at lower flow rates of 450 cc/min following transient ischaemia, indicating that surface oxygen saturation measurement does not reflect global brain O-2 consumption.