犬心脏骤停后脑缺血的病理变化

目的：本文旨在观察心肺脑复苏过程中脑缺血的病理变化。方法：16条成年健康杂种犬，随机分为两组，以同法诱颤后复苏，A组诱颤后5分钟而B组诱颤后10分钟开始复苏，复苏成功后，立即取血、脑脊液标本进行脑型肌酸激酶同功酶（CK－BB）检查，72小时后取脑组织标本进行光、电镜检查。结果：A组脑型肌酸激酶同功酶明显低于B组，且其病理改变也明显轻微。结论：心脏骤停后脑复苏成功与否与时间密切相关，时间短则脑病理改变较轻。     

携氧液对心脏骤停后脑复苏的作用

目的：将携氧液应用于心跳骤停１０分钟实验犬，旨在探讨对心跳骤停后脑复苏的作用。方法；１６条成年健康杂种犬以同法诱颤１０分钟后随机分为两组，实验组；对照组；除实验因素外其余处理措施相同。评估神经损害指数和整体表现评分，记录生命体征恢复情况，观察了中枢神经系统的形态学变化。     

脑型肌酸激酶同功酶在脑血管病中的意义 Ⅰ.人脑中脑型肌酸激酶同功酶的纯化

本文报道改良的脑型肌酸激酶同功酶(CKBB)的纯化方法,其步骤为人脑匀浆经过两次酒精和硫酸铵沉淀和两次 Sephadex-A50梯度柱层析,最后得到十分纯和有一定活性的 CKBB。     

顺行和逆行脑保护与急性主动脉夹层术后并发症的关系

目的回顾性分析顺行和逆行脑保护方法及其与术后并发症的关系。方法对48例A型主动脉夹层病人在深低温体外循环(DHCA)下施行主动脉置换手术。15例行全动脉弓置换,33例行部分主动脉弓部置换。依据脑保护方法不同分为:顺行脑灌注(ACP)组23例(A组);逆行脑灌注(RCP)组25例(B组)。结果 A、B 2组在心肺转流时间、脑缺血时间、脑灌注时间、神经系统永久损伤和病死率方面比较,差异无统计学意义(P>0.05)。暂时性神经损伤的发生率、平均拔管时间、入住ICU的平均时间、平均住院时间比较差异有统计学意义(P<0.05)。结论顺行灌注可以显著性减少暂时性神经系统并发症,更早的拔管,ICU和住院时间更短,费用更低。     

严重头部损伤时的肌酸激酶同功酶

人体内多种组织发现有肌酸激酶(CK),骨骼肌(CK-MM)、心肌(CK-MB)和脑组织(CK-BB)以及其他器官组织还存在着肌酸激酶同功酶,而后者其含量比脑低。但正常人的血清和CSF中不含脑型肌酸激酶同功酶(CK-BB),只有在脑血管病和     

维生素C加尿激酶脑池灌注防治脑血管痉挛(附60例报告)

目的探索颅防迟发性脑血管痉挛的有效手段。方法对60例破裂脑动脉瘤进行了超早期或早期外科手术，术后随机分别行尿激酶脑池灌注(A组)和维生素C(VitC) 尿激酶脑池灌注(B组)。结果脑血管痉挛的临床症状发生率A组为43．3％，B组为13％；脑血管痉挛发生后永久性神经障碍发生率A组为16．6％，B组为10％。结论VitC 尿激酶脑池灌注能有效预防迟发性脑血管痉挛。     

急性脑损伤的肌酸激酶同功酶

作者测定了26例脑损伤患者血中的脑型肌酸激酶同功酶(CK-BB)和心型肌酸激酶同功酶(CK-MB),试图确定此二种酶与脑损伤的严重度和预后之间的关系.26名急性脑损伤患者,男性21名,女性5名.年龄为5-69岁,平均29岁.脑损伤的程度是根据昏迷时间的长短而定,昏迷在30分钟以内为轻度脑损伤10例,昏迷在30分钟至6小时为中度脑损伤4例,昏迷超过6小时为重度脑损伤12例.24例为闭合性脑损伤(其中2例合并硬膜外血肿,2例合并急性硬膜下血肿),2例为枪伤.26例中有6例合并有严重的颅外损伤:其中2例为胸部伤合并肋骨骨     

脑池内灌注与静脉滴注尼莫地平预防蛛网膜下腔出血后脑血管痉挛的效果对比

目的探讨脑池内灌注与静脉滴注尼莫地平预防蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的效果。方法将80例SAH患者随机分为两组,两组患者均行开颅动脉瘤夹闭术,A组(n=40)在术中及术后予以脑池内灌注尼莫地平,B组(n=40)术后静脉滴注尼莫地平,对比两组患者术后的CVS发生率及预后效果。结果 A组术后的症状性CVS发生率为40.0%,明显低于B组(65.0%)(P0.05)。A组术后3d、5d、7d、14d的CVS发生率均显著低于B组;A组术后第2天的脑脊液(CSF)引流量以及引流液中的红细胞含量均明显少于B组(P0.05)。A组患者的预后良好率为75.0%,显著高于B组的50.0%(P0.05)。结论比较静脉滴注尼莫地平,脑池内灌注尼莫地平预防动脉瘤性SAH后CVS的效果更为显著,并发症更少。     

分次栓塞脑血管致犬脑循环自体重建的实验研究

目的建立犬脑循环储备下降动物模型,探讨分次栓塞脑血管分支对犬脑循环的影响以及脑血运自体重建的时间跨度。方法 18只成年杂种犬随机分为A、B、C、D 4组,同时或依次栓塞左、右侧椎动脉、左、右侧颈内动脉,A组为正常对照组(n=3),B组为每隔1 w依次栓塞组(n=5),C组为每隔2 w依次栓塞组(n=5),D组为同时栓组(n=5)。采用MRI灌注成像检测脑血流量(CBF),MRI或CT检测犬脑影像学改变,DSA观察脑血管再生及侧枝循环建立情况,整体行为分类法评定神经功能。结果分次栓塞与一次性栓塞比较,犬脑CBF下降程度明显降低;且C组CBF下降程度较B组轻。依次栓塞左、右侧椎动脉,B、C组颈总动脉与脑底动脉侧枝循环开放,颈内动脉扩张,未见新生血管形成;再依次栓塞左、右侧颈内动脉,B、C组均有新生血管形成,C组更为明显;8 w复查两组颅内血管均明显增粗、增多。影像学检查:D组见多发性梗死灶或(和)大面积脑梗死;B组见个别动物呈现基底节区梗死,C组未见明显梗死灶。神经功能评分:D组5分,所有动物均在术后8 h内死亡;B组1只犬残留2级神经功能缺损;C组均未发生神经功能障碍(1级)。结论分次栓塞犬脑血管可以促使犬脑血管侧枝循环形成、脑循环重建;分次栓塞间隔时间越长,犬脑脑血流量下降越缓慢;犬脑循环储备下降至失代偿期,至少需要2 w时间才能重建充分有效的侧枝循环,分次栓塞4根犬脑主要供血动脉,至少需要8 w才能完成脑循环重建及脑血流储备。     

内皮素与迟发性脑血管痉挛的关系

目的　探讨内皮素与蛛网膜下腔出血 (SAH)后迟发性脑血管痉挛 (DCVS)的关系。　　方法　采用免疫组化与放射免疫方法 ,观察了内皮素 1在SAH后DCVS时痉挛动脉分布的改变 ,测定了DCVS实验动物痉挛动脉内皮素 1的含量。　　结果　 (1 )DCVS组痉挛动脉除内皮细胞外 ,中层平滑肌细胞胞浆中含多量的内皮素 1免疫反应阳性颗粒。 (2 )DCVS组痉挛动脉内皮素 1的浓度为 (1 3 0 40± 1 0 6 0 )pg mg,显著高于对照组的 ( 8 1 40± 0 955)pg mg (P <0 0 1 )。　　结论　内皮素可能是迟发性脑血管痉挛一种重要致病物质。     

Brain enzyme levels in CSF after cardiac arrest and resuscitation in dogs: markers of damage and predictors of outcome

Levels of brain creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD) in CSF after cardiac arrest were studied in dog models. Ventricular fibrillation cardiac arrest lasting 10 min or asphyxiation cardiac arrest lasting 0-10 min was followed by cardiopulmonary resuscitation and 96-h intensive care. Outcome was scored as neurologic deficit (0% = normal, 100% = brain death) and overall performance category (1 = normal, 5 = death). Both measures correlated with EEG return time after asphyxiation cardiac arrest, but not after ventricular fibrillation cardiac arrest. Peak activity of enzymes in CSF at 48-72 h post arrest correlated with outcome, and CK was the best predictor. Brain histopathologic damage score at autopsy 96 h post arrest correlated with CK level in CSF (r = 0.79, n = 39) and neurologic deficit (r = 0.70, n = 50). Ischemic neuronal changes occurred after ventricular fibrillation cardiac arrest of 10 min, and neuronal changes plus microinfarcts occurred after asphyxiation cardiac arrest of 1.5-10 min. Brain enzymes were decreased at 6 h post arrest in regions with worst histologic damage (gray matter of neocortex, hippocampus, caudate nucleus, cerebellum). Brain CK decreased further, ASAT remained low, and LD increased at 72 h after arrest. The temporal changes in CK level paralleled the temporal ischemic neuronal changes in the brain, and time to peak activity was unaffected by the severity of the ischemic insult. Peak activity of individual enzymes in CSF was determined predominantly by the brain concentration, but was also influenced by rate of decomposition. This "chemical brain biopsy method" represents a useful adjunctive tool to predict permanent, severe brain damage during comatose states after cardiac arrest and resuscitation.     

Brief induced hypothermia improves outcome after asphyxial cardiopulmonary arrest in juvenile rats

The American Heart Association has endorsed the use of mild hypothermia for adults after cardiopulmonary arrest. However, there are no contemporary trials testing hypothermia in children after cardiopulmonary arrest and extrapolation from adult studies is problematic given differences in brain development and primary etiology (asphyxia in children vs. ventricular arrhythmia in adults). Accordingly, we tested the effects of mild postresuscitative hypothermia on functional and histopathological outcome after asphyxial cardiac arrest in juvenile rats. Postnatal day 17 rats were subjected to 8 min of asphyxia-induced cardiac arrest followed by resuscitation. Rats were randomized to normothermic (37 degrees C), hypothermic (32 degrees C), or unregulated temperature groups (n = 7-8/group) to begin after return of spontaneous circulation for a duration of 1 h. Brain temperature in the unregulated group dropped to 34.0 +/- 0.4 degrees C at 1 h. The hypothermic group had improved motor function assessed using beam balance and inclined plane tests vs. the normothermic group. The depth of hypothermia was associated with increased CA1 hippocampal neuron survival at 5 weeks. Neurodegeneration in the CA1 hippocampus assessed using Fluoro-Jade B labeling at 5 weeks was not detected in the 32 degrees C group, whereas 2/7 and 4/7 rats in the 34 and 37 degrees C groups, respectively, showed neurodegeneration. Brief treatment with moderate induced hypothermia improved functional outcome and prevented long-term neurodegeneration in a model that mimics the clinical and histopathological scenario of pediatric cardiac arrest. Similar to adults, infants and children may benefit from induced hypothermia after cardiopulmonary arrest, warranting further study.     

Antioxidant Tempol enhances hypothermic cerebral preservation during prolonged cardiac arrest in dogs.

The authors are systematically exploring pharmacologic preservation for temporarily unresuscitable exsanguination cardiac arrest in dogs. They hypothesized that the antioxidant Tempol improves cerebral outcome when added to aortic saline flush at the start of cardiac arrest. In study A, no drug (n = 8), Tempol 150 mg/kg (n = 4), or Tempol 300 mg/kg (n = 4) was added to 25 mL/kg saline flush at 24 degrees C (achieving mild cerebral hypothermia) at the start of 20-minute cardiac arrest. In study B, no drug (n = 8) or Tempol 300 mg/kg (n = 7) was added to 50 mL/kg saline flush at 2 degrees C (achieving moderate cerebral hypothermia) at the start of 40-minute cardiac arrest. Cardiac arrest was reversed with cardiopulmonary bypass. Mild hypothermia lasted for 12 hours, controlled ventilation was sustained to 24 hours, and intensive care was provided for up to 72 hours. In study A, overall performance category 1 or 2 (good outcome) was achieved in all eight dogs treated with Tempol compared with three of eight dogs in the control group ( P = 0.03). In study B, good outcome was achieved in all seven dogs treated with Tempol versus only two of 8 dogs in the control group ( P = 0.007). In both studies, neurologic deficit scores were significantly better in the Tempol group, but not total histologic damage scores. At 72 hours, electron paramagnetic resonance spectroscopy of Tempol revealed direct evidence for its presence in the brain. Single- and double-strand DNA damage, nitrotyrosine immunostaining, total antioxidant reserve, and ascorbate acid levels were similar between groups, and thiol levels were decreased after Tempol in study B. The authors conclude that when added to aortic saline flush at the start of prolonged cardiac arrest, the antioxidant Tempol can enhance mild or moderate hypothermic cerebral preservation in terms of improved functional outcome. The mechanisms involved in this beneficial effect need further clarification.     

Blood-brain barrier integrity during cardiopulmonary resuscitation in dogs

Blood-brain barrier integrity during cardiopulmonary resuscitation may be important because of the potential effects of adrenergic agonists administered during arrest on cerebral metabolism and the cerebral vasculature. As an index of blood-brain barrier permeability to small molecules, we measured the brain uptake of [14C]alpha-aminoisobutyric acid during a 10-minute period in 25 anesthetized dogs. To correct for the amount of carbon-14 label in the plasma space, we administered [3H] inulin 2 minutes before death. The mean transfer coefficient in 14 brain regions of five control dogs ranged from 0.002 to 0.007 ml/g/min. After 8 (n = 15) or 15 (n = 5) minutes of cardiac arrest, external chest compression was instituted to maintain aortic blood pressure above 60 mm Hg. The transfer coefficient was not elevated during chest compression (n = 10), immediately following defibrillation (n = 5), or 4 hours after resuscitation (n = 5); in some brain regions the transfer coefficient decreased. However, the decrease in the transfer coefficient was proportional to the decrease in the cerebral plasma volume as measured by the ratio of the [3H]inulin concentration in the tissue to that in the plasma. Thus, it is unlikely that a decrease in capillary surface area masked an increase in blood-brain barrier permeability. Therefore, we found no evidence of blood-brain barrier disruption during or after cardiopulmonary resuscitation in dogs. Despite the large phasic increases in sagittal sinus pressure associated with external chest compression, concurrent increases in cerebrospinal fluid pressure apparently protect the microcirculation from increased transmural pressure.     

Protective effects of combined superoxide dismutase and deferoxamine on recovery of cerebral blood flow and function after cardiac arrest in dogs

Oxygen free radicals generated during reoxygenation after cardiac arrest may impair recovery of cerebral blood flow and function. In a randomized study in vivo, we tested the following anti-free radical combination therapy administered at the beginning of cardiopulmonary resuscitation after apnea-induced cardiac arrest of 7 minutes: 1) ventilation with 100% nitrogen for 30 seconds to allow the delivery of therapy before oxygen, 2) 10 mg/kg i.a. superoxide dismutase followed by 10 mg/kg i.v. over 1 hour to scavenge the superoxide anion radical, and 3) 20 mg/kg i.v. deferoxamine over 1 hour to prevent membrane lipid peroxidation. We evaluated the effects of this combined treatment on the recovery of cardiovascular variables, cerebral blood flow and oxygen consumption, and somatosensory evoked potentials in 20 dogs 6 hours after resuscitation. Compared with standard treatment (n = 10), the combined treatment (n = 10) did not affect cardiovascular variables, significantly mitigated cerebral blood flow changes after cardiac arrest, and enhanced recovery of somatosensory evoked potentials. We conclude that oxygen free radicals play a role in the pathogenesis of the arrest-related derangements of cerebral blood flow and function that are effectively reduced by this combined treatment; we recommend evaluation of its components in outcome studies.     

Cerebral Edema After Cardiopulmonary Resuscitation: A Therapeutic Target Following Cardiac Arrest?

We sought to review the role that cerebral edema plays in neurologic outcome following cardiac arrest, to understand whether cerebral edema might be an appropriate therapeutic target for neuroprotection in patients who survive cardiopulmonary resuscitation. Articles indexed in PubMed and written in English. Following cardiac arrest, cerebral edema is a cardinal feature of brain injury and is a powerful prognosticator of neurologic outcome. Like other conditions characterized by cerebral ischemia/reperfusion, neuroprotection after cardiac arrest has proven to be difficult to achieve. Neuroprotection after cardiac arrest generally has focused on protecting neurons, not the microvascular endothelium or blood–brain barrier. Limited preclinical data suggest that strategies to reduce cerebral edema may improve neurologic outcome. Ongoing research will be necessary to determine whether targeting cerebral edema will improve patient outcomes after cardiac arrest.     

Global cerebral ischemia and subsequent selective hypothermia

Summary A new method of external selective brain cooling is described, showing its effectiveness in reducing neuronal damage following global cerebral ischemia in cat. The cooling apparatus consists of a specially fitted kind of water jacket in which the animal's head was laid. In a preliminary study it was verified that the device effectively reduces brain temperature without the risk of cardiac arrhythmias due to lowering of core temperature. In the main study cardiac arrest was induced in 23 adult cats, followed after 15 min by cardiopulmonary resuscitation (CPR). Eight cats could not be revived; of the 15 remaining animals, 7 were assigned to the control group (normothermia) and 8 to the treatment group (cerebral hypothermia). The latter received external brain cooling for 30 min, starting as soon as CPR was begun. Four hours after cardiac arrest all animals were transcardiacally perfused with glutardialdehyde. The brains were stored in fixative and subsequently processed for histopathological and morphometrical evaluation by light microscopy. Analysis of the resulting data showed that animals in the treatment group had a significantly higher percentage of undamaged neurons than animals in the control group, both in the cingulate gyrus (38% vs 10%) and in the parietal cortex (39% vs 14%). The treatment group also had more undamaged neurons in the hippocampus and fewer severely damaged neurons in all three regions, but these differences, though suggestive, were not statistically significant.     

心脏骤停大鼠复苏后心脑ICAM-1和MMP-9的变化及药物治疗研究

目的 探讨窒息至心脏骤停大鼠复苏后心脑ICAM-1和MMP-9的变化及血必净对其影响.方法 采用呼气末夹闭气管窒息法建立大鼠心脏骤停模型,并心肺复苏成功后生存24h,将50只健康Wistar大鼠随机分为5组,分别为模型组、正常对照组、小剂量血必净组、中剂量血必净组、大剂量血必净组.复苏24h后处死大鼠,取心、脑组织标本,电镜下观察心、脑组织的病理改变.采用酶联免疫吸附法(ELISA)检测心、脑组织中的ICAM-1和MMP-9含量变化.结果 心、脑组织病理观察显示,与对照组相比其他组心脑细胞超微结构出现损伤性改变,其中模型组损伤最重,大剂量血必净组损伤性改变轻微;心、脑中ICAM-1和MMP-9含量变化,与对照组相比模型组心、脑ICAM-1和MMP-9含量明显升高,与模型组相比血必净治疗组心、脑ICAM-1和MMP-9含量明显下降;治疗组中,大、中剂量较小剂量下降更为明显.结论 心跳骤停复苏后大鼠心、脑组织内ICAM-1和MMP-9等细胞因子含量增多,血必净可明显抑制心、脑组织中的细胞因子,而且存在明显量-效关系,从而缓解心跳骤停大鼠复苏中缺氧及再灌注后炎性因子所带来的损伤.

Abstract：

Objective To observe changes of intercellular adhesion molecule-1 (ICAM-1 ) , matrix metalloproteinase-9 (MMP-9) and the effects of Xuebijing during cardiopulmonary cerebral resuscitation in rats. Methods The animal model of cardiac arrest (CA) was made by clamping endotracheal tube at expiration, and kept alive twent-four hours after cardiopulmonary resuscitation( CPR). Fifty healthy Wistar rats were randomly divided into control group,model group,little dose of Xuebijing group, middle dose of Xuebijing group, high dose of Xuebijing group. The rats were killed after twenty-four hours. The cortex of the brain and the heart was taken out immediately to observe the ultrastructure changes. The levels of ICAM-1 and MMP-9 were determined by ELISA. Results Compared with control group, the ultrstructure of brains and hearts was damadged in the other groups;compared with control group the level of ICAM-1 and MMP-9 was increased significantly in the brains and hearts of model group, compare with model group, the level of ICAM-1 and MMP-9 reduced significantly in the brains and hearts of drug group. In the drug groups,compared with little dose group, the level of ICAM-1 and MMP-9 reduced significantly in the high and middle dose group. Conclusion Quantitation of ICAM-1 and MMP-9 expression after cardiopulmonary cerebral resuscitation rats increases;Xuebijing significantly inhibits the increase of ICAM-1 and MMP-9 expression of cardiopulmonary cerebral resuscitation rats,with dose-dependent characteristics,and reduces the damage led by ischemia/reperfusion from cardiopulmonary cerebral resuscitation rats.     

Emergency preservation and resuscitation with profound hypothermia, oxygen, and glucose allows reliable neurological recovery after 3 h of cardiac arrest from rapid exsanguination in dogs.

We have used a rapid induction of profound hypothermia (<10 degrees C) with delayed resuscitation using cardiopulmonary bypass (CPB) as a novel approach for resuscitation from exsanguination cardiac arrest (ExCA). We have defined this approach as emergency preservation and resuscitation (EPR). We observed that 2 h but not 3 h of preservation could be achieved with favorable outcome using ice-cold normal saline flush to induce profound hypothermia. We tested the hypothesis that adding energy substrates to saline during induction of EPR would allow intact recovery after 3 h CA. Dogs underwent rapid ExCA. Two minutes after CA, EPR was induced with arterial ice-cold flush. Four treatments (n=6/group) were defined by a flush solution with or without 2.5% glucose (G+ or G-) and with either oxygen or nitrogen (O+ or O-) rapidly targeting tympanic temperature of 8 degrees C. At 3 h after CA onset, delayed resuscitation was initiated with CPB, followed by intensive care to 72 h. At 72 h, all dogs in the O+G+ group regained consciousness, and the group had better neurological deficit scores and overall performance categories than the O-groups (both P<0.05). In the O+G- group, four of the six dogs regained consciousness. All but one dog in the O-groups remained comatose. Brain histopathology in the O-G+ was worse than the other three groups (P<0.05). We conclude that EPR induced with a flush solution containing oxygen and glucose allowed satisfactory recovery of neurological function after a 3 h of CA, suggesting benefit from substrate delivery during induction or maintenance of a profound hypothermic CA.