Brain resuscitation by extracorporeal circulation after prolonged cardiac arrest in cats

Objective Brain reanimation after prolonged ischemia is limited by post-ischemic reperfusion deficits (no-reflow phenomenon). The present study was undertaken to establish whether after 30 min cardiac arrest extracorporeal circulation is able to restore brain reperfusion and to promote functional and metabolic recovery.Design Adult normothermic cats were submitted to 30 min cardiac arrest by KCl-induced cardioplegia. Resuscitation was carried out by extracorporeal circulation (ECC) until spontaneous heart function returned. The quality of brain recovery was assessed 3 h later by electrophysiological recording and by imaging of the regional distribution of brain energy metabolites.Results In 6 of 10 cats cardiac sinus rhythm returned after 32±15 min. In the other 4 cats cardiac function did not return or only intermittently returned during the 3 h observation period. Cerebral blood flow measured by laser Doppler flowmetry returned to 102%±40% of control immediately after the beginning of resuscitation but then gradually declined to 43%±32% after 3 h despite normotensive perfusion. In all cats pupils started to constrict within less than 5 min of recirculation but in 2 animals they secondarily dilated 1.5 and 2 h later, respectively. Spontaneous EEG activity reappeared in 4 of the 6 successfully resuscitated cats after 111±40 min but failed to recover in the others. Bioluminescent imaging of ATP after 3 h recirculation revealed near-complete depletion throughout the brain in all 4 cats without cardiac recovery. Of the 6 successfully resuscitated cats 5 exhibited patchy areas of low ATP, glucose and pH in 22%–92% of the cross sectional area of brain; in one cat recovery of energy metabolism and acid-base homoiostasis was homogenous without any focal deficits. The cross sectional area of ATP recovery correlated directly with CBF and hematocrit and inversely with the plasma lactate level.Conclusions This study demonstrates for the first time that ECC is able to restore electrophysiological and metabolic brain function after cardiac arrest of as long as 30 min, but recovery is heavily restricted by delayed postischemic disturbances of recirculation. Progress in cardiac resuscitation by ECC requires substantial improvement in the efficiency of cerebrovascular reperfusion.     

Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease

Cerebral small vessel disease (SVD) is a major cause of age-related cognitive impairment and dementia. The pathophysiology of SVD is not well understood and is hampered by a limited range of relevant animal models. Here, we describe gliovascular alterations and cognitive deficits in a mouse model of sustained cerebral hypoperfusion with features of SVD (microinfarcts, hemorrhage, white matter disruption) induced by bilateral common carotid stenosis. Multiple features of SVD were determined on T2-weighted and diffusion-tensor magnetic resonance imaging scans and confirmed by pathologic assessment. These features, which were absent in sham controls, included multiple T2-hyperintense infarcts and T2-hypointense hemosiderin-like regions in subcortical nuclei plus increased cerebral atrophy compared with controls. Fractional anisotropy was also significantly reduced in several white matter structures including the corpus callosum. Investigation of gliovascular changes revealed a marked increase in microvessel diameter, vascular wall disruption, fibrinoid necrosis, hemorrhage, and blood–brain barrier alterations. Widespread reactive gliosis, including displacement of the astrocytic water channel, aquaporin 4, was observed. Hypoperfused mice also demonstrated deficits in spatial working and reference memory tasks. Overall, gliovascular disruption is a prominent feature of this mouse, which could provide a useful model for early-phase testing of potential SVD treatment strategies.     

丰富环境可改善慢性脑低灌注的认知功能

目的慢性脑低灌注(chronic cerebral hypoperfusion,CCH)可导致认知功能的损害。丰富环境(enrich edenvironment,EE)可通过改善突触可塑性而提高学习和记忆能力。到目前为止EE对CCH所导致的认知功能损害的影响还不明确。为了进一步研究EE对CCH认知功能损害的影响,本科进行了EE对CCH所导致的认知功能损害和突触可塑性影响的研究。方法健康成年雄性Wistar大鼠被随机分为3组:假手术组(sham组),CCH组和CCH+EE干预组。检测各组大鼠的空间学习记忆能力,海马CA1区的长时程增强(long-term potentiation,LTP)、输入-输出关系曲线和双脉冲异化(paired-pulse facilitation,PPF)以及突触相关蛋白的表达水平变化。结果①EE干预可改善CCH所导致的大鼠空间学习记忆功能的损害。②与假手术组比较(195.5%±11.2%),CCH组大鼠的LTP发生显著的下降(128.6%±6.8%,P<0.01)。给予EE干预的CCH大鼠(176.4%±9.4%)LTP出现明显的增加(P<0.01)。③假手术组与CCH组的输入-输出关系曲线和PPF无明显差别(P>0.05)。当给予EE干预后也无显著性差异(P>0.05)。④CCH组大鼠的磷酸化环磷酸腺苷反应元件结合蛋白(phosphorylated cAMP responsive element binding protein,pCREB)的表达与假手术组比较下降了47%(P<0.01),而CCH+EE组的pCREB的表达是CCH组的177%(P<0.01)。对于CCH大鼠的突触素和微管相关蛋白-2(microtubule-associated protein2,MAP-2)的表达与假手术组比较分别减少了23%和29%(分别为P<0.05和P<0.01)。经过EE干预后CCH+EE组的突触素和MAP-2的表达与CCH组比较分别增加了31%和60%(分别为P<0.05和P<0.01)。结论 EE可改善CCH所导致的空间学习记忆功能和突触可塑性的损害,但不影响其基础传递效率和突触前的递质释放的概率。EE对CCH认知功能的改善可能源于其对突触后蛋白的调节起作用。     

Parkinsonism as an initial manifestation of dural arteriovenous fistula

Parkinsonism associated with dural arteriovenous fistula (DAVF) has been described rarely; however, isolated parkinsonism as the presenting symptom of DAVF has not been reported. Here, we describe a patient with DAVF showing reversible isolated parkinsonism after embolization, which was well correlated with perfusion status of basal ganglia, suggesting that a perfusion defect was responsible for the pathogenesis of the parkinsonism in our DAVF patient.     

Curare in the treatment of pulmonary hypertension as it occurs in the idiopathic respiratory distress syndrome

Thirteen infants with pulmonary hypertension occurring in the course of the idiopathic respiratory distress syndrome received curare on 26 occasions. The histaminic effect of curare in relieving the shunting was minimal, whilst its muscle relaxant properties might be important in determining the outcome. The survival rate was 54%— ad those dying having intraventricular haemorrhage. The alveolar-arterial oxygen tension gradient proved the most sensitive index of shunting whilst the arterial/alveolar oxygen tension ratio and the arterial oxygen tension/fraction of inspired oxygen ratio might prove more useful clinically.     

PIGMENTARY GLAUCOMA: A CLINICAL REVIEW OF ANTERIOR SEGMENT PIGMENT DISPERSAL SYNDROME

Sixty-eight cases (44 males, 24 females) of anterior segment pigment dispersal syndrome are reviewed. Five patients had no rise in intraocular pressure, 38 had ocular hypertension and 25 had glaucoma as shown by optic disc cupping and field loss. All cases had heavy deposition of pigment in the drainage angle together with Krukenberg spindles and/or light reflux through the iris. Other evidence of anterior segment pigment dispersal was common. The condition was commonest in young adult males, but could present at any age and in women. Medical treatment was often successful initially, but continued to control pressure in only 17 of 42 patients.
Laser trabeculoplasty helped some patients. Drainage operations of various types were successful in 19 of 23 cases. Iris angiography showed evidence of vascular hypoperfusion of the iris which probably precedes pigment dispersal and suggests that the ultimate aetiology may be a congenital deficiency of the mesodermal support tissues of the iris. Some degree of iris stromal atrophy is also common and may become marked. Pigment dispersal from the pigment epithelium of the iris occurs in susceptible individuals and may be associated with the insertion of the dilator muscle. The term anterior segment pigment dispersal seems appropriate as the condition is limited to the anterior segment.     

Effect of propentofylline on hippocampal brain energy state and amyloid precursor protein concentration in a rat model of cerebral hypoperfusion

Summary. An animal model of graded cerebral hypoperfusion achieved by way of 2- and 4-brain vessel occlusion (vo) was used to test the effect of chronic propentofylline (PPF) administration on hippocampal energy state and amyloid precursor protein (APP) concentration. For this purpose, forty adult rats were subjected to stepwise and permanent 2 vo and 4 vo and PPF in a dose of 25 mg/day per kilogram body weight was continuously administered intraperitoneally for 1 week or 3 weeks, respectively. During the final steady-state experiment arterial blood parameters and blood gases (mean arterial blood pressure, pO₂, pCO₂, pH, hematocrit, hemoglobin, body temperature) were measured. Brain tissue concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine were measured in rat hippocampus by high-pressure liquid chromatography (HPLC) analysis; APP concentration was determined using Western blot techniques. In adult rat brain, long-term PPF treatment induced a striking increase in hippocampal ATP concentration which was paralleled by an enhancement of the ATP/ADP-ratio. Specifically, after 2 vo with 1 week of PPF treatment the ATP concentration in hippocampus was enhanced by 18% when compared with 2 vo without PPF treatment, whereas after 3 weeks PPF administration with 4 vo the concentration of ATP was enhanced by 31%. Furthermore, PPF reduced the tissue concentration of adenosine from 17.75 ± 2.79 to 8.83 ± 3.68 pmol/mg wet weight during 4 vo if compared with animals without PPF. In addition, the APP concentration was enhanced by 35% after 1 week PPF administration when compared with non PPF treated animals. In summary, the results demonstrated that chronic administration of PPF induced an enhancement in ATP concentration in adult rat hippocampus under conditions of long-term brain vessel occlusion. Interestingly, 1 week PPF seems to have a stimulating effect on APP which may act neuroprotectively. Thus, PPF may protect hippocampal neurons from chronic ischemic damage. In conclusion, PPF may have some beneficial effects and could be used in the treatment of patients with chronic cerebrovascular disorders or neurodegenerative diseases such as vascular dementia. Received December 12, 1997; accepted February 19, 1998     

Nobiletin对慢性低灌注损伤后小鼠脑海马神经血管单元的影响

目的观察川陈皮素(NOB)对小鼠慢性脑低灌注(CCH)模型海马区神经血管单元各主要组分的保护作用。方法昆明小鼠随机分为对照组、模型组和NOB高、低剂量处理组各10只,模型组和NOB处理组进行双侧颈总动脉结扎,对照组不结扎。术后2 w进行旷场实验及Y迷宫检测学习记忆功能,Western印迹法测定小鼠海马区神经元生长相关蛋白(GAP)-43、突触素(SYN)、水通道蛋白(AQP)4表达,检测海马神经细胞可塑性及血脑屏障功能。结果与模型组相比,NOB处理组自由活动无显著差异,其中高剂量组探索能力显著增强,逃避潜伏期显著减短(P<0.05);NOB处理组均显著增加海马区GAP-43、SYN、AQP4及Claudin-5表达(P<0.05)。结论NOB可通过对海马的神经血管单元各组分的保护作用,改善CCH所致小鼠学习记忆功能受损。