硝普钠控制性低血压对犬胃粘膜灌注的影响

目的　观察硝普钠控制性低血压对犬胃粘膜灌注的影响。方法　 1 6只健康杂种犬 ,随机分为对照组和控制性低血压组。基础麻醉后气管插管 ,经口置入胃张力计导管 ,股动、静脉置管 ,右颈内静脉放置Swan Ganz四腔漂浮导管。控制性低血压组静脉泵注 0 0 2 %硝普钠溶液进行控制性低血压 ,将MAP维持在 6 0mmHg 30min。监测降压期间血液动力学参数MAP、HR、CVP、肺动脉压 (MPAP)、肺毛细血管楔压 (PCWP)、心输出量 (CO)、每搏指数 (SVI)、体循环阻力指数 (SVRI)、肺循环阻力指数 (PVRI)、左室搏功指数 (LVSWI)、右室搏功指数 (RVSWI)、胃粘膜二氧化碳分压 (Pg CO2 )及胃粘膜与呼气末二氧化碳分压差 (Pg etCO2 )的变化。结果　与对照组相比 ,低血压组SVRI、PVRI显著下降 (P <0 0 5 ) ,LVSWI亦显著下降 (P <0 0 5 ) ;而CO、SVI、CVP、PCWP、RVSWI不变。在MAP 6 0mmHg的低血压水平 ,PgCO2 、Pg etCO2 分别由 4 7.4 5、9 0 7mmHg显著升高至 6 0 5 4、2 1 2 1mmHg(P <0 0 5 ) ,血压回升后上述指标均恢复正常。 结论　在保持充足血管内容量的条件下 ,硝普钠控制性低血压期间全身血管阻力显著下降 ,而心输出量不变。低血压期间胃粘膜灌注短暂受损 ,与血流重分布有关     

Vascular dementia due to cardiac arrhythmias and systemic hypotension

Among 133 consecutive patients with the clinical diagnosis of vascular dementia there were 6 patients (4.5%) in whom dementia was judged to be associated with cerebral hypoperfusion due to cardiac arrhythmias and systemic hypotension. Patients with cardio-pulmonary arrest and resuscitation were excluded from this series. Our findings suggest that cerebral hypoperfusion is not an uncommon mechanism to contribute to the evolution of vascular dementia in the elderly. Besides arrhythmias, also hypovolaemia caused by diuretics medication might have been a contributory factor to hypoperfusion. It is evident that cerebral hypoperfusion is the predominant mechanism responsible for vascular dementia in some cases. It may be a contributing factor also in many cases of multi-infarct dementia. Thus, besides dementia after cardio-pulmonary arrest, vascular dementia of the haemodynamic type as a separate clinical entity is open to discussion.     

中央型肺癌致肺低灌注的数字减影血管造影表现初步研究

目的 分析肺癌侵犯中央肺动脉后致肺低灌注的数字减影血管造影（DSA）影像特征,探讨肺动脉受累程度与肺低灌注间的关系,为临床制定治疗方案提供更多的信息。方法 收集CT显示侵犯肺动脉的中央型肺癌患者26例,行肺血管DSA检查,观察肺低灌注的DSA影像特征,描绘受累肺叶及健侧对应区域肺实质时间－密度曲线（TDC）。结果 26例中38支叶肺动脉受侵,34个肺叶（89．5％）出现肺低灌注,肺低灌注与肺动脉受累后狭窄累后狭窄程度程度密度切相关（P＜0．05）。DSA像上肺血管征表现为肺动脉中断（11．8％,4／34）或分支数量减少（88．2％,30／34）,末梢肺动脉消失（41．2％,14／34）或减少（58．8％,20／34）,肺实质征表现为肺组织毛细血管充盈消失（14．7％,5／34）或减弱（85．3％,29／34）。结论 肺癌侵犯中央肺动脉后致该动脉供血区域出现肺低灌注,肺低灌注与肺动脉狭窄程度密切相关。肺实质征及肺血管征是肺低灌注的重要征象。     

Chronic hypoperfusion due to intracranial large artery stenosis is not associated with cerebral β-amyloid deposition and brain atrophy

Background: Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans.Methods: We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced...     

Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration,cognitive impairment,and Alzheimer's disease

Aging, hypertension, diabetes, hypoxia/obstructive sleep apnea (OSA), obesity, vitamin B12/folate deficiency, depression, and traumatic brain injury synergistically promote diverse pathological mechanisms including cerebral hypoperfusion and glucose hypometabolism. These risk factors trigger neuroinflammation and oxidative‐nitrosative stress that in turn decrease nitric oxide and enhance endothelin, Amyloid‐β deposition, cerebral amyloid angiopathy, and blood–brain barrier disruption. Proinflammatory cytokines, endothelin‐1, and oxidative‐nitrosative stress trigger several pathological feedforward and feedback loops. These upstream factors persist in the brain for decades, upregulating amyloid and tau, before the cognitive decline. These cascades lead to neuronal Ca²⁺ increase, neurodegeneration, cognitive/memory decline, and Alzheimer's disease (AD). However, strategies are available to attenuate cerebral hypoperfusion and glucose hypometabolism and ameliorate cognitive decline. AD is the leading cause of dementia among the elderly. There is significant evidence that pathways involving inflammation and oxidative‐nitrosative stress (ONS) play a key pathophysiological role in promoting cognitive dysfunction. Aging and several comorbid conditions mentioned above promote diverse pathologies. These include inflammation, ONS, hypoperfusion, and hypometabolism in the brain. In AD, chronic cerebral hypoperfusion and glucose hypometabolism precede decades before the cognitive decline. These comorbid disease conditions may share and synergistically activate these pathophysiological pathways. Inflammation upregulates cerebrovascular pathology through proinflammatory cytokines, endothelin‐1, and nitric oxide (NO). Inflammation‐triggered ONS promotes long‐term damage involving fatty acids, proteins, DNA, and mitochondria; these amplify and perpetuate several feedforward and feedback pathological loops. The latter includes dysfunctional energy metabolism (compromised mitochondrial ATP production), amyloid‐β generation, endothelial dysfunction, and blood–brain‐barrier disruption. These lead to decreased cerebral blood flow and chronic cerebral hypoperfusion‐ that would modulate metabolic dysfunction and neurodegeneration. In essence, hypoperfusion deprives the brain from its two paramount trophic substances, viz., oxygen and nutrients. Consequently, the brain suffers from synaptic dysfunction and neuronal degeneration/loss, leading to both gray and white matter atrophy, cognitive dysfunction, and AD. This Review underscores the importance of treating the above‐mentioned comorbid disease conditions to attenuate inflammation and ONS and ameliorate decreased cerebral blood flow and hypometabolism. Additionally, several strategies are described here to control chronic hypoperfusion of the brain and enhance cognition. © 2016 Wiley Periodicals, Inc.     

Changes of arterial blood ketone body ratio following hypoperfusion in old and adult rats

Objective To evaluate the sensitivity of arterial ketone body ratio as an indicator for multiple organ failure.Materials and methods The experimental model of multiple organ failure was made in adult and old rats byhypoperfusion-induced hemorrhagic shock.After blood sampling,the arterial acetoacetate,β-hydroxybutyrate,totalketone body,ALT,AST,BUN,creatinine at 2,4,8 hr in hypoperfusion were examined to compare the differencesof ketone body ratio and organ failure between adult and old rats.Hepatic and mitochondrial metabolism wereassessed by comparing ketone body ratios(AcAc/β-OHB)and free NAD~+/NADH ratios.Results Ketone bodyratio in old rats at 2,4,8 hr after the induction of hemorrhagic shock decreased from 0.68 to 0.31,0.27 and0.22,respectively.In adult rats,it decreased from 1.12 to 0.17,0.12 and 0.09,respectively.Changes of ketonebody ratio in the adult group were larger than in the elderly group(P<0.001).The development of multiple organfailure is associated with the time of hemorrhagic shock development.Conclusions There was a different ketonebody ratio between multiple organ failure in the elderly(MOFE)and multiple organ failure(MOF)in generaladults.Ketone body ratio is a better indicator than ALT and AST in reflecting hepatic function in the early status ofMOF.(J Geriatr Cardiol 2004;1(2):125-128.)     

大鼠脑局灶性低灌注模型的建立

目的探讨应用激光多普勒血流仪监测和改良栓线法建立大鼠可逆性局灶性脑低灌注模型的方法。方法将48只SD雄性大鼠,随机分为假手术组、脑梗死组、低灌注组和低灌注再灌注组,每组12只。在激光多普勒血流仪的监测下,采用直径0.195mm的尼龙线制造大鼠局灶性脑梗死模型,采用直径0.175mm的尼龙线制造局灶性低灌注模型。造模后予以神经功能评分及病理学检查。结果脑梗死组大鼠的神经行为评分高于其他组(P<0.01),TTC染色均有梗死灶,HE染色及透射电子显微镜检查结果表明,神经细胞、星形胶质细胞和微血管损伤严重;低灌注组和低灌注再灌注组TTC染色均未见明显的梗死区,HE染色及透射电子显微镜检查可发现神经细胞、星形胶质细胞出现可逆性损伤,两组改变差异无显著性。结论在激光多普勒监测脑血流量的情况下,采用不同直径的栓线,可以建立较好的可逆性局灶性脑低灌注及再灌注脑梗死模型。     

慢性脑低灌注对2型糖尿病模型大鼠空间学习记忆能力的影响及胆碱能神经元损伤的机制探讨

目的探讨2型糖尿病（DM）是否加重慢性脑低灌注（CCH）大鼠胆碱能神经元及空间学习记忆能力损伤。方法SD大鼠24只,随机分为4组（均n=6）：①对照组（正常饮食＋假手术）;②DM组[高脂饮食＋链脲佐菌素（STZ）];③CCH组[正常饮食＋双侧颈总动脉永久性结扎（2-VO）];④DM-CCH组（高脂饮食＋STZ＋2-VO）。采用Morris水迷宫测试各组大鼠学习记忆能力;免疫组化学法检测海马区乙酰胆碱转移酶（CHAT）阳性细胞表达和免疫印迹法检测海马ChAT相对表达量。结果DM＋CCH组逃避潜伏期与对照组比较明显延长,第2-4天（P〈0．001）、第5天（P〈0．01）;目标象限时『目】百分比明显低干对照组（P〈0．01）、DM组（P〈0．05）和CCH组（尸〈O．05）。DM＋CCH组海马区ChAT阳性细胞表达明显减少,ChAT相对表达量较对照组显著减少（P〈0．01）、DM组（P〈0．05）和CCH组（P〈0．05）显著减少。结论DM可加重CCH大鼠的空间学习记忆能力障碍,可能与海马区胆碱能神经元损伤有关。     

Chronic cerebrovascular hypoperfusion affects global DNA methylation and histone acetylation in rat brain

DNA methylation and histone acetylation can be modified by various pathological or physiological factors such as hypoxia,thus influencing gene expression.In this study,we investigated the changes of global DNA methylation and histone acetylation and the related enzymes in rat brain after chronic cerebrovascular hypoperfusion by bilateral common carotid occlusion（2-VO） surgery.Colorimetric and immunohistochemistry staining were used to evaluate the global DNA methylation and histone acetylation levels,respectively.The expressions of DNA methyltransferase 1/3a（DNMT1/3a）,methyl-CpG binding domain protein 2（MBD2）,histone deacetylase 3（HDAC3） and acetyltransferase（HAT） were assessed by Western blot.We found that the level of global DNA methylation was decreased to 31.7%（P ＆lt;0.01） of the sham-operated group at 10 days and increased by 30%（P ＆lt;0.01） compared with the sham group at 90 days after 2-VO surgery.DNMT3a expression was down-regulated to 75.7% of the sham group,while MBD2 expression was up-regulated by 95% compared with sham group at 90 days after 2-VO.The histone H3 acetylation level was markedly decreased to 75.3% of the sham group at 10 days and 73.5% at 90 days after 2-VO,while no significant change was found for histone H4 acetylation.HDAC3 expression was markedly down-regulated to 36% of the sham group,whereas cAMP-response element binding protein expression was up-regulated by 33.6% compared with the sham group at 90 days after 2-VO.These results suggest that chronic cerebrovascular hypoperfusion influences global DNA methylation and histone acetylation levels through the related enzymes,and therefore might contribute to several neurodegenerative diseases.