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hypoperfusion context as a predictor of 28-d all-cause mortality in septic shock patients:A comparative observational study

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World Journal of Clinical Cases 2023年第16期11卷 3765-3779页

作者： Sahil Kataria Omender Singh Deven Juneja Amit Goel Madhura Bhide Devraj Yadav Institute of Critical Care Medicine Max Super Speciality HospitalSaketNew Delhi 110017India

BACKGROUND As per the latest Surviving Sepsis Campaign guidelines,fluid resuscitation should be guided by repeated measurements of blood lactate levels until ***,raised lactate levels should be interpreted in the clinical context,as there may be other causes of elevated lactate ***,it may not be the best tool for real-time assessment of the effect of hemodynamic resuscitation,and exploring alternative resuscitation targets should be an essential research priority in *** To compare the 28-d mortality in two clinical patterns of septic shock:hyperlactatemic patients with hypoperfusion context and hyperlactatemic patients without hypoperfusion *** This prospective comparative observational study carried out on 135 adult patients with septic shock that met Sepsis-3 definitions compared patients with hyperlactatemia in a hypoperfusion context(Group 1,n=95)and patients with hyperlactatemia in a non-hypoperfusion context(Group 2,n=40).hypoperfusion context was defined by a central venous saturation less than 70%,central venousarterial PCO_(2)gradient[P(cv-a)CO_(2)]≥6 mmHg,and capillary refilling time(CRT)≥4 *** patients were observed for various macro and micro hemodynamic parameters at regular intervals of 0 h,3 h,and 6 ***-cause 28-d mortality and all other secondary objective parameters were observed at specified *** categorical data were compared using theχ^(2)or Fisher’s exact *** distributed continuous variables were compared using the Mann-Whitney U *** operating characteristic curve analysis with the Youden index determined the cutoff values of lactate,CRT,and metabolic perfusion parameters to predict the 28-d all-cause mortality.A P value of<0.05 was considered *** Patient demographics,comorbidities,baseline laboratory,vital parameters,source of infection,baseline lactate levels,and lactate clearance at 3 h and 6 h,Sequential Organ Failure scores,need for inv

关键词： Capillary refill time Central venous saturation hypoperfusion Lactate Mortality PCO_(2)gap Septic shock

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Xiao-Xu-Ming decoction extract regulates differentially expressed proteins in the hippocampus after chronic cerebral hypoperfusion

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Neural Regeneration Research 2019年第3期14卷 470-479页

作者： Yue-Hua Wang Ying-Lin Yang Xiao Cheng Jun Zhang Wan Li Guan-Hua Du State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing Key Laboratory of Drug Target Identification and Drug Screening Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College

Xiao-Xu-Ming decoction has been widely used to treat stroke and sequelae of stroke. We have previously shown that the active fractions of Xiao-Xu-Ming decoction attenuate cerebral ischemic injury. However, the global protein profile and signaling conduction pathways regulated by Xiao-Xu-Ming decoction are still unclear. This study established a two-vessel occlusion rat model by bilateral common carotid artery occlusion. Rats were intragastrically administered 50 or 150 mg/kg Xiao-Xu-Ming decoction for 4 consecutive weeks. Learning and memory abilities were measured with Morris water maze. Motor ability was detected with prehensile test. Coordination ability was examined using the inclined screen test. Neuronal plasticity was observed by immunofluorescent staining. Differentially expressed proteins of rat hippocampus were analyzed by label-free quantitative proteomics. Real time-polymerase chain reaction and western blot assay were used to identify the changes in proteins. Results showed that Xiao-Xu-Ming decoction dramatically alleviated learning and memory deficits, and motor and coordination dysfunction, and increased the expression of microtubule-associated protein 2. Xiao-Xu-Ming decoction extract remarkably decreased 13 upregulated proteins and increased 39 downregulated proteins. The regulated proteins were mainly involved in oxidation reduction process, intracellular signaling cascade process, and protein catabolic process. The signaling pathways were mainly involved in ubiquitin mediated proteolysis and the phosphatidylinositol signaling system. Furthermore, there was an interaction among Rab2 a, Ptpn1, Ppm1 e, Cdk18, Gorasp2, Eps15, Capza2, Syngap1 and Mt-nd1. Protein analyses confirmed the changes in expression of MTND1. The current findings provide new insights into the molecular mechanisms of Xiao-Xu-Ming decoction extract's effects on chronic cerebral hypoperfusion.

关键词： nerve regeneration chronic cerebral hypoperfusion vascular dementia bilateral common carotid artery occlusion Xiao-Xu-Ming decoction label-free quantitative proteomics Morris water maze test Nano-LC-ESI LTQ-Orbitrap MS/MS technology neural regeneration

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Retinal tissue hypoperfusion in patients with clinical Alzheimer’s disease

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Eye and Vision 2018年第1期5卷 196-203页

作者： Giovana Rosa Gameiro Hong Jiang Yi Liu Yuqing Deng Xiaoyan Sun Bernardo Nascentes Bernard Baumel Tatjana Rundek Jianhua Wang Department of Ophthalmology Bascom Palmer Eye InstituteUniversity of Miami Miller School of Medicine1638 NW 10th AvenueMcKnight Building-Room 202AMiamiFL 33136USA Evelyn F.McKnight Brain Institute Department of NeurologyUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Ophthalmology Third Affiliated Hospital of Nanjing University of Chinese MedicineNanjingChina State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhouGuangdongChina School of Nursing and Health Studies University of MiamiMiamiFLUSA

Background:It remains unknow whether retinal tissue perfusion occurs in patients with Alzheimer’s *** goal was to determine retinal tissue perfusion in patients with clinical Alzheimer’s disease(CAD).Methods:Twenty-four CAD patients and 19 cognitively normal(CN)age-matched controls were recruited.A retinal function imager(RFI,Optical Imaging Ltd.,Rehovot,Israel)was used to measure the retinal blood flow supplying the macular area of a diameter of 2.5 mm centered on the *** flow volumes of arterioles(entering the macular region)and venules(exiting the macular region)of the supplied area were *** blood flow was calculated as the average of arteriolar and venular flow *** ultra-high-resolution optical coherence tomography(UHR–OCT)was used to calculate macular tissue *** segmentation software(Orion,Voxeleron LLC,Pleasanton,CA)was used to segment six intra-retinal layers in the 2.5 mm(diameter)area centered on the *** inner retina(containing vessel network),including retinal nerve fiber layer(RNFL),ganglion cell-inner plexiform layer(GCIPL),inner nuclear layer(INL)and outer plexiform layer(OPL),was segmented and tissue volume was *** was calculated as the flow divided by the tissue ***:The tissue perfusion in CAD patients was 2.58±0.79 nl/s/mm^(3)(mean±standard deviation)and was significantly lower than in CN subjects(3.62±0.44 nl/s/mm^(3),P<0.01),reflecting a decrease of 29%.The flow volume was 2.82±0.92 nl/s in CAD patients,which was 31%lower than in CN subjects(4.09±0.46 nl/s,P<0.01).GCIPL tissue volume was 0.47±0.04 mm^(3) in CAD patients and 6%lower than CN subjects(0.50±0.05 mm^(3),P<0.05).No other significant alterations were found in the intra-retinal layers between CAD and CN ***:This study is the first to show decreased retinal tissue perfusion that may be indicative of diminished tissue metabolic activity in patients with clinical Alzheimer’s disease.

关键词： Clinical Alzheimer’s disease Retinal tissue perfusion Blood flow Retinal tissue volume hypoperfusion Retinal function imager Optical coherence tomography

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

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Journal of Geriatric Cardiology 2004年第2期1卷 125-128页

作者： Ling YE Shiwen WANG Songtao YU Wei CHEN Institute of Gerontology and Geriatrics Chinese PLA General Hospital Beijing 100853 China Institute of Geriatric Cardiology Chinese PLA General Hospital Beijing 100853 China Institute of Geriatric Cardiology Chinese PLA General Hospital Beijing 100853 China Institute of Gerontology and Geriatrics Chinese PLA General Hospital Beijing 100853 China

Objective To evaluate the sensitivity of arterial ketone body ratio as an indicator for multiple organ *** and methods The experimental model of multiple organ failure was made in adult and old rats by hypoperfusion-induced hemorrhagic shock. After blood sampling, the arterial acetoacetate, β-hydroxybutyrate, total ketone body, ALT, AST, BUN, creatinine at 2, 4, 8 hr in hypoperfusion were examined to compare the differences of ketone body ratio and organ failure between adult and old rats. Hepatic and mitochondrial metabolism were assessed by comparing ketone body ratios (AcAc/β-OHB) and free NAD+/NADH ratios. Results Ketone body ratio in old rats at 2, 4, 8 hr after the induction of hemorrhagic shock decreased from 0.68 to 0.31, 0.27 and 0.22, respectively. In adult rats, it decreased from 1.12 to 0.17, 0.12 and 0.09, respectively. Changes of ketone body ratio in the adult group were larger than in the elderly group ( P ＜ 0.001). The development of multiple organ failure is associated with the time of hemorrhagic shock development. Conclusions There was a different ketone body ratio between multiple organ failure in the elderly (MOFE) and multiple organ failure (MOF) in general adults. Ketone body ratio is a better indicator than ALT and AST in reflecting hepatic function in the early status of MOF. (J Geriatr Cardiol 2004;1(2) :125-128. )

关键词： multiple organ failure in the elderly arterial ketone body ratio hypoperfusion hemorrhagic shock rat

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Transplanted bone marrow stromal cells improve cognitive dysfunction due to aging hypoperfusion in rats

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Chinese Medical Journal 2010年第24期123卷 3620-3625页

作者： HUANG Jing YIN Shao-jun CHEN Yu-juan BIAN Wei-hong YU Jing ZHAO Yu-wu LIU Xue-yuan Department of Neurology Shanghai 10th People's Hospital Tongji University School of Medicine Shanghai 200072 China Department of Geriatrics Shanghai 10th People's Hospital Tongji University School of Medicine Shanghai 200072 China Department of Neurology Shanghai Sixth People's Hospital Shanghai 200233 China

Background Aging is an important risk factor for vascular dementia, and D-galactose （D-gal） injection can simulate the pathology of aging. Two-vessel occlusion of common carotid arteries （2VO） is the most popular model for vascular dementia. This study was aimed to investigate the possibility of D-gal injection plus 2VO simulating cognitive impairment of aging vascular dementia; and whether transplanted bone marrow stromal cells （BMSCs） can improve the cognitive function induced by D-gal injection plus *** Totally 30 male Sprague-Dawley rats were divided into 5 groups equivalently： control group, D-gal group,D-gal＋2VO group, D-gal＋2VO＋saline water group, and D-gal＋2VO＋BMSCs group. Aging hypoperfusion rats were created by subcutaneous injection of D-gal and occlusion of two common carotid arteries. BMSCs or saline water was stereotactically transplanted into the subventricular zone as treatment vehicles at 24 hours post operation. Two-way repeat analysis of variance （ANOVA） was used for significance analysis of 5 groups at 6 weeks post transplantation;moreover, Tamhane＇s test （equal variance not assumed） and least significant difference （LSD） test （equal variance assumed） were used for pairwise comparison in Morris water maze （MWM）.Results Transplanted BMSCs distributed around the lateral ventricles and acquired the phenotypes of neurons and astrocytes. In terms of swimming path distance and escape latency in MWM, D-gal＋2VO＋BMSC group showed significant improvement than the D-gal＋2VO group but was still obviously worse than the control group （both P ＜0.05）.There was no significant difference in swimming speed for all 5 *** D-gal plus 2VO induces cognitive dysfunction. The engrafted BMSCs exhibit the beneficial effect on cognitive function via promotion interactively with host brain.

关键词： aging hypoperfusion bone marrow stromal cells D-galactose two-vessel occlusion of common carotid arteries

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Outcomes Associated with a Screening and Treatment Pathway for Occult hypoperfusion Following Cardiac Surgery

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World Journal of Cardiovascular Surgery 2013年第2期3卷 34-41页

作者： Ran Xu Greg A. Laine BeeBee Y. Hu R. Thomas Solis Arthur W. Bracey Jr. James M. Wilson Amy R. Miclat Susan Baimbridge George J. Reul Jr. Comprehensive Pharmacy Services St Luke’s The Woodlands Hospital The Woodlands USA St Luke’s Episcopal Hospital Houston USA Texas Heart Institute Houston USA

Introduction: Routinely monitored parameters such as blood pressure (BP) and heart rate may not reliably detect per- fusion abnormalities. However, central venous oxygen saturation (ScvO2) and lactate levels can detect occult hypoper- fusion (OH) and identify patients at risk for complications. The study objective was to assess the impact of an OH treatment pathway on morbidity and length of stay (LOS) post coronary bypass and valve surgery. Methods: This is a prospective cohort observational study following the implementation of a treatment pathway for OH, defined by ScvO2 2 mMol/L with systolic BP ≥ 90 mmHg. Initial treatment included volume resuscitation and/or blood transfusion, followed by additional interventions when ScvO2 remained hours postoperatively. Primary outcomes were intensive care unit (ICU)/hospital LOS and complications. Results: Comparing 53 patients managed by the OH pathway against 21 historical controls, median ICU LOS was 40.4 vs. 49.2 hours (p = 0.122), median hospital LOS 9.2 vs. 11.0 days (p = 0.0093), ICU readmission rate 7.5% vs. 28.6% (p = 0.026), and complication rate 26.4% vs. 47.6% (p = 0.101). Repeat lactate was checked 18 hours postoperatively in 47 of the 53 patients. Comparing 33 patients with repeat lactate at goal ( 2 mMoL/L) with 14 patients not at goal, median ICU LOS was 35.3 vs. 68.4 hours (p = 0.061), median hospital LOS 8.9 vs. 11.2 days (p = 0.058), median length of mechanical ventilation (LOMV) 13.3 vs. 28.4 hours (p = 0.0038), and complication rate 15.2% vs. 50.0% (p = 0.025). Conclusions: An OH screening and treatment pathway following cardiovascular surgery was associated with signifi- cantly shorter hospital LOS and lower ICU readmission rate. Among the OH pathway patients, achieving lactate goal 18 hours postoperatively was associated with significantly shorter LOMV and lower complication rate.

关键词： Occult hypoperfusion Cardiovascular Surgery Lactate Central Venous Oxygen Saturation Outcomes

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Expression Analysis of MiR-124 in Experimental Cerebral hypoperfusion

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Journal of Biosciences and Medicines 2018年第5期6卷 9-14页

作者： Tang Li Huizi Lei Linhui Wang Yu Li Department of Pathophysiology Chongqing Medical University Chongqing China Department of Pathology Institute of Neuroscience Chongqing Medical University Chongqing China

MicroRNAs (miRNAs) are small noncoding single-stranded RNA molecules that act as negative regulators of gene expression and modulate the stability and/or the translational efficiency of target messenger RNAs. Studies have shown that miRNAs control diverse aspects of brain disease. In this study, the expression of miR-124 was investigated to explore the possible impacts of them on cerebral hypoperfusion. The model of aging rats with cerebral hypoperfusion was established by permanent occlusion of bilateral common carotid arteries (2VO). The expression of miR-124 was determined by real-time PCR. Cell cycle analysis was performed by fluorescence-activated cell sorting (FACS). Results showed that compared with control group, the expression of miR-124 decreased at early stage after operation in 2VO rats, the lowest level appeared on day 7 (p hypoperfusion progression which may provide a novel therapeutic strategy for treatment of cerebral hypoperfusion.

关键词： MiRNA-124 Cerebral hypoperfusion 2VO OGD

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IMPAIRED BLOOD-BRAIN BARRIER AFTER CHRONIC CEREBRAL hypoperfusion

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Medical Bulletin of Shanghai Jiaotong University 1999年第2期20卷 83-86页

作者：毛青丁美修程华怡王秉玉吴逸群朱平

Ohjectire To examine the hypothesis of normal perjusion pressure breakthrough (NPPB). Methods A modified Spetzler carotid -jugular (CJ) fistula model was created to imitate NPPB. In 9 male adult Sprague- Dawley rats, the ipsilateral vertebral artery and bilateral external carotid arteries were occluded. The period of hypoperfusion CJ fistula was extended to 14 weeks, as a modofcation of Spetzler model. The histological change were examtned under transmission electron microscope 14 weeks after creation of the listula. Results Ischemic histological changes such as increased pinocytosis, increased lucency of the basal lamina, and frank necrosis of the cerebral capillary were found in rats of CJ fistula group. Conclusion The findings in this study suggest that blood - braln barrier (BBB) was impaired by chronic hypoperfusion. The impaired BBB mny be one of the important causes of the NPPB phenomenon.

关键词： normal perfusion pressure breakthrough blood - brain barrier chronic cerebral hypoperfusion

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Fluoxetine ameliorates cognitive impairments induced by chronic cerebral hypoperfusion via down-regulation of HCN2 surface expression in the hippocampal CA1 area

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中国药理学通报 2015年第B11期31卷 78-78页

Aim To investigate whether tluoxetine, a selective serotonin reuptake inhibitor（ SSRI） , could amelio- rate cognitive impairments induced by chronic cerebral hypopeffusion in rats and to clarify the underlying mecha- nisms of its efficacy. Methods Rats were subjected to permanent bilateral occlusion of the common carotid arteries （two-vessel occlusion, 2VO）. Two weeks later, rats were treated with 30 mg · kg^-1 fluoxetine （intragastric injec- tion, i. g. ） for 6 weeks. Cognitive function was evaluated by Morris water maze （MWM） and novel objects recog- nition （NOR） test. Long-term potentiation （LTP） was used to address the underlying synaptic mechanisms. West- ern blot was used to quantify the protein levels. Results Fluoxetine treatment significantly improved the cognitive 2VO impairments caused by 2VO, accompanied with a reversion of 2VO-induced inhibitory of LTP. Furthermore, caused an up-regulation of hyperpolarization-activated cyclic nueleotide-gated channel 2 （HCN2） surface expres- sions in the hippocampal CA1 area and fluoxetine also effectively recovered the up-regulation of HCN2 surface ex- pressions. Conclusion Fluoxetine can ameliorate cognitive impairments induced by chronic cerebral hypopeffusion and a possible mechanism may via down-regulating HCN2 surface expression in the Hippocampal CA1 area.

关键词： fluoxetine chronic cerebral hypoperfusion cognitive impairments HCN2 subunit hippocampal CA1area rats

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Assessment of cerebrovascular reserve impairment using the breath-holding index in patients with leukoaraiosis

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Neural Regeneration Research 2019年第8期14卷 1412-1418页

作者： Ying Bian Jin-Chun Wang Feng Sun Zi-Yi Sun Yu-Jiao Lin Yang Liu Bin Zhao Li Liu Xiao-Guang Luo Department of Neurology the First Affiliated Hospital of China Medical University Shenyang Liaoning Province China Department of Neurology the Fifth People's Hospital of Shenyang Shenyang Liaoning Province China Department of Endocrinology Shengjing Hospital China Medical University Shenyang Liaoning Province China

Many studies have demonstrated that leukoaraiosis is associated with impaired cerebrovascular reserve function. However, the definitive hemodynamic changes that occur in leukoaraiosis are not clear, and there are many controversies. This study aimed to investigate hemodynamic changes in symptomatic leukoaraiosis using transcranial Doppler ultrasonography and the breath-holding test in a Chinese Han population, from northern China. A total of 203 patients who were diagnosed with ischemic stroke or clinical chronic progressive ischemic symptoms were enrolled in this study, including 97 males and 106 females, with an age range of 43-93 years. The severity of leukoaraiosis was evaluated according to the Fazekas grading scale, and patients were divided into four groups accordingly. Grade 0 was no leukoaraiosis, and grades I, II, and III were mild, moderate, and severe leukoaraiosis, respectively, with 44, 79, 44, and 36 cases in each group. Transcranial Doppler ultrasonography and the breath-holding test were performed. The mean blood flow velocity of the bilateral middle cerebral artery was measured and the breath-holding index was calculated. The breath holding index was correlated with leukoaraiosis severity and cognitive impairment. Patients with a low breath holding index presented poor performance in the Montreal Cognitive Assessment (MoCA) and executive function tests. That is, the lower the breath holding index, the lower the scores for the MoCA and the higher for the trail-making test Parts A and B. These results indicate that the breath-holding index is a useful parameter for the evaluation of cerebrovascular reserve impairment in patients with leukoaraiosis. In addition, the breath-holding index can reflect cognitive dysfunction, providing a new insight into the pathophysiology of leukoaraiosis. This study was approved by the Ethics Committee of the Fifth Peoples Hospital of Shenyang, China (approval No. 20160301) and registered in the Chinese Clinical Trial R

关键词： nerve regeneration cerebral small vascular disease white matter hyperintensities cerebral hemodynamics cerebral hypoperfusion middle cerebral artery blood flow velocity breath-holding test breath-holding index cognitive function neural regeneration

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