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Objective:To explore the role and mechanism of tubastatin A (TubA) in alleviating brain injury after cardiac arrest and cardiopulmonary resuscitation (CA-CPR) by inhibiting endoplasmic reticulum stress-mediated cell apoptosis in swine.Methods:Twenty-three conventional male white swine, weighing 33-40 kg, aged 4 to 6 months, were divided into 3 groups by random number table method: sham group ( n=6), CA-CPR group ( n=9), and TubA group ( n=8). The CA-CPR swine model was established by 9 min of electrically induced CA through pacing catheter in the right ventricle and then 6 min of CPR in the CA-CPR group. The CA-CPR swine model was established by the same method, and then a dose of 4.5 mg/kg of TubA at 5 min after resuscitation was intravenously infused in the TubA group. The serum concentrations of neuron specific enolase (NSE) and S100β protein (S100β) were measured using ELISA before modeling and at 1, 2, 4 and 24 h after resuscitation. Neurological deficit score (NDS) was evaluated at 24 h after resuscitation. Thereafter, the animals were euthanized, and brain cortex tissues were harvested, and the expression levels of caspase-12 and caspase-3 were measured using immunohistochemistry. Cell apoptosis index was detected by TUNEL assay. The variables among the three groups were compared with one-way analysis of variance and the Bonferroni hoc test using SPSS software. Results:Twenty-four h after resuscitation, the serum concentrations of NSE and S100β were significantly increased, and NDS was markedly elevated in the CA-CPR and TubA groups compared with the sham group (all P<0.05). Compared with the CA-CPR group, serum concentration of NSE starting 2 h after resuscitation and serum concentration of S100β starting 1 h after resuscitation were significantly decreased in the TubA group [NSE (ng/mL): (23.1±2.0) vs. (20.2±2.0) at 2 h, (28.4±2.3) vs. (23.7±1.9) at 4 h, (32.1±2.7) vs. (26.6±2.0) at 24 h; S100β (pg/mL): (2239±193) vs. (1923±101) at 1 h, (2817±157) vs. (2360±141) at 2 h, (3384±250) vs. (2691±210) at 4 h, (3965±303) vs. (3119±260) at 24 h, all P<0.05], and NDS was markedly reduced (240±30 vs. 63±44, P<0.05). At 24 h after resuscitation, brain cortex tissue detection showed that the expression levels of caspase-12 and caspase-3 were significantly increased, and cell apoptosis index was markedly elevated in the CA-CPR and TubA groups compared with the sham group (all P<0.05). However, the expression levels of caspase-12 and caspase-3 were significantly decreased [caspase-12:(7.1±0.7) vs. (4.2±0.4); caspase-3: (13.3±1.6) vs. (7.7±0.8), all P<0.05], and cell apoptosis index was markedly reduced in the TubA group compared to the CA-CPR group [(31.1±8.6) vs. (17.3±2.2), P<0.05]. Conclusions:TubA alleviates brain injury and neurological dysfunction after CA-CPR in swine, which may be related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.
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Objective:To explore the correlation between intraoperative regional cerebral oxygen saturation(rScO 2) and nerve damage markers with postoperative neurological dysfunction(PND) in patients undergoing acute Stanford type A aortic dissection surgery. Methods:A total of 57 patients undergoing acute Stanford type A aortic dissection surgery under cardiopulmonary bypass(CPB) in the operating room of Henan Provincial Hospital from July 2020 to May 2021 were enrolled, regardless of gender, aged 35-64 years old, weighed 58.0-90.0 kg and with American Association of Anesthesiologists(ASA) classification status with Ⅱ-Ⅲ. A near infrared spectrometer(NIRS) was used to continuously monitor the bilateral rScO 2 of the patients during the surgery. Central venous blood was drawn 10 min before induction of anesthesia(T0), 10 min after induction of anesthesia(T1), immediately after CPB started(T2), when CPB ended(T3), at the end of the operation(T4), and when exiting ICU(T5), 1 day(T6), 2 days(T7) and 3 days(T8) after operation, and the levels of nerve injury marker S100 calcium binding protein(S100β protein) and neuron-specific enolase(NSE) in serum were measured. Follow up was performed on postoperative 3 to evaluate the occurrence of PND.The value of intraoperative rScO 2 and the concentrations serum S100β protein and NSE were compared between the PND group and the NND(NPND) group. The changes of intraoperative rScO 2 value, the concentrations of serum S100β protein and NSE between the PND group and NPND group were compared. The risk factors of PND and its correlation with the intraoperative rScO 2 value, and the concentrations of serum S100β protein and NSE were analyzed. The prognostic indicators of the two groups of patients were statistically analyzed. Results:Three patients were excluded from the study. A total of 12 patients(22.2%) developed PND(PND group), and 42 patients(77.8%) did not develop PND(NPND group) on postoperative 3 day. Compared with the NPND group, the minimum mean arterial pressure and the minimum rScO 2 during CPB were significantly decreased( P<0.05), the maximum da-rScO 2 during CPB was significantly increased( P<0.05), and duration of da-rScO 2>0.50, duration of da-rScO 2>0.40, duration of rScO 2 reduction >25%, rScO 2<0.50, rScO 2<0.40, during CPB were significantly prolonged( P<0.05) in the PND group. The levels of serum S100β and NSE in the PND group were significantly increased, compared with the NPND group at T2-8, respectively. Logistic regression analysis showed that the reduction of rScO 2 more than 25%( P=0.033), during of rScO 2<0.40( P=0.007) and duration of da-rScO 2>0.50( P=0.001) during CPB were risk factors of PND. Conclusion:Compared with the NPND group, the postoperative mechanical ventilation time, duration of ICU stay, postoperative hospital stay and PND recovery time were significantly prolonged( P<0.05), and the medical expenses were increased significantly( P<0.05) in the PND group. The duration of the reduction of rScO 2>25%, the duration of rScO 2<0.40 and the duration of da-rScO 2>0.50 during CPB are the risk factors of PND in patients with acute Stanford type A aortic dissection under CPB. Significantly increased levels of serum nerve injury markers S100β and NSE are related to the occurrence of PND. The occurrence of PND has a significant adverse effect on the early clinical prognosis of patients.
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Objective:To explore any effect of repeated transcranial magnetic stimulation (rTMS) on the recovery of neurological functioning and the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and inflammatory factors after ischemic stroke.Methods:Sixty-four C57BL/6J mice were randomly divided into a normal control group, a model group, a sham stimulation group and an observation group, each of 16. All mice except those of the normal control group received middle cerebral artery occlusion using the suture method to model an ischemic stroke. After the modeling the observation group was given 1Hz rTMS daily for 7 consecutive days, while the sham stimulation group was given sham rTMS. After the intervention, Zea-Longa scores were used for all of the groups, and the size of the cerebral infarct was measured using triphenyltetrazolium chloride staining. The expression of NLRP3 around the cerebral infarction was detected using immunofluorescence, while that in the brain tissue was measured using Western blotting. The expression of interleukin-1β and IL-18 in the brain tissue was detected using enzyme-linked immunosorbent assays.Results:Compared with the normal control group, a significant increase was observed in the other groups′ average neurological function impairment scores. Expression of NLRP3, IL-1β and IL-18 in the model and sham stimulation groups also increased, with large cerebral infarcts in the cortex and hippocampus. Compared with the sham stimulation and model groups, there was a significant decrease in the average neurological dysfunction scores, the area of cerebral infarction in the cortex and hippocampus, as well as the expression of NLRP3, IL-1β and IL-18 in the observation group.Conclusions:Low-frequency rTMS can promote the recovery of damaged nerve function after an ischemic stroke, at least in mice. It can reduce the size of cerebral infarction, and inhibit neuronal pyroptosis, which is closely related to the down-regulation of NLRP3, IL-1β and IL-18 expression.
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Ischemic stroke(IS)is one of the main causes of long-term morbidity and mortality all over the world, which severely threatens the public health. It has been demonstrated that IS is accompanied by severe neuronal loss that leads to irreversible damage to brain. Thus, effective regeneration of neurons has great potential to the treatment of IS. In recent decades, a large number of studies have shown that newly-generated neurons can exert beneficial effects on repairing the neural damage such as the damaged hippocampus, cortex and striatum after IS. However, although the ischemic injury can activate endogenous neural stem cells to some extent, the stroke-related pathological circumstance can significantly reduce the survival of endogenous neural stem cells, greatly attenuating the neurogenesis- related protective effects on ischemic outcome. Therefore, it is of great clinical importance to seek potential drugs which can promote endogenous neurogenesis. Recent studies have indicated that the anti- apoptosis drugs, endogenous growth factors as well as a series of the bioactive chemical constituents of traditional Chinese medicines and the compound traditional Chinese medicine preparations can protect the brain against the IS by promoting the endogenous neurogenesis. In this review, we summarize the changes in the endogenous neurogenesis induced by the IS and potential drugs which promote the endogenous neurogenesis during the process of IS, hoping to provide a reference for the clinical treatment of IS.
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Background: Double volume exchange transfusion (DVET) for severe unconjugated hyperbilirubinemia has become less common events now days in pediatric practices. But kernicterus is still common in low income country like India. The aim of the study was to determine the clinical profile and outcome in neonates who were treated with DVET.Methods: This was a retrospective study in neonate's ?34 weeks of gestation that were treated with DVET for severe neonatal hyperbilirubinemia over a period of four years.Results: In our study, 37 neonates underwent DVET. Male neonates (62.13%) and normal vaginal delivery (NVD) (70.2%) are common. ABO Isoimmunisation was commonest cause (56.75%) of exchange transfusion.' The mean TSBR at pre exchange and Post Exchange were 27.39 ' 5.99mg/dl and 15.16 ' 4.00mg/dl (p<0.05). Ten neonates (27%) among 37 neonates required twice DVET.Thrombocytopenia14 (37.83%); Seizure 5(13.5%) and Hypocalcaemia 3(8.1%) were common complication noted among total 17 (45.94%) neonates. BIND occurred in 15 neonates (40.5%) at the time of admission and seven (18.9%) neonates had persistent neurological abnormality at discharge. Neonate with BIND had early onset of jaundice (44.13'15.37 hours vs. 61.22'28.23hrs, p<0.05), with' higher' pre exchange TSBR value(28.96 '8.5mg/dl vs. 26.22'3.17mg/dl). Neonates admitted with BIND had higher percentage of persistent encephalopathy (40% vs. 4.5%,p<0.05), abnormal tone (33.3% vs. 4.5%,p<0.05), abnormal feeding (33.3% vs. 4.5%,p<0.05) and abnormal posture (26.6% vs. 0%,p<0.05)' at discharge as compared to those without BIND. No death occurred in this study population.Conclusions: Early detection and aggressive therapy with DVET can prevent neonates from brain injury.
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Objective To analyze preoperative CT angiography (CTA)imaging features of cervical arteries in patients with acute type A aortic dissection followed by postoperative neurological dysfunction (ND),and the correlations between risk factors and ND.Methods Clinical and imaging data of 110 patients who underwent repair of acute type A aortic dissection were analyzed retrospectively.The samples were categorized into two groups based on the presence or absence of ND.The clinical,perioperative and imaging data were compared between the ND group and the non ND (NND)group.Univariate and multivariate analyses were performed to identify predictors related with ND.Results A total of 100 patients were finally included in this study,and 18 patients(18%)developed with ND after aortic surgery.No significant differences in clinical and perioperative variables were observed between the ND group and the NND group (P＞0.05).However,on preoperative CT images,a dissection entry localized in the aortic arch (94.4% in the ND group), common carotid artery tear (83.3% in the ND group)and unilateral internal carotid artery density decrease (44.4% in the ND group) were all significantly higer than those in th NND group (P＜0.05 ).No significant difference were observed in true lumen stenosis of ascending aorta (P=0.053),retrograde dissection (P=0.913)and intimal tear (P=0.267)between ND group and NND group.The Logistic regression analysis revealed that a dissection entry localized in aortic arch (OR=21.325,P=0.008),common carotid artery tear (OR=14.441,P=0.022)and unilateral internal carotid artery density decrease (OR=9.141,P=0.024)were independent determinants of postoperative ND.Conclusion Preoperative CTA of cervical arteries can provide more imaging features,that may be indicative of postoperative ND.
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Objective(s): This study aimed to determine the prevalence of carotid artery stenosis (CAS) due to atherosclerosis in neurologically asymptomatic patients undergoing coronary artery bypass grafting (CABG) for coronary artery disease (CAD). It contemplated a greater role for the cardiac anesthesiologist in the perioperative management of such patients with either previously undiagnosed carotid artery disease or towards re-assessment of severity of CAS. Design: Prospective, observational clinical study. Setting: Operation room of a cardiac surgery centre of a tertiary teaching hospital. Participants: A hundred adult patients with New York Heart Association (NYHA) classification I to III presenting electively for CABG. Interventions: All patients included in this study were subjected to ultrasonic examination by means of acarotid doppler scan to access for presence of CAS just prior to induction of general anesthesia. Measurements and Main Results: Based on parameters measured using carotid doppler, the presence of CAS was defined using standard criteria. The prevalence of CAS was found to be as high as 38% amongst the patients included in our study. The risk factors for CAS were identified to be advanced age, history of smoking, diabetes mellitus, dyslipidaemia and presence of a carotid bruit. Conclusion: This study points towards the relatively wide prevalence of carotid artery disease in neurologically asymptomatic patients undergoing CABG for CAD in the elective setting. It highlights the need to routinely incorporate carotid ultrasonography in the armamentarium of the cardiac anesthesiologist as standard of care for all patients presenting for CABG.
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Objective To investigate whether vitamin B complex supplements would reduce stroke-related disabili-ty in hyperhomocysteinemia (Hhcy) patients with recent ischemic stroke. Methods One thousand patients with brain infarc-tion and Hhcy were assigned to receive either a daily dose of vitamin B complex (treatment group, n=500) or not (control group, n=500) on the base of conventional secondary prevention medications for a period of 2 years. The neurological dys-function was assessed by National Institutes of Health Stroke Scale (NIHSS) and stroke disability was evaluated by Barthel Index (BI) score. High performance liquid chromatographic method with fluorescence detection was used for the determina-tion of total plasma homocysteine levels. After 2 years of follow-up, the patients in the treatment group, whose tHcy level was reduced by 3-μmol/L or more, was defined as the treatment subgroup. Results The homocysteine levels were significantly reduced after 3, 12 and 24-month treatment than those of control group (P＜0.05). A lower NIHSS scale was found at 12, 18 and 24-month in treatment group compared with that in control group (P＜0.05), no significant differences at other time points between two groups (P>0.05). For the BI score, there were no significant differences at any time points between two groups (P>0.05). After 2 years of vitamin B complex supplementation, there were lower NIHSS scale and higher BI scale in treatment subgroup than those of control group (P＜0.05). Conclusion The lower level of tHcy induced by vitamin B inter-vention may be beneficial to the improvement of neurological deficit in patients with ischemic stroke.
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Objective The present study aims to summarize the clinical experience and methods of nervous system protection in the treatment of DeBakey type Ⅰ aortic dissection with hybrid procedure.Methods From Jan 2009 to Jun 2011,56 patients suffering from DeBakey Ⅰ aortic dissection underwent hybrid procedure.The ascending aorta part were replaced under conventional cardiopulmonary bypass,and the0 aortic arch branch vessels were reconstructed,and then a stent graft was implanted to cover the aortic arch and part of the descending aorta.The unilateral antegrade cerebral perfusion(UACP) and/or bilateral antegrade cerebral perfusion (BACP) combined with femoral artery perfusion was used,and the left subclavian arteries were selectively reconstructed according to cerebral arteries and aorta computed tomography angiography scan.Results All the patients went through the procedure successfully.BACP combined with femoral artery perfusion was applied in 16 patients,UACP combined with femoral artery perfusion in 33 patients,and 7 were perfused with only femoral artery cannulation.Of all the patients,19 underwent the innominate artery and left common carotid artery reconstruction and the other 37 patients underwent the innominate artery,the left common carotid artery and the left subclavian artery reconstruction.The cardiopulmonary time was 44 -95 min,mean (65 ±24) min; aortic clamping time was 32 -71 min,mean (48 ±29)min; the cerebral perfusion time was 24 -44 min,mean (32 ± 13) min.One ( 1.8％ ) patient,who was perfused with only femoral artery cannulation,suffered from permanent neurological dysfunction,and 5 (8.9％) had transient neurological dysfunction.One patient died from severe infection,1 patient was given up because of permanent neurological dysfunction,and the rest 54 patients recovered and discharged.The patients were followed up 1 to 25 months,and there was no newly occurred neurological dysfunc tion.The CTA examination 3 months post-operative revealed that the branch bypass vessels were unobstructed.There was no subclavain steal symptom occurred in the 19 patients whose left subclavian arteries were not reconstructed.The left upper limb strength was slightly lessened in 3 patients and recovered 6 - 12 months later.Conclusion In the treatment of DeBakey type Ⅰ aortic dissection with hybrid procedure,the selective use UACP and/or BACP combined with femoral artery perfusion can avoid deep hypothermic and circulatory arrest and provide the continuous cerebral and spinal perfusion.This perfusion strategy in hybrid procedure can decrease the morbidity of post-operative nervous system disorders with satisfactory nervous system protection effect.
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Since we started organic acid analysis in July 1997, we have collected data about organic acidemias in Korea. The data presented herein constitute our 3 years experience in organic acid analysis. We have collected 712 samples from major university hospitals in all over Korea, which are large enough for relatively accurate estimation of incidence of organic acid disorders. We used solvent extraction method with ethylacetate, MSTFA for derivatization and simultaneously quantitation of 83 organic acids. Out of 712 patients sample, 498 samples (70%) showed no evidence of organic acid abnormalities. Out of the 214 remaining samples, we found very diverse disorders such as methylmalonic aciduria (6), propionic aciduria (10), biotinidase deficiency (6), maple syrup urine disease (3), isovaleric aciduria (4), tyrosinemia type II (4), tyrosinemia type IV (1), glutaric aciduria type I (1), glutaric aciduria type II (22), 3-methylglutaconic aciduria type I (3), 3-methylglutaconic aciduria type III (7), HMG-CoA lyase deficiency (1), hyperglyceroluria (2), cytosolic 3-ketothiolase deficiency (55), mitochondrial 3-ketothiolase deficiency (3), 3-hydroxyisobutyric aciduria (2), L-2-hydroxyglutaric aciduria (2), fumaric aciduria (2), lactic aciduria with combined elevation of pyruvate (most likely PDHC deficiency) (28), lactic aciduria without combined elevation of pyruvate (most likely mitochondrial respiratory chain disorders) (35), SCAD deficiency (3), MCAD deficiency (1), 3-methylcrotonylglycineuria (1), orotic aciduria (most likely urea cycle disorders) (7) and 2-methylbranched chain acyl-CoA dehydrogenase deficiency (1). In conclusion, although the incidence of individual organic acidemia is low, the incidence of overall organic acidemia is relatively high in Korea. Most of the patients showed some signs of neurological dysfunction. Therefore, organic acid analysis should be included in the diagnostic work up of all neurological dysfunctions.
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Humans , Acetyl-CoA C-Acyltransferase , Acyl-CoA Dehydrogenase , Biotinidase Deficiency , Cytosol , Electron Transport , Hospitals, University , Incidence , Korea , Maple Syrup Urine Disease , Multiple Acyl Coenzyme A Dehydrogenase Deficiency , Propionic Acidemia , Pyruvic Acid , Tyrosinemias , UreaABSTRACT
PURPOSE: We have done this retrospective study to know the relative incidences and clinical manifestations of organic acidopathies in Korea. METHODS: The results of quantitative organic acid analysis of 1,125 samples of 712 patients, referred from Jul. 1997 to Jun. 2000, were analyzed retrospectively according to four age groups (-2 mon, 3 mon-2 year, 3 years-12 years, over 12 years) and major clinical manifestations. Quantification of 83 organic acids was done with gas chromatography and mass spectrometry(GC/MS). RESULTS: We diagnosed 214 patients with 27 diseases of organic acid metabolism during this study period. Diseases found more than 10 cases are cytosolic 3-ketothiolase deficiency, mitochondrial repsiratory chain disorders, PDHC deficiency, glutaric aciduria type II and propionic aciduria. Other diseases were diagnosed in less than 10 cases, mostly one or two cases during this study period. Most of the patients had some symptoms of neurological dysfunction such as seizure activity(195 patients), developmental delay(122), mental retardation(99), hypotonia(84), movement disorders(81) and vomiting(68). CONCLUSION: Though the incidence of individual organic acidemia is low, the overall incidence of organic acidemia as a whole seems to be relatively high in Korea. Most of the patients showed some signs of neurological dysfunction.