Is valve-sparing aortic root replacement better than total aortic root replacement? An overview of reviews.

Background: Total aortic root replacement (TRR) is certainly beneficial for aortic root disease, but does it still have an advantageous prognosis for patients compared to valve-sparing aortic root replacement (VSRR)? An overview of reviews was conducted to assess each of their clinical efficacy/effectiveness. Review methods: Systematic reviews (SRs)/Meta-analyses comparing the prognosis of TRR and VSRR in aortic root surgery were collected from 4 databases, all searched from the time of database creation to October 2022. Two evaluators independently screened the literature, extracted information and applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) tool, Grading of Recommendations, Assessment, Development and Evaluations (GRADE), and Risk of Bias in Systematic Reviews (ROBIS) to evaluate the quality of reporting, methodological quality, risk of bias, and level of evidence of the included studies. Main results: A total of 9 SRs/Meta-analyses were ultimately included. In terms of the reporting quality of the included studies, PRISMA scores ranged from 14 to 22.5, with issues mainly in reporting bias assessment, risk of study bias, credibility of evidence, protocol and registration, and funding sources. The methodological quality of the included SRs/Meta-analyses was generally low, with key items 2, 7, and 13 having major flaws and non-key items 10, 12, and 16. In terms of risk of bias assessment, the overall assessment of the included 9 studies was high-risk. The quality of the evidence was rated as low to very low quality for the three outcome indicators selected for the GRADE quality of evidence rating: early (within 30 days postoperatively or during hospitalization) mortality, late mortality, and valve reintervention rate. Conclusions: VSRR has many benefits including reduced early and late mortality after aortic root surgery and reduced rates of valve-related adverse events, but the methodological quality of the relevant studies is low, and there is a lack of high-quality evidence to support this. Systematic Review Registration: https://www.PROSPERO, identifier: CRD42022381330.

Does the Digital Economy Promote the Reduction of Urban Carbon Emission Intensity?

The impact of the digital economy is increasing, and its environmental effect has attracted more and more attention. The digital economy promotes the improvement of production efficiency and the government's environmental governance capacity, and contributes to the reduction of urban carbon emission intensity. In order to study the impact of digital economy development on urban carbon emission intensity, this paper analyzes the theoretical basis of the digital economy on the reduction of carbon emission intensity, and then, based on the panel data of cities from 2011 to 2019, uses the two-way fixed effect model for empirical testing. The regression results show that the development of the digital economy has promoted the reduction of carbon emission intensity of cities, promoted the green transformation and upgrading of cities, and lays a foundation for China to achieve carbon peaking and carbon neutralization through the improvement of human capital investment and green innovation level. The basic conclusion is robust by changing core explanatory variables, changing samples, replacing regression methods, and shrinking and truncating tests. The impact of the digital economy on urban carbon emission intensity varies with the location, grade and size of the city. Specifically, the development of the digital economy in cities in the eastern and central regions, cities at or above the sub provincial level, large cities and non-resource-based cities has promoted the reduction of urban carbon emission intensity. In terms of resource-based cities, the development of the digital economy in renewable resource-based cities and resource-based cities dominated by iron ore and oil mining has promoted the decline in urban carbon emission reduction intensity.

One-stage total arch and proximal descending aorta replacement via a single median sternotomy.

For extended arch pathologies involving the proximal descending aorta, the exposure afforded by the median sternotomy is less than ideal, and radical replacement of the distal arch by conventional total arch replacement is difficult. We developed a surgical manoeuvre to replace the total arch and proximal descending aorta in 1 stage through a single median sternotomy.

Surgical Repair of a Quadricuspid Aortic Valve With Severe Regurgitation Utilizing "Tricuspidization" and Annular Banding: A Case and Technique Details Report.

The quadricuspid aortic valve (QAV) is a rare congenital disease with a prevalence of 0. 013-0.043% of cardiac cases. Most patients with QAV are treated with aortic valve replacement. A Type B QAV with dilated ascending aorta of 47.9 mm; combined with severe regurgitation is reported here. In this case, considering the patient's cusps are flexible and reservable, the aortic root was reconstructed utilizing tricuspidization and annular banding technique, and dilated ascending aorta was replaced at the same time.

Outcomes of preoperative antiplatelet therapy in patients with acute type A aortic dissection.

BACKGROUND: Acute type A aortic dissection (ATAAD) is life-threatening and requires immediate surgery. Sudden chest pain may lead to a risk of misdiagnosis as an acute coronary syndrome and may lead to subsequent antiplatelet therapy (APT). We used the Chinese Acute Aortic Syndrome (AAS) Collaboration Database to study the effects of APT on clinical outcomes. METHODS: The AAS database is a retrospective multicentre database where 31 of 3092 patients had APT with aspirin or clopidogrel or both before surgery. Before and after propensity score matching (PSM), the incidence of complications and mortality was compared between APT and non-APT patients by using a logistic regression model. The sample remaining after PSM was 30 in the APT group and 80 in the non-APT group. RESULTS: The sample remaining after matching was 30 in the APT group and 80 in the non-APT group. We found 10 cases with percutaneous coronary intervention in the APT group (33.3%). The APT group received more volume of packed red blood cells, 8.4 ± 6.05 units; plasma, 401.67 ± 727 ml, and platelet transfusion (14.07 ± 8.92 units). The drainage volume was much more in the APT group (5009.37 ± 2131.44 ml, p = .004). Mortality was higher in APT group (26% vs. 10%, p = .027). The preoperative APT was an independent predictor of mortality (odds ratio: 6.808, 95% confidence interval: 1.554-29.828, p = .011). CONCLUSION: APT before ATAAD repair was associated with more transfusions and higher early mortality. The timing of surgery should be carefully considered based on the patient's status and the surgeon's experience.

Bone marrow mesenchymal stem cell derived exosomal miR-455-5p protects against spinal cord ischemia reperfusion injury.

At present, much more studies have focused on the therapeutic effect of exosome-delivered microRNAs on diseases. Previous study has shown that miR-455-5p is downregulated in ischemic stroke, but little is known about the role of exosome-delivered miR-455-5p in spinal cord ischemia reperfusion (SCIR) injury. Herein, we isolated exosomes from bone marrow mesenchymal stem cells (BMSCs) transfected with lentivirus vectors containing miR-455-5p. SCIR rat model was established after the intrathecal injection of exosomes containing miR-455-5p. The expression level of miR-455-5p was downregulated after SCIR, administration of exosomal miR-455-5p enhanced the level of miR-455-5p in the injured spinal cord. Hind-limb motor function scores indicated that exosomal miR-455-5p improved the recovery of hind-limb function of SCIR rats. HE staining and Nissl staining showed that miR-455-5p enriched exosomes reduced histopathological abnormalities after SCIR. Double immunofluorescence staining revealed that exosomes containing miR-455-5p reduced apoptosis of neurons, and activated autophagy in neurons after SCIR. We observed that the expression of Nogo-A, a direct target of miR-455-5p, was decreased in the spinal cord of exosomal miR-455-5p administrated SCIR rats. Targeting relationship between miR-455-5p and Nogo-A was verified by dual-luciferase reporter assay. In summary, exosomes containing miR-455-5p had the neuroprotective effects on SCIR injury by promoting autophagy and inhibiting apoptosis of neurons.

Perillaldehyde Alleviates Spinal Cord Ischemia-Reperfusion Injury Via Activating the Nrf2 Pathway.

BACKGROUND: Spinal Cord ischemia-reperfusion injury (SCII) is one of the most destructive complications in thoracic-abdominal aortic surgery, which can cause physical abnormalities, paralysis and even brain death. Evidence has shown that perillaldehyde (PAH) can ameliorate rat's cerebra ischemia-reperfusion injury. However, the effect of PAH on SCII remains unknown. METHODS: The current study established SCII rat models and oxygen and glucose deprivation/reoxygenation-induced BV2 microglia models to explore whether PAH could alleviate SCII symptoms and to investigate underlying mechanism. RESULTS: SCII rats underwent severe neurologic motor dysfunction and histopathologic injury compared with the normal rats, which are exhibited by loss of motor neurons and decrease of nissl bodies. Treatment with PAH significantly ameliorated motor dysfunction and neuron damage. PAH downregulated the expression of NLR family pyrin domain containing 3, cleaved/pro caspase-1, interleukin-1ß and interleukin-18 in spinal cord tissues of SCII rats. Besides, the contents of oxidative stress-related factors superoxide dismutase, manganese-dependent superoxide dismutase, catalase and glutathione peroxidase were significantly increased and malondialdehyde content was decreased after PAH treatment. PAH treatment upregulated the expression of nuclear factor-E2-related factor 2 and heme oxygenase-1 in spinal cord tissues of SCII rats. Our in vitro study confirmed that PAH inhibited microglial activation by activating the nuclear factor-E2-related factor 2/heme oxygenase-1 pathway, exhibited by alleviated inflammation and oxidative stress. CONCLUSIONS: This study elucidates that PAH has the potential value for treating SCII, which provides an experimental basis for clinical trials in the future.

MiR-105-3p acts as an oncogene to promote the proliferation and metastasis of breast cancer cells by targeting GOLIM4.

BACKGROUND: Dysregulated miRNAs are involved in carcinogenesis of the breast and may be used as prognostic biomarkers and therapeutic targets during the cancer process. The purpose of this study was to explore the effect of miR-105-3p on the tumourigenicity of breast cancer and its underlying molecular mechanisms. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to detect the expression of miR-105-3p in breast cancer tissues and cell lines. The impacts of miR-105-3p on the proliferation, migration, invasion and apoptosis of human breast cancer cells (MCF-7 and ZR-75-30) were evaluated by CCK-8 assays, Transwell chamber assays, TUNEL assays and western blot analyses. In addition, bioinformatics and luciferase reporter assays were used to determine the target genes of miR-105-3p. RESULTS: The expression of miR-105-3p was elevated in breast cancer tissues and increased with tumour severity. Downregulation of miR-105-3p could inhibit cell proliferation, suppress cell migration/invasion, and promote cell apoptosis in MCF-7 and ZR-75-30 cells. Furthermore, Golgi integral membrane protein 4 (GOLIM4) was identified as the direct target gene of miR-105-3p by bioinformatics and luciferase reporter assays. In addition, silencing GOLIM4 restored the anti-breast cancer effects induced by miR-105-3p downregulation. CONCLUSIONS: MiR-105-3p acts as an oncogene to promote the proliferation and metastasis of breast cancer cells by targeting GOLIM4, which provides a new target for the prevention and treatment of breast cancer.

MiR-17-5p-mediated endoplasmic reticulum stress promotes acute myocardial ischemia injury through targeting Tsg101.

Cardiovascular diseases are the leading cause of death globally, among which acute myocardial infarction (AMI) frequently occurs in the heart and proceeds from myocardium ischemia and endoplasmic reticulum (ER) stress-induced cell death. Numerous studies on miRNAs indicated their potential as diagnostic biomarkers and treatment targets for heart diseases. Our study investigated the role of miR-17-5p and its regulatory mechanisms during AMI. Echocardiography, MTT, flow cytometry assay, evaluation of caspase-3 and lactate dehydrogenase (LDH) activity were conducted to assess cell viability, apoptosis in an MI/R mice model, and an H2O2-induced H9c2 hypoxia cell model, respectively. The expression levels of ER stress response-related biomarkers were detected using qRT-PCR, IHC, and western blotting assays. The binding site of miR-17-5p on Tsg101 mRNA was determined by bioinformatic prediction and luciferase reporter assay. The expression levels of miR-17-5p were notably elevated in MI/R mice and hypoxia cell models, accompanied by enhanced cell apoptosis. Inhibition of miR-17-5p led to decreased apoptosis related to ER stress response in the hypoxia model, which could be counteracted by knockdown of Tsg101 (tumor susceptibility gene 101). Transfection with miR-17-5p mimics downregulated the expression of Tsg101 in H9c2 cells. Luciferase assay demonstrated the binding between miR-17-5p and Tsg101. Moreover, 4-PBA, the inhibitor of the ER stress response, abolished shTsg101 elevated apoptosis in hypoxic H9c2 cells. Our findings investigated the pro-apoptotic role of miR-17-5p during MI/R, disclosed the specific mechanism of miR-17-5p/Tsg101 regulatory axis in ER stress-induced myocardium injury and cardiomyocytes apoptosis, and presented a promising diagnostic biomarker and potential target for therapy of AMI.

Gene-modified Exosomes Protect the Brain Against Prolonged Deep Hypothermic Circulatory Arrest.

BACKGROUND: Neurologic deficit remains a major complication after cardiovascular surgeries with deep hypothermic circulatory arrest (DHCA). We hypothesized that exosomes derived from bone marrow mesenchymal stem cells (MSCs) may conduct cerebral protection against prolonged DHCA in rats, and overexpressing microRNA-214 (miR-214) may further enhance the neuroprotection. METHODS: Cultured MSCs were transfected with lentivirus vectors containing pre-miR-214 or control vectors. Exosomes were isolated by centrifugation. The DHCA was conducted for 60 minutes when the pericranial temperature was cooled to 18°C. Exosomes from MSCs, MSCs transfected with control vectors, or pre-miR-214 were administered by intracerebroventricular injection 1 day before DHCA. RESULTS: Transfection of pre-miR-214 significantly enhanced the miR-214 expression in exosomes from MSCs. All exosome-pretreating groups exhibited lower levels of interleukin-1ß and tumor necrosis factor-α, higher capillary density, more significant neurogenesis and angiogenesis, and more normal neurons in the hippocampus than those of the control group. Exosome pretreatment markedly improved the spatial learning and memory function and vestibulomotor function. Compared with exosomes from MSCs or MSCs transfected with control vectors, miR-214-enriched exosomes remarkably enhanced the miR-214 level and expressions of phosphor-protein kinase B and Bcl-2, inhibited expressions of phosphate and tension homology, Bcl-2 interacting mediator of cell death, Bcl-2-associated X protein, and cleaved Caspase-3, and increased the number of survival neurons. Significantly better neurologic functions were also detected in rats pretreated with miR-214-enriched exosomes. CONCLUSIONS: Exosomes from MSCs conduct powerful neuroprotection against cerebral injury induced by DHCA, which can be further enhanced by genetic modification of the exosomes to overexpress miR-214.

Inhibition of long noncoding RNA growth arrest-specific 5 attenuates cerebral injury induced by deep hypothermic circulatory arrest in rats.

OBJECTIVE: We sought to investigate cerebroprotection by targeting long noncoding RNA growth arrest-specific 5 in a rat model of prolonged deep hypothermic circulatory arrest. METHODS: Deep hypothermic circulatory arrest was conducted for 60 minutes when the pericranial temperature was cooled to 18°C in rats. Dual luciferase assay was used to detect the binding relationship between growth arrest-specific 5 and putative target microRNAs. Adeno-associated viral vectors containing growth arrest-specific 5 small interfering RNA or negative control small interfering RNA were administered by intracerebroventricular injection 14 days before deep hypothermic circulatory arrest. Expressions of growth arrest-specific 5, microRNA-23a, phosphate and tension homology, Bcl-2-associated X protein, Bcl-2, phospho-protein kinase B, protein kinase B, and cleaved caspase-3 in the hippocampus were measured by quantitative reverse transcription polymerase chain reaction and Western blot. Spatial learning and memory functions were evaluated by the Morris water maze test. The hippocampus was harvested for histologic examinations and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining. RESULTS: Luciferase assay showed that growth arrest-specific 5 targeted and inhibited microRNA-23a expression. After deep hypothermic circulatory arrest, hippocampal growth arrest-specific 5 expression was significantly enhanced with a robust decrease of hippocampal microRNA-23a expression. Small interfering RNA growth arrest-specific 5 significantly inhibited growth arrest-specific 5 expression and enhanced microRNA-23a expression in the hippocampus, accompanied with decreases of phosphate and tension homology and Bcl-2-associated X protein expression, and increases of Bcl-2 expression and phospho-protein kinase B/protein kinase B ratio. Growth arrest-specific 5 knockdown inhibited neuronal apoptosis, attenuated histologic damages, and increased the number of surviving neurons in the hippocampus. Spatial learning and memory functions after deep hypothermic circulatory arrest were also markedly improved by growth arrest-specific 5 inhibition. CONCLUSIONS: Inhibition of large noncoding RNA growth arrest-specific 5 can provide a powerful cerebroprotection against deep hypothermic circulatory arrest, which may be mediated through microRNA-23a/phosphate and tension homology pathway.

Inhibition of MicroRNA-204 Conducts Neuroprotection Against Spinal Cord Ischemia.

BACKGROUND: MicroRNA(miR)-204 is an autophagy- and apoptosis-related gene. Neuroprotection by the inhibition of miR-204 against spinal cord ischemia was evaluated, and the roles of neuronal autophagy and apoptosis were investigated. METHODS: Spinal cord ischemia was conducted in rats by cross-clamping the descending aorta for 14 minutes. Inhibition of miR-204 was induced by intrathecal injection of lentivirus vectors containing antagomiR-204. Hind-limb motor function was assessed with the motor deficit index. Lumbar spinal cords were harvested for histologic examinations and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining. Autophagy was evaluated by the LC3-II/LC3-I ratio and beclin-1 expression. Expressions of LC3-I, LC3-II, beclin-1, B-cell lymphoma-2 (BCL-2), caspase-3, and miR-204 were measured by Western blot and quantitative real-time polymerase chain reaction. Autophagy was blocked by 3-methyladenine. RESULTS: Transient ischemia enhanced miR-204 expression and the LC3-II/LC3-I ratio and downregulated BCL-2 expression in spinal cords in a time-dependent manner. AntagomiR-204 significantly reduced expressions of miR-204 and caspase-3, dramatically upregulated expressions of beclin-1 and BCL-2 and the LC3-II/LC3-I ratio in spinal cords after reperfusion. Compared with controls, inhibition of miR-204 markedly decreased the motor deficit index scores at 6, 12, 24, and 48 hours after reperfusion; increased the number of viable motor neurons; and decreased the number of apoptotic neurons. 3-Methyladenine completely abolished enhancements of the LC3-II/LC3-I ratio and beclin-1 expression induced by antagomiR-204 and inhibited the protective effect on hind-limb motor function. CONCLUSIONS: Inhibition of miR-204 exerts spinal cord protection against ischemia-reperfusion injury, possibly via promotion of autophagy and antiapoptotic effects.

Exosomes derived from bone marrow mesenchymal stem cells overexpressing microRNA-25 protect spinal cords against transient ischemia.

OBJECTIVE: We investigated the neuroprotection of exosomes derived from bone marrow mesenchymal stem cells overexpressing microRNA-25 on ischemic spinal cords. METHODS: Cultured mesenchymal stem cells were transfected with lentivirus vectors containing pre-microRNA-25 or control vectors. Exosomes were isolated and harvested by centrifugation. Spinal cord ischemia was induced in rats by crossclamping the descending aorta just distal to the left subclavian artery for 15 minutes. Exosomes from mesenchymal stem cells, mesenchymal stem cells transfected with control vector, or pre-microRNA-25 were administered by intrathecal injection before ischemia. Hind-limb motor function was assessed with the motor deficit index. Contents of interleukin-1ß, tumor necrosis factor-α, malondialdehyde, and superoxide dismutase activity were measured using commercial kits. Expressions of NADPH oxidase 2, NADPH oxidase 4, and microRNA-25 were detected by Western blot and quantitative reverse transcription polymerase chain reaction. Lumbar spinal cords were harvested for histologic examination. RESULTS: Transfection of pre-microRNA-25 significantly enhanced microRNA-25 levels in mesenchymal stem cells and their exosomes (P < .001). All exosome-pretreating groups exhibited lower levels of interleukin-1ß and tumor necrosis factor-α (P < .001), more intact motor neurons (P < .001), and lower motor deficit index scores (P < .005) than those of controls. Compared with exosomes, microRNA-25-enriched exosomes markedly enhanced microRNA-25 level (P < .001), inhibited NADPH oxidase 4 expression (P = .012), but not NADPH oxidase 2 expression, decreased malondialdehyde content (P = .022), increased superoxide dismutase activity (P < .001) in spinal cords, and had additional neuroprotective effects as evidenced by lower motor deficit index scores (P < .005) and more survival neurons (P = .002). CONCLUSIONS: The neuroprotection of exosomes from mesenchymal stem cells on ischemic spinal cords can be enhanced by genetic modification of the exosomes to contain elevated microRNA-25.

Chipmunk Brain Is Resistant to Injury from Deep Hypothermic Circulatory Arrest During Cardiopulmonary Bypass.

Chipmunk as a food-storing hibernator naturally undergoes hibernation that is linked to great changes in systemic physiology and could protect the central nervous system during drastically reduced cerebral blood flow and low temperature in hibernation. Deep hypothermic circulatory arrest (DHCA) is associated with neurological dysfunction. We aim to test whether the euthermic chipmunk is resistant to injury from DHCA. Sprague-Dawley (SD) rats were used in a positive control. Ten euthermic chipmunks and 10 rats were subjected to 60-minute DHCA. Sham rats and chipmunks received cannulations. The blood samples after surgery were extracted to measure the tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) level. The levels of opioid receptor delta 1 (OPRD1), mature brain-derived neurotrophic factor (m-BDNF), precursor of BDNF (pro-BDNF), TrkB, GRB2, Erk, p-Erk, P38, Bcl-2, P75NTR, TRAF6, JNK, P53, Bax, and Caspase3 of the hippocampus were analyzed at 24 hours after surgery. The brain of chipmunks and rats were fixed for histopathological assessment. In the DHCA rat group, the levels of TNF-α and IL-6 were greater (p < 0.05) compared with DHCA chipmunks. In the DHCA chipmunk group, the levels of OPRD1, mature BDNF/pro-BDNF, TrkB-FL/TrkB-T1, Bcl-2, and p-Erk/Erk of hippocampus were higher than DHCA rats. The levels of GRB2, P75NTR, TRAF6, P53, Bax, and Caspase3 in DHCA chipmunks were lower than DHCA rats. The histopathological assessment showed that the injury in DHCA rat group was more severe than the DHCA chipmunk group. Euthermic chipmunks were greatly tolerant to global cerebral injury during DHCA. Different isoforms of BDNF might be involved in the resistant strategy.

Clinical study of acute renal injury after deep hypothermic circulatory arrest / 中国胸心血管外科临床杂志

@#Objective    To investigate the incidence of acute kidney injury (AKI) after deep hypothermic circulatory arrest (DHCA), to explore the risk factors and prognosis of postoperative AKI, and to establish a relatively accurate preoperative risk assessment strategy and prevention measures. Methods    The clinical data of 252 patients who underwent deep hypothermic circulatory surgery in our hospital from January 2014 to October 2018 were retrospectively analyzed. There were 179 males and 73 females with an average age of 53.6±11.6 years. The patients were divided into an AKI group and a non-AKI group according to the AKI diagnostic criteria developed by kidney disease improving global outcomes (KDIGO). The data of the two groups were compared, and the risk factors related to AKI after DHCA were analyzed by single factor and multivariate logistic regression. Results    Among the 252 patients enrolled, the incidence of AKI was 69.0%. The postoperative hospital mortality rate was 7.9% (20/252). The univariate analysis showed that the patient's age and body mass index (BMI)≥28 kg/m2, left ventricular ejection fraction<55%, preoperative serum creatinine (Scr)≥110 μmol/L, preoperative estimated glomerular filtration rate (eGFR), Cleveland score and intraoperative cardiopulmonary bypass time, intraoperative infusion of red blood cells, intraoperative infusion of plasma, postoperative  mechanical ventilation time≥40 h and other indicators were significantly different between the two groups (P<0.05); multivariate logistic regression analysis showed that there was significant difference between the two groups in age (OR=1.040, 95% CI 1.017–1.064, P=0.001), BMI≥28 kg/m2 (OR=2.335, 95%CI 1.093–4.990, P=0.029), eGFR<90 mL/(min·1.73 m2) (OR=2.044, 95%CI 1.082–3.863, P=0.028), preoperative Cleveland score (OR=1.300, 95%CI 1.054–1.604, P=0.014) and intraoperative cardiopulmonary bypass time (OR=1.009, 95%CI 1.002–1.017, P=0.014). Conclusion    The incidence of AKI is higher after DHCA. Patients with postoperative AKI have longer hospital stay and higher risk of hospitalization death. The age of patients, BMI≥28 kg/m2, eGFR<90 mL/(min·1.73) m2, Cleveland score, intraoperative extracorporeal circulation time are independent risk factors for AKI after DHCA.

Protection of the rat brain from hypothermic circulatory arrest injury by a chipmunk protein.

OBJECTIVES: The study objectives were to test the hypothesis that special protein exists in hibernating chipmunk albumin and whether this protein has a neuroprotective effect in Sprague-Dawley rats during deep hypothermia circulatory arrest. METHODS: Forty chipmunks were allocated into a hibernation group and an active group (20 chipmunks in each group). Special protein was detected and isolated from hibernating chipmunk albumin. Forty Sprague-Dawley rats were randomly divided into a sham group, deep hypothermia circulatory arrest group, special protein group, and naloxone group (10 rats in each group). Special protein that was detected and collected from hibernating chipmunks were injected in rats in the special protein group for 3 consecutive days before operation, and naloxone was given at the same time in the naloxone group. Rats were subjected to cardiopulmonary bypass and 60-minute deep hypothermia circulatory arrest. Tumor necrosis factor-α and interleukin-6 levels were detected. Animals received neurologic testing. Relative protein expression, malondialdehyde, and superoxide dismutase of hippocampus were detected. The brain was fixed for histopathologic assessment. RESULTS: The rats that received special protein displayed ischemic tolerance after deep hypothermia circulatory arrest. The neuroprotective effect could be reversed by naloxone. The inflammation response was attenuated in the special protein group (P < .008, compared with the deep hypothermia circulatory arrest and naloxone groups). The mature brain-derived neurotrophic factor and SIRT1 levels were higher in the special protein group (P < .01, compared with the deep hypothermia circulatory arrest and naloxone groups). Histopathologic assessment showed that the injury in the special protein group was attenuated (pathological score, P < .05; surviving hippocampal CA1 neurons, P < .01; TUNEL-positive neurons, P < .01; compared with deep hypothermia circulatory arrest and naloxone groups). Intravenous injection of special protein significantly improved neurologic recovery. CONCLUSIONS: We found that a specific protein existed in hibernating chipmunk albumin and could play an important neuroprotective role in rats.

Overexpression of MicroRNA-106b-5p Attenuates Kidney Injuries after Deep Hypothermic Circulatory Arrest in Rats.

BACKGROUND: MicroRNAs (miRNA) have been identified to exert a wide range of biological functions in acute kidney injury (AKI) after deep hypothermic circulatory arrest (DHCA). We sought to investigate the renoprotection of miRNA-106b-5p in a rat model of DHCA by targeting phosphatase and tensin homolog (PTEN). METHODS: Overexpression of miRNA-106b-5p in vivo was conducted by directly injection of lentivirus vectors containing pre-miRNA-106b-5p into the renal parenchyma of the animals under the ultrasound guidance 7 days before DHCA. The vehicle or control lentivirus vectors were given to the control group or the control vector group, respectively. Renal function and apoptosis activity were evaluated by serum cystatin C, serum/tissue neutrophil gelatinase-associated lipocalin (NGAL), and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay (TUNEL) at 24 hours after surgery. Expressions of miRNA-106b-5p, PTEN, and caspase-3 in the kidney were evaluated by quantitative real-time polymerase chain reaction and western blot analysis. RESULTS: Transfection of pre-miRNA-106b-5p significantly enhanced the expression of miRNA-106b-5p and dramatically downregulated the expressions of PTEN in the kidney compared with the control group. Renal functions were markedly protected by pretreatment with pre-miRNA-106b-5p as evidenced by decreases in serum cystatin C and serum/tissue neutrophil gelatinase-associated lipocalin at 24 hours after surgery. The pre-miRNA-106b-5p group showed significantly fewer apoptotic cells and lower levels of caspase-3 activation than the control group. CONCLUSIONS: Overexpression of miRNA-106b-5p attenuates kidney injuries after DHCA, possibly by inhibition of PTEN.

A novel augmented venous-drainage model of cardiopulmonary bypass for deep hypothermic circulatory arrest without blood priming.

OBJECTIVE: Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) are commonly used in cardiac surgery. However, the mortality and morbidity are still high in practice. Developing novel protective stategies and elucidating the underlying mechanisms for the pathophysiological consequences of DHCA have been hampered because of the absence of a satisfactory recovery animal model. The aim of this study was to establish a novel and safe DHCA model without blood priming in rats to study the pathophysiology of potential complications. METHODS: Ten adult male Sprague-Dawley rats (age, 14-16 weeks; weight, 200-300g) were used. The entire CPB circuit consisted of a modified reservoir, a custom-designed small-volume membrane oxygenator, a roller pump and a home-made heat exchanger, all of which were connected via silicon tubing. The volume of the priming solution was less than 10 ml. The right jugular vein, right carotid artery and left femoral artery were cannulated. The blood was drained from the right atrium through the right jugular vein and fed back to the rat via the left femoral artery. CPB was commenced at a full flow rate. The animals were cooled to a pericranial temperature of 18°C and then subjected to 45 minutes of DHCA with global ischemia. Circulatory arrest was followed by rewarming and over 60 minutes of reperfusion. CPB was terminated carefully. Blood in the circuit was centrifuged and slowly transfused to achieve optimal hematocrit. Blood gas and hemodynamic parameters were recorded at each time point before CPB, during CPB and after CPB. RESULTS: All CPB and DHCA processes were achieved successfully. No rat died in our research. Blood gas analyses at different times were normal. Cardiac function and blood pressure were stable after the operation. The vital signs of all the rats were stable. CONCLUSION: The novel augmented venous-drainage CPB and DHCA model in rats could be established successfully without blood priming.