Jiakai Lu

Post-conditioning by xenon reduces ischaemia-reperfusion injury of the spinal cord in rats.

The neuroprotective effects of xenon post‐conditioning following spinal cord injury remain unknown. We monitored the effect of xenon post‐conditioning on the spinal cord following ischaemia‐reperfusion injury and determined its mechanism of action.

Timing of xenon-induced delayed postconditioning to protect against spinal cord ischaemia–reperfusion injury in rats

BACKGROUND This study was designed to assess the neuroprotective effect of xenon-induced delayed postconditioning on spinal cord ischaemia-reperfusion injury (IRI) and to determine the time of administration for best neuroprotection in a rat model of spinal cord IRI. METHODS Fifty male rats were randomly divided equally into a sham group, control group, and three xenon postconditioning groups (n=10 per group). The control group underwent spinal cord IRI and immediately inhaled 50% nitrogen/50% oxygen for 3 h at the initiation of reperfusion. The three xenon postconditioning groups underwent the same surgical procedure and immediately inhaled 50% xenon/50% oxygen for 3 h at the initiation of reperfusion or 1 and 2 h after reperfusion. The sham operation group underwent the same surgical procedure without aortic occlusion, and inhaled 50% nitrogen/50% oxygen. Neurological function was assessed using the Basso, Beattie, and Bresnahan score at 4, 24, and 48 h of reperfusion. Histological examination was performed using Nissl staining and immunohistochemistry, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling staining. RESULTS Compared with the control group, the three xenon postconditioning groups showed improvements in neurological outcomes, and had more morphologically normal neurones at 48 h of reperfusion. Apoptotic cell death was reduced and the ratio of Bcl-2/Bax immunoreactivity increased in xenon-treated rats compared with controls. CONCLUSIONS Xenon postconditioning up to 2 h after reperfusion provided protection against spinal cord IRI in rats, but the greatest neuroprotection occurred with administration of xenon for 1 h at reperfusion.

Serine-threonine protein kinase activation may be an effective target for reducing neuronal apoptosis after spinal cord injury.

The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase (ERK), serine-threonine protein kinase (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt (p-Akt) and phosphorylated ERK (p-ERK) increased immediately after reperfusion, peaked at 4 hours (p-Akt) or 2 hours (p-ERK), decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury.

Mechanism and early intervention research on ALI during emergence surgery of Stanford type-A AAD: Study protocol for a prospective, double-blind, clinical trial.

Background:Stanford type-A acute aortic dissection (AAD) is a severe cardiovascular disease demonstrating the characteristics of acute onset and rapid development, with high morbidity and mortality. The available evidence shows that preoperative acute lung injury (ALI) induced by Stanford type-A AAD is a frequent and important cause for a number of untoward consequences. However, there is no study assessing the incidence of preoperative ALI and its independent determinants before Standford type-A AAD surgery in Chinese adult patients. Methods/design:This is a prospective, double-blind, signal-center clinical trial. We will recruit 130 adult patients undergoing Stanford type-A AAD surgery. The incidence of preoperative ALI will be evaluated. Perioperative clinical baselines and serum variables including coagulation, fibrinolysis, inflammatory, reactive oxygen species, and endothelial cell function will be assayed. The independent factors affecting the occurrence of preoperative ALI will be identified by multiple logistic regression analysis. Trial registration:ClinicalTrials.gov (https://register.clinicaltrials.gov/), Registration number NCT01894334.

Xenon-delayed postconditioning attenuates spinal cord ischemia/reperfusion injury through activation AKT and ERK signaling pathways in rats

Previous studies have shown that xenon-delayed postconditioning for up to 2h after reperfusion provides protection against spinal cord ischemia/reperfusion (I/R) injury in rats. This study was designed to determine the roles of phosphatidylinositol 3-kinase (PI3K)-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection. The rats were randomly assigned to the following nine groups (n=16∗9): 1) I/R+N2 group, 2) I/R+Xe group, 3) I/R+PD98059+N2 group (ERK blocking agent), 4) I/R+wortmannin+N2 group (PI3K-Akt blocking agent), 5) I/R+PD98059+Xe group, 6) I/R+wortmannin+Xe group, 7) I/R+DMSO+Xe group (dimethyl sulfoxide, vehicle control), 8) I/R+DMSO+N2 group, and 9) sham group (no spinal cord ischemia and no xenon). Spinal cord ischemia was induced for 25min in male Sprague-Dawley rats. Neurological function was assessed using the Basso, Beattie, and Bresnahan (BBB) open-field locomotor scale at 6, 12, 24 and 48h after reperfusion. Histological examination of the lumbar spinal cord was performed using Nissl staining and TUNEL staining at 4 (n=8) and 48 (n=8)h after reperfusion. Western blotting was performed to evaluate p-Akt and p-ERK expression in the spinal cord at 4 (n=8) and 48 (n=8) h after reperfusion. Compared with the sham group, all rats in the I/R groups had lower BBB scores, fewer normal motor neurons, more apoptotic neurons and lower p-Akt and p-ERK levels at each time point (P<0.05). Compared with the I/R group, rats in the I/R+Xe group had higher neurological scores, more normal motor neurons, fewer apoptotic neurons and significantly higher levels of p-Akt and p-ERK at each time point (P<0.05). Compared with the I/R+Xe group, the I/R+PD98059+Xe and I/R+wortmannin+Xe groups showed worse neurological outcomes and less p-Akt and p-ERK at each time point (P<0.05). These results suggest that xenon-delayed postconditioning improves neurological outcomes to spinal cord I/R injury in rats through the activation of the AKT and ERK signaling pathways.

Protection of xenon against postoperative oxygen impairment in adults undergoing Stanford Type-A acute aortic dissection surgery: Study protocol for a prospective, randomized controlled clinical trial

Objectives: The available evidence shows that hypoxemia after Stanford Type-A acute aortic dissection (AAD) surgery is a frequent cause of several adverse consequences. The pathogenesis of postoperative hypoxemia after AAD surgery is complex, and ischemia/reperfusion and inflammation are likely to be underlying risk factors. Xenon, recognized as an ideal anesthetic and anti-inflammatory treatment, might be a possible treatment for these adverse effects. Methods/Design: The trial is a prospective, double-blind, 4-group, parallel, randomized controlled, a signal-center clinical trial. We will recruit 160 adult patients undergoing Stanford type-A AAD surgery. Patients will be allocated a study number and will be randomized on a 1:1:1:1 basis to receive 1 of the 3 treatment options (pulmonary inflated with 50% xenon, 75% xenon, or 100% xenon) or no treatment (control group, pulmonary inflated with 50% nitrogen). The aims of this study are to clarify the lung protection capability of xenon and its possible mechanisms in patients undergoing the Stanford type-A AAD surgery. Discussion: This trial uses an innovative design to account for the xenon effects of postoperative oxygen impairment, and it also delineates the mechanism for any benefit from xenon. The investigational xenon group is considered a treatment intervention, as it includes 3 groups of pulmonary static inflation with 50%, 75%, and 100% xenon. It is suggested that future trials might define an appropriate concentration of xenon for the best practice intervention.

Current Status of Cardiovascular Anesthesia in China

High quality and safe cardiac anesthesia is a prerequisite for success in cardiac care. Cardiac surgery has developed rapidly over recent years in China. Because of language barriers, the current status of cardiac anesthesia in China is not well known to Western countries. To assess practice patterns, volume, workforce, and training requirements of Chinese cardiovascular anesthesiologists, we surveyed 92 major cardiovascular centers in China regarding their anesthesia practice, monitoring techniques, resources, staffing, and work hours. We aim to provide a review of the history, new developments, and a current cross section of cardiac anesthesia practice patterns in China. The goal is to allow Western readers to understand the unique achievements and challenges in Chinese cardiovascular anesthesiology, thus promoting further communications with Chinese cardiovascular anesthesiologists.

Delayed xenon post-conditioning mitigates spinal cord ischemia/reperfusion injury in rabbits by regulating microglial activation and inflammatory factors

The neuroprotective effect against spinal cord ischemia/reperfusion injury in rats exerted by delayed xenon post-conditioning is stronger than that produced by immediate xenon post-conditioning. However, the mechanisms underlying this process remain unclear. Activated microglia are the main inflammatory cell type in the nervous system. The release of pro-inflammatory factors following microglial activation can lead to spinal cord damage, and inhibition of microglial activation can relieve spinal cord ischemia/reperfusion injury. To investigate how xenon regulates microglial activation and the release of inflammatory factors, a rabbit model of spinal cord ischemia/reperfusion injury was induced by balloon occlusion of the infrarenal aorta. After establishment of the model, two interventions were given: (1) immediate xenon post-conditioning—after reperfusion, inhalation of 50% xenon for 1 hour, 50% N2/50%O2 for 2 hours; (2) delayed xenon post-conditioning—after reperfusion, inhalation of 50% N2/50%O2 for 2 hours, 50% xenon for 1 hour. At 4, 8, 24, 48 and 72 hours after reperfusion, hindlimb locomotor function was scored using the Jacobs locomotor scale. At 72 hours after reperfusion, interleukin 6 and interleukin 10 levels in the spinal cord of each group were measured using western blot assays. Iba1 levels were determined using immunohistochemistry and a western blot assay. The number of normal neurons at the injury site was quantified using hematoxylin-eosin staining. At 72 hours after reperfusion, delayed xenon post-conditioning remarkably enhanced hindlimb motor function, increased the number of normal neurons at the injury site, decreased Iba1 levels, and inhibited interleukin-6 and interleukin-10 levels in the spinal cord. Immediate xenon post-conditioning did not noticeably affect the above-mentioned indexes. These findings indicate that delayed xenon post-conditioning after spinal cord injury improves the recovery of neurological function by reducing microglial activation and the release of interleukin-6 and interleukin-10.

Pulmonary static inflation with 50% xenon attenuates decline in tissue factor in patients undergoing Stanford type A acute aortic dissection repair

Background The Stanford type A acute aortic dissection (AAD) carries a high risk of mortality and morbidity, and patients undergoing AAD surgery often bleed excessively and require blood products and transfusions. Thus, we studied how xenon alters coagulation using thromboelastography (TEG) and conventional hemostatic tests for patients with AAD undergoing aortic arch surgery involving cardiopulmonary bypass (CPB)/deep hypothermic circulatory arrest (DHCA). Methods This prospective single-center nonrandomized controlled clinical trial, registered in the Chinese Clinical Trial Registry (ChiCTR-ICR-15006435), assessed perioperative clinical variables and serological results from 50 subjects undergoing pulmonary static inflation with 50% nitrogen/50% oxygen from January 2013 to January 2014 and 50 subjects undergoing pulmonary static inflation with 50% xenon/50% oxygen from January 2014 to December 2014 during CPB for Stanford type A AAD. Repeated measures ANOVA were used to identify the effects of xenon on coagulation after surgery. The primary endpoint was perioperative changes in coagulation and fibrinolysis after intubation and 10 minutes, and 6 hours after the operation. The secondary endpoint was to assess the perioperative changes in serum level of tissue factor (TF), tissue factor pathway inhibitor (TFPI) and tissue plasminogen activator (tPA) after intubation and 10 minutes, and 6 hours after the operation. Results Mean prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), median fibrinogen degradation product (FDP), and D-dimer peaked and then decreased over 6 hours after surgery. TEG followed a similar trend. From the start to the end of surgery and until 6 h after surgery, mean TF decreased in controls (β -2.61, P<0.001 and β -2.83, P<0.001, respectively), but was maintained relatively stable in xenon group (β -0.5, P<0.001 and β -0.96, P<0.001, respectively). Conclusions Deterioration of coagulation function and activated fibrinolysis was confirmed by conventional tests and TEG analysis after Stanford type A AAD repair. Pulmonary static inflation with 50% xenon attenuates decline in TF in patients undergoing Stanford type A AAD repair.

Independent factors related to preoperative acute lung injury in 130 adults undergoing Stanford type-A acute aortic dissection surgery: a single-center cross-sectional clinical study

Background Previous retrospective study suggested that acute lung injury (ALI) is frequent (78.49%) in patients undergoing aortic dissection surgery, and accompanied by a number of untoward consequences, and even induces death. Methods This prospective single-center cross-sectional study, registered in the ClinicalTrials.gov (Identifier: NCT01894334), assessed the preoperative clinical variables and serological results from 130 adult patients scheduled for Stanford type-A acute aortic dissection (AAD) surgery at Beijing Anzhen Hospital between January 2013 and July 2014. Exclusion criteria included patients with coronary heart disease, severe heart failure, severe cardiac tamponade and severe nervous system abnormalities. Preoperative ALI was identified according to oxygenation index (OI) calculated by PaO2/FiO2 ratio after anesthesia induction, and all the patients were divided into two groups: non-ALI (OI ≥300 mmHg) and ALI (OI <300 mmHg). The primary endpoint was the incidence of preoperative ALI. The secondary endpoints were the independent factors affecting the occurrence of preoperative ALI. Results The incidence of preoperative ALI was 53.8%. With adjusted multiple logistic regression analysis, age [odds ratio (OR) 1.14, confidence interval (CI), 1.06-1.22; P=0.0002], body mass index (BMI) (OR 1.31, CI, 1.09-1.56; P=0.0033), preoperative diastolic blood pressure (DBP) (OR 0.94, CI, 0.89-0.99; P=0.0109), interleukin-6 (IL-6) (OR 1.03, 95% CI, 1.01-1.06; P=0.0053), and prostaglandin I2/thromboxane B2 (PGI2/TXB2) ratio (OR 0.25, 95% CI, 0.09-0.67; P=0.0055) were significantly related to the occurrence of preoperative ALI. The decreased risk of ALI was related to the preoperative DBP value up to 44 mmHg (OR 0.935, 95% CI, 0.895-0.978; P=0.0033). Interactions analysis revealed that serum lactic acid mediated the relationship between DBP and ALI before Stanford type-A AAD surgery. Conclusions In adults undergoing Stanford type-A AAD surgery, the incidence of preoperative ALI was 53.8%, and age, BMI, preoperative DBP, IL-6, and PGI2/TXB2 ratio were independent factors related to the occurrence of pre-operative ALI. Trial Registration: ClinicalTrials.gov, Identifier: NCT01894334.