Transient Spinal Cord Ischemia Research Articles

Abdominal Aortic Aneurysm Manifested by Transient Spinal Cord Ischemia: a Case Report

Abdominal Aortic Aneurysm Manifested by Transient Spinal Cord Ischemia: a Case Report

Awake rabbit model of ischemic spinal cord injury with delayed paraplegia: The role of ambient temperature.

Paraplegia after spinal cord ischemia is a devastating condition in the clinic. Here, we develop an awake rabbit model of spinal cord ischemia with delayed paraplegia and explore the influence of ambient temperature on the outcomes after injury. A total of 47 male rabbits were involved in the present study. Transient spinal cord ischemia was induced by occluding the infrarenal abdominal aorta of awake rabbits at different ambient temperatures. To find the optimal conditions for developing delayed paraplegia, hindlimb motor function after ischemia was evaluated between experiments. The onset and magnitude of ischemic injury varied with the ambient temperature maintained during the peri-ischemia period. More serious spinal cord injury occurred when ischemia was induced at higher temperatures. At 18°C, 25-minute ischemia resulted in 74% of rabbits developing delayed paraplegia. At a temperature of 28°C or higher, most of the animals developed acute paraplegia immediately. While at 13°C, rabbits usually regained normal motor function without paraplegia. This awake rabbit model is highly reproducible and will be helpful in future studies of delayed paraplegia after spinal cord ischemia. The ambient temperature must be considered while using this model during investigation of therapeutic interventions.

Prophylactic cerebrospinal fluid drainage and spinal cord ischemia in thoracic and thoracoabdominal endovascular procedures: a systematic review and meta-analysis.

Spinal cord ischemia (SCI) is one of the most devastating complications of thoracic endovascular aortic repair (TEVAR). Prophylactic cerebrospinal fluid drainage (CSFD) has been shown to decrease the risk of SCI in open thoracic aortic procedures; however, its utility in TEVAR remains uncertain. This systematic review and meta-analysis aim to determine the role of prophylactic CSFD in preventing SCI in TEVAR. A literature search of five databases was performed and all studies published before September 2022 that reported SCI rates in TEVAR patients undergoing prophylactic CSFD were included. A random effects meta-analysis of means or proportions was performed for single-arm data. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported for comparisons between groups. A total of 4,793 patients undergoing TEVAR from 40 studies were included. The mean age was 68.8 years and 70.9% of patients were male. The overall SCI rate was 3.5%, with a 1.3% rate of immediate SCI and a 1.9% rate of delayed SCI. There were no significant differences in SCI rates between prophylactic CSFD patients and non-drained patients. Routine CSFD did not have a significant impact on SCI rates compared to non-drained patients. There was an increased rate of transient SCI with selective CSFD compared to non-drained patients (OR 2.08; 95% CI: 1.06-4.08; P=0.03). The most common drain-related complication was spinal headache (4.3%). The major complication rate was 1.6%, of which epidural or spinal hematoma (0.9%) was the most common, followed by intracranial or subdural hemorrhage (0.8%) and paraparesis or paraplegia (0.8%). This study found no significant difference in SCI rates between prophylactic CSFD patients and their non-drained counterparts. CSFD is associated with a small but non-negligible risk of serious complications. Multi-center randomized controlled trials (RCTs) are warranted to help stratify the risk of both SCI and CSFD-related complications in patients undergoing endovascular aortic procedures.

Necrostatin-1 Attenuates Delayed Paraplegia after Transient Spinal Cord Ischemia in Rabbits by Inhibiting the Upregulation of Receptor-Interacting Protein Kinase 1 and 3

Delayed-onset paraplegia is a disastrous complication after thoracoabdominal aortic open surgery and thoracic endovascular aortic repair. Studies have revealed that transient spinal cord ischemia caused by temporary occlusion of the aorta induces delayed motor neuron death owing to apoptosis and necroptosis. Recently, necrostatin-1 (Nec-1), a necroptosis inhibitor, has been reported to reduce cerebral and myocardial infarction in rats or pigs. In this study, we investigated the efficacy of Nec-1 in delayed paraplegia after transient spinal cord ischemia in rabbits and assessed the expression of necroptosis- and apoptosis-related proteins in motor neurons. This study used rabbit transient spinal cord ischemia models using a balloon catheter. They were divided into a vehicle-treated group (n=24), Nec-1-treated group (n=24), and sham-controls (n=6). In the Nec-1-treated group, 1mg/kg of Nec-1 was intravascularly administered immediately before ischemia induction. Neurological function was assessed using the modified Tarlov score, and the spinal cord was removed 8hr and 1, 2, and 7days after reperfusion. Morphological changes were examined using hematoxylin and eosin staining. The expression levels of necroptosis-related proteins (receptor-interacting protein kinase [RIP] 1 and 3) and apoptosis-related proteins (Bax and caspase-8) were assessed using western blotting and histochemical analysis. We also performed double-fluorescence immunohistochemical studies of RIP1, RIP3, Bax, and caspase-8. Neurological function significantly improved in the Nec-1-treated group compared with that in the vehicle-treated group 7days after reperfusion (median 3 and 0, P=0.025). Motor neurons observed 7days after reperfusion were significantly decreased in both groups compared with the sham group (vehicle-treated, P<0.001; Nec-1-treated, P<0.001). However, significantly more motor neurons survived in the Nec-1-treated group than in the vehicle-treated group (P<0.001). Western blot analysis revealed RIP1, RIP3, Bax, and caspase-8 upregulation 8hr after reperfusion in the vehicle-treated group (RIP1, P=0.001; RIP3, P=0.045; Bax, P=0.042; caspase-8, P=0.047). In the Nec-1-treated group, the upregulation of RIP1 and RIP3 was not observed at any time point, whereas that of Bax and caspase-8 was observed 8hr after reperfusion (Bax, P=0.029; caspase-8, P=0.021). Immunohistochemical study revealed the immunoreactivity of these proteins in motor neurons. Double-fluorescence immunohistochemistry revealed the induction of RIP1 and RIP3, and that of Bax and caspase-8, in the same motor neurons. These data suggest that Nec-1 reduces delayed motor neuron death and attenuates delayed paraplegia after transient spinal cord ischemia in rabbits by selectively inhibiting necroptosis of motor neurons with minimal effect on their apoptosis.

Intranasal administration of polysulfide prevents neurodegeneration in spinal cord and rescues mice from delayed paraplegia after spinal cord ischemia

BackgroundDelayed paraplegia is a devastating complication of thoracoabdominal aortic surgery. Hydrogen sulfide (H2S) was reported to be protective in a mouse model of spinal cord ischemia and the beneficial effect of H2S has been attributed to polysulfides. The objective of this study was to investigate the effects of polysulfides on delayed paraplegia after spinal cord ischemia. Methods and resultsSpinal cord ischemia was induced in male and female C57BL/6J mice by clamping the aortic arch and the left subclavian artery. Glutathione trisulfide (GSSSG), glutathione (GSH), glutathione disulfide (GSSG), or vehicle alone was administered intranasally at 0, 8, 23, and 32 h after surgery. All mice treated with vehicle alone developed paraplegia within 48 h after surgery. GSSSG, but not GSH or GSSG, prevented paraplegia in 8 of 11 male mice (73%) and 6 of 8 female mice (75%). Intranasal administration of 34S-labeled GSSSG rapidly increased 34S-labeled sulfane sulfur species in the lumbar spinal cord. In mice treated with intranasal GSSSG, there were increased sulfane sulfur levels, and decreased neurodegeneration, microglia activation, and caspase-3 activation in the lumbar spinal cord. In vitro studies using murine primary cortical neurons showed that GSSSG increased intracellular levels of sulfane sulfur. GSSSG, but not GSH or GSSG, dose-dependently improved cell viability after oxygen and glucose deprivation/reoxygenation (OGD/R). Pantethine trisulfide (PTN-SSS) also increased intracellular sulfane sulfur and improved cell viability after OGD/R. Intranasal administration of PTN-SSS, but not pantethine, prevented paraplegia in 6 of 9 male mice (66%). ConclusionsIntranasal administration of polysulfides rescued mice from delayed paraplegia after transient spinal cord ischemia. The neuroprotective effects of GSSSG were associated with increased levels of polysulfides and sulfane sulfur in the lumbar spinal cord. Targeted delivery of sulfane sulfur by polysulfides may prove to be a novel approach to the treatment of neurodegenerative diseases.

Zone 2 hybrid thoracic endovascular aortic repair: Is it a good option for all types of thoracic aortic disease?

BackgroundZone 2 thoracic endovascular aortic repair (TEVAR) is performed for the treatment of various thoracic aortic diseases involving the left subclavian artery. This study aimed to analyze the late clinical outcomes of zone 2 hybrid TEVAR according to the various indications.MethodsA total of 48 patients who underwent zone 2 TEVAR at our institution between December, 2010 and July, 2020 were enrolled. The indications were aortic aneurysm (AA, n = 15), acute type B aortic dissection (AD, n = 14), penetrating aortic ulcer (PAU, n = 8), traumatic aortic injury (TAI, n = 8), and others (n = 3). The clinical outcomes including early complications and mid-term aortic measurements were retrospectively reviewed.ResultsThe technical success rate was 100% and in-hospital mortality occurred in one patient. The early postoperative complications included stroke (n = 1), transient spinal cord ischemia (n = 1), neck wound hematoma (n = 1), and left phrenic or vagus nerve injury (n = 9). In patients with AD, positive remodeling was observed in ten patients (76.9%) (false lumen regression in the entire or thoracic aorta [n = 9], false lumen thrombosis in the thoracic aorta [n = 1]). However, in patients with AA, increased aneurysm was found in six patients (40%). Persistent aneurysmal growth was found in patients with a maximal aortic diameter of > 60 mm on initial imaging (4/6, 50%). No aortic expansion was observed in those with TAI or PAU. Endoleak was noted in five patients (10.4%), and among them, aortic reintervention was required only in patients with large AAs.ConclusionsZone 2 hybrid TEVAR was associated with an acceptable early complication rate and provided acceptable mid-term aortic results for patients with AD, PAU, and TAI. However, patients with large AAs were at increased risk of aortic reintervention. In cases of large AA, clinicians should carefully consider whether zone 2 hybrid TEVAR or open surgical repair will be more effective for the patient.

The Neuroprotective Mechanism of Spinal Cord Stimulation in Spinal Cord Ischemia/Reperfusion Injury

Spinal cord ischemia/reperfusion (I/R) injury following thoracoabdominal aneurysm surgery can lead to severe lower limb neurologic defect. The preliminary result of our study suggested that spinal cord stimulation (SCS) postconditioning effectively protected spinal cord from I/R injury on rabbits. But the mechanism is unknown. In this study, we further investigated the mechanism of SCS postconditioning. New Zealand white rabbits were randomly divided into sham, I/R, I/R + 2 Hz SCS, and I/R + 50 Hz SCS group (n = 24/group). Transient spinal cord ischemia was induced by infrarenal aortic balloon occlusion and performed on all rabbits except rabbits of sham group. Rabbits of I/R group received no further intervention. Rabbits of I/R + 2 Hz SCS and I/R + 50 Hz SCS group received 2 Hz or 50 Hz SCS for 30 min at the onset of reperfusion and then daily. The expression of Akt (serine-threonine kinase)/p-Akt, STAT3 (signal transducer and activator of transcription 3)/p-STAT3 and GSK-3β (glycogen synthase kinase)/p-GSK-3β of spinal cord were measured by Western blot analysis at 8 h, 1 day, 3 day, and 7 day of reperfusion. The Akt expressions of sham, I/R, I/R + 2 Hz SCS, and I/R + 50 Hz SCS group were not significantly different at all prescribed time points, while the p-Akt expression of I/R + 2 Hz SCS group was significantly higher than that of I/R group and sham group at all prescribed time points; The STAT3 and p-STAT3 expression of I/R, I/R + 2 Hz SCS, and I/R + 50 Hz SCS group were not significantly different at all prescribed time points except that at 1day of reperfusion the p-STAT3 expression of I/R + 50 Hz SCS group was significantly lower than I/R group. The GSK-3β and p-GSK-3β expressions of I/R, I/R + 2 Hz SCS and I/R + 50 Hz SCS group were not significantly different at all prescribed time points. The neuroprotective effect of 2 Hz SCS postconditioning in spinal cord I/R injury is related to Akt activation but not regulation of STAT3 and GSK-3β phosphorylation.

New Preoperative Spinal Cord Ischemia Risk Stratification Model for Patients Undergoing Thoracic Endovascular Aortic Repair.

Our objective was to determine significant predictors of spinal cord ischemia (SCI) following Thoracic Endovascular Aortic Repair (TEVAR) and to further develop a simple and clinically orientated risk score model. A retrospective review of data from the Society of Vascular Surgery/Vascular Quality Initiative national data set was performed for all patients undergoing TEVAR from January, 2014 to June 2018. Preoperative demographics, procedure-related variables, and clinical details related to SCI were examined. A SCI risk score was developed utilizing a multivariable logistic regression model. For the 7889 patients in the final analysis who underwent TEVAR during the study period, the mean age was 67.6 ± 13.9, range 18 to 90 years, and the majority was male (65%). Postoperative outcomes included stroke (3.0%), myocardial infarction (2.9%), inhospital mortality (5.4%), transient SCI (1.5%), and permanent SCI (2.1%). Nearly half of the overall cases were performed in high volume centers. Predictors of increased risk for SCI included age by decade (odds ratio [OR]: 1.2), celiac coverage (OR: 1.5), current smoker (OR: 1.6), dialysis (OR: 1.9), 3 or more aortic implanted devices (OR: 1.7), emergent or urgent surgery (OR: 1.5), adjunct aorta-related procedure (OR: 2.5), adjunct not related (OR: 2.6), total estimated length of aortic device (19-31 cm, OR: 1.9 and ≥32 cm, OR: 3.0), ASA class 4 or 5 (OR: 1.6), and procedure time ≥154 minutes (OR: 1.8). Two predictors decreased the risk of SCI, cases from high-volume centers (OR: 0.6) and eGFR ≥ 60 (OR: 0.6). To evaluate the risk score model, probabilities of SCI from the original regression, raw score, and raw score categories resulted in area under the curve statistics of 0.792, 0.786, and 0.738, respectively. Spinal cord ischemia remains one of the most feared complications of TEVAR. Incidence of SCI in this large series of patients with TEVAR was 3.6% with nearly 60% being permanent. The proposed model provides an assessment tool to guide clinical decisions, patient consent process, risk-assessment, and procedural strategy.

Hypothermia Inhibits the Expression of Receptor Interacting Protein Kinases 1 and 3 After Transient Spinal Cord Ischaemia in Rabbits

Hypothermia Inhibits the Expression of Receptor Interacting Protein Kinases 1 and 3 After Transient Spinal Cord Ischaemia in Rabbits

Outcomes of fenestrated and branched endovascular aortic repair for chronic post-dissection thoracoabdominal aortic aneurysms.

Aneurysmal degeneration after acute dissection occurs in a significant proportion of patients. Fenestrated and branched stent-grafting (F/BEVAR) has been increasingly used to treat these post-dissection thoracoabdominal aortic aneurysms (PD-TAAA). The aim of this study was to report early and mid-term outcomes of F/BEVAR in PD-TAAA. Retrospective single center analysis of a prospectively maintained database including all patients undergoing F/BEVAR for PD-TAAA between October 2010-February 2020. Fifty-five patients (45 males, mean age 66±10 years) were included. Technical success was achieved in all patients. Thirty-day mortality was two (3.6%) patients. Major perioperative complications were noted in nine (16.4%) patients including five (9.1%) with transient spinal cord ischemia (SCI) and one (1.8%) with permanent paraplegia. Mean follow-up was 24 months (1-76 months). Cumulative survival rates at 12, 24 and 36 months were 87±5.5%, 83.5±6.3% and 72.2±8.1%, respectively. Estimated freedom from reintervention at 12, 24 and 36 months was 82.2±6.7%, 60.1±9.2% and 55.9±9.5%, respectively. Main reasons for reintervention were endoleaks from target vessels and common iliac arteries. Estimated target vessel patency at 12, 24 and 36 months was 97.8±1.2%, 95.4±2.1%, and 94.1±2.4%, respectively. Mean aneurysm sac regression during follow-up was 7.9±7.1 mm, with complete false lumen thrombosis in 80% of patients. No ruptures occurred during follow-up. F/BEVAR for PD-TAAA is associated with low perioperative mortality and morbidity in a large volume endovascular center. Mid-term results demonstrate a high rate of aneurysm sac regression. Extended sealing with longer bridging stents for target vessels is recommended.

Comparison between Arch Zones in Modified Frozen Elephant Trunk Procedure for Complex Thoracic Aortic Diseases.

IntroductionThe aim of this study is to compare postoperative outcomes and follow-up of two different modifications facilitating surgical technique of frozen elephant trunk (FET) procedure for complex thoracic aortic diseases - zone 0 (fixation with total arch debranching) and zone 3 (fixation with islet-shape arch repair).MethodsFrom May 2012 to December 2018, data were collected from 139 patients who had been treated with FET procedure for complex thoracic aortic diseases. According to Ishimaru arch map, patients with proximal anastomotic site of hybrid graft at zone 0 and zone 3 were grouped as Group A (n=58, 41.7%) and Group B (n=81, 58.3%), respectively. Mean age of study population was 54.7±11.4 years, and 111 patients were male (79.9%).ResultsIn-hospital mortality was observed in 20 (14.4%) patients (n=12, acute type A aortic dissection, and n=4, previous aortic dissection surgery). There was no significant difference between both groups in terms of in-hospital mortality. Four patients from Group A and three patients from Group B had permanent neurological deficit (P=0.32). Three patients from both groups had transient spinal cord ischemia (P=0.334). Although mean total perfusion time was longer in Group A, duration of visceral ischemia, when compared with Group B, was shorter (P<0.001). Five-year survival rate was 82.8% in Group A and 81.5% in Group B (P=0.876).ConclusionFET procedure is a feasible repair technique in the treatment of complex aortic diseases, providing satisfactory early results. Because of its advantageous aspects, zone 0 fixation with debranching is the preferred technique in our clinic.

Hypothermia Inhibits the Expression of Receptor Interacting Protein Kinases 1 and 3 After Transient Spinal Cord Ischaemia in Rabbits

Necroptosis, a form of regulated necrosis, might be a potential mechanism of delayed paraplegia; therefore, its role in transient spinal cord ischaemia was investigated by immunohistochemical analysis of necroptosis related protein receptor interacting protein kinase (RIP) 1, RIP3, and cellular inhibitor of apoptosis protein (cIAP) 1/2. This study used rabbit normothermic (n=24) and hypothermic (n=24) transient spinal cord ischaemia models and sham controls (n=6). Neurological function was assessed according to a modified Tarlov score at 8h, 1, 2, and 7 days after reperfusion (n=6 each). Morphological changes in the spinal cord were examined using haematoxylin and eosin staining in the sham, 2, and 7 day groups. Western blot and histochemical analyses of RIP1, RIP3, and cIAP1/2, and double label fluorescent immunocytochemical studies of RIP3 and cIAP1/2 were performed at 8h, 1, and 2 days after reperfusion (n=6 each). There were significant differences in neurological function between the normothermic and hypothermic groups (median scores 0 and 5at 7 days, p=.023). In the normothermic group, most motor neurons were lost seven days after reperfusion (p=.046 compared with sham), but they were preserved in the hypothermic group. Western blot analysis revealed the upregulation of RIP1, RIP3, and cIAP1/2at 8h in the normothermic group (RIP1, p=.032; RIP3, p<.001; cIAP1/2, p=.041 compared with sham), and the overexpression of RIP3 was prolonged for two days. In the hypothermic group, the expression of these proteins was not observed. The double label fluorescent immunocytochemical study revealed the induction of RIP3 and cIAP1/2 in the same motor neurons. These data suggest that transient normothermic ischaemia induces necroptosis, a potential factor in delayed motor neuron death, and that hypothermia may inhibit necroptosis.

Mid-Term Results of Total Endovascular Arch Repair Using Inner Branch Devices

Introduction - To evaluate aortic arch endovascular repair using inner branched endografts (1). Methods - 32 consecutive patients were enrolled from October 2010 to April 2017. All patients were unfit for open surgery (2,3). Results - The age of the cohort was 69 years (37-84) (27 men). Dissection (19) was the most common pathology (aneurysm 12, penetrating ulcer 1). Fifteen patients had disease in arch zone 0, 6 in zone 1, and 11 in zone 2. Twenty-seven patients had undergone prior aortic surgery (18 ascending aorta). The average number of branches per device was 2 (1-3). Twenty-four patients had surgical revascularization of the left subclavian artery and 2 of the right subclavian artery. Technical success was achieved in 29/32 cases with a procedure time of 240.6 minutes and an X-ray time of 34 minutes. One patient suffered a transient ischaemic attack, one a stroke, one transient spinal cord ischaemia and 2 required temporary dialysis. The average length of stay in intensive care and hospital were 3.4 and 14.1 days respectively. Five patients had endoleak (1a:1, II:4). The median follow-up was 16 (0-72) months during which time 12 patients required secondary procedures, 6 within 30-days. There were 3 in-hospital deaths and 6 during follow-up (none of which were aortic related). In patients that had undergone previous open ascending aortic repair (18/32) there was no incidence of in-hospital death, stroke or spinal cord ischaemia and one transient ischaemic attack. Conclusion - Aortic arch branched endografting is an important treatment option for patients unfit for open surgery. Careful selection of patients is paramount and patients with previous ascending open aortic surgery may represent the best candidates for this type of repair.

The Endocannabinoid Anandamide regulates oxytocin receptor in human placenta

Previous studies have shown that modulation of the receptor-mediated endocannabinoid system during ischemia injury can induce potent neuroprotective effects. However, little is known about whether cannabinoid-2 (CB2) receptor agonist would produce a protective effect on blood–spinal cord barrier (BSCB) during ischemia. Using an in vivo transient spinal cord ischemia model in rats, JWH-015 (1 mg/kg, i.p.), a CB2 receptor selective agonist, or vehicles were injected 20 min before ischemia. The effects of JWH-015 on BSCB permeability, the major structural protein for the formation of caveolae, caveolin-1 (cav-1), tight junction (TJ) protein Occludin and zona occludens protein-1 (ZO-1) were examined at day 1, day 3 and day 7 of reperfusion after transient spinal cord ischemia in rats. Here we demonstrated that JWH-015 significantly down-regulated the expression of cav-1, up-regulated the expression of TJ proteins, and then decreased the permeability of BSCB compared with control group. In addition, using an in vitro BBB model, oxygen glucose deprivation (OGD) was applied to simulate spinal cord ischemia in vitro in Human brain microvascular endothelial cells (HBMECs). JWH-015 greatly increased the transepithelial electrical resistance (TEER) and changed the distribution of ZO-1 and Occludin. Moreover, JWH-015 induced the expression of p-PKB and p-FoxO1 protein and decreased the expression of cav-1, which were greatly reversed by ROS inhibitor or PI3K inhibitor. Taken together, all of these results suggested that JWH-015 might regulate the BSCB permeability and this effect could be related to paracellular and transcellular pathway. And pharmacological CB2R ligands offer a new strategy for BSCB protection during ischemic injury.

Neuroprotective mechanism involved in spinal cord stimulation postconditioning

ObjectivesDelayed paraplegia developed postoperatively after thoracoabdominal aneurysm surgery is primarily associated with spinal cord ischemia/reperfusion injury. Our previous study suggested that spinal cord stimulation postconditioning protected the spinal cord from ischemia/reperfusion injury through microglia inhibition. In this study, we further investigated whether α7 nicotinic acetylcholine receptors were involved in the neuroprotective mechanism of spinal cord stimulation. MethodsRabbits were randomly assigned to sham, control, 2 Hz, α-bungarotoxin, and 2 Hz-α-bungarotoxin groups (n = 24/group). Transient spinal cord ischemia was performed on all rabbits except rabbits in the sham group. Rabbits in the control group received no further intervention, rabbits in the 2 Hz group were given 2 Hz spinal cord stimulation, rabbits in the α-bungarotoxin group received prescribed intrathecal α-bungarotoxin (α-bungarotoxin, a specific α7 nicotinic acetylcholine receptor antagonist) injections, and rabbits in the 2 Hz-α-bungarotoxin group received both α-bungarotoxin injections and 2 Hz spinal cord stimulation. Hind-limb neurologic function was assessed, and spinal cord histologic examination, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and microglia staining were performed at 8 hours, 1 day, 3 days, and 7 days of reperfusion. ResultsRabbits in the 2 Hz group had significantly better neurologic functions, more α-motor neurons, and lower terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling–positive neuron rates and microglia area/anterior horn area ratios (microglia area ratios) than the control group. The neurologic functions of the α-bungarotoxin group were significantly worse than those of the control group, whereas other results were not significantly different from the control group. The results of the 2 Hz-α-bungarotoxin group were insignificant to the control group except for the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling–positive neuron rates, which were significantly lower than in the control group. ConclusionsThe neuroprotective effects of spinal cord stimulation postconditioning against spinal cord ischemia/reperfusion injury were partially mediated by activating α7 nicotinic acetylcholine receptors.

Breathing hydrogen sulfide prevents delayed paraplegia in mice

Delayed paraplegia complicates the recovery from spinal cord ischemia or traumatic spinal cord injury. While delayed motor neuron apoptosis is implicated in the pathogenesis, no effective treatment or preventive measures is available for delayed paraplegia. Hydrogen sulfide exerts anti-apoptotic effects. Here, we examined effects of hydrogen sulfide breathing on the recovery from transient spinal cord ischemia. Breathing hydrogen sulfide starting 23 h after reperfusion for 5 h prevented delayed paraplegia after 5 min of spinal cord ischemia. Beneficial effects of hydrogen sulfide were mediated by upregulation of anti-apoptotic Bcl-XL and abolished by nitric oxide synthase 2 deficiency. S-nitrosylation of NFkB p65 subunit, which is induced by nitric oxide derived from nitric oxide synthase 2, facilitated subsequent sulfide-induced persulfidation of p65 and transcription of anti-apoptotic genes. These results uncover the molecular mechanism of the anti-apoptotic effects of sulfide based on the interaction between nitric oxide and sulfide. Exploitation of the anti-apoptotic effects of delayed hydrogen sulfide breathing may provide a new therapeutic approach for delayed paraplegia.

Single-center experience with an inner branched arch endograft

ObjectiveWhereas open repair is the “gold standard” for most aortic arch diseases, a subgroup of patients might benefit from an endovascular approach. The introduction of branched stent grafts with dedicated design to address the challenges of the ascending aorta and the aortic arch has opened an entirely new area of treatment for these patients. We investigated the early outcomes of branched thoracic endovascular aortic repair (b-TEVAR) in various types of disease of the aortic arch. MethodsA retrospective analysis was conducted of prospectively collected data from a single center of all consecutive patients treated with b-TEVAR. The indication for elective endovascular repair was consented in an interdisciplinary case conference. All patients were treated with a custom-made inner branched arch endograft with two internal branches (Cook Medical, Bloomington, Ind) and left-sided carotid-subclavian bypass. Study end points were technical success, 30-day mortality, and complications as well as late complications and reinterventions. ResultsBetween 2012 and 2017, there were 54 patients (38 male; median age, 71 years) treated with diseases of the aortic arch. Indications for therapy involved degenerative aortic arch or proximal descending aortic aneurysms requiring arch repair (n = 24), dissection with or without false lumen aneurysms (n = 26), and penetrating aortic ulcers (n = 4). Forty-three cases (80%) were performed electively and 11 urgently for contained ruptures (n = 3) or symptomatic aneurysms (n = 8) with endografts already available for the patient or with grafts of other patients with similar anatomy. Technical success was achieved in 53 cases (98%). The 30-day mortality and major stroke incidence were 5.5% (3/54) and 5.5% (3/54), respectively; in-hospital mortality was 7.4% (n = 4), and minor strokes (including asymptomatic new cerebral lesions) occurred in 5.5% (n = 3). There were two cases of transient spinal cord ischemia with complete recovery and one of paraplegia. No retrograde type A dissections or cardiac injuries were observed. Three early stent graft-related reinterventions were necessary to correct proximal endograft kinking with type IA endoleak in one patient, a bridging stent graft stenosis in another patient, and false lumen persistent perfusion from dissected supra-aortic vessels in the last patient. Mean in-hospital stay was 14 ± 8 days. During a mean follow-up of 12 ± 9 months, three nonaorta-related deaths and one aorta-related death distal to the arch repair were observed. ConclusionsTreatment of aortic arch diseases with b-TEVAR is feasible and safe with acceptable mortality and stroke rates.

Spinal Cord Ischaemia in Endovascular Thoracic and Thoraco-abdominal Aortic Repair: Review of Preventive Strategies

Introduction: The incidence of spinal cord ischaemia (SCI) and subsequent paraplegia after thoracic endovascular aneurysm repair (TEVAR) and thoraco-abdominal endovascular aneurysm repair is estimated to be between 2.5% and 8%. The aim of this review is to provide an overview of SCI preventive strategies in TEVAR and thoraco-abdominal repair and recommend an optimal strategy. Methods: Medline, Embase, and the Cochrane Library were searched for studies on TEVAR, thoraco-abdominal endovascular repair, and the use of SCI preventive measures. The review was reported according to the PRISMA statement. Results: The final analysis included 43 studies (7168 patients). All studies are cohort studies (non-comparative cohorts n = 37, comparative cohorts n = 6) and largely performed retrospectively (n = 27). The included studies had an average MINORS score of 9 (range 6-13) for non-comparative studies and 15.5 (range 12-18) for comparative studies. Transient SCI occurred in 5.7% (450/7,168, 95% CI 4.5-6.9%), permanent SCI in 2.2% (232/7,168, 95% CI 1.6-2.8%). There was a trend towards increased SCI incidence for more cohorts. Avoidance of hypotension resulted in a slightly lower permanent SCI rate 1.8% (102/4216, 95% CI 1.2-2.3%) than the overall cohort. A very low SCI estimate (transient and permanent) was found in the subgroup of studies (2 studies, n = 248) using (mild) peri-operative hypothermia (transient SCI 0.8%, permanent SCI 0.4%). In the subgroup using temporary permissive endoleak, there was a transient SCI estimate (15.4%), with a permanent SCI estimate of 4.8%. The remaining preventive measures did not significantly impact transient or permanent SCI estimates. Conclusion: Low overall transient and permanent SCI rates are achieved during endovascular thoracic and thoraco-abdominal aortic repair. Based on the presented data, the use of selective spinal fluid drainage in high risk patients seems justified. Peri-operative hypotension should be avoided and treated where possible. The use of mild hypothermia is promising in small cohorts, but requires further evaluation. Further high quality data are essential to establish a definitive preventive strategy.

EARLY CLINICAL OUTCOMES OF A NOVEL FROZEN ELEPHANT TRUNK PROSTHESIS: THE CANADIAN THORACIC AORTIC COLLABORATIVE EXPERIENCE

Recently, two commercially available frozen elephant trunk (FET) prostheses were introduced into the North American market. Herein, we describe the early experience with these novel frozen elephant trunk prostheses from the Canadian Thoracic Aortic Collaborative (CTAC). Between January 2014 and March 2017, 43 consecutive patients (66±14 years, 44% female) underwent hybrid aortic repair using the FET technique with two commercially available FET prostheses. Surgical indications included distal arch/proximal descending aortic aneurysm in 42 patients (98%), chronic type A dissection in 16 patients (37%), acute type A aortic dissection 3 in (7%), acute Type B dissection in 1 patient (2%) and aortic rupture in 1 patient (2%). Concomitant procedures were performed in 24 patients (56%) including pulmonary autograft (n=1;2%), valve-sparing root replacement (n=2;5%), Bentall procedure (n=3;7%), aortic valve replacement (n=7;16%), aortic valve repair (n=7;16%), sinus/root repair (n=6;14%) and CABG (n=7;16%). Selective antegrade cerebral perfusion and moderate hypothermia were employed in all cases. Mean CPB and cross-clamp times were 242±78 minutes and 151±74 minutes, respectively. The coldest temperature reached on by-pass was 24±2 degrees Celsius, and mean circulatory arrest time was 48±24 minutes. There were 2 (5%) 30-day or in-hospital mortalities. Two patients (5%) suffered a stroke and one patient (2%) had a transient neurological deficit. Two patients (5%) experienced transient spinal cord ischemia, and there were no instances of permanent paraplegia. Other major complications included delirium (n=7;16%), re-operation for bleeding (n=1;2%), myocardial infarction (n=1;2%), renal failure requiring temporary dialysis (n=1;2%), and sepsis (n=3;7%). Twelve patients (30%) experienced a composite of any of 10 major complications. Median ICU and hospital lengths of stay were 2 and 10 days, respectively. Comprehensive patient and outcomes data are shown in Table 1. Despite the early experience with the single stage hybrid arch and FET procedures, we have demonstrated good outcomes in the current series, with mortality and major complication rates similar to the more extensive European experience. An FDA IDE clinical trial is currently underway to better elucidate the feasibility of commercial availability of this hybrid FET prosthesis in the North American market.

SUMO-1 delays neuronal damage in the spinal cord following ischemia/reperfusion.

The present study investigated the protective effects of small ubiquitin-like modifier 1 (SUMO-1) on spinal cord ischemic damage in rabbits. A trans‑activator of transcription (Tat)‑SUMO‑1 fusion protein was prepared, and transient spinal cord ischemia was induced by occlusion of the abdominal aorta for 15min. Vehicle (glycerol) or 1mg/kg Tat-1-SUMO‑1 was administered intraperitoneally to the rabbits immediately following ischemia/reperfusion. Administration of Tat-SUMO-1 did not lead to significant alterations in arterial blood gases [partial pressure (Pa)CO2 and PaO2], pH, or blood glucose levels prior to ischemia, 10min after occlusion or 10min after reperfusion. Mean arterial pressure was significantly decreased only during occlusion. Motor behaviors were assessed at 24, 48 and 72h after ischemia/reperfusion using Tarlov's criteria. Administration of Tat‑SUMO‑1 significantly improved Tarlov scores 24h after ischemia/reperfusion and the number of cresyl violet positive neurons was significantly increased in the ventral horn of the spinal cord compared with the vehicle‑treated group. However, Tarlov scores were consistently decreased at 48 and 72h after ischemia/reperfusion in the Tat‑SUMO‑1‑treated group, and Tarlov scores and the number of cresyl violet positive neurons were not significantly different between the vehicle‑ and Tat‑SUMO‑1‑treated groups after 72h. Tat-SUMO‑1 administration significantly ameliorated a reduction in Cu, Zn‑superoxide dismutase activity and an increase in lipid peroxidation 24h after ischemia/reperfusion; however, these effects were not present at 72h. These results suggested that Tat‑SUMO‑1 may delay, although not protect against, neuronal death by regulating oxidative stress in the ventral horn of the spinal cord and that combination therapy using Tat‑SUMO‑1 with other compounds may provide a therapeutic approach to decrease neuronal damage.