Review Article

A Modern Theory of Spinal Cord Ischemia/Injury in Thoracoabdominal Aortic Surgery and Its Implications for Prevention of Paralysis

Spinal cord injury (SCI) is a devastating disease with no clear molecular mechanisms or effective treatments. Murine models of SCI have been widely used to explore its pathogenesis.

In this study, a comprehensive bioinformatic analysis using GEO datasets was performed to evaluate the characteristics of different SCI models.

We found that the contusion model was similar to the compression model, with inflammation and apoptosis significantly enriched, while more complex biological processes existed in hemisection and transection model. Inflammatory markers can be used as a primary evaluation index of SCI models not only in the acute and subacute phases, but also in the chronic phase. In the meantime, apoptosis markers are more suitable for evaluating mouse SCI models while inflammatory markers are more suitable for rat SCI models. In addition, SCI models with different ages, genders, injury positions, and injury levels were also analyzed.

Our findings indicate that SCI is a heterogeneous disease and play an instructive role in model selecting.

Paraplegia is a distressing complication after open thoracoabdominal aortic aneurysm (TAAA) repair, and revascularization of T8-L2–level segmental arteries is considered pivotal to prevent paraplegia. We employed 3-dimensional (3D) printing to efficiently revascularize segmental/visceral arteries and prospectively evaluated its safety and efficacy.

From January 1, 2020, to June 30, 2022, we prospectively enrolled patients of extent I, II, or III TAAA repair. Guidance models were 3D-printed based on preoperative computed tomography, and multibranched aortic grafts were manually constructed upon this model before surgery. The composite outcome of operative mortality, permanent stroke, and permanent spinal cord deficit (SCD) was compared with the historical control group (n = 77, in 2015-2020), subjected to similar TAAA repair without 3D printing.

A total of 38 patients (58.6 ± 13.2 years) underwent open TAAA repair with the aid of 3D printing. Extent I, II, and III repairs were performed in 14 (36.8%), 17 (44.7%), and 7 (18.4%), respectively. Concomitant arch repair and bi-iliac reconstruction were performed in 7 (18.4%) and 6 patients (15.8%), respectively. Mean pump time was 107.7 ± 55.5 minutes. Operative mortality, permanent stroke, and permanent SCD each occurred in 1 patient (2.6%), and the incidence of the composite outcome was 7.9% (3/38). In the control group, mean pump time was 166.0 ± 83.9 minutes, significantly longer than the 3D-printing group (P < .001), and operative mortality, permanent stroke, permanent SCD, and the composite outcome occurred in 7 (9.1%), 9 (11.7%), 8 (10.4%), and 19 (24.7%), respectively.

Open repairs of extensive TAAA with 3D printing showed favorable safety and efficacy, which need further validation by larger studies.

Spinal cord ischemia (SCI) is a well-known complication of thoracoabdominal aortic aneurysm repair and is associated with profound morbidity and mortality. The purpose of this study was to describe predictors for the development of SCI, as well as outcomes for patients who develop SCI, after branched/fenestrated endovascular aortic repair in a large cohort of centers with adjudicated physician-sponsored investigational device exemption studies.

We used a pooled dataset from nine US Aortic Research Consortium centers involved in investigational device exemption trials for treatment of suprarenal and thoracoabdominal aortic aneurysms. SCI was defined as new transient weakness (paraparesis) or permanent paraplegia after repair without other potential neurological etiologies. Multivariable analysis was performed to identify predictors of SCI, and life-table analysis and Kaplan-Meier methodologies were used to evaluate survival differences.

A total of 1681 patients underwent branched/fenestrated endovascular aortic repair from 2005 to 2020. The overall rate of SCI was 7.1% (3.0% transient and 4.1% permanent). Predictors of SCI on multivariable analysis were Crawford Extent I, II, and III distribution of aortic disease (odds ratio [OR], 4.79; 95% confidence interval [CI], 4.77-4.81; P < .001), age ≥70 years (OR, 1.64; 95% CI, 1.63-1.64; P = .029), packed red blood cell transfusion (OR, 2.00; 95% CI, 1.99-2.00; P = .001), and a history of peripheral vascular disease (OR, 1.65; 95% CI, 1.64-1.65; P = .034). The median survival was significantly worse for patients with any degree of SCI compared with those without SCI (any SCI, 40.4 vs no SCI, 60.3 months; log-rank P < .001), and also worse in those with a permanent deficit (24.1 months) vs those with a transient deficit (62.4 months) (log-rank P < .001). The 1-year survival for patients who developed no SCI was 90.8%, compared with 73.9% in patients who developed any SCI. When stratified by degree of deficit, survival was 84.8% at 1 year for those who developed paraparesis and 66.2% for those who developed permanent deficits.

The overall rates of any SCI at 7.1% and permanent deficit at 4.1% observed in this study compare favorably with those reported in contemporary literature. Our findings confirm that increased length of aortic disease is associated with SCI and those with Crawford Extent I to III thoracoabdominal aortic aneurysms are at highest risk. The long-term impact on patient mortality underscores the importance of preventive measures and rapid implementation of rescue protocols if and when deficits develop.

Spinal cord ischemia-reperfusion (IR) injury (SCIRI) is a significant secondary injury that causes damage to spinal cord neurons, leading to the impairment of spinal cord sensory and motor functions. Excessive reactive oxygen species (ROS) production is considered one critical mechanism of neuron damage in SCIRI. Nonetheless, the molecular mechanisms underlying the resistance of neurons to ROS remain elusive. Our study revealed that the deletion of Git1 in mice led to poor recovery of spinal cord motor function after SCIRI. Furthermore, we discovered that Git1 has a beneficial effect on neuron resistance to ROS production. Mechanistically, Git1 interacted with PGK1, regulated PGK1 phosphorylation at S203, and affected the intermediate products of glycolysis in neurons. The influence of Git1 on glycolysis regulates the dimerization of Keap1, which leads to changes in Nrf2 ubiquitination and plays a role in resisting ROS. Collectively, we show that Git1 regulates the Keap1/Nrf2 axis to resist ROS in a PGK1-dependent manner and thus is a potential therapeutic target for SCIRI.

Spinal cord ischemia (SCI) after endovascular aortic repair is associated with significant morbidity and mortality. Understanding of the pathogenesis and physiologic mechanisms of SCI dictates prevention and treatment when neurologic deficits occur. Currently used or proposed preventive modalities include staged repair, temporary aneurysm sac perfusion, segmental artery embolization, and management of hemodynamic parameters based on decades of experience with open thoracoabdominal and thoracic endovascular aortic repair. The role of cerebrospinal fluid drainage in prevention of SCI remains an area of clinical equipoise. “Rescue maneuvers” when neurologic deficits develop are generally consistent and include cerebrospinal fluid drainage, hemodynamic management, and elevated hemoglobin goals. The role of team communication and education in expedient recognition and treatment initiation in SCI is paramount. Advances in spinal cord protective practices and new therapies in spinal cord injury may play a role in future prevention and treatment protocols. Additional research is needed to further define the optimal use of currently accepted and emerging therapies, and current management practices, to improve patient outcomes with regard to SCI after branched and fenestrated endovascular aortic repair.