Adjunctive hyperbaric oxygen therapy for spinal cord ischemia after complex aortic repair.

OBJECTIVE: Spinal cord ischemia (SCI) with paraplegia or paraparesis is a devastating complication of complex aortic repair (CAR). Treatment includes cerebrospinal fluid drainage, maintenance of hemoglobin concentration (>10 g/L), and elevating mean arterial blood pressure. Animal and human case series have reported improvements in SCI outcomes with hyperbaric oxygen therapy (HBOT). We reviewed our center's experience with HBOT as a rescue treatment for spinal cord ischemia post-CAR in addition to standard treatment. METHODS: A retrospective review of the University Health Network's Hyperbaric Medicine Unit treatment database identified HBOT sessions for patients with SCI post-CAR between January 2013 and June 2021. Mean estimates of overall motor function scores were determined for postoperative, pre-HBOT, post-HBOT (within 4 hours of the final HBOT session), and at the final assessment (last available in-hospital evaluation) using a linear mixed model. A subgroup analysis compared the mean estimates of overall motor function scores between improvement and non-improvement groups at given timepoints. Improvement of motor function was defined as either a ≥2 point increase in overall muscle function score in patients with paraparesis or an upward change in motor deficit categorization (para/monoplegia, paraparesis, and no deficit). Subgroup analysis was performed by stratifying by improvement or non-improvement of motor function from pre-HBOT to final evaluation. RESULTS: Thirty patients were treated for SCI. Pre-HBOT, the motor deficit categorization was 10 paraplegia, three monoplegia, 16 paraparesis, and one unable to assess. At the final assessment, 14 patients demonstrated variable degrees of motor function improvement; eight patients demonstrated full motor function recovery. Seven of the 10 patients with paraplegia remained paraplegic despite HBOT. The estimated mean of overall muscle function score for pre-HBOT was 16.6 ± 2.9 (95% confidence interval [CI], 10.9-22.3) and for final assessment was 23.4 ± 2.9 (95% CI, 17.7-29.1). The estimated mean difference between pre-HBOT and final assessment overall muscle function score was 6.7 ± 3.1 (95% CI, 0.6-16.1). The estimated mean difference of the overall muscle function score between pre-HBOT and final assessment for the improved group was 16.6 ± 3.5 (95% CI, 7.5-25.7) vs -4.9 ± 4.2 (95% CI, -16.0 to 6.2) for the non-improved group. CONCLUSIONS: HBOT, in addition to standard treatment, may potentially improve recovery in spinal cord function following SCI post-CAR. However, the potential benefits of HBOT are not equally distributed among subgroups.

Hyperbaric oxygen therapy for spinal cord ischaemia after complex aortic repair - a retrospective review.

BACKGROUND: Complex aortic repair (CAR) carries high rates of debilitating postoperative complications, including spinal cord injury. The rate of spinal cord deficits post-CAR is approximately 10%, with permanent paraplegia in 2.9% and paraparesis in 2.4% of patients. Treatment options are limited. Rescue therapies include optimization of spinal cord perfusion and oxygen delivery by mean arterial pressure augmentation (> 90 mm Hg), cerebrospinal fluid drainage, and preservation of adequate haemoglobin concentration (> 100 g L⁻¹). Hyperbaric oxygen therapy (HBOT) has been described in several case reports as part of the multimodal treatment for spinal cord ischemia. HBOT has been used in our centre as adjunct rescue treatment for patients with spinal cord injury post-CAR that were refractory to traditional medical management, and we aimed to retrospectively review these cases. METHODS: After Research Ethics Board approval, we performed a retrospective review of all post-CAR patients who developed spinal cord injury with severe motor deficit and were treated with HBOT at our institution since 2013. RESULTS: Seven patients with spinal cord injury after CAR were treated with HBOT in addition to traditional rescue therapies. Five patients showed varying degrees of recovery, with two displaying full recovery. One developed oxygen-induced seizure, medically treated. No other HBOT-related complications were noted. CONCLUSIONS: Our retrospective study shows a potential benefit of hyperbaric oxygen therapy on neurological outcome in patients who developed spinal cord injury after CAR. Prospective research is needed to understand the role, efficacy, benefits and risks of HBOT in this setting.

Reversal of Spinal Cord Ischemia Following Endovascular Thoracic Aortic Aneurysm Repair With Hyperbaric Oxygen and Therapeutic Hypothermia.

BACKGROUND: Neurological adverse events with spinal cord ischemia (SCI) remain one of the most feared complications in patients undergoing thoracic endovascular aortic repair (TEVAR). These patients can develop irreversible paraplegia with lifelong consequences with physical and psychological agony. CASE PRESENTATION: We herein present a patient who developed SCI with bilateral lower leg paraplegia on the third postoperative day following TEVAR. Spinal catheter was inserted for spinal fluid drainage. A hyperbaric oxygen therapy was initiated for 90 minutes for 2 days, which was followed by therapeutic hypothermia for 24 hours with a target temperature of 33°C. The patient exhibited significant neurological recovery following these treatments, and he ultimately regained full neurological function without spinal deficit. DISCUSSION: This represents the first reported case of full neurological recovery of a patient who developed complete SCI following TEVAR procedure. The neurological recovery was due in part to immediate therapeutic hypothermia and hyperbaric oxygen therapy which reversed the spinal ischemia.

Electroacupuncture pretreatment attenuates spinal cord ischemia-reperfusion injury via inhibition of high-mobility group box 1 production in a LXA4 receptor-dependent manner.

Paraplegia caused by spinal cord ischemia is a severe complication following surgeries in the thoracic aneurysm. HMGB1 has been recognized as a key mediator in spinal inflammatory response after spinal cord injury. Electroacupuncture (EA) pretreatment could provide neuroprotection against cerebral ischemic injury through inhibition of HMGB1 release. Therefore, the present study aims to test the hypothesis that EA pretreatment protects against spinal cord ischemia-reperfusion (I/R) injury via inhibition of HMGB1 release. Animals were pre-treated with EA stimulations 30min daily for 4 successive days, followed by 20-min spinal cord ischemia induced by using a balloon catheter placed into the aorta. We found that spinal I/R significantly increased mRNA and cytosolic protein levels of HMGB1 after reperfusion in the spinal cord. The EA-pretreated animals displayed better motor performance after reperfusion along with the decrease of apoptosis, HMGB1, TNF-α and IL-1ß expressions in the spinal cord, whereas these effects by EA pretreatment was reversed by rHMGB1 administration. Furthermore, EA pretreatment attenuated the down-regulation of LXA4 receptor (ALX) expression induced by I/R injury, while the decrease of HMGB1 release in EA-pretreated rats was reversed by the combined BOC-2 (an inhibitor of LXA4 receptor) treatment. In conclusion, EA pretreatment may promote spinal I/R injury through the inhibition of HMGB1 release in a LXA4 receptor-dependent manner. Our data may represent a new therapeutic technique for treating spinal cord ischemia-reperfusion injury.

Aged Garlic Extract Attenuates Neuronal Injury in a Rat Model of Spinal Cord Ischemia/Reperfusion Injury.

Garlic has been used as a food as well as a component of traditional medicine. Aged garlic extract (AGE) is claimed to promote human health through antioxidant/anti-inflammatory activities with neuroprotective effects. We evaluated the possible beneficial effect of AGE neurologically, pathologically, ultrastructurally, and biochemically in a spinal cord ischemia-reperfusion (I/R) model of rats. Twenty-four Sprague-Dawley rats were divided into three groups: sham (no I/R), I/R, and AGE (I/R+AGE); each group consisted of eight animals. Animals were evaluated neurologically with the Basso, Beattie, and Bresnahan (BBB) scoring system. The spinal cord tissue samples were harvested for pathological and ultrastructural examinations. Oxidative products (Malondialdehyde, nitric oxide), antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase), inflammatory cytokines (tissue tumor necrosis factor alpha, interleukin-1), and caspase-3 activity were analyzed. The AGE group had significantly higher BBB scores than the I/R group. Pathologically, AGE group revealed reduced degree of ischemia and spinal cord edema. Ultrastructural results also showed preservation of tissue structure in the AGE group. Oxidative product levels of the I/R group were significantly higher than both the other groups, and antioxidant enzyme levels of AGE group were significantly higher than the I/R group. There was also significant difference between the sham and AGE groups in terms of total antioxidant enzyme levels. Furthermore, AGE treatment significantly reduced the inflammatory cytokines and caspase-3 activity than the I/R group. This study demonstrates the considerable neuroprotective effect of AGE on the neurological, pathological, ultrastructural, and biochemical status of rats with I/R-induced spinal cord injury.

The effect of combined hyperbaric oxygen and iloprost treatment on the prevention of spinal cord ischaemia-reperfusion injury: an experimental study.

OBJECTIVES: Hyperbaric oxygen (HBO) has been shown to be effective in preventing neurological injuries in animal models of ischaemia, whereas iloprost (IL) prevents ischaemia-related mitochondrial dysfunction and reduces infarction size after focal cerebral ischaemia in animal models. The aim of the present study was to investigate the effect of combined HBO and IL treatment on spinal cord ischaemia-reperfusion (IR) injury by neurological, histopathological and biochemical methods in an experimental study. METHODS: Eighty New Zealand white male rabbits were randomly allocated into one of five study groups. The HBO group received a single session of HBO treatment and the IL group received an infusion of 25 ng/kg/min IL; the HBO + IL group received both HBO and IL and the control group received only 0.9% saline; the fifth group was the sham group. Levels of S100ß protein, neuron-specific enolase (NSE) and nitric oxide (NO) were measured at onset, at the end of ischaemia period and at the 24th and 48th hour of reperfusion. Physical activity was assessed using Tarlov criteria 24, and the spinal cords of the sacrificed rabbits were evaluated histopathologically. Additionally, tissue malondialdehyde (MDA) and antioxidant enzyme activities [total superoxide dismutase (SOD); catalase (CAT) and glutathione peroxidase (GSH-Px) were assessed. RESULTS: Neurological scores in the HBO, IL and HBO + IL groups were statistically significantly better compared with the control group at the 24th (P = 0.001 for all) and 48th hour (P = 0.001 for all). Histopathological scores in the HBO, IL and HBO + IL groups were also significantly better compared with the control group (P = 0.003, 0.001 and 0.001, respectively). Whereas MDA, NSE, S100ß protein and NO concentrations were significantly lower, CAT and GSH-PX levels were significantly higher in either sham or treatment groups compared with the control group. CONCLUSIONS: Since we demonstrated beneficial effects on spinal cord IR injury, we think that both HBO and IL, either alone or in combination, may be reasonable in the treatment of IR injury. Furthermore, there did not appear to be synergistic effects with combined treatment. More research is needed for practical application in humans, following thoracoabdominal aortic surgery.

Hyperbaric oxygen preconditioning attenuates early apoptosis after spinal cord ischemia in rats.

This study tested the hypothesis that spinal cord ischemic tolerance induced by hyperbaric oxygen preconditioning (HBO-PC) is mediated by inhibition of early apoptosis. Male Sprague-Dawley rats were preconditioned with consecutive 4 cycles of 1-h HBO exposures (2.5 atmospheres absolute [ATA], 100% O(2)) at a 12-h interval. At 24 h after the last HBO pretreatment, rats underwent 9 min of spinal cord ischemia induced by occlusion of the descending thoracic aorta in combination with systemic hypotension (40 mmHg). Spinal cord ischemia produced marked neuronal death and neurological dysfunction in animals. HBO-PC enhanced activities of Mn-superoxide dismutase (Mn-SOD) and catalase, as well as the expression of Bcl-2 in the mitochondria in the normal spinal cord at 24 h after the last pretreatment (before spinal cord ischemia), and retained higher levels throughout the early reperfusion in the ischemic spinal cord. In parallel, superoxide and hydrogen peroxide levels in mitochondria were decreased, cytochrome c release into the cytosol was reduced at 1 h after reperfusion, and activation of caspase-3 and -9 was subsequently attenuated. HBO-PC improved neurobehavioral scores and reduced neuronal apoptosis in the anterior, intermediate, and dorsal gray matter of lumbar segment at 24 h after spinal cord ischemia. HBO-PC increased nitric oxide (NO) production. L-nitroarginine-methyl-ester (L-NAME; 10 mg/kg), a nonselective NO synthase (NOS) inhibitor, applied before each HBO-PC protocol abolished these beneficial effects of HBO-PC. We conclude that HBO-PC reduced spinal cord ischemia-reperfusion injury by increasing Mn-SOD, catalase, and Bcl-2, and by suppressing mitochondrial apoptosis pathway. NO may be involved in this neuroprotection.

Hyperbaric oxygenation in fluid microembolism.

Because clinicians require objectively demonstrable neurological deficits to confirm a diagnosis, the recognition of embolic events in the nervous system is generally restricted to the effects of ischemic necrosis produced by arterial occlusion. However, magnetic resonance imaging (MRI) has shown that lesser degrees of damage associated with small emboli are common, especially in the mid brain, and are usually clinically silent. They are frequently associated with atheromatous embolism in the elderly, but microembolic debris, such as fat, is common in the systemic venous return of healthy people and generally trapped in the microcirculation of the lung being removed by phagocytosis. However, pulmonary filtration may fail and microemboli may also pass through an atrial septal defect in so-called 'paradoxical' embolism. Studies of bubbles formed on decompression in diving have demonstrated the importance of pulmonary filtration in the protection of the nervous system and that filtration is size dependant, as small bubbles may escape entrapment. Fluid and even small solid emboli, arresting in or passing through the cerebral circulation, do not cause infarction, but disturb the blood-brain barrier inducing what has been termed the 'perivenous syndrome'. The nutrition of areas of the white matter of both the cerebral medulla and the spinal cord depends on long draining veins which have been shown to have surrounding capillary free zones. Because of the high oxygen extraction in the microcirculation of the gray matter of the central nervous system, the venous blood has low oxygen content. When this is reduced further by embolic events, tissue oxygenation may fall to critically low levels, leading to blood-brain barrier dysfunction, inflammation, demyelination and eventually, axonal damage. These are the hallmarks of the early lesions of multiple sclerosis where MR spectroscopy has also shown the presence of lactic acid. Significant elevation of the venous oxygen tension requires oxygen to be provided under hyperbaric conditions. Arterial tension is typically increased ten-fold breathing oxygen at 2 atmospheres absolute (ATA), but this results in only a 1.5-fold increase in the cerebral venous oxygen tension. The treatment of decompression sickness, and both animal and clinical studies, have confirmed the value of oxygen provided under hyperbaric conditions in the restoration and preservation of neurological function in the 'perivenous' syndrome.

[Dynamics of neurophysiological indices in experimental animals with chronic circulatory vertebrobasillar disorders and chronic lumbosacral myeloid ischemia in response to magnetic fields and electric stimulation].

Three series of experiments were made on mature non-inbred male and females rats with body mass 160-200 g. Chronic circulatory vertebrobasilar disorder (CCVD) in the rats was provoked by ligation of subclavian arteries. The animals showed longer latent periods of evoked total motor potentials reflecting impairment of the central motoneuron. Inhibition of impulse conduction along the peripheral nerves and decreased M-response amplitudes in the experimental animals with CCVD and myeloid ischemia in the lumbosacral area points to a significant affection of the segmental system of the spinal cord and other parts of the autonomic nervous system.