The mechanism of spinal cord injury after simple and double aortic cross-clamping

Ischemic spinal cord injury after cross-clamping of the descending aorta can occur independently of aortic disease. In a previous study we had shown a precipitous uniform fall of spinal surface oxygen tension downstream to the clamping site irrespective of level. In the present paper, the hemodynamic changes in the spinal and aortic collateral circulation were investigated. Pressures were measured in the proximal, distal, and excluded aortic segments (descending thoracic and lumbar aorta) as well as in the intercostal and the lumbar arterial beds. Before high aortic occlusion, pressures in the intercostal and lumbar arterial beds were lower than aortic pressure. Along with the postclamping fall in distal arterial pressure, intercostal and lumbar arterial bed pressure decreased further but remained above aortic pressure. Exclusion of the thoracic aorta by double clamping restored intercostal bed pressure almost to control, whereas exclusion of the abdominal aorta hardly affected lumbar bed pressure. We conclude that spinal collateral circulation is more highly developed in the thoracic than in the lumbar region. After aortic cross-clamping, blood tends to drain away from the spinal cord rather than supplying it longitudinally. Under clinical conditions, therefore, retrograde bleeding into the opened aorta as well as into the aorta downstream to the distal clamp should be minimized and larger vessels originating from the aorta should promptly be anastomosed to the graft.     

Pharmacologic interventions for prevention of spinal cord injury caused by aortic crossclamping.

The efficacy of pharmacologic agents for prevention and control of oxygen-derived free radical damage in ischemia-reperfusion injury of the spinal cord was assessed in a swine model of thoracic and thoracoabdominal aortic crossclamping. Animals were exposed to 30 minutes of ischemia that induced lethal, irreversible injury and paraplegia. The experimental groups were as follows: group A (n = 7), control group, receiving no pharmacologic intervention; group B (n = 7), deferoxamine 50 mg/kg/day administered intravenously over 3 to 4 hours before ischemia; group C (n = 7), allopurinol pretreatment 50 mg/kg/day for 3 days; and group D (n = 7), superoxide dismutase 60,000 units administered with 50,000 units before removal of the aortic crossclamp and 10,000 units over 10 minutes of reperfusion. Proximal hypertension was controlled with sodium nitroprusside and volume depletion. The methods of assessment were neurologic by a modified Tarlov criteria and blood flow by radiolabeled microspheres. Results of blood flow assessment confirmed a true ischemic episode of 30 minutes for all animals in all groups. The blood flow fell significantly during ischemia (p less than 0.01) and a hyperemic response was evident in the early reperfusion period. All animals in control group A were paraplegic. The group B (deferoxamine) results were superior; 85% had grade III function on a modified Tarlov scale, with animals in the group standing and even walking with difficulty. Only one animal in this group had good movements of hind limbs but was unable to stand or walk. Neurologic recovery was limited in the allopurinol group (group C), with 85% showing slight neurologic recovery with limited movement of the hind limbs. The animals in the superoxide dismutase group (group D) all had good recovery, with strong motor response of hind limbs, but were not able to stand. In summary, the results of this experimental protocol confirmed the possible role of oxygen-derived free radicals in the pathophysiology of spinal cord injury, induced by aortic crossclamping. Moreover, it proved that ischemia-reperfusion injury could be altered by pharmacologic interventions.     

主动脉转流防止脊髓损伤的研究

目的　探讨主动脉转流对主动脉阻断所致脊髓损伤的防止作用。方法　建立在小猪腹腔动脉开口以上阻断腹主动脉１ 小时和辅助主动脉转流的模型,观察术后动物出现并发症及组织病理学的改变,研究辅助主动脉转流重建肾上腹主动脉的效果。结果　阻断组１ 只小猪于术后死亡,另５ 只小猪术后都出现了下肢截瘫。阻断组术后截瘫评分明显低于转流组（ Ｐ＜ ０ ．０１） ,并能观察到明显的脊髓损伤的病理学变化。转流组和主动脉重建组的动物术后没有截瘫等并发症的发生。结论　当转流量达到腹主动脉近端原血流量的７０％ 时主动脉转流能较好地防止腹主动脉阻断１ 小时所造成的脊髓损伤。流量为主动脉近端原血流量的７０ ％ 是一个较好的远端主动脉灌注的个体化指标。     

Therapeutic option for managing lung injury induced by infrarenal aortic cross-clamping

Background

Operations on the infrarenal aorta can cause ischemic-reperfusion (IR) injury in local tissues, which could result in remote organ (e.g., lung) damage. Treatment of such injuries remains an unresolved problem.

Objectives

Our aim was to reduce remote lung damage after lower limb IR by means of postconditioning.

Materials and methods

Male Wistar rats were divided into three groups: Sham-operated, IR, and Postconditioned (PostC). In the latter two groups rats underwent 180 min of exclusion of the infrarenal aorta. The reperfusion time was 4 h. Serum-free radical levels, tumor necrosis factor-α and interleukin-6 concentrations, histologic changes in the lung, wet/dry-ratio, myeloperoxidase activity, heat shock protein 72 level and blood gas changes were investigated.

Results

Postconditioning reduced histological damage in the lung (P < 0.05). Free radical levels and tumor necrosis factor-α concentrations were significantly lower in the PostC group than in the IR group (P < 0.05 and P < 0.01, respectively). Interleukin-6 concentrations did not significantly differ in the PostC group. Compared with the IR group, lung myeloperoxidase activity was lower in the PostC group. Decreased pulmonary heat shock protein 72 level was observed in the PostC group compared with the IR group and the wet/dry-ratio was also significantly lower in the PostC group (P < 0.05). A noticeably higher arterial pO₂ level was manifest in the PostC group after 2 and 4 h of reperfusion (P < 0.05).

Conclusions

Postconditioning reduced lung damage under experimental conditions, in the early period of reperfusion after lower limb IR injury.     

Does prostaglandin E1 and superoxide dismutase prevent ischaemic spinal cord injury after thoracic aortic cross-clamping?

The beneficial use of prostaglandin E1 (PGE1) and superoxide dismutase (SOD) on the tolerance to ischaemia of the spinal cord was evaluated following thoracic aortic cross-clamping in dogs. Aside from spinally evoked somatosensory potential (SEP) by means of a bipolar epidural catheter, postoperative evaluation of motor deficits was used to determine the efficiency of pharmacological protection when compared with controls. The animals were divided into four groups. Group I (n = 12) served as controls. The dogs of Group II (n = 12) were treated with PGE1 (100 ng/kg/min) during clamping and the first hour after declamping. In the third group (n = 12) SOD was given as an intra-arterial bolus (1 mg/kg) prior to declamping which was followed by a continuous perfusion (0.4 mg/kg/min) into the carotid artery for 25 min. In Group IV (n = 12) the dogs were treated with a combination of PGE1 and SOD in the same manner as in Groups 3 and 4. Results after pharmacological protection were significantly better than controls. In Group I all animals but one (92%) were paraplegic, as were five in Group II (42%) and eight in Group III (67%). In contrast no dog in Group IV developed paraplegia. There was a close correlation of SEP and postoperative recovery. The group with combination therapy (PGE1 plus SOD) was characterised by a loss of the evoked potential for a mean of 15 min, the PGE1 group for 45.8 min and the SOD group for 58.5 min. While the control group was characterised by a loss of 72.7 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of spinal cord injury after cross-clamping of the thoracic aorta

Paraplegia has been a devastating and unpredictable complication following cross-clamping of the thoracic aorta. In this study, the effect of the pressure gradient between the aortic pressure distal to occlusion and cerebrospinal fluid pressure (CSFP), defined as relative spinal cord perfusion pressure (RSPP), on the development of spinal cord injury was investigated. In 32 mongrel dogs, the thoracic aorta just distal to the left subclavian artery was cross-clamped. After a complete loss of somatosensory evoked potentials (SEP) had been confirmed, the dogs were divided into six groups by an additional cross-clamp interval and RSPP as follows: Group I (n = 6): 0 mmHg for 10 minutes; Group II (n = 8): 0 mmHg for 20 minutes; Group III (n = 3): 7.5 mmHg for 20 minutes; Group IV (n = 3): 7.5 mmHg for 40 minutes; Group V (n = 6): 15 mmHg for 40 minutes and Group VI (n = 6): 15 mmHg for 60 minutes. RSPP was adjusted by either withdrawal of cerebrospinal fluid or injection of normal saline solution into the subarachnoid space. SEP were generated by the stimulation of bilateral peroneal nerves. The incidence of postoperative paraplegia was 0% in Groups I and V, 33% in Group III, 50% in Group VI and 100% in Groups II and IV. This study showed that RSPP plays an important role in the development of spinal cord injury during cross-clamping of the thoracic aorta. Therefore, RSPP should be maintained at as high a level as possible in order to prevent spinal cord injury even if SEP disappear during aortic occlusion.     

Prevention of spinal cord injury after cross-clamping of the thoracic aorta

Paraplegia has been a devastating and unpredictable complication following surgical procedures involving temporary occlusion of the thoracic aorta. This study was undertaken to determine the effect of the pressure gradient between the aortic pressure distal to the occluding aortic clamp and cerebrospinal fluid pressure, defined as “Relative spinal cord perfusion pressure” (RSPP) on the development of the ischemic spinal cord injury. In twelve mongrel dogs, the thoracic aorta just distal to the left subclavian artery was cross-clamped. Somatosensory evoked potentials (SEP) were generated by peripheral stimulation of the bilateral peroneal nerves. After complete loss of SEP was evident, six dogs, Group 1, were subjected to occlusion of the descending thoracic aorta for a period of 20 minutes with maintenance of 0 mmHg of RSPP, by an injection of normal saline into the subarachnoid space. Six other dogs, Group 2, likewise underwent 40 minutes of aortic occlusion, keeping the RSPP at 15 mmHg by withdrawal ofcerebrospinal fluid. All the dogs in Group 1 developed paraplegia, whereas all the dogs in Group 2 demonstrated complete postoperative recovery without any neurological sequelae. Thus, RSPP is a most important factor in the development of the ischemic spinal cord injury during the temporary thoracic aortic occlusion.     

Iloprost protects the spinal cord during aortic cross-clamping in a canine model

BACKGROUND: Surgical procedures on the thoracoabdominal part of the aorta make the spinal cord vulnerable to ischemia. Paraplegia is the most severe complication following thoracoabdominal operations. In this study, iloprost was used as an agent to decrease the severity of ischemia and reperfusion injury to the spinal cord during aortic occlusion and declamping. METHODS: Twelve adult mongrel dogs weighing 17+/-2 kg were used in this study. The animals were randomly assigned to either group I, which received saline solution (6 dogs), or group II, which received prostacyclin. Group I was referred to as the control group and group II as the iloprost group. After baseline measurements were completed, the aorta was cross-clamped for sixty minutes distal to the left subclavian artery. No pharmacologic agents were used to control blood pressure in group I. Proximal and distal mean arterial pressures (DMAP) were monitored continuously. DMAP were considered as diastolic pressure in preocclusion and reperfusion periods. Iloprost administration was started at a rate of 5 ng/kg/minute five minutes before the aortic occlusion. This dosage was increased to 25 ng/kg/minute during aortic occlusion. RESULTS: Mean proximal arterial pressure was 147+/-12 mmHg in the control group and 116+/-13 mmHg in the iloprost group at occlusion (p<0.01). Mean distal arterial pressure was 19+/-7 in the control group and 37+/-5 in the iloprost group during clamping (p<0.05). Functional outcome was evaluated according to Tarlov scores 24 hours after the study. Although none of the animals recovered completely from the control group, 4 animals from the iloprost group recovered (p<0.05). Following the neurologic assessment, animals were sacrificed and specimens were taken for the electron microscopic study. Electron microscopic changes documented that severe mitochondrial damage and vacuolisation occurred in the control group. However these changes were more subtle in the iloprost group. CONCLUSIONS: As a result of this study we concluded that iloprost infused before and during clamping of the thoracic aorta mitigates the spinal cord injury due to ischemia and reperfusion following unclamping.     

Prevention of ischemic spinal cord injury: comparative effects of magnesium sulfate and riluzole

PURPOSE: Excitotoxic mechanisms have been implicated in the pathophysiology of spinal cord ischemic injury induced by aortic cross-clamping. We investigated the effects of the anti-excitotoxic drugs magnesium sulfate (MgSO(4)) and riluzole in a rabbit model of spinal cord ischemia. METHOD: The infrarenal aorta of New Zealand albino white rabbits (n = 68) was occluded for 40 minutes. Experimental groups included: a control group, which received only vehicle (n = 17); group A (n = 17), which received riluzole (8 mg/kg) before clamping; group B (n = 17), which received MgSO(4) (100 mg/kg) before clamping; and group C (n = 17), which received riluzole (8 mg/kg) and MgSO(4) (100 mg/kg) before clamping. Five additional rabbits had the same operation, but did not undergo aortic clamping (sham operation). The neurological status of the rabbits was assessed at 24 hours, 48 hours, and then daily for as long as 120 hours by using a modified Tarlov scale. The rabbits were killed at 24 hours (n = 3 per group), 48 hours (n = 4 per group), and 120 hours (n = 10 per group) postoperatively. Spinal cords were harvested for histopathologic and immunohistochemistry examinations for microtubule-associated protein-2 (MAP-2), a cytoskeletal protein specific from neurons. RESULTS: No major adverse effect was observed with either riluzole or MgSO(4). All control rabbits became severely paraplegic. All riluzole-treated and MgSO(4)-treated animals had a better neurological status than control animals. Typical morphological changes characteristic of neuronal necrosis in the gray matter of control animals was demonstrated by means of the histopathological examination, whereas riluzole or magnesium prevented or attenuated necrotic phenomenons. Moreover, MAP-2 immunoreactivity was completely lost in control rabbits, whereas it was preserved, either completely or partially, in rabbits treated with riluzole or magnesium. Riluzole was more effective than MgSO(4) in preventing paraplegia caused by motor neuron injury (P <.01 ). Riluzole and MgSO(4) had no additive neuroprotective effect. CONCLUSION: These results demonstrate that riluzole and, to a lesser extent, MgSO(4) may afford significant spinal cord protection in a setting of severe ischemia and may, therefore, be considered for clinical use during "high-risk" operations on the thoracic and thoracoabdominal aorta.     

The effects of FK506 on neurologic and histopathologic outcome after transient spinal cord ischemia induced by aortic cross-clamping in rats

Spinal cord injury is a devastating complication of thoracoabdominal aortic surgery. We investigated the effect of the immunosuppressant FK506, a macrolide antibiotic demonstrated to have neuroprotective effects in cerebral ischemia models, in a rat model of transient spinal cord ischemia. Spinal cord ischemia was induced in anesthetized rats by using direct aortic arch plus left subclavian artery cross-clamping through a limited thoracotomy. Experimental groups were as follows: sham-operation; control, receiving only vehicle; FK506 A, receiving FK506 (1 mg/kg IV) before clamping; and FK506 B, receiving FK506 (1 mg/kg IV) at the onset of reperfusion. Neurologic status was assessed at 24 h and then daily up to 96 h with a 0 to 6 scale (0, normal function; 6, severe paraplegia). Rats were randomly killed at 24, 48, or 96 h, and spinal cords were harvested for histopathology. Physiologic variables did not differ significantly among experimental groups. All control rats suffered severe and definitive paraplegia. FK506-treated rats had significantly better neurologic outcome compared with control. Histopathologic analysis disclosed severe injury in the lumbar gray matter of all control rats, whereas most FK506-treated rats had less injury. These data suggest that FK506 can improve neurologic recovery and attenuate spinal cord injury induced by transient thoracic aortic cross-clamping. IMPLICATIONS: A single dose-injection of the immunosuppressant FK506 significantly improved neurologic outcome and attenuated spinal cord injury induced by transient thoracic aortic cross-clamping in the rat.     

Adequacy of ascending aorta-descending aorta shunt during cross-clamping of the thoracic aorta for prevention of spinal cord injury

The effectiveness of various sized shunts placed between the ascending and the descending aorta to prevent paraplegia in dogs with the thoracic aorta cross-clamped for 1 hour was tested. Three tapered shunts sizes were used with tip dimensions of 3.8, 5.2, and 6.3 mm inner diameter, with cross-sectional areas of 11.34, 21.23, and 33.18 mm2, respectively, and with an equal midportion diameter of 10 mm (3/8 inch). These shunts carried 40%, 60%, and 72% respectively, of baseline descending aortic flow during the cross-clamping period. Flow distribution was measured with radioactive microspheres in the spinal cord (gray and white matter) and kidneys. All dogs without shunts (Group I) developed paraplegia, severe proximal circulatory embarrassment, and severe ischemia of the spinal cord (mainly gray matter) that was followed by marked hyperemia persisting up to 24 hours following the experiment. Mortality was 33%. Only animals treated with large shunts (Groups III and IV) avoided paraplegia and postischemic injury. An effective shunt was characterized as carrying 60% or more of baseline descending aortic flow, having a cross-sectional area at its tip equal to or larger than 29% of the descending aorta, and equaling at least 54% of its diameter. Porportionately, the size of the tridodecylmethylamonium-heparin shunts being used in human beings (even the largest 9 mm inner diameter) is significantly inadequate to maintain distal flows and pressures for the prevention of spinal cord injury. Four clinical options are discussed.     

Antinociceptive effect of riluzole in rats with neuropathic spinal cord injury pain

Symptoms of neuropathic spinal cord injury (SCI) pain include cutaneous hypersensitivity and spontaneous pain below the level of the injury. Riluzole, an FDA-approved drug for the treatment of amyotrophic lateral sclerosis, has been demonstrated to attenuate neural excitotoxicity by blocking the effects of the excitatory amino acid glutamate on glutamate receptors and by inhibiting voltage-gated Na(+) and Ca(2+) channels. Neuropathic pain in rat models of SCI is thought to be mediated by dysfunctional ion channels and glutamate receptors expressed on CNS neurons. Thus riluzole's mechanism of action could be relevant in treating neuropathic SCI pain. The current study evaluated the antinociceptive potential of riluzole in rats following a SCI. Four weeks after a brief compressive injury to the mid-thoracic spinal cord, rats displayed significantly decreased hind paw withdrawal thresholds, suggestive of below-level cutaneous hypersensitivity. A single systemic dose of riluzole (8?mg/kg) injected intraperitoneally (i.p.) reversed cutaneous hypersensitivity in SCI rats. To identify riluzole's CNS site of action, riluzole was injected intrathecally (i.t.) and intracerebroventricularly (i.c.v.) in SCI rats. Significant antinociceptive effects were obtained following i.c.v., but not i.t., injection. Systemic riluzole was also antinociceptive in uninjured rats, increasing the latency to respond to an acute noxious thermal stimulus in the tail flick test. Unlike in SCI rats, however, riluzole was not effective when administered directly into the CNS, indicating a peripherally mediated antinociceptive mechanism. Although riluzole appears to have a general antinociceptive effect, the site of action may be model dependent. In total, these data indicate that riluzole may be an effective clinical analgesic for the treatment of below-level neuropathic SCI pain. Although the exact mechanism of action is not clear, there is a predominant supraspinal component of riluzole-induced antinociception in SCI rats.     

Effect of sodium nitroprusside on spinal cord perfusion and paraplegia during aortic cross-clamping

To evaluate the effects of sodium nitroprusside (SNP) on hemodynamics, cerebrospinal fluid dynamics, and neurological outcome after 30 minutes of thoracic aortic occlusion, we monitored proximal and distal blood pressure, cerebrospinal fluid pressure, spinal cord blood flow, and somatosensory evoked potentials. In group 1 (n = 6), no attempts were made to control proximal hypertension, whereas in group 2 (n = 6), proximal blood pressure was controlled with intravenous infusion of SNP. There was no significant difference in proximal or distal blood pressure or cerebrospinal fluid pressure between the two groups at baseline. During the crossclamp interval, the mean proximal aortic pressure rose from 108 +/- 21 to 146 +/- 14 mm Hg (p less than 0.001) in the control group, whereas the mean blood pressure in the SNP group was maintained at 99.8 +/- 12 mm Hg (p = not significant compared with baseline blood pressure). Mean distal aortic pressure decreased from systemic values to 23 +/- 7 mm Hg in control animals and to 11 +/- 5 mm Hg in the SNP group (p less than 0.005). In the latter group, cerebrospinal fluid pressure increased significantly from 10.6 +/- 1.9 to 20.1 +/- 5.5 mm Hg (p less than 0.005). In animals receiving SNP, spinal cord blood flow was decreased in the lower spinal cord segments and increased in the upper cord segments. When compared with controls, this difference did not reach significance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microdialysis of the spinal cord during thoracic aortic cross-clamping in a porcine model

OBJECTIVE: Utilising microdialysis to measure the changes of glucose, lactate, pyruvate and glutamate levels in the spinal cord after cross-clamping of the thoracic aorta in an established porcine model to monitor the degree of ischaemia. DESIGN: Experimental study with a porcine model. SETTING: University Hospital, Trondheim. SUBJECTS: Six pigs. MAIN OUTCOME MEASURE: Lactate, pyruvate and glutamate concentrations in the microdialysis perfusate from the spinal cord. RESULTS: A significant increase of the lactate-pyruvate ratio during the last 30 min of the 1 h clamping period, with a maximum increase of 169% from the basal value the last 10 min before declamping. No evident change in this ratio between the clamping and the reperfusion period. No significant change in glutamate levels during clamping or reperfusion period. CONCLUSION: Microdialysis reflects the ischaemic state of the spinal cord during cross-clamping of the thoracic aorta in pigs, and is well suited to study each phenomena.     

Winner of the ESVS prize 1989. Microcirculation of the spinal cord during proximal aortic cross-clamping

The relationship between the cerebrospinal fluid pressure (CSFP) and the microcirculation of the spinal cord was studied during cross-clamping (XC) of the thoracic aorta in pigs. CSFP was recorded via an intrathecal catheter. The microcirculation was measured by the laser Doppler technique using a needle probe inserted percutaneously into the spinal cord. A left thoracotomy was performed, and the thoracic aorta was cross-clamped for 30 minutes distal to the left subclavian artery. Prior to XC a pulsatile flux recording from the spinal cord (SCF) was observed. Following cross-clamping of the aorta SCF was dramatically reduced (P less than 0.001), then stabilised at 40% of base-line values. During XC, variations in CSFP were observed but these changes were not statistically significant. CSFP gradually increased to pre cross-clamp levels following release of XC (P less than 0.05). SCF increased 51% following removal of 1 ml of cerebrospinal fluid (P less than 0.05). By injection of 0.9% saline at body temperature SCF was totally inhibited at CSFP above 15 mmHg. Occlusion of the azygos vein increased CSFP 1.3 mmHg (P less than 0.05) whereby SCF decreased 58% (P less than 0.01). Following release of XC of a hyperaemic period of the SCF was demonstrated in ten out of 13 animals. In conclusion, SCF was significantly influenced by changes in CSFP during XC of the thoracic aorta. The findings support the theory that removal of spinal fluid during XC of the thoracic aorta may increase the perfusion pressure to the spinal cord, thereby improving its blood supply.     

Riluzole prevents ischemic spinal cord injury caused by aortic crossclamping

BACKGROUND: Recent studies support the involvement of glutamate neurotoxicity in the pathophysiology of spinal cord injury induced by aortic crossclamping. We investigated the effects of riluzole, a neuroprotective drug that blocks glutamatergic neurotransmission, in a rabbit model of spinal cord ischemia. METHODS: The infrarenal aortas of New Zealand White albino rabbits (n = 40) were occluded for 40 minutes. Experimental groups were as follows: sham operation group (n = 5), control group undergoing occlusion but receiving no pharmacologic intervention (n = 10), experimental group A (n = 10) receiving 8 mg/kg riluzole intravenously 30 minutes before ischemia, experimental group B (n = 10) receiving 4 mg/kg riluzole intravenously 30 minutes before ischemia and at the onset of reperfusion, and experimental group C (n = 10) receiving 8 mg/kg riluzole intravenously at the onset of reperfusion. Neurologic status was assessed at 6, 24, and 48 hours after the operation and then daily until the fifth day. All animals were killed at 24, 48, or 120 hours after the operation. Spinal cords were harvested for histopathologic studies, immunohistochemical studies for microtubule-associated protein 2, and search for morphologic features of apoptosis by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining method. RESULTS: All animals in the control group became paraplegic. Except for 1 rabbit in group C, all riluzole-treated animals had better neurologic function. Luxol fast blue and terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining methods demonstrated typical morphologic changes characteristic of necrosis and apoptosis in control animals. Riluzole prevented or attenuated ischemia-induced necrosis, apoptosis, and cytoskeletal proteolysis, depending on the dose and the timing of administration. CONCLUSION: Riluzole may have therapeutic utility during high-risk operations on the thoracoabdominal aorta.