Ischemic spinal cord injury induced by aortic cross-clamping: prevention by riluzole.

OBJECTIVE: Recent studies confirmed the deleterious role of glutamate in the pathophysiology of spinal cord ischemia induced by aortic cross-clamping. We investigated the effect of riluzole, an anti-glutamate drug, in a rat model of spinal cord ischemia. MATERIALS AND METHODS: Spinal cord ischemia was induced in normothermia for 14 min in Sprague-Dawley rats using direct aortic arch plus left subclavian artery cross-clamping through a limited thoracotomy. Experimental groups were as follows: sham-operation (n=15), control (n=15) receiving only vehicle, riluzole (n=15) receiving riluzole (4 mg/kg) before clamping and at the onset of reperfusion. Separate animals were used for monitoring physiologic parameters in the sham-operation (n=3), control (n=5), and riluzole (n=5) groups. Neurologic status was assessed at 6, 24 h, and then daily up to 96 h. Rats were randomly killed at 24, 48, or 96 h (n=5 for each time). Spinal cords were harvested for histopathology, immunohistochemistry for microtubule-associated protein 2 (MAP-2), TUNEL staining, and analysis of DNA fragmentation by agarose gel electrophoresis. RESULTS: All sham-operated rats had a normal neurologic outcome, whereas all control rats suffered severe and definitive paraplegia. Riluzole-treated rats had significantly better neurologic function compared to the control. Histopathology disclosed severe neuronal necrosis in the lumbar gray matter of control rats, whereas riluzole-treated rats suffered usually mild to moderate injury. Riluzole particularly prevented motor neurons injury. MAP-2 immunoreactivity was completely lost in control rats, whereas it was preserved either completely or partly in riluzole-treated rats. TUNEL staining revealed numerous apoptotic neurons scattered within the whole gray matter of control rats. Riluzole prevented or dramatically attenuated apoptotic neuronal death in treated rats. DNA extracted from lumbar spinal cords of sham-operated and riluzole-treated rats exhibited no laddering, whereas spinal cords from control rats showed DNA laddering with fragmentation into approximately 180 multiples of base pairs. CONCLUSIONS: Riluzole may protect the spinal cord in a setting of severe ischemia by preventing neuronal necrosis and apoptosis. This drug may therefore be considered for clinical use during 'high risk' surgical procedures on the thoracoabdominal aorta.     

Mild hypothermia protects the spinal cord from ischemic injury in a chronic porcine model.

OBJECTIVES: During thoracoabdominal aortic aneurysm repair, prolonged compromise of spinal cord blood supply can result in irreversible spinal cord injury. This study investigated the impact of mild hypothermia during aortic cross-clamping on postoperative paraplegia in a chronic porcine model. METHODS: The thoracic aorta was exposed and cross-clamped in 30 juvenile pigs (20-22 kg) for different intervals at normothermia (36.5 degrees C), and during mild hypothermia (32.0 degrees C). Three pigs were evaluated at each time and temperature. Myogenic motor-evoked potentials (MEPs) were monitored, and postoperative recovery evaluated using a modified Tarlov score. RESULTS: There were no significant hemodynamic or metabolic differences between individual animals, and the groups had equivalent arterial pressures (mean 64.3+/-3.6 mmHg). Time to recovery of MEPs correlated with severity of injury; all animals with irreversible MEP loss suffered postoperative paraplegia. At normothermia, animals with 20 min of aortic cross-clamping emerged with normal motor function, but those cross-clamped for 30 min suffered paraplegia. With mild hypothermia, animals tolerated 50 min of aortic cross-clamping without evidence of neurologic injury, but were all paraplegic after 70 min of ischemia. Animals appeared to recover normal motor function after 60 min of aortic cross-clamping at hypothermia initially, but exhibited delayed-onset paraplegia 36 h postoperatively. CONCLUSIONS: Our observations indicate that mild hypothermia dramatically increases the tolerance of the spinal cord to ischemia in the pig, and therefore suggests that cooling to 32.0 degrees C should be encouraged during surgery which may compromise spinal cord blood supply. An ischemic insult of borderline severity may result in delayed paraplegia.     

Neuroprotective effects of FK-506, L-carnitine and azathioprine on spinal cord ischemia-reperfusion injury.

OBJECTIVE: In our experimental study, we aimed to test the effect of FK506, azathioprine and L-carnitine on protection of spinal cord injury due to ischemia-reperfusion. METHODS: Twenty-seven Sprague-Dawley male rats were randomly divided into five groups. They were subjected to spinal cord ischemia by clamping the abdominal aorta for 45 min. Thirty minutes before the aortic clamping, group I received 0.5 mg/kg FK506, group II received 100 mg/kg L-carnitine, group III received 4 mg/kg azathioprine, the fourth group was the control group and received only normal saline injection intravenously and the last group was the sham group. Neurological status was scored by using the Tarlov scoring system. Sections of the lumbar cord were harvested for histopathological grades (1-4), having regard to percentage of the apoptotic cells. RESULTS: Hind-limb motor function had recovered normally 48 h after the operation in all rats which received FK506, azathioprine and L-carnitine prophylactically. In contrast, all rats in the control group had deteriorated to paraplegia by 48 h after the operation (P<0.05). Histopathologic sections in the involved spinal cord segment showed that a greater number of motor neuron cells were preserved and there were less apoptotic cells in the rats that received FK506, azathioprine and L-carnitine than those in control group. CONCLUSIONS: These results suggest that prophylactic use of FK506, azathioprine and L-carnitine protects motor neuron cells from ischemic spinal cord injury.     

Immediate ischemic preconditioning based on somatosensory evoked potentials seems to prevent spinal cord injury following descending thoracic aorta cross-clamping.

OBJECTIve: Delayed ischemic preconditioning has demonstrated neuroprotective effects in spinal cord ischemia. We investigated the effects of immediate ischemic preconditioning based on somatosensory evoked potentials monitoring in a model of spinal cord injury due descending thoracic aorta occlusion in dogs. METHODS: Twenty-one dogs were submitted to spinal cord ischemia induced by descending thoracic aorta cross-clamping for 45 min. Control group underwent only the aortic cross-clamping (n=7), group A underwent one cycle of ischemic preconditioning (n=7) and group B underwent three equal cycles of ischemic preconditioning (n=7), immediately before the aortic cross-clamping. Ischemic preconditioning cycles were determined by somatosensory evoked potentials monitoring. Neurologic evaluation was performed according to the Tarlov score at 72 h of follow-up. The animals were then sacrificed and the spinal cord harvested for histopathology. RESULTS: Aortic pressures before and after the occluded segment were similar in the three groups. Ischemic preconditioning periods corresponded to a mean ischemic time of 3+/-1 min and a mean recovery time of 7+/-2 min. Severe paraplegia was observed in three animals in Control group, in four in group A and in none in group B. Tarlov scores of group B were significantly better in comparison to the Control group (P=0.036). Histopathologic examination showed severe neuronal necrosis in the thoracic and lumbar gray matter in animals who presented paraplegia. CONCLUSIONS: Immediate repetitive ischemic preconditioning based on somatosensory evoked potentials monitoring seems to protect spinal cord during descending aorta cross-clamping, reducing paraplegia incidence.     

Präklinisches Kleintiermodell zur Erforschung von Ischämie- und Reperfusionsschäden des Rückenmarks nach Crossclamping der Aorta

Spinal ischemia and the resulting reperfusion is a crucial problem in aortic cross-clamping. In pig models, such as the Ulm model, with sacrifice of the animal at the end of the experiment the neurological outcome cannot be determined. In New Zealand white rabbits spinal ischemia can be induced by cross-clamping of the infrarenal aorta due to segmental blood supply of the spinal cord. In preliminary trials a clamping time of 15 min was defined as being optimal. Functional neurologic outcome was assessed by using the modified Tarlov score. Animals were anesthetized by a mixture of ketamine (50mg/kg body weight) and xylazine (5mg/kg). Blood pressure, heart rate, oxygen saturation and temperature were monitored intraoperatively. Due to positive effects found in former investigations carbamylated erythropoietin (cEPO) was selected for the treatment group. Neurological examinations were undertaken after declamping and subsequently every 12 h. At 96 h the animals were sacrificed and the spinal cords were removed for histopathological examination. Overall 20 animals could be examined, 10 in the treatment group and 10 in the placebo group. After aortic cross-clamping all animals showed complete paraplegia (Tarlov score 0/5). Within the first 12-24 h animals showed an incomplete neurological recovery (Tarlov score 4.25/5) while a decline in hind limb motion was observed in the following days (Tarlov score 3.55/5). Histopathological examination did not reveal any injury in thoracic sections of the spinal cord whereas damage in lumbal sections correlated significantly with neurological symptoms (p=0.007). The treatment group (cEPO) and the placebo group showed no differences in neurological or histopathological outcome. This is a highly reproducible model which allows clinical neurological assessment after aortic cross-clamping. Using this model promising pharmaceutics influencing ischemia tolerance can be tested clinically and histopathologically. In the initial experimental series with a cross-clamping time of 15 min no significant improvement of the clinical or histological damage could be achieved by administration of cEPO.     

Monitoring of somatosensory evoked potentials during surgical procedures on the thoracoabdominal aorta. I. Relationship of aortic cross-clamp duration, changes in somatosensory evoked potentials, and incidence of neurologic dysfunction

To determine if intraoperative monitoring of somatosensory evoked potentials detects spinal cord ischemia, we subjected 21 dogs to aortic cross-clamping distal to the left subclavian artery. Group I animals (short-term studies, n = 6) demonstrated decay and loss of somatosensory evoked potentials at 8.5 +/- 1.1 minutes after aortic cross-clamping. During loss of somatosensory evoked potentials, significant decreases in spinal cord blood flow occurred in cord segments below T6. Significant reactive hyperemia occurred without normalization of somatosensory evoked potentials after reperfusion. Fifteen Group II animals (long-term studies) were studied to determine the relationship between duration of spinal cord ischemia (evoked potential loss) and subsequent incidence of paraplegia. Extension of aortic cross-clamping for 5 minutes after loss of somatosensory evoked potentials in six dogs resulted in no paraplegia (mean cross-clamp time 12.7 +/- 0.6 minutes). Prolongation of aortic cross-clamping for 10 minutes after evoked potential loss in nine dogs (mean cross-clamp time 17.6 +/- 0.6 minutes) resulted in a 67% (6/9) incidence of paraplegia 7 days postoperatively (p = 0.02 versus 10 minutes of aortic cross-clamping). These findings demonstrate that simple aortic cross-clamping uniformly results in spinal cord ischemia and that such ischemia is detectable by monitoring of somatosensory evoked potentials. Duration of ischemia, as measured by the time of evoked potential loss during the cross-clamp interval, is related to the incidence of postoperative neurologic injury.     

Spinal cord injury in experimental thoracic aortic occlusion: investigation of combined methods of protection.

The efficacy of combined methods of spinal cord protection during thoracoabdominal aortic reconstruction was evaluated because a recent clinical study failed to substantiate the value of cerebrospinal fluid drainage when used alone in the prevention of paraplegia. The effect of cerebrospinal fluid drainage and aortofemoral shunting were analyzed with regard to neurologic outcome and spinal cord blood flow in a model of thoracic aortic occlusion. In addition, we studied the use of motor-evoked potentials as compared with somatosensory-evoked potentials in monitoring cord perfusion. Thirty-two dogs underwent proximal and distal thoracic aortic occlusion for 60 minutes. The control group (n = 8) underwent thoracic aortic cross-clamping only. Spinal cord protection was used in three groups: cerebrospinal fluid drainage alone (n = 8), aortofemoral shunting alone (n = 8), and cerebrospinal fluid drainage and aortofemoral shunting (n = 8). Neurologic outcome improved in all treatment groups as compared with controls (p less than 0.001). The addition of cerebrospinal fluid drainage to aortofemoral shunting did not further improve neurologic outcome. Spinal cord blood flow measured with microspheres in the lumbar gray matter was significantly higher in the dogs with aortofemoral shunting (+/- cerebrospinal fluid drainage) as compared with those with cerebrospinal fluid drainage alone (p less than 0.05) or the controls (p less than 0.001). Aortofemoral shunting also prevented the development of acidosis and hyperglycemia. Loss or changes in amplitude and latency of motor-evoked potentials did not distinguish between the groups. Loss of somatosensory-evoked potentials had a high sensitivity (92%) but lower specificity (68%) in predicting neurologic injury, whereas loss of motor-evoked potentials had a high specificity (100%) but a very low sensitivity (16%). We conclude that cerebrospinal fluid drainage or aortofemoral shunting significantly improve spinal cord blood flow and neurologic outcome. The greatest increase in spinal cord blood flow was seen with aortofemoral shunting, which also prevented metabolic disturbances of reperfusion. Although the addition of cerebrospinal fluid drainage to aortofemoral shunting was the only group in which no neurologic injury occurred, this group did not have a significant improvement in outcome when compared with aortofemoral shunting alone. Spinal cord ischemia was more accurately detected with somatosensory-evoked potentials when aortofemoral shunting was used, whereas motor-evoked potentials recorded from the spinal cord were not sensitive enough to predict neurologic injury.     

Neuroprotective Effect of Epidural Electrical Stimulation against Ischemic Spinal Cord Injury in Rats: Electrical Preconditioning

Background: Electroconvulsion therapy is likely to serve as an effective preconditioning stimulus for inducing tolerance to ischemic brain injury. The current study examines whether electrical stimuli on the spinal cord is also capable of inducing tolerance to ischemic spinal cord injury by transient aortic occlusion.

Methods: Spinal cord ischemia was induced by occlusion of the descending thoracic aorta in combination with maintaining systemic hypotension (40 mmHg) during the procedure. Animals implanted with epidural electrodes were divided into four groups according to electrical stimulation and sham. Two groups consisted of rapid preconditioning (RE group, n = 8) and sham procedure (RC group, n = 8) 30 min before 9 min of spinal cord ischemia. In the two groups that underwent delayed preconditioning, rats were exposed to 9 min of aortic occlusion 24 h after either pretreatment with epidural electrical stimulation (DE group, n = 8) or sham (DC group, n = 8). In addition, rats were exposed to 6-11 min of spinal cord ischemia at 30 min or 24 h after epidural electrical stimulation or sham stimulation. The group P50 represents the duration of spinal cord ischemia associated with 50% probability of resultant paraplegia.

Results: Pretreatment with electrical stimulation in the DE group but not the RE group protected the spinal cord against ischemia, and this stimulation prolonged the P50 by approximately 15.0% in the DE group compared with the DC group.     

Delayed onset of neurologic deficit: significance and management

As contemporary adjuncts have substantially reduced the overall incidence of paraplegia and paraparesis after the surgical repair of thoracoabdominal aortic aneurysm, delayed-onset neurologic deficit has emerged as a significant clinical entity. It is generally agreed that neurologic deficits are attributable to the duration of spinal cord ischemia sustained during aortic cross-clamping. Factors known to increase the risk of spinal cord injury include the aneurysm extent, aortic cross-clamp time, aneurysm rupture, and associated acute aortic dissection. Clinically and experimentally, studies have shown different adjuncts to improve spinal cord protection, providing further insights into the pathophysiology of spinal cord ischemia. However, the pathophysiology of delayed-onset spinal cord deficit after thoracoabdominal aortic aneurysm repair remains largely controversial. This review discusses the significance and management of delayed-onset neurologic deficit.     

Neuroprotective effect of epidural electrical stimulation against ischemic spinal cord injury in rats: electrical preconditioning

BACKGROUND: Electroconvulsion therapy is likely to serve as an effective preconditioning stimulus for inducing tolerance to ischemic brain injury. The current study examines whether electrical stimuli on the spinal cord is also capable of inducing tolerance to ischemic spinal cord injury by transient aortic occlusion. METHODS: Spinal cord ischemia was induced by occlusion of the descending thoracic aorta in combination with maintaining systemic hypotension (40 mmHg) during the procedure. Animals implanted with epidural electrodes were divided into four groups according to electrical stimulation and sham. Two groups consisted of rapid preconditioning (RE group, n = 8) and sham procedure (RC group, n = 8) 30 min before 9 min of spinal cord ischemia. In the two groups that underwent delayed preconditioning, rats were exposed to 9 min of aortic occlusion 24 h after either pretreatment with epidural electrical stimulation (DE group, n = 8) or sham (DC group, n = 8). In addition, rats were exposed to 6-11 min of spinal cord ischemia at 30 min or 24 h after epidural electrical stimulation or sham stimulation. The group P50 represents the duration of spinal cord ischemia associated with 50% probability of resultant paraplegia. RESULTS: Pretreatment with electrical stimulation in the DE group but not the RE group protected the spinal cord against ischemia, and this stimulation prolonged the P50 by approximately 15.0% in the DE group compared with the DC group. CONCLUSIONS: Although the optimal setting for this electrical preconditioning should be determined in future studies, the results suggest that epidural electrical stimulation will be a useful approach to provide spinal protection against ischemia.     

Spinal cord ischemia after endovascular repair of the descending thoracic aorta in a sheep model.

OBJECTIVES: Spinal cord ischemia remains a devastating complication after thoracic aortic surgery. The aim of this study was to investigate the pathophysiology of spinal cord ischemia after thoracic aortic endografting and the role of intercostal artery blood supply for the spinal cord in a standardized animal model. METHODS: Female merino sheep were randomized to either I, open thoracotomy with cross-clamping of the descending aorta for 50 min (n=7), II, endograft implantation (TAG, WL Gore & Ass.), (n=6) or III open thoracotomy with clipping of all intercostal arteries (n=5) . CT-angiography was used to assess completion of surgical protocol and assess the fate of intercostal arteries. Tarloy score was used for daily neurological examination for up to 7 days post-operatively. Histological cross sections of the lumbar, thoracic and cervical spinal cords were scored for ischemic damage after stained with Hematoxylin-Eosin, Klüver-Barrrera and antibodies. Exact Kruskall-Wallis-Test was used for statistical assessment (p<0.05). RESULTS: Incidence of paraplegia was 100% in group I and 0% in group II (p=0.0004). When compared to the endovascular group, there was a higher rate of histological changes associated with spinal cord ischemia in the animals of the control group (p=0.0096). Group III animals showed no permanent neurological deficit and only 20% infarction rate (p=0.0318 compared to group I). CONCLUSIONS: In sheep, incidence of histological and clinical ischemic injury of the spinal cord following endografting was very low. Complete thoracic aortic stent-grafting was feasible without permanent neurologic deficit. Following endovascular coverage or clipping of their origins, there is retrograde filling of the intercostal arteries which remain patent.     

Improvement in thoracic aortic pressure after proximal aortic cross-clamping by balloon occlusion of the distal aorta

Spinal cord hypoperfusion injury is a devastating complication of cross-clamping the proximal thoracic aorta. The collateral circulation around the cross-clamp is generally poorly developed, and the run-off is immense, resulting in extremely low thoracic aortic and spinal cord perfusion pressures. The authors postulated that balloon occlusion of the abdominal aorta might confine this reduced collateral flow around the cross-clamp to the thoracic aorta. In 8 of 16 dogs subjected to aortic cross-clamping of the aorta just beyond the arch vessels, the abdominal aorta was also occluded by a balloon. Thoracic aortic pressure and spinal cord perfusion pressure were significantly higher in the animals with aortic balloon occlusion than in those without balloon occlusion (77 +/- 8 mm Hg versus 26 +/- 1 mm Hg, p less than 0.01, and 67 +/- 8 mm Hg versus 18 +/- 2 mm Hg, p less than 0.01, at 10 minutes after cross-clamping). Abdominal aortic balloon occlusion increases thoracic aortic pressure after the aorta is cross-clamped proximally. Further studies are necessary in primates to assess the effect of this procedure in spinal cord perfusion and the rate of paraplegia.     

Neuroprotective effect of KR-31378, a novel potassium channel activator, on spinal cord ischemic injury in rabbits.

Neurologic deficits after the surgical repair of thoracic and thoracoabdominal aortic disease are devastating complications. Recently, pharmacologic preconditioning with potassium channel openers was reported to protect the spinal cord against neurologic injury in a model of spinal cord ischemia. A novel benzopyran derivative with an N-cyanoguanidine group, KR-31378, has been synthesized as a new therapeutic agent against ischemic injury. In the present study, we evaluated the protective effects of KR-31378 on spinal cord ischemic injury and compared its neuroprotective activities and hemodynamic stabilities with those of diazoxide. Thirty-four New Zealand white rabbits were randomly divided into four groups: ischemia group (n = 10, 25 min of aortic cross-clamping without any intervention), diazoxide group (n = 8, diazoxide [5 mg/kg] intravenously 15 min before the 25-min cross-clamping), KR20 group (n = 8, KR-31378 [20 mg/kg] intravenously 30 min before the 25-min cross-clamping), and the KR50 group (n = 8, KR-31378 [50 mg/kg] intravenously 30 min before the 25-min cross-clamping). Neurologic functions were evaluated for 72 h postoperatively using modified Tarlov's scores. All rabbits were sacrificed for histopathologic observations after finally scoring neurologic function. All rabbits but three survived. The rest were completely evaluated 72 h postoperatively. Unlike diazoxide-treated rabbits, KR-31378-treated rabbits showed relatively stable hemodynamics. Tarlov's score outcomes showed a marked improvement in the diazoxide group, in the KR20 group, and in the KR50 group compared to the ischemia group (p = .005, .002, and .001, respectively). However, Tarlov's scores in the KR50 group were not significantly different from those of the diazoxide group. Histopathologic data were not significantly different between the groups, but the degree of degenerative change in motor neurons showed a significant correlation with Tarlov's scores 3 days postoperatively (gamma = -.378, p = .036). Thus, the administration of KR-31378 before the aortic cross-clamping resulted in a significant improvement in neurologic outcome with stable hemodynamics in this rabbit model.     

The value of motor evoked potentials in reducing paraplegia during thoracoabdominal aneurysm repair

OBJECTIVE: Paraplegia after thoracoabdominal aortic aneurysm (TAAA) repair mainly occurs in patients with Crawford extent I and II. We assessed the impact of monitoring spinal cord integrity and the subsequent adjusted surgical maneuvers on neurologic outcome in repairs of type I and II TAAAs. METHODS: Surgical repair of TAAAs was performed in 112 consecutive patients with extent type I (n = 42) and type II (n = 70) aneurysms. The surgical protocol included cerebrospinal fluid drainage, moderate hypothermia, and left heart bypass with selective organ perfusion. Spinal cord function was assessed by means of monitoring motor evoked potentials (MEPs). Significant decreased MEPs always generated adjustments, including raising distal aortic and mean arterial pressure, reattachment of visible intercostal arteries, or endarterectomy of the excluded aortic segment with revascularization of back bleeding intercostal arteries. RESULTS: Motor evoked potential monitoring could be achieved in all patients. By maintaining a mean distal aortic pressure of 60 mm Hg, MEPs were adequate in 82% of patients. Increasing distal aortic pressure restored MEPs in all patients. In 19 patients (17%), MEPs decreased significantly during aortic cross-clamping because of critical spinal cord ischemia. MEPs returned in all patients after spinal cord blood flow was re-established except in three patients with type II TAAA in whom MEPs could not be restored, and absent MEPs at the end of the procedure corresponded with neurologic deficit. Delayed paraplegia developed in two patients owing to hemodynamic instability with insufficient mean arterial blood pressure to maintain adequate spinal cord perfusion. CONCLUSION: Monitoring MEPs is a highly reliable technique to assess spinal cord ischemia during TAAA repair. A surgical protocol including cerebrospinal fluid drainage, left heart bypass, and monitoring of MEPs can reduce the paraplegia rate significantly. Adjusted hemodynamic and surgical strategies induced by changes in MEPs could restore spinal cord ischemia in most patients, preventing early and late paraplegia in all type I patients. In type II patients, early paraplegia occurred in 4.2% and delayed neurologic deficit in 2.9%. Despite all available measures, complete prevention of paraplegia in type II aneurysms seems to be unrealistic.     

Spinal cord retrograde perfusion: review of the literature and experimental observations

BACKGROUND: Spinal cord damage represents a devastating complication of thoracic and thoracoabdominal aortic surgery. Retrograde perfusion as an alternative route to protect the spinal cord has recently been investigated with controversial results. We reviewed the literature and analyzed additional experimental observations. METHODS: Ten juvenile pigs were divided into control and study groups (A and B, respectively). Through a lateral thoracotomy the distal aortic arch was cannulated and connected to a cardiotomy reservoir. All animals underwent 40-minute single cross-clamping of the proximal descending aorta while keeping proximal systolic arterial pressure above 100 mmHg. In group B, normothermic arterial blood was delivered retrogradely through the azygos vein, maintaining perfusion pressure within 25-30 mmHg. Animals were allowed to recover to perform a primary neurologic evaluation. RESULTS: Flaccid paraplegia was uniformly observed in group A. In group B, all animals showed mild-to-moderate voluntary hind limb movements on awakening (p = 0.007). Controls also showed urine incontinence short after cross-clamping, and this was not observed in group B (p = 0.008). A different veno-arterial oxygen step-down was observed in blood collected from the excluded aorta in the two groups (p < 0.001). CONCLUSIONS: Preliminary results indicate that controlled retrograde normothermic perfusion alone through the azygos system provides some degree of protection from spinal cord ischemia. Bladder dysfunction may represent a simple test to detect massive cord damage intraoperatively. Retrograde spinal cord perfusion warrants further investigation.     

Neuroprotective effect of regional carnitine on spinal cord ischemia--reperfusion injury.

OBJECTIVE: The purpose of this study was to investigate the effect of regional infusion of carnitine on spinal cord ischemia--reperfusion (I--R) in rabbits. METHODS: The 36 rabbits were divided into four equal groups, group I (sham operated, no I--R injury), group II (control, only I--R), group III (I--R+intraaortic lactated Ringer's, LR, during aortic occlusion), group IV (I--R+LR plus 100mg/kg carnitine). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the aortic bifurcation. The spinal cord function of all animals was assessed clinically 24h after aortic declamping. Spinal cord samples were taken to measure the levels of tissue malondialdehyde (MDA) and to evaluate the histopathological changes. RESULTS: We found significant increases in the levels of MDA in groups II and III compared with group I (P<0.01), and elevation of MDA in group IV was insignificant. In group II, all animals (100%) were paraplegic with Tarlov's score of 0 and in group III, eight animals (88%) were paraplegic with Tarlov's score of 0 or 1. None of the animals (0%) from group IV was paraplegic. Histologic examination of spinal cords from group IV animals revealed that the appearance of the spinal cord was relatively preserved, whereas spinal cords from groups II and III had evidence of acute neuronal injury. CONCLUSION: The results suggest that regional infusion of carnitine during aortic clamping reduces spinal cord injury and prevents neurologic damage in rabbit spinal cord I--R model.     

A study of spinal cord ischemia during aortic cross-clamp--evoked spinal cord potential and histological analysis of the spinal cord

The relationship between the evoked spinal cord potential (ESP) and the histological findings of the spinal cord after thoracic aortic cross-clamp was studied. Thoracic aorta was cross-clamped in 23 dogs and ESP was monitored before, during, and after cross-clamping. Incidence of paraplegia and histological findings were studied after the dogs recovered from the procedure. Aortic cross-clamp was maintained for 60 minutes in 20 dogs (Group A). And cross-clamp was released 10 minutes after the amplitude of ESP became lower than 20% of control in 3 dogs. (Group B). In group A, three types of ESP changes were detected; ESP became lower or lost during cross-clamping in type 1 response, ESP remained unchanged in type 2 response, and ESP returned after transient loss during cross-clamping in type 3 response. Four of five dogs with type 1, none of nine with type 2, two of five with type 3 response showed paraplegia. One of the dogs with type 2 response showed paraparesis. ESP could not detected in one dog, in which traumatic spinal cord injury during laminectomy caused paraplegia. In Group B, all dogs showed type 1 response and paraplegia. Characteristic histological finding of the spinal cords of the dogs with paraplegia was the ischemic necrosis mainly in the gray matter. Necrotic foci were limited in the posterior horn in mild, in the anterior and posterior horn in moderate changes. And neurons were lost in entire gray matter in severe histological changes. In the spinal cords of the dogs with spastic paraplegia, severe histological changes were limited in the lower lumbar region.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ischemic Preconditioning to Prevent Lethal Ischemic Spinal Cord Injury in a Swine Model

Objective: Paraplegia is a serious complication of thoracic and thoracoabdominal aortic operations and is the result of ischemic spinal cord injury induced by low perfusion pressure during cross-clamping of the aorta. Ischemic preconditioning (IPC) of the heart or brain with reversible sublethal ischemic injury induces resistance to subsequent lethal ischemia. The aim of this study is to investigate whether ischemic tolerance can be induced by IPC of the spinal cord in a swine model. Study Design: The animals were randomly divided into three groups: the sham group (n = 3), control group (n = 6) and IPC group (n = 8). In the sham group, we performed a left thoracotomy without any ischemic injury. In the IPC group, the swine received a reversible ischemic spinal cord injury by aortic clamping for 20 min, whereas in the control group, no aortic cross-clamping was performed. Forty-eight hours later, the animals in both the IPC and control groups underwent aortic clamping for 30 min. Neurological examination was done 24 h later, and then the animals were euthanized for histopathology and a malonedialdehyde spectrophotometry assay of the spinal cord tissue. Results: A statistically significant difference in neurological outcome was observed between the control and IPC groups at 24 h after ischemic injury. The incidence of paraplegia and severe paresis was 100% in the control group and 62.5% in the IPC group (p =. 028). Between control and IPC groups, there was no statistically significant difference in histopathology and only a borderline statistical difference in the malonedialdehyde assay of the ischemic spinal cord (p =. 0745). Conclusion: In this study, IPC induced protection against a 30-min ischemic insult of the spinal cord, although complete recovery was not achieved (standing up or walking). We expect that combining this IPC with other existing protective methods might lead to a synergistic effect, which warrants further investigation.     

Prevention and detection of spinal cord injury during thoracic and thoracoabdominal aortic repairs

BACKGROUND: Spinal cord injury is a most dreaded and unpredictable complication. In this study, based on our experimental results in dogs and early clinical results, we reviewed the incidence of paraplegia and the detection of spinal cord injury. METHODS: Eighty-two patients who underwent elective surgical repair of the descending thoracic and thoracoabdominal aorta over 17 years were subjects for this study. Sixty-two patients were male and 20 were female. Their mean age was 61.6 years (range, 17 to 81 years). Monitoring somatosensory evoked potentials (SEP) and measurement of mean distal aortic pressure and cerebrospinal fluid pressure were performed perioperatively. RESULTS: Sixty patients had no ischemic change in SEP. In 17 patients with significant ischemic changes of SEP, SEP recovered by increasing spinal cord perfusion pressure to more than 40 mm Hg. Two patients with complete loss of SEP experienced paraplegia. One patient had delayed paraplegia. CONCLUSIONS: These results strongly suggest that SEP, mean distal aortic pressure, cerebrospinal fluid pressure should be monitored during aortic cross-clamping. Maintaining spinal cord perfusion pressure at more than 40 mm Hg by increasing mean distal aortic pressure or withdrawal of cerebrospinal fluid is valuable for preventing paraplegia.