Prevention of reperfusion injury of the ischemic spinal cord: use of recombinant superoxide dismutase

We investigated the effect of recombinant superoxide dismutase, an oxygen free radical scavenger, on the prevention of reperfusion injury of the ischemic spinal cord. Somatosensory evoked potentials (SEPs) were obtained in 23 dogs. Spinal cord ischemia was produced by cross-clamping the descending thoracic aorta just distal to the origin of the left subclavian artery through a left thoracotomy. Mean proximal aortic blood pressure was maintained between 90 and 100 mm Hg by partial exsanguination. Serial SEPs were obtained at 60-second intervals until the SEP disappeared. Aortic cross-clamping was continued for 10 additional minutes after the disappearance of the SEP. In Group 1 (N = 8), no medication was given when the aortic cross-clamp was removed. In Group 2 (N = 8), a bolus of 25,000 units of superoxide dismutase was injected into the proximal aorta prior to removal of the aortic cross-clamp, and was followed by 5,000 units per minute for 10 minutes after release of the cross-clamp. In Group 3 (N = 7), 50,000 units of superoxide dismutase was administered as a bolus prior to removal of the aortic cross-clamp, followed by an additional 10,000 units per minute for 10 minutes as in Group 2. The postoperative neurological status was assessed by Tarlov's criteria. There was no significant difference in aortic cross-clamp time among the three groups. Paraplegia developed in 4 animals in Group 1; the remaining 4 dogs had paraparesis. In Group 2, paraparesis developed in 2 of 8 dogs; the other 6 had no neurological injury. All the animals in Group 3 had complete recovery.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

Effect of Cerebrospinal Fluid Drainage and/or PartiaI Exsanguination on Tolerance to Prolonged Aortic Cross-Clamping

Paraplegia as a consequence of spinal cord ischemia associated with procedures on the thoracic and thoracoabdominai aorta has been linked to the interaction of proximal hypertension with elevated cerebrospinal fluid pressure (CSFP) during aortic cross-clamping (AXC). CSFP reduction via cerebrospinal fluid (CSF) drainage is thought to significantly prolong the cord's tolerance to AXC. Likewise, partial exsanguination is reported to effectively reduce ischemic injury by controlling proximal hypertension. To evaluate the individual and collective efficacy of both techniques, 18 mongrel dogs (25 to 35 kg), divided into three equal groups, underwent a fourth interspace left thoracotomy AXC. Baseline proximal arterial blood pressure (PABP), distal arterial blood pressure (DABP), and CSFP were established and monitored at 5-minute intervals during 120 minutes of AXC, and for 30 minutes thereafter. Group I animals were partially exsanguinated prior to AXC to maintain PABP at a mean of 115 to 120 mmHg. Group II animals had sufficient (16 ± 5 cc) CSF withdrawn to maintain a DABP-CSFP gradient, i.e., spinal cord perfusion pressure (SCPP) of 20 mmHg. Group III animals were treated with both CSF drainage and partial exsanguination in the same manner as groups I and II, respectively. Periop-erative somatosensory evoked potential (SEP) monitoring evaluated cord function. Postoperative neurological outcome was assessed with Tariov's criteria. SEPs degenerated approximately 22 minutes following AXC for groups II and III. In contrast, group I exhibited rapid (10 ± 7 min) SEP loss. All five surviving group I animals displayed paralysis 48 hours postopera-tively. Mean PABP was significantly higher in group II (155 ±18 mmHg) than in either group 1 (117 ± 9 mmHg) or Ill (120 ± 14 mmHg) (p < 0.001). CSFP was significantly higher in group I (14 ± 4 mmHg) than in either group II or III (5 ± 2 mmHg) (p < 0.0001). The only parameter associated with neurological injury was low SCPP, which inversely correlated with CSF dynamics. Group I animals, with a mean SCPP of 4.6 mmHg, exhibited paraplegia, while groups II and Ill, with SCPP values above 20 mmHg, were free of neurological injury. Proximal hypertension did not play a role in cord injury. This study underscores the potential of CSF drainage to protect the ischemic spinal cord. (J Card Surg 7994;9:637–637)     

Monitoring of somatosensory evoked potentials during surgical procedures on the thoracoabdominal aorta. II. Use of somatosensory evoked potentials to assess adequacy of distal aortic bypass and perfusion after thoracic aortic cross-clamping

Pulsatile left atrial-femoral artery bypass was instituted after aortic cross-clamping distal to the left subclavian artery in a canine experimental model to determine the relationship of distal aortic perfusion pressure with spinal cord blood flow and somatosensory evoked potentials. In six animals (Group I) distal aortic perfusion pressure was maintained at 100 mm Hg throughout a 1 hour interval of aortic cross-clamping. During this period, somatosensory evoked potentials and spinal cord blood flow (radioactive microspheres) showed no significant change from baseline. In six other dogs (Group II) distal aortic perfusion pressure was initially maintained at 100 mm Hg after aortic cross-clamping and then progressively decreased to 70, 40, and 25 mm Hg. Somatosensory evoked potentials and spinal cord blood flow were preserved at baseline levels for all distal perfusion pressures greater than 70 mm Hg. At 40 mm Hg, abnormalities in amplitude of the somatosensory evoked potentials were noted in all animals with progression to complete loss of evoked potential activity at lower perfusion pressures. Maintenance of adequate somatosensory spinal cord conduction after thoracic aortic cross-clamping is dependent on a critical level of distal aortic perfusion that can be accomplished by use of an adjunct such as pulsatile left atrial-femoral artery bypass. The critical level of distal aortic perfusion pressure to maintain normal somatosensory evoked potentials and spinal cord blood flow in this canine experimental study was 70 mm Hg or greater. Because inadequate distal aortic perfusion can be easily detected by monitoring of somatosensory evoked potentials, these techniques should prove helpful in evaluating the effectiveness of distal perfusion techniques during clinical aortic cross-clamping for procedures on the thoracoabdominal aorta.     

Somatosensory evoked potentials and spinal cord perfusion pressure are significant predictors of postoperative neurologic dysfunction

Paraplegia after thoracoabdominal aneurysm repair can occur in 3% to 40% of patients. This study investigated the efficacy of cerebrospinal fluid (CSF) drainage to protect the spinal cord during aortic cross-clamping (AXC) and the interrelationship between drainage, spinal cord perfusion pressure (SCPP), and changes in somatosensory evoked potentials (SEP) in a canine model of spinal cord ischemia. SCPP was defined as the mean distal aortic pressure minus the CSF pressure. In the experimental group, CSF was drained before AXC. SEP changes were quantitated as time to latency increase of 10% (L-10) and time to complete SEP loss. Drainage of CSF had no significant effect on the distal aortic pressure but significantly increased SCPP from 9.4 to 21.8 mm Hg and decreased the incidence of postoperative neurologic injury. Ischemic SEP changes were highly significant predictors of postoperative neurologic injury, occurring more than two times earlier in the paralyzed and paraparetic animals. Dogs without neurologic injury had significantly higher SCPP, delayed L-10 time, and delayed SEP loss.     

Direct noninvasive monitoring of spinal cord motor function during thoracic aortic occlusion: use of motor evoked potentials

Spinal cord monitoring during thoracic aneurysmectomy by somatosensory evoked potentials has been criticized for its failure to measure anterior (motor) spinal cord function. We have developed a clinically applicable, noninvasive technique for intraoperative monitoring of motor evoked potentials (MEP), which allows direct functional assessment of spinal cord motor tracts during thoracic aortic occlusion. Twelve dogs underwent continuous intraoperative monitoring of MEP before, during, and after thoracic aortic cross-clamping. Motor tract response to noninvasive cord stimulation (5 to 10 mA, 0.02 msec, 4.3 H2) was recorded by subcutaneous electrodes placed along the length of the spine (T-10, L-1, and L-4). Six animals (group I) subjected to aortic cross-clamping alone demonstrated a characteristic time- and level-dependent deterioration and loss of MEP. Ischemic cord dysfunction (as determined by time from clamping to loss of MEP) progressed from the distal to the proximal cord (L-4 = 11.3 +/- 1.5 minutes; L-1 = 14.9 +/- 2.3 minutes; T-10 = 16.9 +/- 2.3 minutes; p less than 0.05 between all levels). Reperfusion of the distal aorta 20 minutes after clamping resulted in MEP return that progressed from the proximal (T-10) to distal (L-1 and L-4) cord. In another six animals (group II), distal perfusion (mean blood pressure = 95 mm Hg) was maintained for 1 hour after cross-clamping by left atrial-femoral artery bypass. Normal configuration and amplitude of MEP was maintained throughout the cross-clamping period. These data suggest that distinctive changes in MEP indicative of reversible ischemia of spinal cord motor tracts occur after aortic cross-clamping. Such ischemia begins in the most distal cord, exhibits upward progression with time, and can be prevented by maintenance of adequate distal aortic perfusion. Clinical use of MEP monitoring during thoracic aneurysmectomy may provide a method for intraoperative assessment of the adequacy of motor tract perfusion.     

Spinal oxygenation, blood supply localization, cooling, and function with aortic clamping.

Similar to other methods of organ preservation, "spinoplegia" may protect the spinal cord from the effects of oxygen desaturation during aortic cross-clamping. In porcine experiments, spinal cord O2 saturation was studied during intraoperative localization of the blood supply to the spinal cord using hydrogen; division of arteries not supplying the spinal cord; aortic cross-clamping for 60 minutes; and 60 minutes after unclamping. In 5 animals, 120 mL of cold saline solution with lidocaine (100 mg/dL) was infused into the aorta during aortic cross-clamping. During sequential localization, O2 saturation dropped by 40.02% (standard deviation, 20.16%) for T-14 artery testing versus a decrease of 17.27% (standard deviation, 11.88%; p = 0.0075) for L-5 artery segment testing in the control animals and returned to baseline thereafter. During aortic cross-clamping maximal O2 desaturation was 5% of baseline (15.7%; p less than 0.0001), which improved slightly by 30 minutes after clamping (48% of baseline +/- 37.37%; p = 0.048 versus maximum) and then returned to baseline (97.1% of baseline +/- 41%) with unclamping; 5 minutes later, hyperoxygenation occurred with a progressive decline thereafter (68% of baseline +/- 29.3%; p = 0.025, 45 minutes after unclamping versus baseline). The decrease in spinal motor evoked potentials was significantly less (p less than 0.02) in the treated group. Intraoperative hydrogen testing in 8 patients was demonstrated to be safe. It accurately localized reattached arteries, and O2 saturation of the spinal cord fell by 56% (standard deviation, 29%; p = 0.0025) with aortic cross-clamping. We conclude that spinal cord ischemia occurs with aortic cross-clamping in both animals and humans.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of paraplegia in pigs by selective segmental artery perfusion during aortic cross-clamping

PURPOSE: During thoracoabdominal aortic aneurysm repair, a prolonged interruption of the spinal cord blood supply can result in irreversible spinal cord damage. The aim of this study was to investigate whether selective segmental artery perfusion during aortic clamping could prevent paraplegia in pigs. METHODS: Specially designed segmental artery perfusion catheters, which could be attached to an extracorporeal bypass graft system, were used. In experiment I (n = 10), it was assessed whether selective segmental artery perfusion could reverse electrophysiologic evidence of spinal cord ischemia and maintain transcranial motor evoked potentials (tc-MEPs) during 60 minutes of aortic cross-clamping. The abdominal aorta, containing critical segmental arteries, was bypassed through use of an aortoaortic bypass graft system. After the disappearance of tc-MEPs, an aortotomy was followed by selective segmental artery perfusion. In experiment II (n = 10), the aim was to determine whether selective segmental artery perfusion could prevent paraplegia. In five animals (group A), aortic cross-clamping was followed by selective segmental artery perfusion; five control animals (group B) underwent segmental artery blockade only. Postoperative hind limb function and spinal cord histopathology were evaluated on the third postoperative day. RESULTS: In experiment I, tc-MEPs disappeared within 3.7 +/- 3.7 minutes after cross-clamping and returned in all animals in 8.5 +/- 5.3 minutes after selective perfusion. During the study period, tc-MEP amplitudes recovered to a median of 49% (range, 28%-113%) of baseline values. Total bypass graft flow was 880 +/- 294 mL/min, of which 184 +/- 54 mL/min was directed to the selective perfusion catheters. The flow in individual catheters was 52 +/- 13 mL/min. In experiment II, all perfused animals demonstrated normal hind limb function, whereas four of five control animals were paraplegic on day 3 (P =.04) In the perfused animals, histopathologic examination showed either no spinal cord damage or eosinophilic neurons only, whereas in paraplegic controls there was infarction in large areas of the cord (P <.0001). CONCLUSION: In pigs, selective segmental artery perfusion can provide sufficient spinal cord blood flow to prevent paraplegia resulting from 60 minutes of aortic clamping, as shown by clinical outcomes and histopathologic examination.     

Ischemia-reperfusion injury of the spinal cord: the influence of normovolemic hemodilution and gradual reperfusion

Recent studies have suggested that oxygen-derived free radicals play an important role in ischemia-reperfusion injury of the spinal cord. In other organ systems, reperfusion injury has been reduced by limiting the availability of oxygen in the reperfusion phase. The purpose of this study was to test the effect of normovolemic hemodilution and gradual reperfusion on spinal cord function after aortic cross-clamping in 84 New Zealand White rabbits. All animals underwent 21 min of infrarenal aortic cross-clamping in the conscious state by means of a previously placed aortic occlusion device and were randomized to four groups. Group 1 animals were hemodiluted to a mean(s.e.m.) hematocrit of 28(2)% by extracting 25% of the effective blood volume and reinfusing the plasma component after centrifugation concurrently with a volume of normal saline three times that of the discarded red cells. Group 2 animals (controls) were bled similarly but both plasma and red cells were reinfused, resulting in a mean(s.e.m.) hematocrit of 38(2)%. In the next two groups, distal aortic flow was recorded via an implantable Doppler device. After cross-clamping, flow was returned gradually over 45 min in animals of group 3, and abruptly in group 4. Animals were observed for 5 days and neurologic function was graded by an independent observer. Paraplegia at 5 h after clamping occurred in 75% of animals in group 1 versus 32% in group 2 (P < 0.05), and in 33% of group 3 versus 28% in group 4 (not significant). Of those animals showing initial neurologic recovery, delayed-onset paraplegia was seen in 100% in group 1 versus 87% in group 4 (not significant), and in 50% of group 3 versus 92% of group 4 (P < 0.03). The findings that the incidence of delayed-onset paraplegia in rabbits is reduced after gradual reintroduction of blood flow supports the hypothesis that this phenomenon is caused by reperfusion injury. Ischemic spinal cord injury is worsened by normovolemic hemodilution in this model.     

Somatosensory evoked potentials in the detection of spinal cord ischemia in aortic coarctation repair

Cortical somatosensory evoked potential (SEP) monitoring was used in 15 patients 2 to 50 years old undergoing repair of aortic coarctation to detect the onset of spinal cord ischemia during the cross-clamp period. Three different response patterns were observed. In 8 patients (53%), the SEP remained unchanged throughout the cross-clamping. This was designated a type 1 response. Six patients (40%) showed a gradual deterioration in the SEP after 15 minutes of cross-clamping (type 2 response). All SEPs returned to normal levels within 5 minutes of release of the clamp. One patient (7%) demonstrated a decline in SEP commencing prior to the application of the cross-clamp when an intercostal vessel was controlled with slings. The SEP completely disappeared within 5 minutes of cross-clamping, but after 19 minutes the repair was completed and the SEP returned within 3 minutes of reperfusion (type 3 response). No patient sustained neurological sequelae of repair. We believe that SEP monitoring offers the potential to identify the patient at risk of developing spinal cord ischemia intraoperatively before irreversible damage occurs. However, it is susceptible to deep halothane anesthesia, which abolishes all cortical responses and requires expert monitoring.     

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.     

Sustained spinal cord compression: part II: effect of methylprednisolone on regional blood flow and recovery of somatosensory evoked potentials

BACKGROUND: The efficacy of methylprednisolone in the treatment of traumatic spinal cord injury is controversial. We examined the effect of methylprednisolone on regional spinal cord blood flow and attempted to determine whether recovery of electrophysiological function is dependent on reperfusion, either during sustained spinal cord compression or after decompression. METHODS: The effects of methylprednisolone therapy on recovery of somatosensory evoked potentials and on spinal cord blood flow were examined in a canine model of dynamic spinal cord compression. Methylprednisolone (30 mg/kg intravenous loading dose followed by 5.4 mg/kg/hr intravenous infusion) or saline solution was administered to thirty-six beagles (eighteen in each group) five minutes after cessation of dynamic spinal cord compression and loss of all somatosensory evoked potentials. After ninety minutes of sustained compression, the spinal cords were decompressed. Somatosensory evoked potentials and spinal cord blood flow were evaluated throughout the period of sustained compression and for three hours after decompression. RESULTS: Seven dogs treated with methylprednisolone and none treated with saline solution recovered measurable somatosensory evoked potentials during sustained compression. After decompression, three more dogs treated with methylprednisolone and seven dogs treated with saline solution recovered somatosensory evoked potentials. Four dogs treated with methylprednisolone lost their previously measurable somatosensory evoked potentials. In the methylprednisolone group, spinal cord blood flow was significantly higher (p < 0.05) in the dogs that had recovered somatosensory evoked potentials than it was in the dogs that had not. Reperfusion blood flow was significantly higher (p < 0.05) in the saline-solution group than it was in the methylprednisolone group. Spinal cord blood flow in the saline-solution group returned to baseline levels within five minutes after decompression. It did not return to baseline levels in the dogs treated with methylprednisolone. CONCLUSIONS: The methylprednisolone administered in this study did not provide a large or significant lasting benefit with regard to neurological preservation or restoration. Methylprednisolone may reduce regional spinal cord blood flow through mechanisms affecting normal autoregulatory blood-flow function.     

Prevention of spinal cord ischemia after cross-clamping of the thoracic aorta--monitoring of spinal cord perfusion pressure and somatosensory evoked potentials

The pressure difference between the mean distal aortic pressure (MDAP) and the cerebrospinal fluid pressure (CSFP), defined as the spinal cord perfusion pressure (SCPP), as well as somatosensory evoked potentials (SEP) were monitored intraoperatively to detect and prevent intraoperative spinal cord ischemia in 24 patients who required cross-clamping of the descending thoracic aorta. A temporary axillo-femoral shunt, utilizing a 10 mm woven Dacron tube graft, was employed in 10 patients and partial cardiopulmonary bypass was employed in fourteen. Ischemic SEP changes were seen in six patients. Two patients, whose SCPPs were 32 and 35 mmHg, showed a complete loss of SEP and subsequently developed paraplegia. In the other four cases, increase of the MDAP and/or withdrawal of cerebrospinal fluid were performed to increase the SCPP to more than 60 mmHg when ischemic SEP changes occurred. The SEP gradually recovered in two of these cases. The ischemic SEP changes seen in one patient, who had the longest aortic cross-clamping time, (175 minutes) returned to normal immediately after unclamping. In another case, who had a thoracoabdominal aortic aneurysm, the intercostal arteries were reimplanted since the ischemic SEP changes did not revert. These four patients recovered without any neurological deficit. In the other 18 cases without ischemic SEP change, SCPP was kept at more than 40 mmHg during aortic cross-clamping. We conclude that the SCPP should be maintained at more than 40 mmHg during aortic occlusion, and increased to more than 60 mmHg when ischemic SEP changes occur, by increasing MDAP and/or withdrawing cerebrospinal fluid in order to prevent postoperative paraplegia.     

Spinal cord protection during aortic occlusion: efficacy of intrathecal tetracaine

Spinal cord ischemia and resultant paraplegia are devastating sequelae in up to 40% of patients undergoing repair of thoracoabdominal aneurysms. We investigated the effect of intrathecal tetracaine on the neurological sequelae of spinal cord ischemia and reperfusion with aortic occlusion. Cocaine-derived anesthetics (lidocaine and its analogues) have been shown to decrease neuronal cell metabolism and also have specific neuronal membrane stabilizing effects. New Zealand white rabbits were anesthetized and spinal cord ischemia was then induced by infrarenal aortic occlusion. Animals were divided into six treatment groups. Tetracaine (groups 2 and 4) or normal saline solution (group 5) was administered intrathecally before aortic cross-clamping. Groups 1 and 3 functioned as controls. Group 6 animals received intravenous thiopental. Rabbits were classified as either neurologically normal or injured (paralyzed or paretic). Among controls, 25 minutes of aortic occlusion produced varied neurological sequelae (group 1, 3/6 injured, 50%) whereas 30 minutes resulted in more consistent injury (group 3, 5/6 injured, 83%). All rabbits that received intrathecal saline solution were paralyzed (group 5, 4/4 injured, 100%). Animals treated with intrathecal tetracaine and aortic occlusion of 30 minutes (group 4) showed significantly better preservation of neurological function (6/7 normal, 86%) than controls and saline-treated animals (groups 3 and 5). All animals treated with intrathecal tetracaine and aortic occlusion for 25 minutes (group 2) showed no signs of injury (5/5 normal, 100%), but this was not significant versus controls (group 1). Intravenous thiopental (group 6, 5/5 injured, 100%) had no beneficial effect. Intrathecal tetracaine significantly and dramatically abrogated the neurological injury secondary to spinal cord ischemia and reperfusion after aortic occlusion at 30 minutes in the rabbit model.     

Intraoperative Detection of Spinal Cord Ischemia Using Somatosensory Cortical Evoked Potentials during Thoracic Aortic Occlusion

Paraplegia remains a devastating and unpredictable complication of surgical procedures requiring temporary occlusion of the thoracic aorta, interruption of important spinal radicular vessels, or both. Intraoperative monitoring of the physiological integrity of the spinal cord should permit the early detection of spinal cord ischemia, the judicious and timely institution of corrective measures, including bypass or shunting, and the preservation of important intercostal arteries in appropriate circumstances. A model of spinal cord ischemia was created by temporary proximal and distal occlusion of the canine thoracic aorta. Serial measurement of somatosensory cortical evoked potentials (SCEP) generated by peripheral nerve stimulation, reflecting the status of long-tract neural conduction, was used to monitor alterations in spinal cord function during ischemia. Twelve animals subjected to aortic occlusion demonstrated a characteristic time-related deterioration of the SCEP with virtual extinction of the signal at a mean interval (± standard error of the mean) of 12.4 ± 1.5 minutes. Six animals in which reperfusion was established immediately following the loss of the SCEP (Group 1) demonstrated complete recovery without neurological sequelae, as assessed by clinical and histological criteria. In 6 animals (Group 2), the period of aortic occlusion was extended for an additional 15 minutes following loss of the SCEP (27.3 ± 2.3 minutes); postoperatively, 4 of 6 animals sustained major neurological lesions characterized by spastic paraplegia and histological evidence of spinal cord infarction (Group 1 versus Group 2, p < 0.05).     

Coadministration of methylprednisolone with hypertonic saline solution improves overall neurological function and survival rates in a chronic model of spinal cord injury

OBJECTIVE: We previously demonstrated that administration of 7.5% hypertonic saline (HS) significantly improved spinal cord blood flow and neurological outcomes after spinal cord injury. The aim of this study was to determine whether hypertonicity would enhance the effects of methylprednisolone (MP), further improving neurological function. METHODS: Rat spinal cords were compressed for 10 minutes with 50 g of weight, and neurological function was assessed for 28 days, using the Basso-Beattie-Bresnahan locomotor rating scale. The control group received an intravenous injection of isotonic saline (IS) (5 ml/kg). Group 1 received an intravenous injection of 7.5% HS (5 ml/kg). Group 2 received an intravenous injection of MP (30 mg/kg) and IS (5 ml/kg). Group 3 received an intravenous injection of MP (30 mg/kg) administered with 7.5% HS (5 ml/kg). RESULTS: At 24 hours after spinal cord injury, the combination of MP plus HS provided significant (P < 0.01) neurological improvements, compared with all other treatment groups. At 10 days after injury, the animals that had received MP plus HS exhibited significantly (P < 0.01) higher Basso-Beattie-Bresnahan scores, compared with the MP plus IS and control groups. The median survival time was significantly (P < 0.01) increased for the MP plus HS group (28 d), compared with the MP plus IS group (16 d). Because of the dramatic decrease in survival rates at 28 days after injury, there was a significant (P < 0.01) difference in neurological function only between the MP plus HS group and the control group. CONCLUSION: The results indicate that the administration of HS may enhance the delivery of MP and prevent immunosuppression, leading to improvements in overall neurological function and survival rates after spinal cord injury.     

Doppler ultrasonographic identification of the critical segmental artery for spinal cord protection.

OBJECTIVE: The purpose of this study is to evaluate the possibility of identifying critical segmental arteries (CSAs) based on Doppler ultrasonographic hemodynamics. METHODS: In 18 mongrel dogs, the descending aorta was scanned directly with a 5-MHz linear probe through left thoracotomies and the flow velocities in segmental arteries were measured by pulsed Doppler. The aorta was cross-clamped between Th13 and L1, and flow velocity changes were recorded. According to flow increases, segmental arteries were divided into three groups: arteries with the largest flow increase (L-arteries), arteries with the smallest increase (S-arteries) and other arteries (O-arteries). Animals were divided into three groups. One aortic segment including an L-artery or an S-artery was perfused via a temporary shunt during 30-min aortic cross-clamping distal to the left subclavian artery (Group L or Group S) and neurological outcomes were compared with those of animals without shunting (Group N) after 24 and 48 h. RESULTS: L-arteries had significantly larger flow increases than S- and O-arteries (74.3+/-33.8, 20.4+/-9.8 and 33.3+/-17.8 cm/s, P<0.01). In Group N, five of the six animals were completely paraplegic (Tarlov Grade 0) and the other was Grade 1. In Group S, four animals were Grade 4 and two were Grade 0 after 24h. However, two animals showed delayed paraplegia. Therefore, four animals were Grade 0 and two were Grade 4 after 48 h. All animals in Group L were neurologically normal (Grade 4) at both after 24h (vs. Group N, P=0.0013) and 48 h (vs. Group N, P=0.0013; vs. Group S, P=0.019). CONCLUSIONS: Flow responses to aortic cross-clamping differed among segmental arteries and selective perfusion of L-arteries completely prevented paraplegia. Therefore, L-arteries were considered to be CSAs. Hemodynamic measurement of segmental arterial flow using Doppler ultrasonography could be clinically useful for spinal cord protection during thoracoabdominal aortic surgery.     

Ischemia-reperfusion injury of the spinal cord: Protective effect of the hydroxyl radical scavenger dimethylthiourea

Purpose: This study was undertaken to evaluate whether neurologic outcome after aortic cross-clamping in rabbits could be improved with perioperative infusion of the hydroxyl radical scavenger dimethylthiourea and, if so, to determine whether it is effective during the period of ischemia, reperfusion, or both. Methods: In 41 New Zealand White rabbits, a snare occlusion device was placed at operation around the infrarenal aorta and tunneled into a subcutaneous position. Animals were then allowed to recover and, 48 hours later, randomized into four groups. In each group, the infrarenal aorta was occluded by tightening the snare in the awake animal. In groups 1, 2, and 3, cross-clamp time was 21 minutes. Group 1 (control) animals received saline solution, whereas group 2 (preclamp 21) received dimethylthiourea 750 mg/kg intravenously just before aortic clamping. In group 3 (prerep 21), dimethylthiourea was given just before reperfusion. Group 4 received dimethylthiourea before clamping, with cross-clamp time extended to 31 minutes. A second dose of saline solution or dimethylthiourea was given 12 hours after clamping in controls and the three treatment groups, respectively. Animals were observed for 5 days, and final neurologic recovery was graded by an independent observer. Animals were then killed, and their spinal cords were removed for histologic examination. Results: Complete paraplegia and marked histologic spinal cord injury at 5 days were seen in 91% (10/11) of group 1 (control) animals, whereas all animals in group 2 (preclamp 21) showed neurologic recovery (p < 0.0001). In group 3 (prerep 21), the final paraplegia rate was 50% (5 of 10), in group 4 (preclamp 31), 100% (10 of 10). Conclusions: Our results suggest that hydroxyl radicals play an important role in ischemia-reperfusion injury of the spinal cord and that treatment with dimethylthiourea can prevent paraplegia after 21 minutes of aortic cross-clamping in rabbits. (J VASC SURG 1994;20:444-50.)     

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.