Ischemic preconditioning reduces neurologic injury in a rat model of spinal cord ischemia.

BACKGROUND: Ischemic preconditioning (IPC) is an endogenous cellular protective mechanism whereby brief, noninjurious periods of ischemia render a tissue more resistant to a subsequent, more prolonged ischemic insult. We hypothesized that IPC of the spinal cord would reduce neurologic injury after experimental aortic occlusion in rats and that this improved neurologic benefit could be induced acutely after a short reperfusion interval separating the IPC and the ischemic insult. METHODS: Forty male Sprague-Dawley rats under general anesthesia were randomly assigned to one of two groups. The IPC group (n = 20) had 3 minutes of aortic occlusion to induce spinal cord ischemia 30 minutes of reperfusion, and 12 minutes of ischemia, whereas the controls (n = 20) had only 12 minutes of ischemia. Neurologic function was evaluated 24 and 48 hours later. Some animals from these groups were perfusion-fixed for hematoxylin and eosin staining of the spinal cord for histologic evaluation. RESULTS: Survival was significantly better at 48 hours in the IPC group. Sensory and motor neurologic function were significantly different between groups at 24 and 48 hours. Histologic evaluation at 48 hours showed severe neurologic damage in rats with poor neurologic test scores. CONCLUSIONS: Ischemic preconditioning reduces neurologic injury and improves survival in a rat model of spinal cord ischemia. The protective benefit of IPC is acutely invoked after a 30-minute reperfusion interval between the preconditioning and the ischemic event.     

Aprotinin reduces injury of the spinal cord in transient ischemia

Objective: The protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit spinal cord ischemia model. Design: Randomized, controlled, prospective study. Setting: University research laboratory. Subjects: New Zealand white rabbits (36) of both sexes. Methods: In 24 animals, ischemia was induced with midline laparotomy and clamping the aorta just distal to left renal artery and proximal to aortic bifurcation for 20 min. Aprotinin was given 30 000 KIU as a short intravenous injection after anesthesia, and was followed by 10 000 KIU/h by continuous infusion in group 1 (n=12). Similar volume of saline solution was used in control group of animals (group 2, n=12). Group 3 of animals (sham group, n=12) were anesthetized and subjected to laparotomy without aortic occlusion. Physiological parameters and somatosensory evoked-potentials (SEP) were monitored in animals before ischemia, during ischemia and in the first 60 min of reperfusion. Their neurological outcome was clinically evaluated up to 48 h postischemia. Their motor function was scored, and the intergroup differences were compared. The animals were sacrificed after two days of postischemia. Their spinal cord, abdominal aorta, and its branches were processed for histopathological examination. Results: In group 3, SEP amplitudes did not change during the procedures, and all animals recovered without neurologic deficits. At the end of ischemic period, the average amplitude was reduced to 53±7% of the baseline in all ischemic animals. This was followed by a gradual return to 89±8 and 81±13% of the initial amplitude after 60 min of reperfusion in group 1 and group 2 correspondingly (P>0.05). The average motor function score was significantly higher in group 1 than group 2 at 24 and 48 h after the ischemic insult (P<0.05). Histological observations were clearly correlated with the neurological findings. Conclusion: The results suggest that aprotinin reduces spinal cord injury and preserves neurologic function in transient spinal cord ischemia in rabbits.     

Transcranial motor-evoked potentials monitoring can detect spinal cord ischemia more rapidly than spinal cord-evoked potentials monitoring during aortic occlusion in rats

In this study, we evaluated the efficacy of transcranial motor-evoked potentials (tc-MEPs), compared with segmental spinal cord-evoked potentials (SCEPs), for detecting spinal cord ischemia (SCI) and assessed the relationship between neurological outcome and tc-MEPs or SCEPs in the rat aortic occlusion model. In the rats, SCI was induced by aortic occlusion for 10 min with a balloon catheter. At first, tc-MEPs (Group A: n = 6) or segmental SCEPs (Group B: n = 6) was recorded during SCI. Second, in using the quantal bioassay for the relationship between an interval of aortic occlusion and the probability of positive response in tc-MEPs or segmental SCEPs, the P50_MEP and P50_SCEP which represent the interval of aortic occlusion associated with 50% probability of assessment of ischemic spinal cord dysfunction by tc-MEP and SCEP were analyzed. The amplitude of tc-MEPs decreased significantly at 30 s and disappeared completely at 2 min after aortic occlusion. In Group B, it took about 6 min after aortic occlusion to diminish SCEP signal amplitude by approximately 50%. P50_MEP obtained in the quantal analysis was 0.3 ± 0.1 min. P50_SCEP was calculated as 6.2 ± 0.5 min that was significantly (P < 0.01) longer than P50_MEP. Our data indicated that tc-MEP monitoring could detect the onset of SCI so rapidly in comparison with segmental SCEP monitoring, which could provide therapeutic windows in a surgical approach that includes spinal cord protection.     

Postconditioning, a series of brief interruptions of early reperfusion, prevents neurologic injury after spinal cord ischemia

OBJECTIVE: We sought to test whether postconditioning, a series of brief mechanical interruptions of reperfusion applied during the onset of reperfusion, can prevent neurologic injury of the spinal cord after transient ischemia. SUMMARY BACKGROUND DATA: Ischemia-reperfusion injury of the spinal cord is the principal mechanism leading to the paraplegia after surgery for descending and thoracoabdominal aortic aneurysms. Postconditioning has recently been demonstrated to confer cardioprotection by attenuating reperfusion injury. METHODS: Spinal cord ischemia was induced in rabbits by infrarenal aorta occlusion for 25 minutes. Control animals underwent no additional intervention. Two groups of animals underwent postconditioning consisting of 4 or 6 cycles of 1-minute occlusion/1-minute reperfusion, respectively, which were applied 1 minute after the start of reperfusion. In 2 additional groups, 6 cycles of postconditioning started 5 or 10 minutes after the onset of reperfusion, respectively. Hind-limb motor function was assessed during a 10-day recovery period using the modified Tarlov criteria. Histologic examination of the spinal cord was performed, and the number of intact motor neurons was counted. RESULTS: Compared with controls, 4 cycles of postconditioning significantly increased the Tarlov score and the number of intact motor neurons. Six cycles of postconditioning did not further improve the neuroprotection. Postconditioning starting 5 minutes after reperfusion still resulted in powerful neuroprotection, but the neuroprotection disappeared completely when postconditioning was delayed for 10 minutes. CONCLUSIONS: Postconditioning prevents neurologic injury of the spinal cord after ischemia, and the first few minutes of reperfusion are crucial to neuroprotection by postconditioning.     

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.     

芦荟多糖对脊髓缺血损伤的神经保护作用

目的:探讨芦荟多糖(aloe polysaccharide,AP)对兔脊髓缺血损伤是否有神经保护作用.方法:32只成年雄性新西兰兔随机分成4组(每组8只 ),即对照组(C 组)、芦荟多糖组(A组)、溶剂对照组( V组 ) 及假手术组(S组).A组在脊髓缺血前30min经耳缘静脉给予50m·kg-1芦荟多糖;V组以同样方式给予等容量生理盐水;C组仅仅制备脊髓缺血损伤模型,不进行其它处理;S组仅仅暴露腹主动脉,而不阻断它,其他处理同C组;兔脊髓缺血模型采用夹闭兔腹主动脉肾下段20min.再灌注后48h,对所有动物神经功能评分,然后处死动物取脊髓(L5-7),制作标本行组织病理学观察.结果:A组的神经功能评分和脊髓前角正常神经细胞数明显多于C组及V组(P<0.01);C组及V组的神经功能评分和脊髓前角正常神经细胞数组间无明显差异(P>0.05);神经功能评分与其对应脊髓前角正常神经细胞计数之间有显著相关性(r=0.804,P<0.01).结论:芦荟多糖对兔脊髓缺血再灌注损伤有明显的神经保护作用.     

Protection against spinal cord ischemia with insulin-induced hypoglycemia

The effect of insulin-induced reduction in blood glucose to 65 +/- 20 mg/dl (mean +/- standard deviation) on recovery of electrophysiological function and extracellular lactate concentration was studied in a rabbit model of spinal cord ischemia. These results were compared to findings in animals with spinal cord ischemia that either were fasted overnight (fasted group: blood glucose 97 +/- 26 mg/dl) or had no pretreatment (control group: blood glucose 172 +/- 65 mg/dl). The aorta was occluded until the postsynaptic waves of the spinal somatosensory evoked potentials (SSEP's) had been absent for 20 minutes, a period of ischemia that produces paraplegia in 100% of untreated rabbits. The total aortic occlusion time was not significantly different in the three groups. Recovery of the SSEP's was significantly better in the insulin-treated animals than in the fasted or control animals. The N3 wave of the SSEP's, which has been found to correlate best with neurological recovery, returned to 65% +/- 48% of the preischemia amplitude in the insulin-treated animals, compared to 40% +/- 34% in the fasted group and 26% +/- 24% in the control animals. Extracellular lactate concentration in the spinal cord increased immediately after occlusion of the aorta, reached a plateau as the postsynaptic waves disappeared from the SSEP's, and then increased a second time during the first 15 minutes of reperfusion. The peak lactate concentration during ischemia and during reperfusion correlated with the preischemia glucose concentration (r = 0.60336 and r = 0.76930, respectively). Lactate concentration in the spinal cord was higher during ischemia and throughout the first 2 hours of reperfusion in the control and fasted animals than in the insulin-treated animals. During the 2nd hour of reperfusion, lactate concentration was significantly higher in the control animals than in the fasted animals. Reduction in blood glucose with insulin improves recovery of electrophysiological function after spinal cord ischemia, probably because of reduced lactic acid production, especially during the early reperfusion period.     

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.     

Effect of the free radical scavenger MCI-186 on spinal cord reperfusion after transient ischemia in the rabbit

Objective: Paraplegia remains a serious complication of aortic operations. The production of free radicals during reperfusion after transient ischemia is believed to induce secondary spinal neuronal injury, resulting in paraplegia. The aim of the present study was to clarify the protective effect and method of administration of antioxidants on the neurological and histological outcome in the animal model for reperfusion injury after transient spinal cord ischemia. Methods: New Zealand white rabbits underwent surgical exposure of the abdominal aorta that was clamped for 15 minutes to achieve spinal cord ischemia. Group A animals received two 10 mg/kg doses of 3-methyl-l-phenyl-2-pyrazolin-5-one (MCI-186) at the time of release of the aortic clamp and 30 minutes later. In group B, MCI-186, 5 mg/kg, was given three times, at the time of aorta clamp release, 30 minutes and 12 hours later. In group C (control group), one dose of vehicle was administered. Neurological status was assessed using modified Tarlov’s score until 168 hours after operation. Spinal cord sections were examined microscopically to determine the extent of ischemic neuronal damage. Results: Groups A and B animals had better neurological function than group C (p(0.001). In contrast, group C animals exhibited paraplegia or paraparesis with marked neuronal necrosis. The number of surviving neurons within examined sections of the spinal cord was significantly greater in group B than in group C (p(0.001). Conclusion: In a 15-minute ischemia-reperfusion model using rabbits, systemic repetitious administration of MCI-186, a free radical scavenger, was found to have a protective effect on the spinal cord neurons both neurologically and histologically. We postulate that the drug minimizes the delayed neuronal cell death for reperfusion injury after transient ischemia by reducing the free radical molecules. Moreover, it was thought that we could protect delayed neuronal cell death more effectively by administering MCI-18612 hours later.     

Spinal cord ischemia and reperfusion metabolism: The effect of hypothermia

Purpose: The metabolic and neurologic functional effects of regional hypothermia induced by cold (4° C) heparinized saline perfusion on spinal cord ischemia were evaluated in 35 rabbits.Methods: Spinal cord ischemia was induced for 20 minutes by infrarenal aortic occlusion in anesthetized animals. Regional spinal cord hypothermia was obtained by perfusing the lumbar arteries supplying the spinal cord through an infrarenal aortic catheter. The lumbar spinal cord was "snap frozen" in situ with liquid nitrogen and harvested immediately at the conclusion of the ischemic period or after 24 hours of normothermic reperfusion and neurologic observation. Spinal cord metabolic studies included determination of the energy charge and the intracellular concentrations of adenosine triphosphate, glucose, lactate, glutamate, and aspartate.Results: Postoperative neurologic function was normal in all but one animal treated with hypothermia, while normothermic ischemia resulted in paralysis in all animals ( p = 0.002). Spinal cord temperature during 20 minutes of ischemia and hypothermic perfusion decreased from 37.5° ± 0.43° C to 22.8° ± 0.00° C ( p = 0.0001) compared to a fall in systemic temperature from 38.8 to 36.1 ( p = 0.0001). Hypothermia reduced the decline in energy charge, adenosine triphosphate concentration and glucose concentration during ischemia but had no effect on markedly elevated levels of lactate acid. High-energy phosphates were restored after reperfusion in both normothermic and hypothermic animals and were not predictive of postoperative paraplegia. Intracellular glutamate and aspartate concentrations were unchanged during normothermic ischemia but decreased after reperfusion in all paralyzed animals. Intracellular glutamate and aspartate concentrations increased during hypothermic perfusion and remained elevated after reperfusion in animals with a normal or mildly abnormal neurologic examination result.Conclusions: We conclude that spinal cord hypothermia induced by cold heparinized saline perfusion is a simple technique that prevents paraplegia after 20 minutes of ischemia and preserves intracellular concentrations of important metabolites. (J VASC SURG 1994;19:332-40.)     

Systemic adenosine A2A agonist ameliorates ischemic reperfusion injury in the rabbit spinal cord

BACKGROUND: The adenosine A2A agonist ATL-146e (4-[3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxytetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-cyclohexanecarboxylic acid methyl ester) has been shown to prevent reperfusion injury in multiple organ systems through inhibition of activated leukocyte-endothelial interaction. We hypothesized that systemic ATL-146e could reduce spinal cord reperfusion injury after aortic clamping. METHODS: Twenty-six rabbits underwent cross-clamping of the infrarenal aorta for 45 minutes. One group received intravenous ATL-146e for 3 hours during reperfusion. A second cohort received only vehicle and served as controls. Animals were assessed at 24 and 48 hours using the Tarlov (0 to 5) scoring system for hind limb function. To evaluate neuronal attrition, immunostaining of lumbar spinal cord sections was performed using anti-SMI 33 antibody against neurofilament. RESULTS: Systemic ATL-146e was tolerated without hemodynamic lability. Animals that received ATL-146e had significantly improved neurologic outcomes 24 and 48 hours after spinal cord ischemia (p < 0.001). There was preservation of neuronal architecture in the ventral horn of spinal cord sections from animals receiving ATL-146e compared with control animals. CONCLUSIONS: Intravenous ATL-146e given during reperfusion is tolerated without hemodynamic lability, and results in substantially improved spinal cord function after ischemia by preservation of ventral horn neurons.     

Effect of puerarin on neural function and histopathological damages after transient spinal cord ischemia in rabbits

Ischemicspinalcordinjuryremainsadisastrouscomplicationofthedescendingandthoracoabdominalaortaeafteroperation .Thereportedincidenceofparaplegiarangesfrom 4 %to 33% .1Therefore ,agreatnumberofeffortshavebeenfocusedonsolvingthisproblem ,whichincludehypothermia ,cerebrospinalfluiddrainage ,temporarybypassandpharmacologicalagents .2 Thecellularandmolecularmechanismsofischemicspinalcordinjuryhavenotbeentotallyelucidated .Butvariousstudieshavesuggestedthatfreeradicalproduction ,calciumaccumulationand…     

The effects of tyrphostine Ag 556 on experimental spinal cord ischemia reperfusion injury

BACKGROUND: To investigate the effects of Tyrphostin Ag 556 on spinal cord ischemia reperfusion injury. METHODS: The inhibition of tyrosine kinase may represent a novel approach in the treatment of spinal cord ischemia reperfusion injury. Recently, a family of tyrosine kinase inhibitors, the tyrphostins, has been successfully used in models of endotoxemia, peritonitis, and hypovolemic shock. MATERIALS AND METHODS: Twenty-four Wistar rats were used in the study. Rats were divided into 4 groups of 6 animals. The groups were named as sham operated group, injury group, vehicle group, and treatment group. Clamping of the abdominal aorta was performed for 45 minutes with all of the groups except sham-operated group. All of the rats were sacrificed 24 hours after the operation for biochemical and ultrastructural studies. RESULTS: Tyrphostin Ag 556 treatment was found effective on experimental spinal cord ischemia reperfusion injury. The Malondialdehyde (MDA) values of the treatment group were statistically significant lower then the other reperfusion injury groups. The histologic examination showed better cellular structure in the treatment group than the other reperfusion injury groups. The neurologic scores of the treatment group also improved after treatment. CONCLUSIONS:Tyrphostin Ag 556 alters spinal cord ischemia reperfusion injury by inhibiting protein kinases. Further investigations will be required to determine the long-term effects of this drug.     

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.     

Collaborative therapy with nebivalol and L-NAME for spinal cord ischemia/reperfusion injury

Postoperative neurologic deficit is the most devastating complication after thoracoabdominal aortic aneurysm repair. Our aim was to investigate whether nebivolol has protective effects during ischemia or reperfusion and the most effective mechanism of protection via inhibiting nitric oxide (NO) release with an NO synthase inhibitor in an experimental model of spinal cord ischemia/reperfusion injury. Spinal cord ischemia was induced by occlusion of the infrarenal aorta for 30 min. Thirty-one rabbits were divided into five groups according to the administration period of nebivolol and/or N(G)-nitro-L-arginine methyl ester (L-NAME): control group; group NI, nebivolol during ischemic period; group NR, nebivolol during reperfusion period; group NILR, nebivolol during ischemic period and L-NAME during reperfusion period; and group LINR, L-NAME during ischemic period and nebivolol during reperfusion period. Blood samples were taken at both ischemia and reperfusion periods to obtain nitrite/nitrate levels. After neurologic evaluation at 24 hr of reperfusion, malondialdehyde (MDA) levels were measured. Neurologic impairment was significantly lower in group LINR (Tarlov score 3.4 +/- 0.6, p < 0.05). MDA levels were lower in nebivolol-treated animals, but the lowest value was achieved in the NR group, 35.6 +/- 2.7 nmol/g (p < 0.001). Nitrite levels were decreased significantly in all nebivolol-treated animals in the reperfusion period, but the lowest value was measured in the LINR group (455 +/- 137 vs. 1,760 +/- 522 nmol/mL, p < 0.001). Prophylactic use of nebivolol reduced neurologic injury, and combining with L-NAME provided the best clinical improvement by attenuating the inflammatory mileu in this experimental model. Combination of nebivolol and L-NAME appears to be an effective option for spinal cord protection against ischemia/reperfusion injury.     

Thoracic aortic occlusion: somatosensory evoked potential monitoring and neurologic outcome in a canine model

Somatosensory evoked potentials (SEPs) were monitored in 17 canines during spinal cord ischemia induced by balloon occlusion of the thoracic aorta. Graded distal aortic hypotension to 40 mmHg in seven animals had no significant effect upon the evoked potential. A significant alteration in the SEP did result in 21 +/- 9.8 minutes when distal aortic pressures were reduced in a graded fashion below 30 mmHg. Acute occlusion of the thoracic aorta (10 animals, distal pressure 15-25 mmHg) was associated with a change in the SEP in 8.4 +/- 4.3 minutes. Continuation of aortic occlusion for 30 minutes beyond an evoked potential change resulted in a moderate to severe motor deficit in all cases. Somatosensory evoked potentials obtained 72-96 hours after the ischemic injury were closely correlated with sensory deficits, but were not predictive of motor examination. Histologic examination of the spinal cords demonstrated central gray necrosis of the lumbar region in all animals with a severe deficit, and a variable degree of neuronal loss in the intermediate and dorsal gray matter zones in animals with moderate deficits. This balloon occlusion method is relevant as a model of spinal cord injury during aortic occlusion, such as may occur during aortic surgery.     

A Novel Canine Model of Spinal Cord Ischemia with Reproducible Neurologic Outcomes

Purpose To develop a canine model of spinal cord ischemia (SCI) with highly reproducible neurologic outcomes.Methods Spinal cord ischemia was induced by cross-clamping the proximal descending aorta. To produce substantial ischemia in the critical lumbar region, the proximal aortic blood pressure (PAP) was reduced to 80 mmHg by withdrawing blood into a reservoir connected to the left subclavian artery. We conducted an intraischemia spinal cord electrophysiologic study and a postischemia assessment of hindlimb motor function in six animals subjected to this procedure with an aortic occlusion time of 40 min, and in six animals subjected only to aortic occlusion for 60 min.Results All the animals subjected to this procedure exhibited a significant decrease in motor-evoked spinal cord potentials to transcranial electric stimulation (MEPs) during the acute ischemic phase, and they were paraplegic 48 h after ischemia. In contrast, two of the animals not subjected to PAP reduction showed complete functional recovery with intact MEP findings.Conclusion This model is feasible for experimental SCI studies because it can reliably and easily reproduce substantial ischemia.     

The role of transcranial motor evoked potentials in predicting neurologic and histopathologic outcome after experimental spinal cord ischemia

BACKGROUND: Monitoring of myogenic motor evoked potentials to transcranial stimulation (tcMEPs) is clinically used to assess motor pathway function during aortic and spinal procedures that carry a risk of spinal cord ischemia (SCI). Although tcMEPs presumably detect SCI before irreversible neuronal deficit occurs, and prolonged reduction of tcMEP signals is thought to be associated with impending spinal cord damage, experimental evidence to support this concept has not been provided. In this study, histopathologic and neurologic outcome was examined in a porcine model of SCI after different durations of intraoperative loss of tcMEP signals. METHODS: In 15 ketamine-sufentanil-anesthetized pigs (weight, 35-45 kg) the spinal cord feeding lumbar arteries were exposed. tcMEP were recorded from the upper and lower limbs. Under normothermic conditions, animals were randomly allocated to undergo short-term tcMEP reduction (group A, < 10 min, n = 5) or prolonged tcMEP reduction (group B, 60 min, n = 10), resulting from temporary or permanent clamping of lumbar segmental arteries. Neurologic function was evaluated every 24 h, and infarction volume and the number of eosinophilic neurons and viable motoneurons in the lumbosacral spinal cord was evaluated 72 h after induction of SCI. RESULTS: In all animals except one, segmental artery clamping reduced tcMEP to below 25% of baseline. All but one animal in group A had reduced tcMEP for less than 10 min and had normal motor function and no infarction at 72 h after the initial tcMEP reduction. Seven animals in group B (70%) had reduced tcMEP signals for more than 60 min and were paraplegic with massive spinal cord infarction at 72 h. Two animals (one in both groups) had tcMEP loss for 40 min, with moderate infarction and normal function. In general, histopathologic damage and neurologic dysfunction did not occur when tcMEP amplitude recovered within 10 and 40 min after the initial decline, respectively. CONCLUSION: Prolonged reduction of intraoperative tcMEP amplitude is predictive for postoperative neurologic dysfunction, while recovery of the tcMEP signal within 10 min after the initial decline corresponds with normal histopathology and motor function in this experimental model. This finding confirms that intraoperative tcMEPs have a good prognostic value for neurologic outcome during procedures in which the spinal cord is at risk for ischemia.     

Cold spinoplegia and transvertebral cooling pad reduce spinal cord injury during thoracoabdominal aortic surgery

OBJECTIVE: We examined the protective effects of the new selective spinal cord cooling by using cold saline infusion into the cross-clamped aorta and a transvertebral cooling pad placed over the lumbar vertebral column from paraplegia caused by ischemic spinal cord injury on thoracoabdominal aortic surgery. METHODS: Eighteen rabbits were divided into three groups: groups I, II, and III (n = 6 for each group). In group I (37 degrees C; 5 mL) and group II (3 degrees C; 5 mL), saline was infused into the isolated aortic segment twice, at 0 and 5 minutes after aortic cross clamping. In group III, a 3 degrees C saline solution plus cooling pads placed just after cross clamping were combined. The infrarenal aorta was then isolated proximally and distally by vascular clamps for 12 minutes. In our preliminary study, only the abdominal aorta just distal to the left renal artery was clamped. At 48 hours after reperfusion, the groups clamped for 12 and 15 minutes were all paraplegic. The time of clamping the aorta was set at 12 minutes as the critical point when paraplegia occurred upon simple clamping of the infrarenal aorta only. The spinal cord temperature was monitored at the L4 level continuously during the procedures in all three groups. At 8, 24, and 48 hours after the operation, hind limb function was estimated by using the Tarlov score, which is often used for evaluating motor function in animals. A histopathologic study using hematoxylin and eosin stains was also performed. RESULTS: At 48 hours after the operation, the Tarlov scores in groups I, II, and III were 0 +/- 0, 2.0 +/- 1.9, and 4.0 +/- 0 (mean +/- SD), respectively. The Tarlov score and histopathologic analysis in group III were significantly superior to those of groups I (P < .01) and II (P < .05). The spinal cord temperature in groups II and III decreased by -1.8 degrees C and -4.3 degrees C at its minimum. The rabbits in group III were also protected from paraplegia. CONCLUSIONS: Selective spinal cord cooling with cold saline infusion into the isolated aortic segment and transvertebral regional cooling can reduce the neurologic damage of spinal cord ischemia.     

Does ischemic preconditioning reduce spinal cord injury because of descending thoracic aortic occlusion?

OBJECTIVE: Ischemic preconditioning has been found to protect various organs from a subsequent longer ischemic insult. We investigated whether the late phase of ischemic preconditioning reduces spinal cord injury from occlusion of the descending thoracic aorta. METHODS: Twenty-four pigs (27 to 30 kg) were randomly divided in four groups: group I (n = 4) underwent a sham operation, group II (n = 4) underwent aortic occlusion for 20 minutes, group III (n = 8) underwent aortic occlusion for 35 minutes, and group IV (n = 8) underwent aortic occlusion for 20 minutes and, 48 hours later, aortic occlusion for 35 minutes. Aortic occlusion was accomplished with two balloon occlusion catheters placed fluoroscopically at T(6) to T(8) above the diaphragm and at the aortic bifurcation. Neurologic evaluation was performed by an independent observer according to Tarlov's scale (0 to 4, with 4 as normal). The lower thoracic and lumbar spinal cords were harvested at 120 hours and examined histologically with hematoxylin and eosin stain. Histologic results (number of neurons and grade of inflammation) were scored 0 to 4 (4, intact spinal cord; 0, no neurons and high inflammation) and were similarly analyzed. Results were expressed as the mean +/- the standard error of the mean, and statistical analysis used the Kruskal-Wallis test. RESULTS: Group IV had a better neurologic outcome at 24, 48, and 120 hours in comparison with group III (P <.001), although 120 hours after the end of the experiment, the neurologic outcome in group IV was worse than at 24 hours (P =.014). The histologic changes were proportional to the neurologic test scores, with the more severe and extensive gray matter damage in the animals of group III (number of neurons, P <.001; and grade of inflammation, P <.001). CONCLUSION: Ischemic preconditioning (late phase, 48 hours after the first occlusion) reduces spinal cord injury after aortic occlusion, as estimated with Tarlov's score and histopathology.