Effect Of Propofol Infusion Through Aorta On Ischemic Injury To Spinal Cord

Background: An ischemic reperfusion injury to the spinal cord after a surgical operation on the thoracic aorta, thoracoabdominal aorta or vertebral column remains to be a clinical problem. Although a series of attempts have been made to decrease the risk of this devastating complication, the incidence of paraplegia or other neurological impairment after these kinds of operations is still high. This study was designed to determine a safe clamping duration relevant to the ischemic tolerance of the spinal cord at normothermia and to investigate effects of propofol infusion through the aorta on the ischemic reperfusion injury to the spinal cord and the underlying mechanisms. Methods: The spinal cord ischemia was induced by the infrarenal aortic occlusion in New Zealand white rabbits. Under anesthesia with intramuscular injections of ketamine, midazolam, and atropine, the rabbits were endotracheally intubated and then ventilated. The anesthesia was intravenously maintained with midazolam, fentanyl, and vecuronium. The proximal and distal arterial pressures, electrocardiogram, percutaneous oxygen saturation, and nasopharynx temperature were continuously monitored.In the first part of this study, the rabbits were assigned randomly to 5 groups (10 in each) with different clamping durations, ranging from 20 min to 60 min. The neurological status was assessed, with the Tarlov scale system(0 or 1 meaning the rabbit was paraplegic), at 6 h, 24 h, and 48 h after the reperfusion. After the last scoring, the lumbar segments of the spinal cord (L4-6) were removed for pathological examination, and the normal motor neurons in the anterior horn were counted.In the second part, the rabbits were equally randomized into 6 groups, and the infrarenal aorta of each rabbit was clamped for the same duration (30 min) to induce the spinal cord ischemia. Simultaneously, normal saline (Group NS), 10% intralipid (the vehicle of propofol) (Group P0), and 1% propofol at various doses (30 mg/kg in Group PI, 40 mg/kg in Group P2, 50 mg/kg in Group P3, and 60 mg/kg in Group P4) were infused through a catheter into the aorta distal to the clamping site at the speed of 12 mL/kg/h during the occlusion process. 10% intralipid was added to the infused solutions of Group PI, P2, and P3 to make all the groups equal in volume. Meanwhile, the bilateral common iliac arteries were also occluded temporarily to increase the local propofol aggregation in the distal aorta. The neurological status and the normal motor neurons were also evaluated. The superoxide dismutase activity and the malondialdehyde production of the spinal cord tissue were measured with the Xanthine Oxidase method and thiobarbituric acid assay. The intracellular calcium concentration was monitored by the combined use of Laser Scan Confocal Microscope (LSCM) and Fluorescence-3 labelling. Neurocyte apoptosis was examined by the Terminal deoxynucleotidyl transferase-mediated DUTP-biotin nick end labeling (TUNEL) method and by the expression of Caspase-3 studied immunohistochemically. The ratio of apopotosis and IOD (Integrated optical density) of Caspase-3 expression was determinated. Statistical analysis was performed by the Kruskal-wallis Test and the one-way ANOVA. Results: Forty-eight hours after the infusion, the rabbits undergoing 60 min of clamping became totally paraplegic, and 90%, 80%, and 20% of therabbits developed paraplegia after 40, 30, and 25 min of occlusion, respectively. However, severe neurological impairments were not detected in the rabbits whose aorta was only clamped for 20 min.The propofol-treated rabbits had significantly better neurological functions than those treated with normal saline and intralipid (/><0.05). There was no significant difference between Group NS and Group P0 (P>0.05). The neurological function of the rabbits ranked in the decreasing order in the following groups: Groups P3, P2, P4, PI, P0, and NS. The histopathological results were parallel to the neurological scores, and the median numbers of normal motor neurons were 0 and 0.5 in Groups NS and P0, and 3, 7, 10.5, and 5 in Groups PI, P2, P3, and P4, respectively. All the propofol-treated groups showed a significantly lower mean arterial pressure than the control groups at 15 min after the occlusion, during the reperfusion, and at 5 min and 15 min after the reperfusion, especially Group P4 (.P<0.05). The superoxide dismutase activity was lower in the injured tissue than in the normal tissue; whereas, the malondialdehyde production, the intracellular calcium concentration and the numbers of TUNEL-positive cells were significantly greater in both Group NS and Group P0, and so was the IOD of Caspase-3 expression (PO.05). But the propofol-treated groups had significantly smaller changes of all above items than Groups NS and P0 (P<0.05). Furthermore, the differences among the propofol-treated groups were statistically significant, especially Group P3 that had the best outcome (P< 0.05).Conclusions: An ischemic injury to the spinal cord can be successfully induced by the infrarenal aorta occlusion for no less than 30 minutes. The safe clamping duration without spinal cord ischemia is not more than 20 minutes. The intra-aortic propofol infusion can dose-dependently antagonize the changes in superoxide dismutase, malondialdehyde,intracellular calcium concentration, and neuron apoptosis induced by the ischemic injury to the spinal cord. But normal saline and intralipid have no effect, which indicates that propofol infusion through the aorta during the clamping process can provide a significant protection to the spinal cord against its ischemic injury. Propofol 50 mg/kg is the most appropriate choice. The underlying mechanisms may be associated with its effects of relieving the oxidative stress and attenuating the intracellular calcium overload and caspase-3 mediated neurocyte apoptosis.