A pharmacological analysis of the pathophysiological mechanisms of posttraumatic spinal cord ischemia

1986 ◽  
Vol 64 (6) ◽  
pp. 951-961 ◽  
Author(s):  
Edward D. Hall ◽  
Daniel L. Wolf

✓ A pharmacological analysis was carried out to determine the possible role of aberrant calcium fluxes, vasoactive arachidonic acid metabolites, and microvascular lipid peroxidation in the development of posttraumatic spinal cord white matter ischemia. Pentobarbital-anesthetized cats were treated intravenously 30 minutes before a 500-gm-cm contusion injury to the lumbar spinal cord with one of the following test drugs: the Ca++ channel antagonists verapamil, diltiazem, or nifedipine; the cyclo-oxygenase inhibitors ibuprofen or meclofenamate; the thromboxane A2 (TXA2) synthetase inhibitor furegrelate sodium; or the stable epoprostenol (prostacyclin, or PGI2) analogue ciprostene calcium alone or in combination with furegrelate sodium. Another group of animals was pretreated for 5 days before spinal injury with a combination of the antioxidants vitamin E and selenium in high doses. The hydrogen clearance technique was used to make repeated measurements of spinal cord blood flow (SCBF) in the dorsolateral funiculus of the injured segment before and for 4 hours after injury. In 11 untreated uninjured cats, the mean preinjury SCBF was 12.7 ± 1.5 ml/100 gm/min. Following contusion, there was a progressive decline in SCBF to 6.8 ± 0.4 ml/100 gm/min, or 53.5% of the preinjury level at 4 hours. In comparison, the Ca++ antagonists diltiazem and nifedipine (but not verapamil) prevented a significant posttraumatic decrease in SCBF. Similarly, both cyclo-oxygenase inhibitors (ibuprofen and meclofenamate) maintained SCBF within normal limits (10 ml/100 gm/min or greater). However, neither TXA2 synthetase inhibition nor the stable PGI2 analogue alone had a significant effect in preventing ischemia, whereas a combination of the two agents did serve to support SCBF. The most impressive preservation of posttraumatic SCBF, however, was observed in the antioxidant-treated animals. Based upon these results, a hypothesis is presented concerning the pathogenesis of posttraumatic central nervous system ischemia which integrates an injury-induced rise in intracellular Ca++, the increased synthesis of vasoactive prostanoids (such as prostaglandin F2α and TXA2), and progressive microvascular lipid peroxidation.

1984 ◽  
Vol 61 (1) ◽  
pp. 124-130 ◽  
Author(s):  
Edward D. Hall ◽  
Daniel L. Wolf ◽  
J. Mark Braughler

✓ The ability of a single large intravenous dose of methylprednisolone sodium succinate (MPSS: 15, 30, or 60 mg/kg) to modify the evolution of lumbar spinal cord ischemia in cats undergoing a contusion injury of 500 gm-cm is examined. Repeated measurements of spinal cord blood flow (SCBF) in the dorsolateral funiculus were made via the hydrogen clearance technique before and for 4 to 5 hours after injury. The mean preinjury SCBF for all animals was 12.29 ± 0.77 ml/100 gm/min. Following injury, SCBF began to decrease progressively in vehicle-treated animals to a level of 7.71 ml/100 gm/min, a fall of 37.3%. In contrast, cats that received a 30-mg/kg intravenous dose of MPSS at 30 minutes after injury maintained SCBF within normal limits (p < 0.05 at 3 and 4 hours after contusion). A 15-mg/kg MPSS dose was less effective at preventing posttraumatic white matter ischemia, and a 60-mg/kg dose was essentially ineffective. It was determined that the 30-mg/kg MPSS dose was optimal for supporting SCBF when the drug was given at 30 minutes after spinal trauma, and a second series of experiments was carried out to examine the ability of this dose, when given at longer latencies, to improve decreased flow. Methylprednisolone given at 1½ hours after injury in four cats produced a slight (12.7%) but transient improvement in SCBF, and when administered at 4½ hours in another three animals was totally ineffective. These results show that MPSS in a 30-mg/kg dose can prevent posttraumatic spinal cord ischemia. However, it would appear that the ability of the steroid to reverse the ischemia once it has developed is limited, and probably lost, within a few hours of onset. This further suggests that the ischemic process is irreversible and underscores the need for early treatment with a large MPSS dose in order to prevent full development of ischemia and to promote neurological recovery.


2004 ◽  
Vol 4 ◽  
pp. 892-898 ◽  
Author(s):  
David Zvara ◽  
James M. Zboyovski ◽  
Dwight D. Deal ◽  
Jason C. Vernon ◽  
David M. Colonna

Spinal cord blood flow after ischemic preconditioning is poorly characterized. This study is designed to evaluate spinal cord blood flow patterns in animals after acute ischemic preconditioning. Experiment 1: After a laminectomy and placement of a laser Doppler probe over the lumbar spinal cord to measure spinal cord blood flow, 16 male Sprague-Dawley rats were randomized into two groups: ischemic preconditioning (IPC, n = 8), and control (CTRL, n = 8). Rats in the CTRL and the IPC groups were subjected to 12 min of ischemia directly followed by 60 min of reperfusion. IPC rats received 3 min of IPC and 30 min of reperfusion prior to the 12-min insult period. Experiment 2: After instrumentation, the rats were randomized into three groups: control (CTRL, n = 7), ischemic preconditioning (IPC, n = 7), and time control (TC, n = 4). Rats in the CTRL and the IPC groups were subjected to the same ischemia and reperfusion protocol as above. The TC group was anesthetized for the same time period as the CTRL and the IPC groups, but had no ischemic intervention. Microspheres were injected at baseline and at 15 and 60 min into the final reperfusion. All rats were euthanized and tissue harvested for spinal cord blood flow analysis. In Experiment 1, there was a slight, significant difference in spinal cord blood flow during the ischemic period; however, this difference soon disappeared during reperfusion. In experiment 2, there was no difference in blood flow at any experimental time. The results of these experiments demonstrate that IPC slightly enhances blood flow to the spinal cord during ischemia; however, this effect is not sustained during the reperfusion period.


1977 ◽  
Vol 47 (4) ◽  
pp. 567-576 ◽  
Author(s):  
Robert A. Crawford ◽  
Ian R. Griffiths ◽  
James McCulloch

✓ The effect of intra-arterially administered norepinephrine (NE) upon spinal cord blood flow (SCBF), before and after disruption of the blood-cord barrier was studied in dogs. Barrier disruption was accomplished with an intra-arterial bolus injection of 2.5 M urea. Multiple ligations of branches of the posterior aorta and cannula placements ensured that the urea was directed to the lumbar and sacral segments of the cord. The SCBF was measured by the hydrogen clearance method. Intra-arterial urea by itself had no significant effect on SCBF. The intra-arterial infusion of NE (12 µg/min and 30 µg/min) was without overall effect on SCBF. However, if the blood-cord barrier had been previously disrupted with hypertonic urea, both concentrations of NE resulted in large reductions in SCBF. No such reductions in SCBF were seen with blood-cord barrier disruption and NE if the animals had been pre-treated with the α-blocker, phenoxybenzamine (1.5 mg/kg). Some aspects of the possible involvement of NE in the pathophysiology of acute spinal injury are discussed.


1983 ◽  
Vol 58 (5) ◽  
pp. 742-748 ◽  
Author(s):  
Oscar U. Scremin ◽  
Emilio E. Decima

✓ Spinal cord blood flow (SCBF) and the effect of end-tidal CO2 concentration (ETCO2) on SCBF (CO2 reactivity) were studied in the lumbar spinal cord of cats by means of the hydrogen-clearance technique. Hydrogen gas was administered by inhalation, and its level in spinal cord tissue was estimated amperometrically with small (75 µm) platinum electrodes. The average SCBF's at normocapnia (ETCO2 = 4%) of the ventral horn gray matter and of the white matter at several locations were 43.2 and 16.2 ml·100 gm−1·min−1, respectively. For gray and white matter, the values of CO2 reactivity, estimated by the coefficient of the regression of SCBF (ml·100 gm−1·min−1) on ETCO2 (ml·100 ml−1) were 11.6 and 2.1, respectively. No differences in SCBF or CO2 reactivity were observed between intact animals kept under N2O-O2 ventilation and decerebrated animals with no anesthesia. After an acute spinal section, ventral horn SCBF and CO2 reactivity (measured eight segments below the cordotomy) were not altered, in spite of the profound neural depression present (that is, spinal shock). Orthodromic (dorsal root) stimulation of the ventral horn neurons induced an average increase in blood flow of 128% above control values. Antidromic (ventral root) motoneuron activation failed to produce any significant changes in ventral horn blood flow.


1980 ◽  
Vol 52 (3) ◽  
pp. 387-391 ◽  
Author(s):  
Douglas K. Anderson ◽  
Eugene D. Means ◽  
Thomas R. Waters

✓ The purpose of this study was to determine 1) normal concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), phosphocreatine (P-creatine), glucose, lactate, and pyruvate in upper (L-2) and lower (L-5) feline lumbar spinal cord, and 2) whether previously reported laminectomy-induced reduction in spinal cord blood flow (SCBF) resulted in disturbance of spinal cord energy metabolism. Concentrations of ATP, P-creatine, pyruvate, and glucose were significantly higher at L-5 than at L-2, probably as the result of larger amounts of gray matter at L-5 than L-2. Significant increases in ADP and AMP levels were the only metabolite changes noted 15 minutes following laminectomy. The authors speculate that the increase in ADP and AMP is due to a laminectomy-induced stimulation of ATP utilization. However, lack of change in other metabolites implies an efficient energy homeostasis. These results indicate that although laminectomy can reduce SCBF, the degree of this reduction is insufficient to adversely affect spinal cord energy metabolism. Thus, tissue from beneath or near the laminectomy site is viable and essentially normal.


1989 ◽  
Vol 70 (5) ◽  
pp. 780-784 ◽  
Author(s):  
Toshihisa Sakamoto ◽  
William W. Monafo

✓ Spinal cord ischemia may accompany surgical procedures on the aorta or vertebral column. Regional spinal cord blood flow (SCBF) was measured at five vertebral levels in the spinal cords of pentobarbital-anesthetized rats based on the distribution of intravenously injected carbon-14-labeled butanol. In seven normal rats, mean SCBF (± standard error of the mean) ranged from 52.7 ± 5.4 to 68.5 ± 4.9 ml ⋅ min−1 ⋅ 100 gm−1 (depending on the level, being lowest at the thoracic levels) and mean arterial blood pressure (MABP) was 126 mm Hg. Corporal hypothermia (mean rectal temperature 28.1° ± 0.6°C) was induced by cold exposure in seven other rats, and SCBF, measured immediately thereafter, was significantly elevated at all five levels by 52% to 69% compared to the normal group. However, MABP was elevated in the hypothermic group to 165 ± 4 mm Hg (p < 0.0001). Therefore, in seven additional hypothermic rats, MABP was maintained at the control level by withdrawal of arterial blood as necessary. In these animals, SCBF at all levels was still significantly elevated compared with the normal group and the values were nearly identical to those measured in the hypertensive hypothermic rats. It was concluded that hemodynamic autoregulation of SCBF is impaired in the presence of moderate systemic hypothermia in pentobarbital-anesthetized rats.


1983 ◽  
Vol 58 (4) ◽  
pp. 526-530 ◽  
Author(s):  
Nariyuki Hayashi ◽  
Barth A. Green ◽  
Mayra Gonzalez-Carvajal ◽  
Joseph Mora ◽  
Richard P. Veraa

✓ Using a reliable and reproducible microelectrode technique, consistent simultaneous measurements of local spinal cord blood flow (SCBF), tissue oxygen tension, and tissue oxygen consumption were made at cervical, thoracic, and lumbar levels in the rat spinal cord. These observations showed that the metabolic state is maintained constant along the cord, despite significant variations in vasculature. The physiological and anatomical aspects of these findings are discussed.


1984 ◽  
Vol 60 (6) ◽  
pp. 1317-1319 ◽  
Author(s):  
Alfred G. Kaschner ◽  
Wilhelm Sandmann ◽  
Heinz Larkamp

✓ This article describes a new flexible bipolar neuroelectrode which is inserted percutaneously into the epidural space for segmental spinal cord stimulation. This electrode was used in experiments with dogs and monkeys for recording cortical somatosensory evoked potentials in order to identify intraoperative spinal cord ischemia during periods of aortic occlusion.


1979 ◽  
Vol 50 (5) ◽  
pp. 611-616 ◽  
Author(s):  
Frederick M. Maynard ◽  
Glenn G. Reynolds ◽  
Steven Fountain ◽  
Conal Wilmot ◽  
Richard Hamilton

✓ Between January, 1974, and December, 1976, 123 patients with traumatic quadriplegia were admitted to the California Regional Spinal Cord Injury Care System. The spinal cord injury resulted from gunshot wounds in five, from a stab wound in one, from neck injuries with no bone damage seen on x-ray studies in 10, and from fracture dislocations of the cervical spine in 107. One-year follow-up information was available on 114 patients. Neurological impairment using the Frankel classification system was compared at 72 hours postinjury to the 1-year follow-up examination. Fifty of 62 patients with complete injury at 72 hours were unchanged at 1 year. Five of these 62 patients had developed motor useful function in the legs or became ambulatory by 1 year, but all had sustained serious head injuries at the time of their trauma making initial neurological assessment unreliable. Ten percent of all cases had combined head injury impairing consciousness. Among 103 cognitively intact patients, none with complete injury at 72 hours were walking at 1 year. Of patients with sensory incomplete function at 72 hours postinjury, 47% were walking at 1 year; 87% of patients with motor incomplete function at 72 hours postinjury were walking at 1 year. Spinal surgery during the first 4 weeks postinjury did not improve neurological recovery. A method of analyzing neurological and functional outcomes of spinal cord injury is presented in order to more accurately evaluate the results of future treatment protocols for acute spinal injury.


1988 ◽  
Vol 68 (1) ◽  
pp. 25-30 ◽  
Author(s):  
John R. Ruge ◽  
Grant P. Sinson ◽  
David G. McLone ◽  
Leonard J. Cerullo

✓ Maturity of the spine and spine-supporting structures is an important variable distinguishing spinal cord injuries in children from those in adults. Cinical data are presented from 71 children aged 12 years or younger who constituted 2.7% of 2598 spinal cord-injured patients admitted to the authors' institutions from June, 1972, to June, 1986. The 47 children with traumatic spinal cord injury averaged 6.9 years of age and included 20 girls (43%). The etiology of the pediatric injuries differed from that of adult injuries in that falls were the most common causative factor (38%) followed by automobile-related injuries (20%). Ten children (21.3%) had spinal cord injury without radiographic abnormality (SCIWORA), whereas 27 (57%) had evidence of neurological injury. Complete neurological injury was seen in 19% of all traumatic pediatric spinal cord injuries and in 40% of those with SCIWORA. The most frequent level of spinal injury was C-2 (27%, 15 cases) followed by T-10 (13%, seven cases). Upon statistical examination of the data, a subpopulation of children aged 3 years or younger emerged. These very young children had a significant difference in level of injury, requirement for surgical stability, and sex distribution compared to 4- to 12-year-old children.


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