SUSTAINED SPINAL CORD COMPRESSION

The current study was designed to determine whether progressive spinal cord damage during residual compression is caused by low blood flow and ischemia. The purpose of this experiment was to determine the effects of sustained spinal cord compression on regional blood flow and evoked potential recovery after time-dependent decompression. Spinal cord injury after trauma is commonly associated with residual cord compression. Although decreased blood flow has been reported after spinal cord contusion, the effect of residual spinal cord displacement on reperfusion of blood flow or recovery of neurologic function remains unclear. Eighteen beagles were anesthetized, and the spinal cord at T13 was loaded dorsally under precision loading conditions until evoked potential amplitudes were reduced by 50%. At this function endpoint, spinal cord displacement was maintained for 90 minutes. Somatosensory-evoked potentials were measured at regular intervals until 3 hours after decompression. Regional spinal cord blood flow was measured with a fluorescent microsphere technique at regular time points during and after spinal cord decompression. Within 5 minutes after dynamic cord compression was discontinued, evoked potential signals were absent in all dogs. Evoked potential recovery was observed after decompression in 7 of 18 dogs. Regional spinal cord blood flow at baseline, 21.8 +/- 1.9 mL/100 g. min (mean +/- SE), decreased to 3.9 +/- 0.9 mL/100 g. min after dynamic compression was discontinued. Although spinal cord-piston interface pressure dissipated by 87% of maximum interface pressure during sustained compression, mean blood flow recovered to only 34% of baseline flow. In the 7 dogs that recovered evoked potential function, blood flow increased to 11.3 +/- 2.7 mL/100g. min immediately before decompression (P < or = 0.05). In the 11 dogs that did not recover evoked potential function after decompression, regional blood flow did not improve during sustained compression. Recovery of evoked potential function after decompression corresponded with a greater return of blood flow during sustained displacement and greater reperfusion of blood flow associated with decompression.

To assess influence of durotomy on spinal cord blood flow (SCBF) in chondrodystrophic dogs with thoracolumbar disk extrusion. Prospective cohort study. Chondrodystrophic dogs with thoracolumbar disk extrusion (n = 11). Diagnosis was based on neurologic signs, magnetic resonance imaging (MRI) findings, and surgical confirmation. Regional SCBF was measured 3 times intraoperatively by laser-Doppler flowmetry: (1) before surgical decompression; (2) immediately after decompression by hemilaminectomy-durotomy; and (3) after 15 minutes of lesion lavage. A standardized hemilaminectomy and durotomy performed by the same neurosurgeon, was used to minimize factors that could influence measurement readings. A significant increase in intraoperative SCBF was found immediately after spinal cord decompression and durotomy in dogs but SCBF returned to previous levels or lower after 15 minutes of lavage. Changes in SCBF were not associated with duration of clinical signs; neurologic status, degree of spinal cord compression, or signal intensity changes as assessed by MRI. Durotomy does not increase SCBF in dogs with disk extrusion associated spinal cord compression.

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 degrees +/- 0.6 degrees 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 less than 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.

Regional spinal cord blood flow was measured in 12 halothane-anesthetized mongrel dogs by means of 15 +/- 3 u radiolabeled microspheres under (1) control conditions, (2) 60-torr mean arterial blood pressure (MAP) using sodium nitroprusside (NPS), (3) 50-torr MAP using NPS, and (4) after reestablishment of normotension. With the onset of either level of hypotension, there were nonsignificant decreases from control conditions in cardiac output and pulmonary capillary wedge pressure (PCWP). A rise in heart rate was seen at 50 torr MAP. There were no significant changes in spinal cord blood flow (SCBF) under either hypotensive condition in any region of the cord, indicating an intact autoregulatory response. Sensitivity of SCBF to changes in the PaCO2 was shown to be 1.02 ml/min/100 g tissue per torr PaCO2. These data showed that (1) deliberate hypotension with NPS did not change SCBF in the dog; (2) sensitivity to PaCO2 was high under halothane anesthesia; and (3) SCBF was relatively homogeneous throughout the length of the cord.

Coupling of the cardiovascular and cerebrospinal fluid (CSF) system is considered to be important to understand the pathophysiology of cerebrovascular and craniospinal disease and intrathecal drug delivery. A coupled cardiovascular and CSF system model was designed to examine the relation of spinal cord (SC) blood flow (SCBF) and CSF pulsations along the spinal subarachnoid space (SSS). A one-dimensional (1-D) cardiovascular tree model was constructed including a simplified SC arterial network. Connection between the cardiovascular and CSF system was accomplished by a transfer function based on in vivo measurements of CSF and cerebral blood flow. A 1-D tube model of the SSS was constructed based on in vivo measurements in the literature. Pressure and flow throughout the cardiovascular and CSF system were determined for different values of craniospinal compliance. SCBF results indicated that the cervical, thoracic, and lumbar SC each had a signature waveform shape. The cerebral blood flow to CSF transfer function reproduced an in vivo-like CSF flow waveform. The 1-D tube model of the SSS resulted in a distribution of CSF pressure and flow and a wave speed that were similar to those in vivo. The SCBF to CSF pulse delay was found to vary a great degree along the spine depending on craniospinal compliance and vascular anatomy. The properties and anatomy of the SC arterial network and SSS were found to have an important impact on pressure and flow and perivascular fluid movement to the SC. Overall, the coupled model provides predictions about the flow and pressure environment in the SC and SSS. More detailed measurements are needed to fully validate the model.

Delayed deterioration of neurological function after central nervous system ischemia is a well-documented clinical problem. The purpose of our study was to elucidate the role of spinal cord blood flow and spinal cord-blood barrier integrity in the evolution of delayed neurological deterioration after transient spinal cord ischemia in rabbits. Anesthetized rabbits were subjected to lumbar spinal cord ischemia (25 minutes) and variable periods of reperfusion (30 minutes to 48 hours after ischemia). Regional spinal cord blood flow was monitored by carbon-14-labeled iodoantipyrine autoradiography; vascular permeability was assessed by quantitative microhistofluorescence of Evans blue-albumin in frozen sections of spinal cord. Hindlimb motor function was assessed by standard scoring system and tissue edema by wet/dry weight method. Hindlimb motor function indicated complete paralysis during ischemia and partial gradual recovery upon reperfusion (up to 8 hours), followed by progressive deterioration to severe deficits over 48 hours. Severe vascular permeability disruption was noticed early (30 minutes) after reperfusion, but almost complete recovery reestablished at 8 hours was followed by a secondary progressive increase in vascular permeability. Blood flow was reduced by 20-30% (p less than 0.01) 4 hours after ischemia in the gray matter, but hyperemia (200-300%, p less than 0.01) was observed 12-24 hours after ischemia. Spinal cord water content increased by 5.7% (p less than 0.05) 24 hours after ischemia. This study demonstrates that delayed neurological and motor deterioration after spinal cord ischemia is associated with severe progressive breakdown of spinal cord-blood barrier integrity that develops late (hours) after the injury. Our data suggest that no ischemic insult in early or late reperfusion is associated with delayed motor deterioration.

The mechanism of central nervous system (CNS) protection during proximal descending thoracic aortic cross-clamping (PDTAC) for aortic surgery using calcium channel blocking agents is not known. In order to determine the effect of verapamil on CNS blood flow during PDTAC, we calculated cerebral cortical (CC), proximal spinal cord (PSC), and distal spinal cord (DSC) blood flow using the microsphere method in Grade I beagles. Flow calculations were obtained at baseline (pre-PDTAC), following mobilization of the proximal descending aorta for 5-8 cm by ligating 3-5 pairs of intercostal arteries (ICA), during PDTAC (45 min), and during maximal reperfusion. Two groups were studied: 1) control (Cont) untreated (n = 5); 2) verapamil (Ver) treated (0.4 mg/kg IV just before PDTAC and just before reperfusion) (n = 5). I) Proximal ICA ligation produces no compromise to SC blood flow. II) Verapamil may protect the CNS by: 1) maintaining cerebral autoregulation during reperfusion; and 2) dampening hyperperfusion of the distal SC during reperfusion.

The extent to which nitric oxide (NO) is involved in the modulation of spinal cord blood flow (SCBF) in the uninjured and injured cord is unknown. To elucidate these questions, the following experiments in anesthetized rats were conducted. Because NO is an unstable free radical with a half-life of seconds, its role can be understood through the study of the NO synthase inhibitor L-NG-nitroarginine (L-NOARG). L-NOARG was administered intravenously for 30 minutes at a dose of 100 or 500 micrograms/kg/min in 12 and 10 uninjured animals, respectively. SCBF fluctuations at C7-T1 were measured using laser doppler flowmetry. In a second set of 12 rats, L-NOARG (500 micrograms/kg/min) was administered 10 minutes before spinal cord injury using a modified aneurysm clip at C7-T1 and continued for 30 minutes thereafter. In the uninjured animals, L-NOARG was associated with a dose-dependent increase in mean arterial pressure of 20 to 80% above baseline (P = 0.0001), together with a dose-related decrease in SCBF (P = 0.0373). In the injured animals, L-NOARG was associated with a 48% increase in mean arterial pressure. With L-NOARG, the changes in SCBF from baseline after injury were similar to those of noninjured controls (n = 25) and significantly less than injury controls (n = 18) or those receiving phenylephrine (n = 8). NO synthase inhibitors, by reducing available NO, cause systemic vasoconstriction and a decrease in SCBF in the uninjured spinal cord. In the injured spinal cord, the administration of L-NOARG results in a redistribution of blood flow with an augmentation in posttraumatic SCBF at the injury site.

The study of spinal cord blood flow (SCBF) after spinal drug application is an important aspect of preclinical neurotoxicological screening. This investigation was designed to study how a new local anesthetic, ropivacaine, affects SCBF after intrathecal (IT) administration in the rat. SCBF was measured continuously in spontaneously breathing, enflurane/N2O-anesthetized rats, using the laser-Doppler flowmetry technique. The spinal cord was exposed by laminectomy, and a laser-Doppler probe was placed over the dorsal horn, allowing on-line registration of spinal blood flow in a tissue hemisphere of 1-2 mm. Relative changes in spinal blood flow over time were then measured after IT administration of either 0.9% saline, 5 mg/mL ropivacaine, i.e., a concentration within the pharmacological range, or a high, provocative concentration of 20 mg/mL ropivacaine. A minor and transient decrease in SCBF was seen after administration of 5 mg/mL ropivacaine (50 micrograms given IT), but this decrease was not significantly different from that in the saline group. SCBF decreased significantly to approximately 45% of the predrug value after the high concentration of 20 mg/mL ropivacaine (200 micrograms given IT), and this reduction was reversible within a period of 20 - 40 min after the injection. Whereas a high concentration of ropivacaine caused a definite reduction in spinal cord blood flow when administered IT to anesthetized rats, clinically relevant concentrations induced only minor changes. These results suggest that ropivacaine may be used to induce spinal anesthesia without causing clinically relevant effects on SCBF.

Spinal cord blood flow (SCBF) was measured in 12 albino rats following acute cord injury produced by the extradural clip compression technique. Severe injury was produced with the clip compressing the cord with a force of 180 gm for 5 minutes, an injury previously shown to produce a severe functional deficit. Regional SCBF was measured 15 minutes, 2 hours, and 24 hours after injury by the 14C-antipyrine autoradiographic technique and a scanning microscope photometer. At 15 minutes and 2 hours, white and gray matter blood flow was severely diminished, and, at 24 hours, there was only minimal improvement. Focal decreases in blood flow were seen in white and gray matter for a considerable distance proximal and distal to the site of cord trauma. Thus, it has been confirmed in this model that severe cord compression injury produces severe posttraumatic ischemia in the cord which lasts for at least 24 hours.

The effect of epidural lidocaine on spinal cord blood flow (SCBF) was measured in mongrel dogs. Spinal evoked potentials were used to measure spinal cord conduction and enabled us to time the measurement of SCBF associated with maximum reduction in latency and amplitude of spinal evoked potentials produced by instillation of 5 ml of 2% lidocaine in the epidural space. We used the radioactive microsphere technique to quantitate SCBF in the cervical, upper thoracic, lower thoracic, and lumbar regions of the spinal cord. A narcotic/relaxant technique was used to eliminate SCBF changes associated with other anesthetic agents. Other parameters known to affect SCBF were kept constant and within normal physiologic values. As compared with saline solution controls, there were significant decreases in SCBF in all the four areas of spinal cord in animals given epidural lidocaine, most marked in the lumbar area.

The effect of traumatic spinal cord injury (TSCI) on spinal cord blood flow (SCBF) in humans is unknown. Whether intervention to achieve the recommended mean arterial pressure (MAP) guideline of 85-90 mm Hg improves SCBF is also unclear. Here, we use laser speckle contrast imaging intraoperatively to visualize blood flow at the injury site in 22 patients with acute, severe spinal cord injuries (American Spinal Injuries Association Impairment Scale, grades A-C). In 17 of 22 patients, injury-site metabolism was also monitored with a microdialysis catheter placed intradurally on the surface of the injured cord. We observed three different SCBF patterns, characterized by distinct injury-site metabolic signatures, which we term necrosis-penumbra, hyperperfusion, and patchy-perfusion. The necrosis-penumbra pattern, only observed in thoracic injuries, had a core of low blood flow (necrosis) with regions of intermediate blood flow on either side (penumbra). The hyperperfusion pattern, only observed in cervical injuries, had very high blood flow throughout the injury site. The patchy-perfusion pattern, found in cervical and thoracic injuries, had irregular regions of low, intermediate, and high blood flow. Though intervention to increase MAP by 20 mm Hg increased overall blood flow at the injury site, in 5 of 22 patients, blood flow increased in some regions, but, surprisingly, decreased in other regions. We term this phenomenon blood pressure-induced local steal. In 7 of 19 patients with MAP 85-90 mm Hg, parts of the injury site were only perfused in systole, but not in diastole, which we term diastolic ischemia. We conclude that acute, severe TSCI produces three pathological blood flow patterns at the injury site. Intervention to increase blood pressure may elicit potentially detrimental SCBF responses in some patients.

The effects of low and high doses of propofol on global cerebral blood flow (CBF) and spinal cord blood flow (SCBF) as a function of mean arterial blood pressure were investigated. CBF and SCBF during propofol infusion were compared to the levels in rats anesthetized with nitrous oxide (N2O) and fentanyl. Rats in the fentanyl/N2O group (control, n = 13) received 70% N2O in O2 plus fentanyl (bolus: 10 micrograms/kg; infusion: 25 micrograms.kg-1 x h-1). Rats in the low-dose propofol group (n = 10) received 30% O2 in air and propofol infusion (0.5 mg.kg-1 x min-1). Rats in the high-dose propofol group (n = 8) received 30% O2 in air and propofol infusion (2.0 mg.kg-1 x min-1). Blood flow autoregulation was tested by manipulating the mean arterial blood pressure with phenylephrine infusion or trimethaphan infusion and blood withdrawal by measuring CBF and SCBF using radioactive microspheres. Arterial blood gases, pHa, and skull temperature were controlled. Cerebral and spinal cord vasculature showed autoregulation in all treatment groups with a pressure range of 50-140 mm Hg. Within this pressure range, when compared to fentanyl/N2O, propofol decreased cortical CBF 60% (P < 0.001), subcortical CBF 40% (P < 0.001), midbrain blood flow 30% (P < 0.001), and SCBF 20% (P < 0.05). These results indicate that propofol maintains CBF and SCBF autoregulation.

Lipid peroxidation has been identified as a deleterious consequence of contusive spinal cord trauma and of thermal injury. The L3-L6 spinal cord segment was thermally injured using a radiofrequency heating chamber mounted on the vertebral column of anesthetized rats. Hind limb function was assessed 2 hours later. A bolus of methylprednisolone (MP, 30 mg/kg) was then given intravenously, followed by 5.4 mg/kg/hr MP for 6 or 24 hours. Cord water content and regional spinal cord blood flow (RSCBF, 14C-butanol distribution) were measured at seven cord levels after function had been reassessed following treatment. Untreated rats were given vehicle. The study was randomized and blinded. Edema in heated segments was progressive over 24 hours, but was the same in treated vs untreated rats. RSCBF in heated segments was the same in treated vs uninjured controls at 6 and 24 hours. In untreated rats, RSCBF in the heated segment was elevated by 30% at 6 hours, but was the same as uninjured control by 24 hours. In the unheated segments of untreated rats, RSCBF was elevated at 24 hours. At 24 hours, RSCBF was lower in treated vs untreated rats at all levels, including the heated one. Limb function deteriorated equivalently in both groups. MP obviated the early rise in RSCBF in heated segments and the elevations in RSCBF in uninjured segments, but had no effect on cord edema or on limb function.

7.5% hypertonic saline was administered following spinal cord injury to test its effect on spinal cord blood flow. Four different groups of rats underwent 10 minutes of spinal cord compression (45 g) at the C3 to C5 levels. A fifth group was not injured, but received hypertonic saline (5 ml/kg) at 5, 15 and 60 minutes following injury. Somatosensory evoked potentials and spinal cord blood flow were measured prior to and for 4 hours following the injury. The administration of hypertonic saline caused a significant increase in flow when administered 5 minutes following injury. Topical nitroprusside administration did not cause any increase in spinal cord blood flow during this time period. Hypertonic saline administration at the later time periods did not increase spinal cord blood flow. The group of animals which were not injured, but received hypertonic saline also showed no significant change in flow. The somatosensory evoked response of the treated animals was maintained for 4 hours after the injury where as the untreated animals began to lose their evoked responses 3 hours after injury.