Increase In Spinal Cord Blood Flow Research Articles

Cerebrospinal fluid drainage and induced hypertension improve spinal cord perfusion after acute spinal cord injury in pigs.

Acute spinal cord injury (SCI) is commonly treated by elevating the mean arterial pressure (MAP). Other potential interventions include cerebrospinal fluid drainage (CSFD). To determine the efficacy of aggressive MAP elevation combined with intrathecal pressure (ITP) reduction; our primary objective was to improve spinal cord blood flow (SCBF) after SCI. All 15 pigs underwent laminectomy. Study groups included control (n = 3); SCI only (n = 3); SCI combined with MAP elevation (SCI + MAP) (n = 3); SCI combined with CSFD (SCI + CSFD) (n = 3); and SCI combined with both MAP elevation and CSFD (SCI + MAP + CSFD) (n = 3). SCBF was measured with laser Doppler flowmetry. In the SCI group, SCBF decreased by 56% after SCI. MAP elevation after SCI resulted in a 34% decrease in SCBF, whereas CSFD resulted in a 59% decrease in SCBF. The combination of CSFD and MAP elevation resulted in a 24% increase in SCBF. The SCI + MAP group had an average ITP increase of 5.45 mm Hg after MAP elevation 1 hour after SCI and remained at that level throughout the experiment. Both MAP elevation alone and CSFD alone led to only short-term improvement of SCBF. The combination of MAP elevation and CSFD significantly and sustainably improved SCBF and spinal cord perfusion pressure. Although laser Doppler flowmetry can provide flow measurements to a tissue depth of only 1.5 mm, these results may represent pattern of blood flow changes in the entire spinal cord after injury.

Laser‐Doppler Measurements of Spinal Cord Blood Flow Changes During Hemilaminectomy in Chondrodystrophic Dogs with Disk Extrusion

(1) To assess spinal cord blood flow (SCBF) during surgical treatment of disk extrusion in dogs and (2) to investigate associations between SCBF, clinical signs, presurgical MRI images, and 24-hour surgical outcome. Cohort study. Chondrodystrophic dogs with thoracolumbar disk extrusion (n=12). Diagnosis was based on clinical signs and MRI findings, and confirmed at surgery. Regional SCBF was measured intraoperatively by laser-Doppler flowmetry before, immediately after surgical spinal cord decompression, and after 15 minutes of lavaging the lesion. Care was taken to ensure a standardized surgical procedure to minimize factors that could influence measurement readings. A significant increase in intraoperative SCBF was found in all dogs (Wilcoxon's signed-rank test; P=.05) immediately after spinal cord decompression and after 15 minutes. Changes in SCBF were not associated with duration of clinical signs; initial or 24-hour neurologic status; or degree of spinal cord compression assessed by MRI. SCBF increases immediately after spinal cord decompression in dogs with disk herniation; however, increased SCBF was not associated with a diminished 24-hour neurologic status. An increase in SCBF does not appear to be either associated with the degree of spinal cord compression or of a magnitude sufficient to outweigh the benefit of surgical decompression by resulting in clinically relevant changes in 24-hour outcome.

Interleukin-1 beta enhances spinal cord blood flow after intrathecal administration in the normal rat

The effects of acute intrathecal recombinant human interleukin-1 beta (rhIL-1 beta) administration on spinal cord blood flow (SCBF), volume, and velocity were determined by laser-Doppler flowmetry in normal anesthetized rats with the use of a randomized and blinded protocol. The intrathecal administration of rhIL-1 beta (0.16-16 ng) produced a dose-dependent increase in SCBF that was not related to changes in blood pressure; arterial pH, PO2, PCO2; or spinal cord temperature. The IL-1 beta-induced enhancement of SCBF was directly proportional to the resultant elevation of spinal cord rhIL-1 beta content and was significantly correlated with an elevated blood velocity. The IL-1 receptor antagonist (IL-1ra) in concentrations 50- and 200-fold higher than IL-1 beta completely blocked the IL-1 beta-induced increase in SCBF when both compounds were administered concomitantly, but when administered alone, IL-1ra did not affect SCBF or other parameters. This suggests that IL-1 beta action was mediated by a specific interaction with an IL-1 membrane receptor site. The results suggest a role of IL-1 beta in the regulation of spinal cord hemodynamics. A potential pharmacological approach using IL-1 agonists for the treatment of the delayed appearance of posttraumatic spinal ischemia is proposed.

Laser-Doppler Evaluation of Spinal Cord Blood Flow After Intrathecal Administration of an N???Methyl???D???Aspartate Antagonist in Rats

The N-methyl-D-aspartate (NMDA) receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), which produces antinociception in experimental animal models after spinal administration, may be of value in clinical pain treatment. Safety screening of drugs intended for spinal administration includes evaluation of the drug's effect on spinal cord blood flow (SCBF). In the present study, laser-Doppler flowmetry technique was used to assess SCBF in an experimental model using anesthetized, spontaneously breathing rats. Methodologic aspects of the experimental set-up were studied, and the effects on SCBF were evaluated after intrathecal (IT) administration of saline or CPP in a dose range of 1-100 nmol. The spontaneously breathing rats, anesthetized with enflurane/N2O had stable mean arterial blood pressure values throughout the study, and no difference was found in arterial blood gas values or acid-base status measured either before or after the 80-min observation period. A reproducible increase in SCBF of approximately 10% during an 80-min measuring period was found in saline-treated rats. The trauma of the IT injection procedure gave a disturbance in the registered SCBF that lasted less than 10 min. No difference was found in SCBF between rats injected IT with either saline or CPP in a dose range from 1 nmol, i.e., a pharmacologically active dose, to 100 nmol, i.e., a provocative dose 400-fold the smallest dose that produces antinociception. When acidic solutions were injected, the SCBF increased in inverse proportion to pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of electrical stimulation of motor and cutaneous nerves on spinal cord blood flow.

The effects of electrical stimulation of the motor and cutaneous branch of the radial nerve on spinal cord blood flow (SCBF) in the cervical region and the correlation between the changes in SCBF and the amplitudes of spinal cord evoked potentials were investigated in cats anesthetized with alpha-chloralose. When measured by the hydrogen clearance technique, with stimuli of the cutaneous branch, the SCBF significantly (P < 0.01) increased from 37 +/- 8 (mean +/- SD) to 59 +/- 27 ml.100 g-1.min-1 at 10 Hz and from 39 +/- 6 to 54 +/- 9 ml.100 g-1.min-1 at 30 Hz, but stimulation of the motor branch had no effect. When measured by laser Doppler flowmetry, stimulation of the motor branch caused a small, transient, and significant increase in SCBF ending within 2 minutes. Stimulation of the cutaneous branch produced a large, prolonged, and significant increase in SCBF. The increase in SCBF produced by stimulation of the cutaneous nerve was significantly greater than that by stimulation of the motor branch. The SCBF was correlated linearly with the amplitude of the spinal cord evoked potential (r = 0.504; P < 0.01). The increase in SCBF caused by radial nerve stimulation may arise from changes in neuronal metabolism via peripheral nerve activation.

R-phenylisopropyl-adenosine increases spinal cord blood flow after intrathecal injection in the rat.

The A1-adenosine receptor agonist, R-phenylisopropyl-adenosine (R-PIA), demonstrated antinociceptive properties in animal studies after intrathecal administration. In the evaluation of a drug for possible spinal injection in humans, the effects of intrathecal R-PIA on spinal cord blood flow (SCBF) were investigated using the laser-Doppler flow-metry technique in anesthetized rats. In low doses (0.1-1 nmol), no change in SCBF was recorded, whereas larger doses (10-100 nmol) caused a significant increase in SCBF. No change in systemic arterial blood pressure could be seen, except for a decrease after administration of the largest dose of R-PIA (100 nmol). It is concluded that R-PIA in doses of 10 nmol and larger induces an increase in SCBF after intrathecal injection in anesthetized rats and that an increase in blood flow is seen before any effect on the systemic circulation is detected. It can also be deduced that the antinociceptive effects of R-PIA after intrathecal injection are not a consequence of spinal ischemia and that disturbances in local blood flow cannot be expected to constitute a neurotoxic factor.

Further Studies of Nimodipine in Experimental Spinal Cord Injury in the Rat

Previously in our laboratory, nimodipine was effective in reversing posttraumatic ischemia and promoting electrophysiologic recovery in a rat spinal cord injury (SCI) model. However, these beneficial effects were achieved when nimodipine was combined with adjuvant therapy to reverse posttraumatic hypotension, by either volume expansion or vasopressor therapy. The present experiments determined if nimodipine alone can increase spinal cord blood flow (SCBF) and improve function after SCI. The hydrogen clearance technique was used to measure SCBF, and motor and somatosensory evoked potentials (MEP and SSEP) were used to quantitate electrophysiologic function. SCBF, MEP, and SSEP were recorded before and after a 52 g clip compression injury at the T1 segment and then repeated after a 35 minute infusion of nimodipine. Twenty-five rats were allocated randomly to five equal groups, each of which received 35 minute infusions of one of the following doses of nimodipine: (1) 0 mg/kg, (2) 0.005 mg/kg, (3) 0.01 mg/kg, (4) 0.025 mg/kg, or (5) 0.05 mg/kg. SCBF decreased after injury in all groups, and there was no increase in SCBF after nimodipine infusion in any group. MEP and SSEP were abolished by the injury in all rats, and there was no recovery of the evoked potentials in any group. It is concluded that adjuvant therapy for posttraumatic hypotension may be necessary for nimodipine to improve SCBF and promote recovery of function in the injured spinal cord.