Effects of a single large dose of methylprednisolone sodium succinate on experimental posttraumatic spinal cord ischemia

1984 ◽  
Vol 61 (1) ◽  
pp. 124-130 ◽  
Author(s):  
Edward D. Hall ◽  
Daniel L. Wolf ◽  
J. Mark Braughler
Keyword(s):  
Spinal Cord ◽  
Sodium Succinate ◽  
Spinal Cord Ischemia ◽  
Repeated Measurements ◽  
Intravenous Dose ◽  
Lumbar Spinal Cord ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Methylprednisolone Sodium Succinate ◽  
Fine Print

✓ 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.

Effects of the 21-aminosteroid U74006F on posttraumatic spinal cord ischemia in cats

1988 ◽  
Vol 68 (3) ◽  
pp. 462-465 ◽  
Author(s):  
Edward D. Hall
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Sodium Succinate ◽  
Spinal Cord Ischemia ◽  
Intravenous Dose ◽  
Content Type ◽  
Methylprednisolone Sodium Succinate ◽  
Surprising Effect ◽  
Surgical Preparation ◽  
Dorsolateral Funiculus

✓ The ability of a single intravenous dose of the 21-aminosteroid U74006F to affect the development of posttraumatic spinal cord ischemia was examined in pentobarbital-anesthetized cats. After surgical preparation, each animal received a 300 gm-cm contusion injury to the exposed L-3 vertebral segment, followed by a single bolus injection of vehicle or U74006F (3 or 10 mg/kg) at 30 minutes postinjury. Spinal cord white matter blood flow (SCBF) was measured by hydrogen clearance in the dorsolateral funiculus in the center of the injured segment before and at various times up to 4 hours after injury. In vehicle-treated cats, there was a progressive decline in SCBF over the course of the experiment. By 4 hours postinjury, SCBF had decreased from a preinjury value of 15.9 ± 2.4 ml/100 gm/min (mean ± standard error of the mean) to 5.8 ± 0.8 ml/100 gm/min, representing a decline of 63.5%. In contrast, the SCBF measured 4 hours postinjury in cats that were treated with a single 10-mg/kg dose of U74006F was 13.6 ± 1.7 ml/100 gm/min (p < 0.001 vs. vehicle). Animals that received a 3-mg/kg intravenous dose of U74006F displayed a drop in SCBF equal to that of vehicle-treated cats. However, when a 3-mg/kg dose of U74006F was given to four vehicle-treated cats at the end of the experiment, a partial reversal of ischemia was recorded. Blood flow increased within 30 minutes from a mean of 4.5 ± 0.8 to 7.4 ± 1.0 ml/100 gm/min or an increase of 64.4% (p < 0.05). This rather surprising effect of U74006F in reversing posttraumatic ischemia once it has developed significantly is not shared by a 30-mg/kg intravenous dose of methylprednisolone sodium succinate (MP), although MP has previously been shown to attenuate the posttraumatic drop in SCBF when given before the SCBF drop occurs. The mechanism of action of U74006F in antagonizing posttraumatic ischemia development is believed to involve the ability of the compound to inhibit iron-dependent lipid peroxidation in central nervous system tissue.

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
Keyword(s):  
Spinal Cord ◽  
Lipid Peroxidation ◽  
Spinal Injury ◽  
Spinal Cord Ischemia ◽  
Repeated Measurements ◽  
Lumbar Spinal Cord ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Pharmacological Analysis ◽  
Prostaglandin F

✓ 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.

Effects of multi-dose methylprednisolone sodium succinate administration on injured cat spinal cord neurofilament degradation and energy metabolism

1984 ◽  
Vol 61 (2) ◽  
pp. 290-295 ◽  
Author(s):  
J. Mark Braughler ◽  
Edward D. Hall
Keyword(s):  
Spinal Cord ◽  
Sodium Succinate ◽  
Energy Charge ◽  
Lumbar Spinal Cord ◽  
Spinal Cord Tissue ◽  
Injured Spinal Cord ◽  
Neurofilament Protein ◽  
Content Type ◽  
Methylprednisolone Sodium Succinate ◽  
Spinal Cord Segment

✓ Thirty minutes after experimental spinal cord contusion (500 gm-cm) injury, cats were treated with an initial intravenous dose of either vehicle (V) or 30 mg/kg of Solu-Medrol sterile powder (methylprednisolone sodium succinate; MPSS). Two hours later, cats received a second intravenous injection of either V or 15 mg/kg MPSS, giving three treatment groups: V/V; MPSS/V; MPSS/MPSS. At 4½ hours following injury of the cat lumbar spinal cord, the gray and white matter neurofilament protein content was reduced by over 70% within the injured segment of V/V-treated animals. The three major cat spinal cord neurofilament protein subunits of 200,000, 152,000, and 76,000 daltons were reduced in parallel by the injury. Treatment of cats with a single 30-mg/kg dose of MPSS (MPSS/V) provided a clear, although not significant, protection against neurofilament degradation compared with V/V-treated cats when measured at 4½ hours after injury. The lactic acid content of the injured spinal cord segment at 4½ hours after injury was significantly elevated in both V/V- and MPSS/V-treated cats, while the adenosine triphosphate (ATP) content, total adenylates, and energy charge were significantly reduced. The administration of a second intravenous 15-mg/kg dose of MPSS 2 hours after the initial 30-mg/kg dose (MPSS/MPSS) provided complete (p < 0.01) preservation of neurofilaments within the injured spinal cord segment measured at 4½ hours after injury. The levels of lactate, ATP, total adenylates, and tissue energy charge in MPSS/MPSS-treated cats were not different from those of uninjured spinal cords following laminectomy. The (Na+ + K+)-ATPase activity in the injured spinal segment was enhanced, although highly variable, in MPSS/V-treated animals. On the other hand, spinal cord enzyme activity was significantly and consistently elevated in the MPSS/MPSS-treated group. The results demonstrate that a 30-mg/kg dose of MPSS followed at 2 hours by a 15-mg/kg dose provides significantly better protection against injury-induced ischemia and Ca++-dependent neurofilament degradation than a single 30-mg/kg dose. These findings are in agreement with the spinal cord tissue pharmacokinetics and time-action characteristics of methylprednisolone observed in earlier studies.

Control of blood flow in the cat spinal cord

1983 ◽  
Vol 58 (5) ◽  
pp. 742-748 ◽  
Author(s):  
Oscar U. Scremin ◽  
Emilio E. Decima
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
White Matter ◽  
Ventral Horn ◽  
Hydrogen Gas ◽  
Lumbar Spinal Cord ◽  
Spinal Cord Tissue ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Fine Print

✓ 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.

Effect of mexiletine on lipid peroxidation and early ultrastructural findings in experimental spinal cord injury

1999 ◽  
Vol 91 (2) ◽  
pp. 200-204 ◽  
Author(s):  
Erkan Kaptanoglu ◽  
Hakan H. Caner ◽  
H. Selçuk Sürücü ◽  
Filiz Akbiyik
Keyword(s):  
Spinal Cord ◽  
Lipid Peroxidation ◽  
Spinal Cord Injury ◽  
Sodium Succinate ◽  
Content Type ◽  
Methylprednisolone Sodium Succinate ◽  
Cord Injury ◽  
Group 3 ◽  
Ultrastructural Findings ◽  
Fine Print

Object. The purpose of this study was to investigate the effect of mexiletine on lipid peroxidation and on ultrastructural findings after induced spinal cord injury (SCI). The authors also compared the activity of mexiletine to that of the well-known antioxidant, methylprednisolone sodium succinate (MPSS). Methods. Wistar rats were divided into seven groups, (Groups 1–7). Those in Groups 1 and 2 were control animals that underwent laminectomy only, after which nontraumatized spinal cord samples were obtained immediately (Group 1) and 2 hours postsurgery (Group 2). Spinal cord injury was induced in all other groups, and cord samples were obtained at 2 hours postsurgery. The rats in Group 3 underwent SCI alone; those in Group 4 received 30 mg/kg of MPSS intraperitoneally immediately after trauma was induced; and those in Groups 5, 6, and 7 received 1, 10, and 50 mg/kg of mexiletine, respectively, by intraperitoneal injection immediately after trauma was induced. Compared with the levels in control animals, lipid peroxidation was significantly elevated in rats in Groups 3 and 5, but there were no statistical differences among those in Groups 1, 2, 4, 6 and 7 in this regard. Compared with the findings in rats in Group 3, ultrastructural damage post-SCI was minor in rats in Groups 4 and 5, and there was even less damage evident in rats in Group 7. Conclusions. Analysis of these findings showed that administration of 50 mg/kg mexiletine significantly decreased the level of lipid peroxidation and protected spinal cord ultrastructure following SCI.

Percutaneous flexible bipolar epidural neuroelectrode for spinal cord stimulation

1984 ◽  
Vol 60 (6) ◽  
pp. 1317-1319 ◽  
Author(s):  
Alfred G. Kaschner ◽  
Wilhelm Sandmann ◽  
Heinz Larkamp
Keyword(s):  
Spinal Cord ◽  
Evoked Potentials ◽  
Epidural Space ◽  
Somatosensory Evoked Potentials ◽  
Spinal Cord Stimulation ◽  
Spinal Cord Ischemia ◽  
Aortic Occlusion ◽  
Content Type ◽  
Fine Print

✓ 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.

scholarly journals Spinal Cord Blood Flow after Ischemic Preconditioning in a Rat Model of Spinal Cord Ischemia

2004 ◽  
Vol 4 ◽  
pp. 892-898 ◽  
Author(s):  
David Zvara ◽  
James M. Zboyovski ◽  
Dwight D. Deal ◽  
Jason C. Vernon ◽  
David M. Colonna
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cord Blood ◽  
Ischemic Preconditioning ◽  
Spinal Cord Ischemia ◽  
Flow Analysis ◽  
Lumbar Spinal Cord ◽  
Sprague Dawley ◽  
Spinal Cord Blood Flow ◽  
Significant Difference

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.

Methylprednisolone half-life during simultaneous barbiturate treatment and mechanical hyperventilation of neurosurgical patients

1985 ◽  
Vol 62 (2) ◽  
pp. 182-185 ◽  
Author(s):  
Jørgen Gabrielsen ◽  
Asger Bendtsen ◽  
Henrik Eriksen ◽  
Steen Andersen
Keyword(s):  
Enzyme Induction ◽  
Half Life ◽  
Marked Reduction ◽  
Sodium Succinate ◽  
Steroid Treatment ◽  
Blood Samples ◽  
Content Type ◽  
Methylprednisolone Sodium Succinate ◽  
Neurosurgical Patients ◽  
Fine Print

✓ The pharmacokinetics of methylprednisolone sodium succinate (MP) were studied in six neurosurgical patients under intensive treatment with large doses of MP, barbiturates, and mechanical hyperventilation. The study showed a remarkable level of enzyme induction within 24 hours after starting treatment, when the first blood samples were taken. The half-life (t½) for MP during barbiturate and hyperventilation therapy was found to be reduced by a mean 55% (p < 0.01) in relation to the t½ of MP when administered alone. Studies on the day after termination of barbiturate intake indicated a tendency for an increase in the t½ of MP, but it was not significantly different from the pretermination assessment (p > 0.05). On the basis of this study it is not possible to determine if the change in t½ alone is governed by enzyme induction or by a combination of this plus a change in the distribution and clearance of the steroid. The clinical implication of these findings is that patients who are undergoing steroid treatment and at the same time are sedated with barbiturates should have their MP dose increased in order to compensate for the marked reduction of t½ of MP.

Effects of laminectomy on spinal cord blood flow

1978 ◽  
Vol 48 (2) ◽  
pp. 232-238 ◽  
Author(s):  
Douglas K. Anderson ◽  
Gregory R. Nicolosi ◽  
Eugene D. Means ◽  
L. Edward Hartley
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cord Blood ◽  
Reference Sample ◽  
Significant Decline ◽  
Entire Length ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Sample Method ◽  
Fine Print

✓ The effect of a one-segment (L-2) laminectomy on spinal cord blood flow (SCBF) was determined by the reference sample method using isotope-labeled microspheres. The SCBF was measured before laminectomy (control) and at 15 minutes postlaminectomy with the dura exposed (Series 1), 1 hour postlaminectomy with the laminectomy site closed (Series 2), 24 hours postlaminectomy with the laminectomy site closed (Series 3), and 24 hours postlaminectomy with the dura exposed (Series 4). With the laminectomy site open, SCBF was significantly depressed (22% to 45%) along the entire length of the spinal cord at 15 minutes postlaminectomy. At 1 hour postlaminectomy (with the laminectomy site closed), SCBF approached control values, although areas with significantly lowered flow were still observed in all portions of the spinal cord. By 24 hours postlaminectomy, SCBF had returned to prelaminectomy levels. However, if within 1 hour preceding the 24-hour SCBF measurement, the laminectomy site was reopened, SCBF tended to fall at and caudad to the laminectomy site. These data indicate that laminectomy can cause a significant decline in SCBF. At the present time, the mechanism(s) for this laminectomy-induced depression of SCBF are unknown, although a temperature-induced vasoconstriction is suspected.

The effect of norepinephrine on the spinal cord circulation and its possible implications in the pathogenesis of acute spinal trauma

1977 ◽  
Vol 47 (4) ◽  
pp. 567-576 ◽  
Author(s):  
Robert A. Crawford ◽  
Ian R. Griffiths ◽  
James McCulloch
Keyword(s):  
Spinal Cord ◽  
Bolus Injection ◽  
Spinal Injury ◽  
Spinal Cord Blood Flow ◽  
Arterial Infusion ◽  
Content Type ◽  
Barrier Disruption ◽  
Before And After ◽  
Hydrogen Clearance ◽  
Fine Print

✓ 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.

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