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.

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.

Lactate and pyruvate metabolism in injured cat spinal cord before and after a single large intravenous dose of methylprednisolone

1983 ◽  
Vol 59 (2) ◽  
pp. 256-261 ◽  
Author(s):  
J. Mark Braughler ◽  
Edward D. Hall
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Sodium Succinate ◽  
Pyruvate Metabolism ◽  
Early Therapy ◽  
Content Type ◽  
Methylprednisolone Sodium Succinate ◽  
Before And After ◽  
Lactate And Pyruvate ◽  
Lactate Levels

✓ The lactate content and the lactate/pyruvate ratio of the acutely traumatized cat spinal cord have been studied and were found to rise rapidly following a 400 gm-cm injury. Lactate levels rose nearly twofold within 5 minutes after injury, peaked at 2 hours after injury, and remained significantly elevated for at least 8 hours compared to an adjacent uninjured segment of traumatized cord. Pyruvate levels, on the other hand, fell acutely in the injured section of cord during the 1st hour after injury then rose slowly over an 8-hour period. The changes in tissue lactate and pyruvate metabolism in the spinal cord following injury are consistent with a marked injury-induced reduction in blood flow. The elevation in lactate and the fall in pyruvate levels observed at 1 hour after injury were completely prevented by the intravenous administration of a single 30-mg/kg dose of methylprednisolone sodium succinate at 30 minutes after injury. Lower or higher doses of methylprednisolone were far less effective. The effects of the 30-mg/kg dose of methylprednisolone on tissue lactate content were associated with high tissue levels of the glucocorticoid and were short-lived, paralleling the accumulation and elimination pattern of steroid from the injured tissue. The results suggest that, in addition to other reported beneficial actions of large intravenous doses (30 mg/kg) of methylprednisolone on the injured cord, the glucocorticoid may also improve blood flow to the injured segment as has been suggested by others. The use of high glucocorticoid doses, early therapy initiation, and rigorous maintenance dosing is discussed.

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.

The effects of ischemia on long-tract neural conduction in the spinal cord

1979 ◽  
Vol 50 (5) ◽  
pp. 639-644 ◽  
Author(s):  
Arthur I. Kobrine ◽  
Delbert E. Evans ◽  
Hugo V. Rizzoli
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Spinal Cord Ischemia ◽  
Evoked Response ◽  
Content Type ◽  
Neural Conduction ◽  
Progressive Development ◽  
Normal Blood Flow ◽  
Lower Limits ◽  
Hydrogen Clearance

✓ In this experiment, the effects of ischemia on neural conduction in the monkey spinal cord were studied. In six monkeys generalized ischemia of the spinal cord was created by bleeding the animals to a hypotensive level below the lower limits of autoregulation in the spinal cord. The progressive development of spinal cord ischemia was documented by blood-flow measurement using the hydrogen clearance method. Physiological integrity of the spinal cord was monitored and recorded by the spinal evoked response. The spinal evoked response did not disappear until at least 10 minutes of profound ischemia. At levels of ischemia 20% to 25% of normal blood flow, the spinal evoked response was unchanged. It is concluded that long-tract neural conduction in the spinal cord is relatively resistant to the effects of ischemia.

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.

Experimental acute balloon compression of the spinal cord

1979 ◽  
Vol 51 (6) ◽  
pp. 841-845 ◽  
Author(s):  
Arthur I. Kobrine ◽  
Delbert E. Evans ◽  
Hugo V. Rizzoli
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Spinal Cord Ischemia ◽  
Evoked Response ◽  
Physical Injury ◽  
Thoracic Spinal Cord ◽  
Content Type ◽  
Balloon Compression ◽  
Thoracic Spinal ◽  
Flow Changes

✓ Acute balloon compression of the thoracic spinal cord for 15, 7, 5, 3, and 1 minute in monkeys caused immediate disappearance of the spinal evoked response and complete focal ischemia of the compressed segment in all animals. Only the animals in the 1-minute group, however, demonstrated return of the evoked response. These data, coupled with data from previous experiments of slow balloon compression of the spinal cord and spinal cord ischemia, suggest that the major pathological substrate for neural dysfunction after balloon compression of the spinal cord, be it acute or slow, is physical injury of the neural membrane, irrespective of blood flow changes. These findings also suggest that the ability of that membrane to recover is related to rapidity and length of time of compression. Focal changes in blood flow do not appear to be significant in this mechanism.

The effect of hypothermia on regional spinal cord blood flow in rats

1989 ◽  
Vol 70 (5) ◽  
pp. 780-784 ◽  
Author(s):  
Toshihisa Sakamoto ◽  
William W. Monafo
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cord Blood ◽  
Spinal Cord Ischemia ◽  
Control Level ◽  
Normal Group ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Arterial Blood ◽  
Anesthetized Rats

✓ 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.

Altered blood flow and secondary injury in experimental spinal cord trauma

1978 ◽  
Vol 49 (4) ◽  
pp. 569-578 ◽  
Author(s):  
Howard J. Senter ◽  
Joan L. Venes
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Pharmacological Intervention ◽  
Secondary Injury ◽  
Thoracic Spinal Cord ◽  
Content Type ◽  
Thoracic Spinal ◽  
Dorsolateral Funiculus ◽  
Altered Blood ◽  
Hydrogen Clearance

✓ A modification of the hydrogen clearance technique was used to study blood flow in the dorsolateral funiculus of traumatized thoracic spinal cord in cats. The results of this study show that ischemia occurred in all animals both at the level of trauma, and 1 cm below the site of trauma. There was, however, a period of over 1 hour after trauma during which blood flow was maintained at both sites. This investigation not only confirms the presence of ischemia in the lateral funiculus of the injured spinal cord but suggests that a period of time exists in the posttraumatic period during which pharmacological intervention may alter the ischemic response and possibly prevent secondary injury resulting from the ischemia.

Local blood flow, oxygen tension, and oxygen consumption in the rat spinal cord

1983 ◽  
Vol 58 (4) ◽  
pp. 526-530 ◽  
Author(s):  
Nariyuki Hayashi ◽  
Barth A. Green ◽  
Mayra Gonzalez-Carvajal ◽  
Joseph Mora ◽  
Richard P. Veraa
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Oxygen Tension ◽  
Tissue Oxygen ◽  
Local Blood Flow ◽  
Rat Spinal Cord ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Tissue Oxygen Consumption

✓ 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.

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.

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