✓ Cytochrome oxidase activities were determined by a microspectrophotometric method on microdissected samples of gray and white matter from frozen-dried sections of dog spinal cord. Experimental animals received 400 gm-cm impact at the T-3 to T-4 level. Sections for enzyme analysis and histological study were taken at the center of the trauma site, at successive 1-mm distances from the center, and at non-traumatized segments. A drop in cytochrome oxidase activities to approximately 50% of normal value was found as early as 15 minutes post-trauma, with greatest decrease at the trauma center and lesser effects at successive distances. This effect was related to known morphological defects in mitochondrial cristae and inner membranes. The enzyme change was significantly correlated with histological estimates of gray matter and neuronal damage, but was also partially independent of these processes. A small but significant increase of enzyme activity in white matter at the trauma site was considered most likely attributable to mitochondrial accumulations due to impaired axoplasmic flow.
Terifumi Ito, Norman Allen and David Yashon
Report of two cases
Eric Zimmerman, John Grant, W. Michael Vise, David Yashon and William E. Hunt
✓ Two patients with bursting fractures of the atlas vertebra are presented. The use of a halo apparatus as an effective alternative to bedrest and cervical traction in these patients is discussed. Polytomography was helpful in establishing an accurate diagnosis.
David Yashon, Alfred P. Magness II and W. Michael Vise
✓ The authors review the intraoperative use of elective hypotension to reduce the probability of hemorrhage, to increase pliability of the aneurysmal sac for ease of clip application, and to control hemorrhage. The optimum agent and techniques for lowering systemic blood pressure remain controversial, but trimethaphan, sodium nitroprusside, and halothane have been found most useful. When cerebral blood flow falls below the brain's capacity to autoregulate, distinct time-related alterations occur biochemically and histologically. The profile of prolonged reduced adenosine triphosphate (ATP), low phosphocreatine, low glucose, and elevated lactate and lactate/pyruvate ratio is associated with swelling of perivascular astrocytes and “blebbing” of vascular endothelial cells with subsequent cerebral damage. To prevent permanent alteration it is desirable to observe time constraints and to employ other means of protection such as hypothermia, although the authors believe the latter unnecessary for short hypotensive periods. It has been proposed, but not substantiated, that anesthetics which depress rate of cerebral oxygen consumption but do not affect cerebral ATP level protect the brain from hypotension. Several investigations suggest that halothane, a vasodiltor, satisfies the safety requirement. The most prominent contraindication to halothane, however, is elevation of intracranial pressure. At present hypotensive surgery for aneurysmorrhaphy is usually performed when intracranial pressure has returned to normal. Experimentally the electroencephalogram has been observed to show alterations prior to biochemical parameters for following brain vulnerability, so that it conceivably could be an effective monitoring technique during prolonged profound hypotension.
W. George Bingham, Harold Goldman, Stewart J. Friedman, Sharon Murphy, David Yashon and William E. Hunt
✓ The authors used indicator fractionation techniques to determine blood flow in normal and bluntly traumatized spinal cords of Macaca rhesus monkeys. Normal flow rates were determined for several levels of spinal cord as well as differential values for white and gray matter from representative areas. Flow rates in traumatized tissue, obtained at several different time intervals up to 4 hours after injury, demonstrated marked differences in regional perfusion of the white matter and gray matter after trauma. Gray matter perfusion was nearly obliterated while white matter blood flow persisted and in fact was higher than uninjured controls. The findings do not support the concept of ischemia as a factor in white matter failure. If toxic pathobiochemical alterations are induced by trauma, it may be possible to reverse these changes by exploiting the preserved white matter blood flow for chemotherapeutic intervention.
W. Michael Vise, David Yashon and William E. Hunt
✓ Vascularity and blood-brain barrier (BBB) function within spinal cord were studied with fluorescent microscopy at 14 intervals following 300 gm-cm injuries to the thoracolumbar spinal cord in 32 dogs. Histochemical staining with formaldehyde brought out a yellow-green fluorescence of vascular origin that was unrelated to tracer dye. This fluorescence accumulated in perivascular sites and is possibly related to catecholamine elevation within damaged spinal cord. Intrinsic CNS mechanisms for catecholamine build-up (increased transport, increased synthesis, increased release) are reviewed as well as the pharmacological action of alpha methyl tyrosine. It is hypothesized that an intrinsic CNS source of norepinephrine build-up is unlikely and that elevation of circulating catecholamine levels following stress and trauma leads to the extravasation of this material across injured BBBs within contused spinal cord.
David Yashon, William Stone, Alfred Magness, William E. Hunt and William Hamelberg
✓ The effect of halothane-induced profound systemic arterial hypotension on brain ischemia was evaluated by comparison with hypotension caused by oligemia and trimethaphan as well as nonhypotensive controls. Mean cerebral tissue lactate concentrations after halothane-induced hypotension at 5, 30, and 60 minutes were 4.34, 5.92, and 7.48 mM/kg. There was no significant difference between halothane and control animals during the experimental period. At 30 and 60 minutes, both oligemic and trimethaphan groups were higher than the control and halothane series. Definite protection from cerebral ischemia is provided by halothane during induced hypotension. Exact mechanisms of protection conveyed by halothane are unclear, but are probably not related to relative increased blood flow since cerebral vasodilation is maximal in these low blood-pressure ranges irrespective of etiology.
David Yashon, W. Michael Vise, Richard C. Dewey and William E. Hunt
✓ The temperature of the spinal cord parenchyma during local hypothermia was recorded in 18 dogs with and without a 300 to 500 gm-cm spinal cord injury. Other variables included opening the dura, location of the inflow stream, and the use of alcohol bath cooling. In nontraumatized cord, the temperature varied between 5.4° and 23.5°C depending on the location of the inflow stream; the variable range of 10–15 minutes of perfusion to reach these levels was unexpected. Temperatures of the injured cord fell to those of the reservoir (1.0° to 3.8°C) within 2½ minutes. The fact that the temperature of nontraumatized areas two segments cephalad to the injury was also reduced showed the capacity of the cord for thermal conduction. Opening the dura or use of an alcohol bath had little effect on cord temperature. Lack of heat transport due to ischemia is postulated as the primary cause of the rapid reduction of temperature in the injured cord to that of the surrounding environment.
David Yashon, W. George Bingham Jr., Edward M. Faddoul and William E. Hunt
✓ Identification of central nervous system edema is based on increased water content in relation to nonvolatile residue per unit weight. Nonvolatile residue in spinal cord tissue following impact trauma was determined to ascertain the magnitude and persistence of edema. High and low thoracic laminectomies were carried out on each of 17 rhesus monkeys. The lower exposed cord was traumatized with a calibrated blow of 300 gm cm. All upper exposed cords and the lower exposed cord in one monkey served as nontraumatized controls. At time intervals of 5 minutes to 20 days after trauma, cord segments were removed and assayed for water content. Increased tissue water was evident within 5 minutes and persisted for 15 days. By the 20th day it had essentially subsided. Increased tissue water content in the traumatized segment reached a maximum of 7.4% over control values at 5 days and then gradually diminished. These findings support the concept that edema following spinal trauma is unrelated to secondary effects of ischemia after 18 hours. The protracted course of increased water content (15 to 20 days) was unexpected and may indicate that edema-reducing measures should be continued for 2 to 3 weeks following spinal cord trauma with severe neurological dysfunction.
David Yashon, George E. Locke and William E. Hunt
✓ Thirty-seven dogs were studied to establish the level of mean arterial pressure (MAP) causing cerebral tissue lactate (CTL) accumulation as a result of anaerobic metabolism and to assess the extent of preservation of aerobic metabolism afforded by autoregulation during oligemia. Specimens were removed prior to oligemia and at 5, 30, and 60 min following hypotension created by blood withdrawal. In four control animals, CTL averaged 4.83 (range 3.26 to 7.07) mMol/kg. At 60 min after induction of oligemic hypotension, 13 animals with a MAP of 30 and 40 mm Hg showed concentrations of CTL between 16.56 and 20.89. At a MAP of 50 mm Hg six animals showed a CTL concentration between 4.39 and 15.88; at a MAP of 60 mm Hg eight animals showed a CTL between 3.76 and 14.93; and at a MAP of 70 mm Hg six animals had a CTL between 2.43 and 4.27. At 5 min, at all mean arterial pressures the cerebral tissue lactate varied between 2.07 and 5.50. By 30 min the elevations were similar to those at 60 min. CTL elevation was independent of pre-oligemic MAP. In the canine brain there is a uniform incremental elevation of CTL between a MAP of 30 to 50 mm Hg directly related to the time of hypotension; there is variable intolerance to MAP in the range of 50 to 70 when related to a time longer than 5 min.
Robert A. Feldman, David Yashon, George E. Locke and William E. Hunt
✓ Eleven anesthetized dogs underwent bilateral craniectomies. Four control dogs had serial resections of cerebral tissue in the normotensive state. After one control sample was removed from the remaining seven dogs, they were bled to a mean arterial pressure of 30 to 35 mm Hg and had cerebral tissue samples resected at 0, 30, and 60 min after the onset of hypotension. The tissue samples from the four normotensive dogs averaged 4.83 mM lactate/kg tissue with a range of 4.67 to 7.22 mM/kg. At 0 time post-shock the samples averaged 7.18 mM/kg, at 30 min post-shock 14.31 mM/kg, and at 60 min 18.76 mM/kg. It can be concluded that hemorrhagic shock causes a progressive elevation in cerebral tissue lactate, which correlates with the duration of shock. At low mean arterial pressures the brain is susceptible to the effects of poor tissue perfusion, which results in both inadequate oxygenation and lactate washout in spite of well-established mechanisms for preferential shunting of blood to the brain.