A new model of transient, bilateral hemispheric ischemia in the unanesthetized rat is described. During ether anesthesia the rat's vertebral arteries were electrocauterized through the alar foramina of the first cervical vertebra and reversible clasps placed loosely around the common carotid arteries. Twenty-four hr later, the awake rats were restrained and the carotid clasps tightened to produce 4-vessel occlusion. The carotid clasps were removed after 10, 20 or 30 min of 4-vessel occlusion and the animals killed by perfusion fixation 72 hr later. Rats which convulsed during the ischemic or post-ischemic period were excluded from further study. All rats subjected to 20 or 30 min of 4-vessel occlusion demonstrated ischemic neuronal damage. The H1 and paramedian hippocampus, striatum and layers 3, 5 and 6 of the posterior neocortex were the regions most frequently damaged. The advantages of this model are the ease of preparation of large numbers of animals, a high rate of predictable ischemic neuronal damage, a low incidence of seizures and the absence of anesthesia.

A new model of bilateral hemispheric ischemia in the unanesthetized rat.

We have tested whether small intraischemic variations in brain temperature influence the outcome of transient ischemia. To measure brain temperature, a thermocouple probe was placed stereotaxically into the left dorsolateral striatum of rats prior to 20 min of four-vessel occlusion. Rectal temperature was maintained at 36-37 degrees C by a heating lamp, and striatal temperature prior to ischemia was 36 degrees C in all animals. Six animal subgroups were investigated, including rats whose intraischemic striatal brain temperature was not regulated, or was maintained at 33, 34, 36, or 39 degrees C. Postischemic brain temperature was regulated at 36 degrees C, except for one group in which brain temperature was lowered from 36 degrees C to 33 degrees C during the first hour of recirculation. Energy metabolites were measured at the end of the ischemic insult, and histopathological evaluation was carried out at 3 days after ischemia. Intraischemic variations in brain temperature had no significant influence on energy metabolite levels measured at the conclusion of ischemia: Severe depletion of brain ATP, phosphocreatine, glucose, and glycogen and elevation of lactate were observed to a similar degree in all experimental groups. The histopathological consequences of ischemia, however, were markedly influenced by variations in intraischemic brain temperature. In the hippocampus, CA1 neurons were consistently damaged at 36 degrees C, but not at 34 degrees C. Within the dorsolateral striatum, ischemic cell change was present in 100% of the hemispheres at 36 degrees C, but in only 50% at 34 degrees C. Ischemic neurons within the central zone of striatum were not observed in any rats at 34 degrees C, but in all rats at 36 degrees C. In rats whose striatal temperature was not controlled, brain temperature fell from 36 to 30-31 degrees C during the ischemic insult. In this group, no ischemic cell change was seen within striatal areas and was only inconsistently documented within the CA1 hippocampal region. These results demonstrate that (a) rectal temperature unreliably reflects brain temperature during ischemia; (b) despite severe depletion of brain energy metabolites during ischemia at all temperatures, small increments of intraischemic brain temperature markedly accentuate histopathological changes following 3-day survival; and (c) brain temperature must be controlled above 33 degrees C in order to ensure a consistent histopathological outcome. Lowering of the brain temperature by only a few degrees during ischemia confers a marked protective effect.

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.1987.127

Small Differences in Intraischemic Brain Temperature Critically Determine the Extent of Ischemic Neuronal Injury

Complement and the damaging effects of cardiopulmonary bypass

Early reports of therapeutic hypothermia for severe traumatic brain injury can be traced back to the first half of the 20th century. It is only within the last two decades that clinical studies have demonstrated that therapeutic moderate hypothermia for brief durations can improve patient outcomes following brain injury. The historical background, recent clinical experience, and mechanisms of action of moderate hypothermia are reviewed.

https://www.nejm.org/doi/pdf/10.1056/NEJM199702203360803

Treatment of Traumatic Brain Injury with Moderate Hypothermia

✓ The mechanisms that give rise to ischemic brain damage have not been definitively determined, but considerable evidence exists that three major factors are involved: increases in the intercellular cytosolic calcium concentration (Ca++i), acidosis, and production of free radicals. A nonphysiological rise in Ca++i due to a disturbed pump/leak relationship for calcium is believed to cause cell damage by overactivation of lipases and proteases and possibly also of endonucleases, and by alterations of protein phosphorylation, which secondarily affects protein synthesis and genome expression. The severity of this disturbance depends on the density of ischemia. In complete or near-complete ischemia of the cardiac arrest type, pump activity has ceased and the calcium leak is enhanced by the massive release of excitatory amino acids. As a result, multiple calcium channels are opened. This is probably the scenario in the focus of an ischemic lesion due to middle cerebral artery occlusion. Such ischemic tissues ca...

Pathophysiology and treatment of focal cerebral ischemia. Part II: Mechanisms of damage and treatment.

SCh is unequivocally contraindicated in the management of patients who have sustainded thermal trauma or direct muscle trauma and those who have neurologic disorders involving motor deficits, including tetanus. The mechanism is clear in some, but not all, of these conditions, and is related to increased chemosensitivity of the muscle membrane due to the development of receptor sites in extrajunctional areas. Though SCh induces a small release of K+ in normal muscle, it produces a potentially lethal efflux in the presence of increased sensitivity. This K+-releasing action of SCh begins about 5 to 15 days after injury and persists for 2 to 3 months in patients who have sustained burns or trauma, and perhaps 3 to 6 months in patients with upper motor neuron lesions.

Pathophysiology of hyperkalemia induced by succinylcholine.

ATP and lactate in the canine brain were determined before and during cerebral anoxia induced by decapitation, both at 30 C during halothane anesthesia (0.8 per cent) and at 37 C during four anesthetic circumstances (nitrous oxide, 70 per cent; halothane, 0.8 per cent; halothane, <0.1 per cent; and

The effects of anesthesia and hypothermia on canine cerebral ATP and lactate during anoxia produced by decapitation.

The effects of thiopental on rates of cerebral ATP depletion and lactate accumulation in dogs anesthetized with N2O during two different circumstances of impaired oxygen delivery were examined. In ten dogs, five with and five without prior thiopental (13 mg/kg), acute hemorrhagic shock (mean arteria

Cerebral protection by thiopental during hypoxia.

Effect on Canine Brain and Whole-body Metabolism

NPLEASANT dreams or hallucinations U are reported by up to 30 percent of adult patients following the anesthetic state produced by ketamine hydrocholoride. 112 Such an effect is not common to other anesthetics when administered in effective concentrations. This study was designed to test the hypothesis that this unusual cerebral functional r&ponse to ketamine may be accompanied by an unusual effect on cerebral metabolism as well. Such a relationship between functional and metabolic effects has been established for sodium thi0pental.3

Richard A. Theye

Papers

Pathophysiology of hyperkalemia induced by succinylcholine.

The effects of anesthesia and hypothermia on canine cerebral ATP and lactate during anoxia produced by decapitation.

Cerebral protection by thiopental during hypoxia.

Effect on Canine Brain and Whole-body Metabolism

Effects of ketamine on canine cerebral blood flow and metabolism: modification by prior administration of thiopental.