Experimental Brain Damage in Dogs Due To Systemic, Induced Hypotension and Head-Up Tilt for Short Periods

Abstract

In the evaluation of various procedures designed to protect the brain against hypoxic damage, an objective and, if possible, quantitative assessment of the brain damage is necessary. Further investigations of these problems are indicated, among other reasons, because of recent developments in cardiovascular and neurologic surgery which may be complicated by temporary or permanent brain damage. Since the dog has been the principal experimental animal in these fields, this animal was chosen for the present study. It is self-evident that certain types of human brain damage cannot be investigated in the dog, for instance, insults to higher centers. Changes of conditioned reflexes in the experimental animal following the procedure may provide evidence of some insult to the cerebral cortex, but this procedure was considered to be impractical in our laboratory. Certainly short-term survival with persistence of the vital functions, including food and water intake, does not indicate an absence of brain damage. The value of the electroencephalogram under the artificial conditions of extracorporeal circulation and/or hypothermia also has been questioned.2 2 On the other hand, histologic examination of the brain may be useful in the assessment of brain damage, provided the animals can be kept alive until the pathologic changes develop, and provided specific histologic changes are found. Several authors have regarded the presence of pyknosis, metachromasia, vacuolization or a decrease in the number of ganglion cells, as evidence of brain damage. 3-5 It would appear that neither criteria for these changes nor significance is easily defined, so they remain too uncertain to be useful as an assessment of brain damage.The experiments reported here were undertaken as an attempt to produce brain damage associated with obvious clinical signs in dogs surviving long enough to allow the development of histologic lesions. The clinical signs and the histologic findings could then be correlated. In the event that the method was standardized and the results were reasonably uniform, the method could be used in the assessment of various types of treatment designed to protect the brain during periods of hypoxia, such as hypothermia or hyperventilation.These studies were carried out over a prolonged period of time and the many unsuccessful experiments will not be presented. The difference between a period at UNIVERSITE DE MONTREAL on June 12, 2015 ang.sagepub.com Downloaded from

Cerebral blood flow distribution and hypoxic–ischemic brain damage in newborn rats

“…21 To date, many investigators have recognized systemic hypotension as one of the most important factors in hypoxic-ischemic stress which cause perinatal brain damage. 22 Animal studies using sheep, 23 monkeys, 24 piglets, 25 and dogs 26 showed a strong association of histological change in the brain following systemic hypotension. Meanwhile, there have been many stud- Figure 1 The three grades of brain damage by MAP-2 disappearance in the surface areas of the cerebral cortex, hippocampus and thalamus.…”

Neurologic and cardiovascular effects of hypotension in the monkey.

“…79 Most of these studies had a high mortality during the early hours following hypotension whether or not brain lesions were produced. 2 -*" 9 The present study had 3 major goals: 1) to produce focal or diffuse brain injury in monkeys exposed to hypotension in the absence of significant hypoxemia, hypercarbia, or acidosis, 2) to attain survival for intermediate or prolonged periods, and 3) to correlate various parameters of the hypotensive insult with outcome with respect to the brain and the cardiovascular system.…”