Citations

The right middle cerebral artery was occluded in cats, and Pa o o2 was increased by increasing the amount of oxygen inhaled by the animals at atmospheric pressure. Cortical blood flow (CBF) was measured with Krypton-85, and observations and photographs of the superficial cortical microvasculature were made bilaterally. In two of five animals, increasing the Pa o o2 caused constriction of surface arterioles of the nonischemic hemispheres, with an associated decrease of CBF; in the three other animals, there were no circulatory responses to the increased Pa o o2 . In seven animals, increasing the Pa o o2 had no apparent effect on CBF or arteriolar caliber of the ischemic cerebral hemispheres. In four animals, at Pa o o2 greater than 400 torr, reactivity to increases of Pa CO CO2 was preserved in nonischemic cortex but impaired in ischemic cortex. Reddening of venous blood of the microvasculature of ischemic cerebral cortex occurred when Pa o o2 was increased, indicating that more oxygen was made available to the ischemic cerebral tissue. However, no beneficial effects could be demonstrated on the changes in the microvasculature produced by ischemia.

We have shown the difficulty in producing a reliable model of vasospasm secondary to recurrent subarachnoid hemorrhage from carotid puncture in a squirrel monkey. In this animal, mild systemic hypertension had little or no effect on the clinical status after hemorrhage. The consistent production of a saccular aneurysm on the intracranial arteries was an unexpected result of the arterial puncture and the interruption of the internal elastic membrane. At this time, there is insufficient knowledge regarding the entire subject of vasospasm for correlation with human vessel reaction to injury.

The case histories are given of 12 patients who had transient cerebral attacks in association with subacute bacterial endocarditis. The attacks are similar to those that accompany atherosclerotic occlusive cerebrovascular disease. All patients had manifestations of general illness, particularly fever, malaise, and elevated sedimentation rate. Subsequently, cerebral infarcts occurred in three patients and cerebral hemorrhages in four patients. A definite relationship between anticoagulant therapy and hemorrhage could not be established.

An infrared microscope was used for the remote detection of the surface temperature of the cerebral cortex of experimental cats. With this instrument a qualitative assessment of the circulation of the cerebral cortex can be made without interference with the integrity of the brain or vascular tissues or the reactivity of blood vessels. Although the instrument is sensitive enough to detect minor changes of cortical blood flow, its use appears limited to the detection of rapid or transient changes of cerebral circulation and is not suitable for long-term measurements of surface temperature of the brain.

In order to compare the difference in the vulnerability of macromolecular syntheses, protein, RNA, and lipid syntheses were studied with ischemic brain tissue three hours following unilateral carotid ligation in gerbils. Precursor incorporation was measured in various subcellular fractions following in vitro incorporation with brain slices. There was marked inhibition of protein synthesis, but RNA and phospholipid syntheses showed little or no change. On the basis of available information on rapid deterioration of polysomal system for polypeptide synthesis, a hypothesis was proposed that messenger ribonucleic acid (RNA) at the polysomal level is promptly affected in this pathophysiologic condition.

Regional cerebral blood flow (rCBF) measurements with krypton-85 (100 separate determinations) were compared in squirrel monkeys anesthetized with sodium pentobarbital (a cerebral vasoconstrictor) and halothane (a cerebral vasodilator) before, during, and after middle cerebral artery (MCA) occlusion. Prior to MCA occlusion, a normal physiological response to alterations in arterial carbon dioxide tensions (Paco 2 ) was demonstrated in both groups of monkeys; the cerebral vascular resistance was significantly lower in those anesthetized with halothane. During ischemia, there was loss of autoregulation and a failure to respond to alterations in Paco 2 , in both groups. Flow in the ischemic region remained uniform in the barbiturate group but decreased progressively in the halothane group, suggesting a "paradoxical response" to the dilating agent. Reactive hyperemia (luxury perfusion) was demonstrated in both groups after restoration of flow. The use of a beta-emitting isotope ensured that measurements in regions of ischemia accurately reflected rCBF and were free of the artifacts ("look through" and Compton scatter) related to use of a gamma-emitting indicator.

Regional cerebral ischemia was produced by common carotid artery occlusion in gerbils and by middle cerebral artery occlusion in dogs, cats, and squirrel monkeys. Anesthesia was induced with either pentobarbital or halothane and maintained for two to there hours after vessel occlusion. In acute studies, the effect of regional cerebral ischemia on cerebral concentrations of ATP, phosphocreatine, lactate, and pyruvate was determined at the end of this period in gerbils, cats, and squirrel monkeys. In chronic studies, the degree of neurological deficit and size of cerebral infarction were determined 48 hours after a two-hour to three-hour period of vessel occlusion in cats and squirrel monkeys and permanent occlusion in dogs. In gerbils, dogs, and cats, there were no differences in the metabolic, functional, or pathological effects of anesthesia with pentobarbital or halothane. However, in the squirrel monkey, in acute studies the metabolic alterations were significantly less with pentobarbital, and in chronic studies the frequency and magnitude of functional deficits and cerebral infarction were significantly less. We conclude that pentobarbital does provide a degree of protection during regional cerebral ischemia but that such effects are only consistently demonstrable in primates. In nonprimates, we assume that variability in the collateral circulation renders demonstration of significant differences difficult or impossible.

The fluorescence of reduced nicotinamide adenine dinucleotide (NADH) from cerebral cortex was measured before, during, and after middle cerebral artery (MCA) occlusion and then at death of the animal. In normal cortex, NADH remained constant throughout a wide range of variations in blood pressure and Pa co co2 . In ischemic cortex, NADH levels were higher in hypovolemic hypotensive animals than in normotensive normovolemic animals. Neither hypercapnia nor hypocapnia was effective in decreasing NADH in regions of ischemia, but the latter was associated with a degree of hypotension that interfered with interpretation of data. NADH returned to normal with restoration of flow, supporting the reversibility of this degree of ischemia. The high levels of NADH at death, compared to those during ischemia, are consistent with incomplete ischemia in this model of cerebral infarction.

Reduced nicotinamide adenine dinucleotide (NADH) fluorescence was recorded from an avascular area on the squirrel monkey cortex prior to, during, and after focal incomplete ischemia. By using the instrumentation described, stable recordings were obtained free from hemoglobin artifact and with only minimal photodecomposition. Pentobarbital was compared to urethane and halothane as the anesthetic agent and was found acceptable for these types of studies in the dosages used. NADH levels were constant prior to ischemia, increased during ischemia, returned to pre-ischemic levels after restoration of blood flow, and then increased greatly at death produced by anoxia. The use of the infrared microscope for semiquantitative measurements of cortical blood flow throughout the duration of these acute studies was investigated and found to be reliable.

Regional cerebral blood flow (CBF) was measured (intra-arterial injections of 133 Xe) and electroencephalograms (EEG) were recorded periodically before, for two hours during, and for one and one-fourth hours after middle cerebral artery (MCA) occlusion in 20 squirrel monkeys ( Saimiri sciureus ). A CBF-Pa co co2 response curve for these animals under barbiturate anesthesia was created from CBF values prior to MCA occlusion and during the time a steady state was being achieved. The animals were subdivided into four groups (five monkeys in each) on the basis of Pa co co2 values: 20, 36, 40, and 60 mm Hg. CBF values from this study were compared to previous results obtained with 35 Kr. The phenomenon of "look through" and the importance of recognizing this artifact and its significance in analyzing CBF results in areas of focal ischemia are discussed. The present results were correlated with cerebral ATP and lactate concentrations in ischemic regions determined in previous studies using this preparation at these Pa co co2 values and at comparable time intervals before, during, and after MCA occlusion. The EEG appears to reflect the state of ischemic brain accurately. However, CBF measured by the 133 Xe method can be misleading in regard to the true degree of ischemia resulting from occlusion of an intracranial vessel and cannot be relied on to demonstrate accurately "steal" or "reverse steal" due to changes in Pa co co2 .