Arthur G. Waltz

Transorbital Approach for Occluding the Middle Cerebral Artery Without Craniectomy

An experimental model of cerebral ischemia and infarction can be produced by occluding a middle cerebral artery in animals. Most surgical approaches to the artery require removal of some portion of the cranium, which may modify or prevent the changes of intracranial pressure and the development of pressure gradients that are caused by ischemic cerebral edema or brain swelling. A transorbital approach for the exposure of a middle cerebral artery requires only enlargement of the optic foramen, which can be sealed immediately after occlusion of the artery. The lack of disturbance and manipulation of the brain and the maintenance of the integrity of the cranium result in a superior experimental model.

Patterns of Changes of Blood Flow and Relationships to Infarction in Experimental Cerebral Ischemia

Regional cerebral blood flow (CBF) was measured in both middle ectosylvian gyri of ten cats by recording the clearance of molecular hydrogen (H2) with implanted polarized electrodes 125 n in diameter, before and up to seven days after occlusion of the left middle cerebral artery (MCA) with a device implanted in the intact cranium. Five patterns of changes of CBF were recorded with the leftsided electrodes. In eight cats MCA occlusion caused immediate decreases of CBF; in the other two cats CBF values were lowest two days after occlusion, presumably because of ischemic edema. Both persistent severe ischemia and early spontaneous postischemic hyperemia were associated with severe neurological deficits, marked swelling of the left cerebral hemispheres, and large infarcts. Late postischemic hyperemia was associated with less severe deficits, less swelling, and smaller infarcts, but the least severe deficits and smallest infarcts were noted in association with persistent moderate ischemia. No consistent patterns were recorded with the rightsided electrodes in this study. Hyperemia which develops spontaneously or is induced shortly after the onset of cerebral ischemia potentially may be harmful because of secondary increases of cerebral edema.

Ineffectiveness of Dexamethasone for Treatment of Experimental Cerebral Infarction

Ischemic cerebral edema occurring with cerebral infarction may cause increases of intracranial pressure and neurological deficits or death. Certain other types of cerebral edema are influenced by adrenal glucocorticoids; there is conflicting evidence about effects on ischemic edema, largely due to differences in experimental models and dosages. Therefore, dexamethasone in large doses was studied in 15 cats with experimental cerebral ischemia and infarction produced by transorbital occlusion of one middle cerebral artery (MCA). Five cats received dexamethasone, 4 mg per kilogram intramuscularly, twice daily for two weeks before and two weeks after MCA occlusion; five received dexamethasone for two weeks after occlusion; and five received no dexamethasone. There were no apparent differences among the three groups in the neurological deficits resulting from MCA occlusion, and no statistically significant differences in the sizes of cerebral infarcts. Dexamethasone is ineffective for the treatment of experimental cerebral ischemia produced by MCA occlusion.

Regional Cerebral Blood Flow During Stimulation of Seventh Cranial Nerve

The right seventh cranial nerve (n. VII) was exposed intracranially via a suboccipital approach in each of eight cats. Measurements of cerebral blood flow (CBF) were made from superficial cortex, sulcal cortex, basal cortex, the basal ganglia, and the centrum semiovale of each cerebral hemisphere of each cat by autoradiography using 14Cantipyrine. In six cats, measurements of CBF were made during electric stimulation of n. VII; in two of these, the nerve was sectioned before stimulation. In the remaining two cats, measurements were made after exposure but without stimulation of n. VII; in these cats, there were no side-to-side differences of CBF. In each of the four cats with n. VII intact, CBF values were lower on the stimulated side. In each of the two cats with n. VII sectioned, CBF values were higher on the stimulated side. Thus, stimulation of n. VII causes regional increases of CBF only when centripetal effects of stimulation are prevented. Cerebral vasodilatation has been observed by others during stimulation of a sectioned or an intact n. VII. When an intact nerve is stimulated, vasodilatation apparently is unable to compensate for decreases of CBF mediated centripetally through brain stem structures and extracranial or basal cerebral vessels; moreover, such vasodilatation may be due in part to regulatory responses of vessels to decreases of perfusion pressure.

Intracranial Pressure Gradients Caused by Experimental Cerebral Ischemia and Edema

To assess the development and resolution of ischemic cerebral edema and brain swelling, measurements of intracranial pressure (ICP) were made in cats after the transorbital occlusion of one middle cerebral artery. Measurement of ICP gradients was difficult: epidural, subdural and intraventricular catheters caused brain damage or failed to function; the accuracy of a miniature strain gauge could not be determined after implantation; and absolute values for intradural pressures could not be obtained with epidural devices. However, variable increases of ICP were recorded on the sides of occlusion from three cats, and were directly related to the severity of the neurological deficits. On the sides opposite occlusion ICP increased slightly or not at all. Several days after occlusion ICP decreased and gradients could not be demonstrated with certainty. Thus, measurements of ICP gradients can be used to assess ischemic cerebral edema and brain swelling, but the usefulness of such measurements is limited at present by methodological problems.

Changes of epidural pressures after experimental occlusion of one middle cerebral artery in cats

Epidural pressures (EDP) were measured in 29 cats. Twenty cats had the left middle cerebral artery (MCA) occluded; pentobarbital was used for anesthesia for 10 of these, and halothane was used for the other 10. Two cats had sham operations: the MCA was manipulated but not occluded. Seven cats were used for testing the reliability of the EDP devices. EDP was measured successfully and was directly related to the swelling of the brain and to the size of the cerebral infarct resulting from MCA occlusion. Side-to-side pressure gradients were demonstrated in 7 cats with marked increases of EDP after occlusion; in these cats, EDP may have reflected the pressure of compressed cerebral tissue rather than the pressure of cerebrospinal fluid. Cats anesthetized with pentobarbital had greater increases of EDP and died before the end of the period of observation more frequently than cats anesthetized with halothane, probably because of respiratory depression and slower recovery with pentobarbital. Measurements of EDP may be useful for studies of the treatment of cerebral edema in experimental models of acute cerebral ischemia.

Effects of Inhalation of Oxygen on Blood Flow and Microvasculature of Ischemic and Nonischemic Cerebral Cortex

The right middle cerebral artery was occluded in cats, and PaO2 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 PaO2 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 PaO2. In seven animals, increasing the PaO2 had no apparent effect on CBF or arteriolar caliber of the ischemic cerebral hemispheres. In four animals, at PaO2 greater than 400 torr, reactivity to increases of PaO2 was preserved in nonischemic cortex but impaired in ischemic cortex. Reddening of venous blood of the microvasculature of ischemic cerebral cortex occurred when PaO2 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.

Responses of Surface Arteries and Blood Flow of Ischemic and Nonischemic Cerebral Cortex to Aminophylline, Ergotamine Tartrate, and Acetazolamide

In cats in which one middle cerebral artery was occluded, cortical blood flow (CBF) was measured and the superficial cortical microvasculature was observed bilaterally before and after the intravenous injection of a vasoactive drug. Aminophylline produced decreased CBF in the nonischemic cerebral hemispheres of five of seven animals and arterial constriction in three. Ergotamine tartrate produced arterial constriction in the nonischemic hemispheres of four animals and decreased CBF in three. Neither drug consistently produced increased CBF in ischemic cerebral tissue. Acetazolamide caused vasodilatation in the nonischemic hemispheres of seven animals and increased CBF in five. Increased CBF was not due entirely to changes of PaCO2. CBF also increased in ischemic hemispheres of four of the seven animals given acetazolamide.

Effects of Acetazolamide on Cerebral Ischemia and Infarction After Experimental Occlusion of Middle Cerebral Artery

Acetazolamide was given to five of ten cats for 48 to 54 hours after extradural occlusion of a middle cerebral artery (MCA). At seven to eight days later, measurements of regional cerebral blood flow (CBF) and estimates of the sizes of the ischemic and infarcted areas of the brains were made. Neurological deficits were more severe and the ischemic and infarcted regions were larger in the cats given acetazolamide. Cerebral edema (brain swelling) was present and reactive hyperemia was common in the treated cats, even one week after MCA occlusion. The hypercapnia and decreases of pH of nonischemic brain tissue that are caused by acetazolamide are harmful for ischemic brain tissue, presumably because of vasodilatation in nonischemic brain tissue with resultant increases of intracranial pressure and decreases of CBF of ischemic regions.

Effects of Dexamethasone on Distributions of Water and Pertechnetate in Brains of Cats After Middle Cerebral Artery Occlusion

Large parenteral doses of dexamethasone were given to five of ten cats after transorbital occlusion of one middle cerebral artery and to two of four cats after sham operations. Two days later the water content and brain/blood ratios of pertechnetate were measured in samples of cerebral tissue that were categorized as nonischemic, ischemic, or infarcted. Values for infarcted tissue were greater than those for ischemic tissue in untreated cats, but not in cats that received dexamethasone. The drug had no apparent effect in ischemic tissue that was not necrotic. These results help explain inconsistencies in previous studies and help define the potential usefulness of dexamethasone for treatment of cerebrovascular disease.