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Measurement of Maximal Permissible Cerebral Ischemia and a Study of Its Pharmacologic Prolongation*

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Measurement of Maximal Permissible Cerebral Ischemia and a Study of Its Pharmacologic Prolongation* Measurement of Maximal Permissible Cerebral Ischemia and a Study of Its Pharmacologic Prolongation* R. LEWIS WRIGHT, M.D., AND ADELBERTAMES, III., M.D. Neurosurgical Service, Massachusetts General Hospital and Department of Surgery, Harvard Medical School, Boston, Massachusetts H YPOTHERMIA. has been used effec- brain is difficult to achieve in commonly tively to protect tissues from irre- available laboratory animals because of the versible damage caused by circula- large vertebral-anterior spinal artery axis tory arrest, whether the latter is of acciden- and the abundant muscular collateral vessels tal occurrence or induced in the course of an which communicate with the carotid system. operative procedure. Relatively little atten- Previously described methods have had the tion, however, has been given to the possibil- undesirable features of damage to the spinal ity of providing such protection by chemical cord, impairment of circulation to other or- means. Chemical protection against ischemia gans, or problems of recovery from thoracot- might be expected to be more easily and omy. quickly induced than hypothermia and to be In the experiments described below, a rela- free of some of the undesirable cardiovascu- tively simple operative technique has been lar side effects of the hypothermic state. developed and tested for producing tempo- Three classes of potential protective agents rary cerebral ischemia in cats. This tech- can be envisaged: (1) agents designed to nique has been used to determine possible maintain the patency of the vasculature effects of several substances on the period of during the ischemia in order to insure com- ischemia that can be reversibly sustained. plete perfusion of the tissue following its The substances tested included two barbitu- termination; (~) inhibitors of cellular activity rates, ethyl alcohol and solutes added to the that would lower the metabolic demandc of blood to increase its osmolarity. the tissue during the ischemia; (3) physiolog- ical compounds, added in excess of their nor- Methods mal concentrations, to forestall the first ir- Technique for Producing Temporary Cerebral reversible changes in the cells. Beneficial Ischemia. The procedure developed involved oc- clusion, by means of an initial operative tech- effects from pretreating ischemic kidneys nique, of all arterial inflow to the brain except that with heparin 24 and studies demonstrating ex- provided by the common carotid arteries. The tension of the period of permissible cardiac animal then was allowed to recover. At the time of standstill with compounds producing cardio- the experiment it was anesthetized again, this plegia 21,23,2~,37 have suggested the feasibility time very lightly, and both common carotid ar- teries were exposed and occluded temporarily with of the first two approaches. Surprisingly little rubber-shod clamps. systematic study has been devoted to the In preliminary studies to identify the collateral third possibility. circulation to the cat's brain, Micropaque* barium Controlled study of cerebral ischemia and sulfate was injected into the left auricle with the of factors modifying its effects has been ham- basilar and both common carotid arteries oc- cluded. The chief collaterals were found to be: (a) pered by the unavailability of suitable ex- the superior thyroid arteries which anastomose perimental preparations. Production of tem- with branches of the inferior thyroids; and (b) porary but total arrest of circulation to the branches of a large muscular artery which arise laterally from the common carotid near the level Received for publication October 7, 1968. of the superior thyroid artery and communicate * This investigationwas supported by research grants with divisions of the thyrocervical trunk and ex- from the National Institute of MentaJ Health (MH-K3- 3769) and from the National Institute of Neurological * Made by Damancy and Co., Ltd., Ware, Herts., Diseases and Blindness (NB-0451~). England. The size of the particle is between 0.5 and 3/~. 567 568 R. Lewis Wright and Adelbert Ames, III expose the ventral rim of the foramen magnum. The dura mater was separated gently from the foramen magnum with a dental spatula, and a craniectomy was performed extending rostrally approximately 8 by 1s mm. between the tym- panic bullae. The dura mater was opened in a cruciate manner with careful avoidance of the cir- cular sinus just inferior to the foramen magnum. A segment of basilar artery free of branches was selected caudal to the posterior inferior cerebellar arteries (which in the cat arise from the basilar in- stead of the vertebral arteries). This was mobil- ized gently with fine forceps and occluded with a metal clip (Fig. 3). A small piece of gelatin foam was placed over the dural opening and the wounds were closed with interrupted sutures of 4-0 black silk. In this preparation no bone is removed from the the convexity of the skull, and since the tentorium of cats is bony it seems unlikely that the small amount of bone removed over the ventral aspect of the medulla provided any significant decom- pression for the brain. It was not possible, how- ever, to obtain a watertight closure of the small in- cision in the meninges at the site of craniectomy, so some drainage of cerebrospinal fluid into the soft tissues of the neck presumably occurred. Each animal received penicillin, 300,000 units, by intramuscular injection at this initial proce- dure. The mortality for this first-stage operation FIG. 1. Angiogram of head and neck of cat made by in- was approximately 10 per cent. Anisocoria was jecting Micropaque into the left auricle after the frequent in the surviving animals, which other- basilar artery and both common carotid arteries had wise seemed intact neurologically. been occluded. Note that the contrast agent fills the distal carotid circulation by entering chiefly through the large muscular branch. ternal carotid arteries (Fig. 1). The ramifications of these muscular vessels are largely in the pos- terior cervical region. The relative paucity of these arterial collaterals in the cat ~3'14 led to its selection, rather than the dog, for these studies. At a first-stage procedure, using sterile precau- tions, the basilar artery, the superior thyroids and the ascending and descending branches of the large muscular arteries were occluded (Fig. ~). The technique for occlusion of the basilar artery was similar to that used in dogs by White and Donald24 A longtitudinal incision, approximately 4 cm. in length, was made just to the right of the thyroid cartilage and trachea. The fascial plane between trachea and carotid sheath was de- FIG. ~. Sites of arterial occlusion in the cat whereby veloped by blunt dissection; and, after placing a the brain is made dependent for its blood supply on #15 gauge needle in the distal portion of the both common carotid arteries. CCA= common carotid artery. MB = mscular branches. STA = superior thyroid trachea, a self-retaining retractor was inserted to artery. ICA= internal carotid artery. PA= pharyngeal displace the trachea and esophagus to the left. artery. AB = anastomotic branch. IMA = internal maxil- This metal cannula was used to prevent suffoca- lary artery. ACA=anterior cerebral artery. MCA tion from the necessarily forceful retraction of =middle cerebral artery. PCA=posterior cerebral the trachea. The longus capitis muscle was de- artery. PICA=posterior inferior cerebellar artery. tached from its origin at the base of the skull to VA=vertebral artery. ASA=anterior spinal artery. .
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