EXPERIMENTAL AND CLINICAL OBSERVATIONS ON THE USE OF HYPOTHERMIA TO PREVENT ISCHEMIC DAMAGE TO THE CENTRAL NERVOUS SYSTEM* Robert G. Pontius, M.D., and Michael 2, De Bakey, M.D, ** The tissues of the central nervous system are particularly vulnerable to ischemic damage from even brief periods of circulatory arrest. This constitutes a serious hazard in the performance of certain cardiovascular procedures such as resection of aortic aneurysm, in which it may be * = 2 4 thy ow necessary to interrupt aortic circulation for periods up te one hour , Since it has been well established that hypothermia reducez total body metabotgsr:. and oxygen requirements of tissues, itis reasonable to assume that the central nervous system is similarly affected and that this might provide a useful measure in minimizing tne ischemic dangers aasociated with these : 2,3 . be . ; operative procedures - Accordingly, studies have been directed toward determining the protective value of hypothermia against such ischemic damage to the central nervous system during periods of temporary aortic occlueion. &xperiments along these lines have been done by a number ot investi- . . od, 7,712 : | ; gators ag well as by us . Thus, in a control group of 50 dogs occlusion of the aorta just distal to the left subclavian artery for a period of one hour was associated with an immediate mortality of 32 per cent anda *supported in part by grants from the Houston Heart Association and the Cora and Webb Mading Fund for surgical Kesearch, **F rom the Department of Surgery, Baylor University College of Medicine, and the Surgical Services of the Jefferson Davis, Veterans Administration, and Methodist Hospttals, clouston, Pexas, 2 paraplegia rate in the surviving animals of 65 per cent. The sare pro- cedure in a comparable group of 47 hypothermic dogs (body temperature was reduced to between 75 and 80° F.) was associated with an immediate mortality of 25 per cent and with a paraplegia rate of zero in the surviving animais, (#ig. i) On the basis of these experiments as weli as similar observations reported by other workers, the conclusion has been drawn that hypothermia has a céiinite protective influence against ischemic uam- age to the spinal cord ioliowing high aortic occlusion. While the exact mechanism of proteciicu aiforded by hypothermia is not entirely clear, gross and histologic studies of the damaged spinal cord provide some ciues to the problem, Gruss examination oi the spinal cords of the paraplegic animals showed bilateral symmetrical malacia of the grey matter vu: the lumbar, sacral, and coccygezl segments. serial end L. and 12 é continue distally. On microscopic examination pronounced changes were sections showed the lesions to begin consistently between T present in the grey watter, but the white matter was spared, As the specimens were ootained ig days aiter injury evidence of repair by mic- roglial phagocytes or gitter cells with foamy cytoplasm and proliieration of new capillaries through the destroyed area waa present (Figs. 2, 3, 4). These cnanges are quite similiar to those ovagerved in the brain tollowing anoxemic damage to this organ. They do not suggest thrombosis or in- iarction as the vessel lumens were patent. ‘The aninials protected by 3 hypothermia failed to show these changes. axperiments along similar lines directed toward determining the protective effects of hypothermia againat ivchewic damage to the brain proved rruch more difficult, owing to the fact that in the dog extensive re §, = ae collateral circulation exists in the head and nack. nus, occlusiog of both carotid anc vertebral arteries bilaterally produced no apparent dis~ fturbances. A preparation was jinally developed, however, that resalted in a significant jacidence of brain damage. This coneisted in placing 4 silver clip on the basgilur artery through the foramen magnum, avplying occluding clamps to both carotid and vertebral arteries bilaterally and placing a tourni«- quet around the neck to produce cowpression of the wuseular collateral vessels, in the control group of 9 dugs in which this was done for a period of 30 minates, 6 (67 per cent) showed serious brain damavye a3 manifested by convulesions, coma, and death. Significantly, none of the 9 hypothermic dogs treated in like fashion developed any neurologic disturbances. These observations, therefore, suggest that hypother:nia is equally effective in preventing ischemic darmage to the brain as to the spinal cord following temporary arrest of the circulation to these highly vuln«-ible tissues. These experimental observations on the protective value of hypo- thernila in preventing ischemic damage te the central nervous system are supported by our clinical experience with its use in the excisional there py of aortic aneurysm. Im such cases in which the lesion is Located in the 4 thoracic aorta above the level of the seventh dorsal vertebra the procedure of resection and graft replacement is asaocilated with the jeopardous effecta oi ischemic injury to the tissues of the central nervous system during the period of ter:porary interruption of aortic circulation, Thus, among the five cagee of aneuryam of the aorta in our verias, located at this high level and treated by resection without hypothermia, spinal cord damage occurred in four patients (Fig. 5). Fortunately these changes were mild and trangient in three, but probably contributed to the death of the fourth vatient. On the other hand, none of the 14 casea with comparable lesions similarly treated but in which hypothermia was employed showed any mani- festations of spinal cord dar.age. Both in this as well as the former group the period af aortic occlusion averaged about one hour. In the hypothermic group body temperature was reduced to about 85° F, (Figs. 6, 7). SUMMARY i. in a control group of 30 dogs in which the thovacic aurta wee occluded just distal to the leic audclavian artery for a poriad of one hour the immediate mortasity Was 34 per cent and the incidence go ischerwic damage to the spinal as sf cord ag maniiested by paraplegia in the surviving animale 35 per cent, sia coupurably treated group of 47 degs in which bypothermia was used there wag an limmediate mortality of 25 per cont, bat none devoloped para-~ plegia. Be In & comtcol series of 9 dogs im which the circulation to the brain ” Was arrested for a period of 50 minutes evidente of ischevic damage te the FR Drain occurred in 6 (67 psx cent), but none of the ¢ reated group in which hypotherrcia wag ercployed shows such manifestations. 3. Four ot five patients with enearysrn’ vt the therecice uorte in whon the aorta was occluded for 2 period of about one hour developed avidence of epinai cord damage followiag cesection, Wore of 14 similar cxaea in which hypothermia waa employsd developea amy evidence af spinal cord damage. 4. Un the basis of thave axperin.ental and clinical observations it would appear that hypothertwia increases the tolerance of the tiasues o° the central Rerveus system to periods a. temporary ischemia, Figure 1: Figure 2: Pigure 3: oy Figure 4 Figure 5: Yigure 6 and 7: LEGEND? Graph showing rioitality for occlusion of descendin aorta for one hour. Microscopic section of normal spinal cord, Io level, of dog, Microscopic sectica of spinal cord following aortic occlusion without hypothermia. Microscopic section of spinal cord following aurtic occlusion with hynothermi:. Chart of clinical cases without hypotherrci- Chart of clinical cases with hypothermia. 3. BIBLIOGRAPHY Baattie, &. J., Jr., Adovasio, b., “eshishian, J. M., and Blades B.: Refrigeration in Experimental surgery o: the Aorta, surg., Gynec, & Obst. 96: 7il-713 (June) 1953. Bigelow, W. G., Callaghan, J. G., and Hopps, J. A.: General Hypothermia for Experimental Intracardiac ourgery, Ann. Surg. 132: 531, 1950. Bigelow, W. G., Lindsay, w. K., Harrison, vA. 0., Gordon, HK. A., and Greenwood, W. F.: Oxygen Transport and Utilization in Dogs at Low Body Temperatures, Am. J. Paysiol. 100: 125, i954, Garrel, A.: Report on the Experimental surgery of the Thoracic Aorta and Heart, Ann, Surg, 52: 83, 1910. De Bakey, M. &., and Cooley, 0. 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