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✓ Cerebral oxygen metabolism was studied in the dog at brain temperatures ranging from 37° to 8°C. As brain temperature decreased, the cerebral oxygen metabolism (CMRO2) decreased following the Arrhenius equation. The natural logarithm of the CMRO2 was a linear function of the reciprocal of the absolute (K) brain temperature. Oxygen metabolism, although much decreased, continued at very low brain temperatures. The CSF composition was unchanged after 1 hour at brain temperatures down to 10°C. Circulatory arrest for tolerable periods and longer caused changes only in the CSF potassium concentration. The interval between the onset of circulatory arrest and the beginning of the CSF K concentration increased with decreasing temperature and the rate of CSF K increase was increasingly slower at lower temperatures. At all temperatures the rate of CSF K changed gradually increased with time. The interval before the CSF K started to increase was dependent upon the amount of O2 available in the brain and the length of this interval was inversely proportional to the CMRO2. The amount of CSF K concentration was not clearly related to the tolerable periods of circulatory arrest, but at normal temperatures an obviously increased CSF K following a period of acute cerebral anoxia without CSF hemorrhage may indicate brain damage.

Experience with intracardiac surgery in infants indicates that for most anomalies the operative and late mortality after primary total correction is lower than the combined mortality after early palliation and delayed correction. In addition, there are secondary benefits of primary total correction in terms of reversal of retarded physical growth and social development and alleviation of parental anxiety. The relative merits of conventional cardiopulmonary bypass versus profound hypothermia, circulatory arrest, and limited cardiopulmonary bypass are as yet incompletely elucidated, particularly regarding the long-term effects of the second method on cerebral function. Indications for the use of each method will undoubtedly become clearer as reports of longer follow-up become available. At the University of Oregon Medical School, intracardiac operation using conventional cardiopulmonary bypass has been carried out in 108 infants under 2 years of age. Late hemodynamic studies and intellectual and social developmental testing indicate gratifying long-term results with this technique.

Acid-base and electrolyte changes are reported in 11 infants undergoing profound hypothermia for cardiac surgery by the technique of initial surface cooling followed by further bypass cooling and rewarming. Seven patients (group 1) underwent initial surface cooling to a mean oesophageal temperature of 26.6° C and four (group 2) to a mean oesophageal temperature of 32° C.

Summary Development of an improved method for instantaneous freezing (-196° C.) of sequential cerebral biopsies permits the accurate determination of ATP (adenosine triphosphate) disappearance during complete circulatory arrest and recovery. Control cerebral ATP concentrations in biopsies from 30 normothermic dogs equalled 2.42 ± 0.16 micromoles per gram (S.D.). Simultaneous aortic and vena caval occlusion, for periods of 4, 6, or 8 minutes, resulted in a 50 per cent decrease of cerebral ATP within 3.8 minutes. Electroen-cephalographic silence occurred at 20.9 ± 3.1 seconds, coincident with the loss of less than 10 per cent of control ATP content. Reappearance of brain ATP after resumption of flow correlated inversely with the duration of circulatory arrest. Eleven dogs were cooled to 5° to 11° C. (esophageal) with the use of high-flow extracorporeal perfusion for 50 minutes with attendant reduction of cerebral ATP to 88.6 ± 7.4 per cent of normothermic control levels. EEG silence occurred at 16.8° ± 3.5° C. (esophageal), coincident with the loss of less than 10 per cent of control ATP concentrations. Circulatory arrest resulted in a 50 per cent reduction in cerebral ATP after 13.3 minutes. Recovery of ATP with rewarming was observed after 30 and 60, but not 90, minutes of hypothermic arrest. EEG recovery was associated with return of ATP concentrations to 89 per cent of normothermic control levels. Profound hypothermia results in a three- to fourfold increase in survival of cerebral ATP during circulatory arrest. We wish to thank Robert Gelein and Marvin Nunn for valuable technical assistance.

The authors' experience using hypothermia for neurosurgical procedures over a three-year period is described. For the majority of patients in whom hypothermia is indicated, some conventional form of surface cooling to approximately 30°C is satisfactory. In a smaller number of cases profound hypothermia, or hypothermia to 30°C with interruption of the carotid and vertebral blood flow, has been employed. In the latter technique the great vessels are temporarily occluded after median sternotomy. Both these series of cases are too small for statistical comparison.

SUMMARY Profound hypothermia is an alternative to the heart-lung machine with oxygenator. The different perfusion techniques, their development and details are described. A total of 27 patients has been operated upon under profound hypothermia. Fourteen of these died. In three cases, the hypothermic technique itself was considered to be the cause of death. In the other cases, the cardiac defects were inoperable for anatomical reasons. With increasing experience of perfusion under both normo- and hypothermia, the indications for the use of profound hypothermia were reduced. The anaesthesia used in these cases was as light as possible with nitrous oxide and a neuromuscular blocking agent. Ventilation was adjusted, so that the patients had an acid-base balance as near to normal as possible. Moderate metabolic acidosis was found in only a few cases apart from the final stages. ZUSAMMENFASSUNG Tiefe Unterkuhlung ist eine Alternativmethode zur Herz-Lungenmaschine mit Oxygenator. Die verschiedenen Perfusionstechniken, ihre Entwicklung und Einzelheiten werden beschrieben. Insgesamt wurden 27 Patienten in tiefer Hypothermie operiert. 14 von diesen starben. In 3 Fallen musste die Unterkuhlungstechnik selbst fur den todlichen Ausgang verantwortlich gemacht werden. In den ubrigen Fallen lagen anatomisch inoperable Defekte vor. Bei zunehmender Erfahrung mit der kunstlichen Perfusion sowohl unter Normo- als auch unter Hypothermie wurden die Indikationen zur tiefen Unterkuhlung eingeschrankt. Die Narkose wurde bei diesen Fallen so oberflachlich wie moglich gehalten und bestand in der Hauptsache aus Stickoxydul und einem neuromuskularen Blocker. Die Beatmung wurde so eingestellt, dass das Saure-Basengleichgewicht so nahe wie moglich der Norm blieb. Eine massige metabolische Acidose wurde—abgesehen von den Endstadien—nur in ganz wenigen Fallen gefunden.

Two cases of common pulmonary vein atresia (CPVA) are presented. In one, the diagnosis was suspected on clinical grounds, and in both it was c onfirmed by cardiac catheterization and angiocardiography. Surgical correction was attempted unsuccessfully in one. Prompt identification of the defect followed by immediate operation, using a technic of profound hypothermia and circulatory arrest, offers hope of successful correction in this rare anomaly.

Biopsies of myocardium were taken at operation from patients undergoing open heart surgery using profound hypothermia and total circulatory arrest. Electron microscopic studies of these specimens were undertaken and the results compared with controls. The significance of the described abnormalities is discussed.

DURING THE EARLY 1960% profound hypothermia with cardiac arrest gained popularity in neurosurgery as an adjunct to the surgical treatment of intracranial aneurysms. The surgeon had the advantage of a wide operative exposure in a bloodless operative field. The techniques, physiology, and metabolic changes of profound hypothermia were described by several authorities [ 1, 3, 5, 7, 8, 11-141. During the late 1960’s, aneurysm surgery became more refined and these improvements along with the technical, metabolic and hemorrhagic problems encountered with profound hypothermia and cardiac arrest led to the general disuse of this procedure in neurosurgery. Our interests in profound hypothermia with cardiac arrest as an adjunct to the surgical treatment of certain intracranial vascular lesions has continued, and we agree wit’h Sundt and coworkers who recently stated “. . . there are aneurysms presently considered inoperable that might be approached utilizing profound hypothermia . . . [and] . . . it is suggested that the approach, virtually abandoned a

Summary The use of deep hypothermia (about 12°C.)in cardiac surgery raises problems concerning the measurement of blood gas tensions at different temperatures. The theoretical aspects of changes in blood gas tensions with temperature are discussed. Measurements of pO2, using a Clark electrode, and of pCO2, using a Severinghaus electrode, have been made on blood equilibrated at different temperatures and with the electrode maintained at either a high (37° C.) or a low (about 10 to 14° C.) temperature. The measurements confirm the view that pCO2 can be corrected for differences between the temperature of collection and the temperature of measurement although the theoretical and the experimental correction curves did not coincide. The measurements also confirm that changes of pO2 with temperature are affected by the level of saturation of the hemoglobin and cannot be corrected simply. Some aspects of blood gas tension changesduring deep hypothermia are discussed.

Clinical experience obtained during the last 18 mo in 45 patients with surface-induced profound hypothermia and circulatory arrest is presented here. Thirty-two of these patients were under 2 yr of age and 21 were under 1 yr of age. Initially, this method was reserved for patients in whom palliation was either not available or had failed, but subsequently, as confidence in the technique increased, all surgically correctable lesions have been offered primary repair regardless of age or weight. Surgical mortality in the under-2-yr group was 22%, which compares favorably with the combined risk of staged procedures for congenital heart disease. Use of the pump oxygenator has made rewarming more efficient and predictable. Primary repair of potentially correctable surgical lesions is advocated in infancy.

T O PROVIDE circulatory arrest in the brain during intracranial surgery, total body profound hypothermia has been successfully accomplished with extracorporeal circulat ion in a number of neurosurgical centers th roughout the world? ,4,G,7,9 Unfort una te ly , inherent in this techniquc are a t least ~ ma jo r l imitations: 1) the necessity of a prolonged period of systemic anticoagulat ion dur ing the cooling and rewarming phases which causes t roublesome bleeding during and af ter surgery; ~) the complexity of the m e t h o d itself which requires ~ well-trained surgical t eams and presupposes complete fami l ia r i ty with the pump-oxygena tor -hea t exchanger systems. Since the surgical target of cooling and ischemic ar res t is the brain itself and not the b o d y as a whole, we have become interested in overcoming the present l imitations of ext racorporeal ly-produced, profound hypothermia . Th is could be accomplished by selective cerebra l cooling via carotid perfusion during t e m p o r a r y arres t of the cerebral circulation b y occlusion of the extracranial cervical arter ia l sys tem. Uti l izing a simple a r te ry to a r te ry extracorporeal circuit to cool the brain alone would avoid cooling of the entire body and would thus eliminate the need for an oxygena to r and the mechanically controlled rew a r m i n g phase. In addition, the period of an t icoagula t ion would be significantly shortened and with the absence of the oxygenator , add i t iona l problems in blood coagulation would be obv ia ted? 's While we, as others, 2'1~ have demons t ra ted the feasibi l i ty of differentially reducing the bra in t empe ra tu r e in the experimental anim a l uti l izing direct cooling via the carotid ar te r ia l sys tem, this method to da te has en joyed only limited clinical application.

This new method of prolonged total body circulatory interruption is devised under extremely profound hypothermia by means of the exchange perfusion of a blood substitute using extracorporeal circulatory machine.There are several significances of this method:1) Prolonged total body circulatory interruption is obtained.2) Temperature near 0°C is obtained very rapidly.3) An absolutely bloodless surgical field is secured under this condition.4) No sequelae are noticed after recovery.5) No blood is perfused during the cooling period. This procedure facilitates high flow and rapid cooling.6) A great future is expected to perform a riskful operation radically and safely under this new method.

Summary These studies evaluate the effect of alcohol on cardiac action in rats in profound hypothermia. Two milliliters of 50% alcohol were injected intraperitoneally in 250-g rats, and the animals were respired with room air with diminishing tidal volumes while cooled by immersion in iced salt water (−15°C). Rectal temperatures and electrocardiograms were monitored. Rewarming was by 40°C waterbath and a heat lamp focused over the chest. In 24 alcoholic rats cardiac standstill occurred at 3.1°C (range 0 to 6°C), with body temperatures dropping to an average of 0°C and a range of −2 to 1°C. The heart restarted at 12 to 15°C compared to 25 to 30°C in the controls. All 10-min arrested animals were permanent survivors; all 30-min arrested animals returned to normal cardiac action and spontaneous respiration. In 16 control rats cardiac arrest occurred at 5.1°C (range 2 to 9.0°C), with body temperature falling to 1°C average (range −1.0 to + 2°C). Only 3 animals (with only 10-min arrests) survived—2 for 2 hrs and one permanently. Arterial blood gases at the end of arrest showed pCO2 ranging from 21 to 63 mm Hg, pO2 from 32 to 90, pH from 6.7 to 7.1, and profound base deficits. Alcoholic rats did not cool or warm appreciably faster, and fibrillation occurred only twice in each group. The electrocardiographic changes were modified by alcohol, which prevented A-V dissociation and disappearance of the P wave until much lower temperatures had been reached than in the controls. Thus, alcohol does offer definite cardiac protection and better survival during profound hypothermia, apparently by allowing cardiac function to continue to a low temperature.