broadly classed together as 'chemical regulation' must inevitably remain

Transcription

1 189 J. Physiol. (1952) II6, I89-20I OBSERVATIONS ON TEMPERATURE DISTRIBUTION AND LIVER BLOOD FLOW IN THE RAT BY J. H. BIRNIE* AND J. GRAYSON From the Departments of Pharmacology and Physiology, University of Bristol (Reeived 24 Augtust 1951) Body temperature is one of the fundamental attributes of the higher forms of life; its maintenance must be regarded as a vital function. Yet it is one the study of which is frequently neglected. There is considerable information relating to the physical processes of heat elimination, but those functions broadly classed together as 'chemical regulation' must inevitably remain incompletely understood until more precise information is made available concerning the sites of heat production. Recent evidence suggests that the main sources of body heat are intra-abdominal (Federov & Shur, 1942), probably in the liver, and that the role of skeletal muscle, at least in the resting state, is minimal (Grayson, 1951 a). There is, thus, evidence ofcentralization in the processes of heat production. The work of Feitelberg & Lampl (1935), however, suggests that there may be other major centres of heat production than the liver. They have shown that in the conscious animal the resting brain temperature is higher than that of the carotid blood. Nearly 200 years ago Stevenson (quoted by Leslie, 1778) demonstrated in the cow that the temperature of the blood in the jugular vein was higher than that in the carotid artery. He did not apparently realize the full significance of this observation, but there can be little doubt that the brain, even in the resting animal, is an important centre of heat production. The primary object of this paper is to describe observations correlating liver and brain temperatures in unanaesthetized rats, and to study the effect of anaesthesia in this respect. But blood flow in the liver might also be considered to be of importance in relation to its metabolism. Experiments were therefore also performed, using the method of 'internal calorimetry', for the simultaneous recording of temperature and blood flow in the liver. * Present address: Department of Biology, Morehouse College, Atlanta, Georgia, U.S.A.

2 190 J. H. BIRNIE AND J. GRAYSON METHODS Copper-constantan thermocouples were used in the measurement of tissue temperatures. The couples were made from 35 s.w.g. copper and constantan wires soldered at the tip. A junction box (Grayson, 1949) was used so that readings could be taken from several points. Recording was by means of a Cambridge D'Arsonval galvanometer (internal resistance 50 Q1), a slit lamp and scale. With a 50 cm scale at 5 m, sensitivity was adjusted by means of the external resistance to give 5 cm deflexion per 10 C. In certain experiments temperature changes were recorded continuously, using a manually operated mechanical device whereby the movements of the light on the scale could be followed and registered directly on a kymograph (Grayson, 1951a). Temperatures were recorded from the brain, liver and abdominal cavities. Thermocouples were implanted under ether anaesthesia. A ventral, mid-line incision was made exposing the upper part of the abdominal cavity. A broad-gauge hypodermic needle was introduced under one or other skin flap, and passed subcutaneously around the body of the animal until it emerged through the dorsal skin as near as possible to the mid-line. The thermocouple was threaded down the needle which was then withdrawn, leaving the recording point and about 1 in. of wire free in the abdominal wound. The naked leads for connexion to the recording apparatus emerged from the dorsum of the animal well away from the ventral wound. A small loop was made in the wire so that a suture might be passed through it to anchor it to the anterior abdominal wall on closing the incision. The thermocouple was inserted into the largest lobe of the liver from the lowest margin (caudal) upwards (cephalically) and backwards (dorsally); about H in. of wire was buried in liver substance. A second thermocouple was similarly positioned, except that its recording tip was bent backwards and downwards to record from the lower abdominal cavity. Brain implantations were made using a small incision over the vertex of the skull and a burr hole penetrating the bone. A broad-gauge hypodermic needle was passed from the wound to emerge from the skin over the occiput. The thermocouple was passed down the needle which was then withdrawn leaving about J in. of wire for anchoring and implantation. In animals where the leads were brought out over the dorsum of the body it was found that movements of the head frequently caused the leads to break where they passed over the dorsum of the neck. Where the leads were made to emerge directly from the head wound, firm anchoring was difficult to secure. Liver implantations in themselves appeared to have no permanent affect on the animal's health or behaviour. Brain implantations, however, were more drastic in their effects. Seven out of seventeen animals died within 28 hr of implantation. All showed marked disturbances ofbehaviour pattern, being quieter than normal animals when left alone, yet more excitable when interfered with. There was a variable loss of weight and impairment of appetite. In those animals which survived, recovery was usually complete after 4-5 days, and thereafter they appeared normal and unaffected. The measurement of temperature. Daily temperature readings were made in all animals. The animals were restrained for this purpose in a tube made of perforated zinc. An oval hole in the top of the tube gave access to the leads from the implanted thermocouples which were connected to the leads from the connexion box by means of 'crocodile' clips. Rats would remain quiet in the tube for periods up to 2-3 hr. Most simple readings, however, were complete within 15 min or less. Measurement of liver blood flow. Liver blood flow was recorded using the method of 'internal calorimetry' described in full detail elsewhere (Grayson, 1951 b, c). It consists of the measurement of the current required to maintain a plus 10C thermal equilibrium in a heater embedded in the tissue. The temperature of the heater is measured thermoelectrically. The heat output of the wire is given by the equation H=CI2R (where C is a constant, I= the current in amperes and R =resistance of heater in ohms). It has been shown that heat is lost from the wire partly to the circulating blood and partly by direct conduction to the tissues. Conduction back along the wires is in effect a negligible factor. Heat losses by conduction are governed by the formula J2R =l4rr9 (where ki=thermal conductivity of the tissue, r=radius of a theoretical sphere with equivalent thermal properties to the heater, and G=temperature increment over the surroundings). Where

3 TEMPERATURE DISTRIBUTION AND LIVER BLOOD FLOW 191 o = 1 C the fraction ls/k is constant for any given recorder. This fraction has been used throughout as the standardization factor (F). Its measurement is simple and has been described elsewhere (Grayson, 1951 b, c). In the present work standard blood-flow recorders made to a fixed specification were used throughout. It was found that in each case the standardization factor (F) = 140 (±2 %). It follows from the above oonsiderations that the thermal conductivity of any material or tissue is given by the fraction 12/F, where 6 is 1 C. In the determination of thermal conductivity, therefore, the essential measurement is of the square of the current required to maintain an elevation of 10C in temperature. This will be referred to henceforth as the P2 value. Where blood is flowing through a tissue the Is value is increased, leading to an apparent rise in the thermal conductivity. The conductivity increment due to circulating blood may be calculated simply by subtracting the IP value obtained in dead liver from the IP value in living liver (the subtracted IP value) and dividing by the standardization factor. It has been shown elsewhere (Grayson, 1951 b) that the conductivity increment is a linear function of blood flow. Moreover, recent evidence suggests that there is a provisional correlation factor of 12-5, whence the blood flow in ml./ml./seo = 12*5 x the conductivity increment. In the present work, therefore, results will be expressed in terms of conductivity increment, and, using the provisional factor, in terms of blood flow/100 ml. tissue/min. The heated thermocouple was implanted in the liver of the rat, using the methods already described for the implantation ofsimple thermocouples. It was found, however, that the positioning of the instrument was critical. It is essential that it should be completely buried in liver substance. In vitro experiments have shown that intimate contact with the tissue under investigation is essential. A thermocouple lying between liver lobes does not give a reproducible quantitative picture. It was found in practice, by performing careful post-mortem examinations of all rats after use, that blood-flow readings outside the normal range were a sure indication that the thermocouple was between the lobes or outside the liver. During the first 24 hr, before scarring anchored the instrument firmly in position, there was always a tendency for the thermocouple to move. In some cases it was found to have slipped out of the liver altogether; in others the liver was transfixed. In all such cases a low reading was obtained. For the purpose of measurement the rat was handled in the perforated zinc tube as already described. Crocodile clips were used to connect the leads from the recording apparatus. RESULTS Temperature in the normal rat In a series of ten rats, liver, brain and intra-abdominal temperatures were measured on the day after implantation and thereafter daily for periods varying from 2 to 12 days. All measurements were made under similar environmental conditions with the rats quiescent in the tube and the room temperature at 180 C. Observations on any given rat were made as far as possible at the same time of the day. Temperatures of most animals were recorded for a period of 15 min; however, in four animals observations were continued for min. In all cases the temperatures were stable and no significant fluctuations were observed in liver, brain or intra-abdominal temperatures with the animals at rest. Table 1 shows the temperatures recorded in this series of rats, in each case 2 days after implantation. There were considerable differences between different animals but the mean liver temperature was 38.7 C. In a different

4 192 J. H. BIRNIE AND J. GRAYSON series of twenty-three rats, where liver temperatures were recorded alone, the mean temperature was C. In the ten rats recorded in Table 1 the mean brain temperature was 38-0 C and the mean intra-abdominal temperature was C. In all cases the highest temperatures were recorded from the liver. There was no consistent quantitative relationship between liver, brain and abdominal cavity in this respect; however, the temperature of the liver was from 04 to 1.10 C above that of the brain and from 0-2 to 1V5' C above that of the abdominal cavity. This latter relationship varied, of course, with the TABLE 1. The distribution of temperature between liver, brain and peritoneal cavity in normal, resting rats. Temperature in 0 C Rat no Mean Liver Brain *0 Abdominal cavity * exact position of the intra-abdominal thermocouple; in cases where the intraabdominal temperature approached that of the liver, post-mortem examination usually confirmed that the thermocouple was lying near or in surface contact with the liver. In all cases where the intra-abdominal thermocouple was placed low in the abdominal cavity, the temperature recorded from it was slightly lower than that of the brain. 0 1 % Time (days) Fig. 1. The independence of brain from liver and intra-abdominal temperature. The rats from which these records were obtained showed no clinical sign of abnormality during the period of raised liver temperature. *- *, liver; , abdominal cavity (A.c.); A- --A, brain. Temperature variations in individual rats. Although no abrupt changes were observed on any single occasion, there were frequently considerable differences between temperatures in the same animal on different days, even when measured at the same time of the day under apparently similar conditions. The fluctuations in liver temperature were usually accompanied by parallel changes in intra-abdominal temperature. Fluctuations in brain temperature, however, bore little relationship to those occurring in the liver. Thus, in the experiment shown in Fig. 1, the liver and intra-abdominal temperatures each

5 TEMPERATURE DISTRIBUTION AND LIVER BLOOD FLOW 193 rose by about 1.40 C in 2 days with only a very slight change in brain temperature. In other examples, where the fluctuations in liver and intraabdominal temperatures were slight, the changes in brain temperature were completely unrelated. The effect ofether on temperatures in the rat. The effect of light ether anaesthesia was investigated in the rat using thermocouples implanted 1-6 days previously. One of two procedures was followed. In some experiments liver, brain and intra-abdominal temperatures were recorded from the conscious rat restrained in the tube. The animals were removed from the tube, anaesthetized and then returned to the tube. Ether inhalation sufficient to maintain unconsciousness Liver 30Brain A.C. E Fig. 2. I-l Ether Time (min) The effect of ether on temperature distribution in the rat. but not to abolish deep reflexes was continued for periods of 15 min. Temperature observations were made only when the animal was in the tube and were continued during the subsequent recovery period. In other experiments the animals were anaesthetized in the restraining tube. This enabled some continuous records to be obtained of all stages of ether administration, but had the disadvantage that during the excitement stage of induction the rats were prone to break their leads. In all experiments temperatures were recorded continuously on the kymograph by the method already referred to. The results of a typical experiment are shown in Fig. 2. There was a rapid drop in all recorded temperatures. The brain temperature in most cases was the first to fall, followed about 30 sec later by the liver. The temperature in the abdominal cavity began to fall about sec after the liver. On withdrawing the anaesthetic, liver and brain temperatures continued to PH. CXVI.- 13

6 194 J. H. BIRNIE AND J. GRAYSON drop for 2-10 m, then slowly began to recover. The intra-abdominal temperature usually continued to drop for 1-2 mi after recovery had begun in the brain and liver. Normal temperatures were regained in about mn. Table 2 gives the lowest temperatures reached in a series of six rats. The mean liver temperature after 15 mi light ether anaesthesia was 34.7 C, representing a drop of 4 0 C below the average for normal conscious rats. The mean brain temperature was 33 8 C, a depression of 4.20 C, and the mean intra-abdominal temperature was C, a depression of 3.80 C. TABiL 2. The lowest temperatures reached in the rat following 15 min of ether inhalation. Temperature in ' C Rat no Mean Liver Abdominal cavity * Brain * *8 The effect of pentobarbitone sodium. Rats were restrained in the perforated zinc tube, their leads connected to the apparatus and initial temperature readings taken in the usual way. 1 ml. of 0-8 % pentobarbitone sodium (Nembutal) was injected intraperitoneally with the animal still in the tube. In a series of five rats this dose produced loms of consciousness without abolition of deep reflexes. All temperatures began to drop within 2 m of the 380 ULver E 37,0 c, %,, _ 0 I-.~~~~~~~~~~~~~~~~~~~~~~~~~~J0 Nembutal 36x0 + ',,., Time (min) Fig. 3. The effect of pentobarbitone sodium (1 ml. of 0.8 %) on temperature distribution in the rat. injection. Change occurred first in the brain, followed by the liver, followed by the abdominal cavity. The rates of fall were slower than those produced by ether, minimum temperatures being reached after mm (Fig. 3). Subsequent recovery was also slower, normal temperatures being regained 24-3 hr after the injection. Again the brain was usually the first organ to show signs of recovery, followed by the liver and the abdominal cavity.

7 TEMPERATURE DISTRIBUTION AND LIVER BLOOD FLOW 195 The lowest temperatures reached are recorded in Table 3. The mean liver temperature was C-a depresion of 2-0 'C below the mean normal-the mean brain temperature was C, a depression of 2 3 C, and the mean intra-abdominal temperature was C, a depression of 1-9' C. TABLm 3. Lowest temperatures recorded following 1 ml. of 0.8 % Nembutal (intra-peritoneal). Temperature in0 C Rat no Mean Liver Abdominal cavity B9 35B8 Brain *5 36B The effects of pentobarbitone sodium were therefore slower than those of ether, but otherwise qualitatively similar. The depression of temperature produced by the dose administered was about half that produced by ether but the effect was more sustained. The effect on brain temperature was more rapid with both anaesthetics than the effect on the liver. Moreover, the temperature depression was relatively greater in the brain than in the liver. Intra-abdominal temperature reactions, however, lagged behind the liver at all times and were les pronounced. The temperature recovery with both ether and pentobarbitone sodium bore no relation to the recovery of consciousness. In the experiments shown in Figs. 2 and 3, for example, full spontaneous activity was present and reactions to auditory and visual stimuli were normal, indicating a full return to consciousness, at a time when the temperatures of liver and brain were stil near their minimum. Liver blood flow and body temperature In the following experiments liver temperature and liver blood flow were recorded from the livers ofrats previously implanted with blood-flow recorders as already described. The subtracted P values were obtained by recording from the living rat, then recording the I2 value at and beyond the point of death. In most of the experiments an external cold junction immersed in a Dewar flask conta ning water at 370 C was used for the temperature records. One to two minutes is required for the accurate determination of the Is value. During this period it is essential that the 'cold junction' temperature and absolute liver temperature should not change relative to each other. In experiments, therefore, where rapid changes in absolute liver temperature occurred (e.g. following the admiinistration of ether anaesthesia) it was found necessary to implant an additional fine-gauge thermocouple in the liver to serve as a cold junction. Under these circumstances temperature changes affecting the liver as a whole produced no fluctuations in the thermoelectric circuit. 13-2

8 196 J. H. BIRNIE AND J. GRAYSON The standardization factor (140) was used as already described to convert subtracted 12 values into conductivity increments. It has already been stated that the flow of blood in ml./ml./sec is given by 12-5 x conductivity increment. Using this correlation the present results have been expressed in terms of blood flow. Liver blood-flow fluctuations in resting rats. Fluctuations in blood flow in individual rats were observed on different days. In the experiment shown in Fig. 4 the 12 values recorded on different days ranged between 0-32 and The subtractedi2 values (non-circulatoryvalues determined after death = ) were thus The standardization factor of the blood-flow recorder was 140; conductivity increments, calculated as previously described, ranged, therefore, from 10-3 to x The resting blood-flow range in this rat was 12-5 x 10-3 to x 1o-3 ml./ml./sec, or ml./100 ml./min. 2 1F30 Liver flow o.0 0 Liver temp. Fig Time after implantation (days) Temperature and liver blood-flow variations in the rat. Continuous observations of blood flow in the resting, normal animal were only continued in two cases for periods of 1 and 3 hr respectively. Large spontaneous changes were not observed, the blood flow on each occasion remaining steady over a narrow range. No correlation was observed between liver temperature and liver blood flow in resting rats, recorded fluctuations on different days being frequently opposed. Table 4 gives the results of resting liver blood flows in eight different rats. Observations were taken in each instance 2 days after implantation. Liver temperature was also recorded using the 'cold junction' couple implanted in the liver for the purpose. Subtracted 12 values fell between and Conductivity increments were thus 10- to 1-23 x The blood-flow range, therefore, between different rats was ml./100 ml./min. The mean subtracted 12 value was

9 TEMPERATURE DISTRIBUTION AND LIVER BLOOD FLOW , giving a conductivity increment of 1-05 x 10-3 and a mean blood flow of 79 ml./100 ml./min. The effect ofether on liver bloodflow. The same procedure as already described for the investigation of temperature changes during anaesthesia was adopted. Rats with thermocouples implanted 1-4 days previously were restrained in TABLE 4. Conductivity increment, blood flow and liver temperature in resting rats Rat no Subtracted * Cond. incr. ( x 10-3) 1* P236 1P Flow, ml./100 ml./min * Liver temp. 0 C the tube and resting measurements taken. Some were then anaesthetized outside the tube and returned to it. Fig. 5 shows a typical result of ether administration with the rat restrained in the tube throughout. There was a pronounced drop in blood flow which in many cases preceded the drop in temperature. OE 0.9 b -3 Liver temp <) EL Fig Time (min) The effect of ether anaesthesia on temperature and blood flow in the rat liver. Recovery began as soon as the ether was withdrawn. There was usually a short phase during which the blood flow rose to above its previous resting level followed by a subsidence to base-line. The levels of blood flow reached after 15 min are shown in Table 5. The mean subtracted 12 value recorded at this stage of ether administration was 0078, corresponding to a conductivity increment of 0557 x 103. The mean blood flow under ether was, therefore, 42 ml./100 ml./min, a drop of 47-6 % from the mean resting level.

10 198 J. H. BIRNIE AND J. GRAYSON The effect ofpentobarbitone sodium. The effect of pentobarbitone sodium was investigated in only two animals. In these experiments, however, the effects TABLE 5. Blood flow in the rat liver after 15 mm ether anaesthesia or 1 ml. of 0-8 % Nembutal Ether Nembutal Rat no, Subtra&,ted 12 0* * * ' Cond. incr. ( x 10-3) * Flow, nal./ 100 ml./min * F Liver ta3mp. C were similar to those of ether (Fig. 6). There was a drop in blood flow which was rather faster in onset than the drop in temperature, but not so rapid as the similar effect described for ether. The diminution of flow produced by 1 ml. of 0O8 % solution was 36*3 % in one case, and 48-3 % in the other. Recovery was slower and in neither case was there any recovery beyond the initial conscious level of flow. Fig. 6. Time (min) The effect of pentobarbitone sodium on temperature and blood flow in the rat liver. DISCUSSION In so far as the present observations relate to the abdominal cavity they confirm the pre-eminence of the liver as a source of heat production. Thus the liver temperature was the highest recorded in the body. When fluctuations occurred the intra-abdominal temperature lagged behind that of the liver, but did not react independently. The brain temperature, however, manifested throughout a marked independence. It was never so high as the liver temperature but, following ether administration, for example, it reacted as quickly as, sometimes even more

11 TEMPERATURE DISTRIBUTION AND LIVER BLOOD FLOW 199 quickly than, the liver. Its recovery was equally prompt. On other occasions, when observations were extended over several days, brain temperature fluctuations occurred directionally opposed to those of the liver. These could scarcely have been secondary to the liver changes, and it may be concluded that whereas the temperature of the brain reacts similarly in response to certain stimuli, e.g. anaesthesia, to the temperature of the liver, it does so independently. The conclusions of Feitelberg & Lampl (1935), implicit also in the observations of Stevenson (quoted by Leslie, 1778), are thus fully confirmed. It may be stated, therefore, that whereas the liver may be a principal centre of metabolism, the brain possesses a considerable degree of autonomy. The effect of ether and pentobarbitone sodium anaesthesia on both brain and liver temperature was dramatic. Both these agents produced temperature diminutions of several degrees centigrade, changes too great to have been purely circulatory in origin. The fact that the brain and liver reacted before the abdominal cavity suggested that the effect was primarily on these centres of heat production, and indicated that these anaesthetics have a marked effect on metabolism in such regions. The extent of the metabolic depression indicated by these dramatic temperature drops makes it clearly essential to review most carefully the results of any acute experiment where anaesthetic agents are involved. The liver blood-flow observations were intended in the first place as a background to the temperature investigation. However, in view of their bearing on the study of the liver circulation in general, it is felt that the present results should be reviewed from a wider standpoint. It is first essential to visualize what, in fact, internal calorimetry measures. It should be realized that, whereas there can be little doubt that conductivity increment is directly related to blood flow, its conversion to quantitative flow rates depends upon a calibration factor which has only been determined experimentally by perfusion of isolated organs. It is hoped that a careful examination of the physical and mathematical principles underlying the method will provide a theoretical vindication of the figure used. Until this is forthcoming, however, it is felt that the conversion of the present results into quantitative bloodflow figures should be regarded as merely provisional, a convenient approximation affording some basis for comparison with the results of other workers. The limiting conditions ofthe method should, moreover, be clearlyrecognized. It has been shown (Chester & Grayson, 1951) that, using a standard blood flow recorder immersed in a 75 % water/gelatin gel, with the heater raised to plus 10 C, temperature gradients exist in a core of material approximately 4 mm in diameter by 1 cm long. Dead liver has similar thermal characteristics (Grayson, 1951 b). Where the instrument is embedded, therefore, in living liver, its range of influence might still be expected to be similar, and the blood flow calculated on the basis of 'conductivity increment' is virtually a mean of

12 200 J. H. BIRNIE AND J. GRAYSON the total blood flow in this core of tissue. Blood-flow estimations made by the present technique thus refer to quite small sections of tissue and are in no way direct measures of total liver flows. The blood flows determined in normal rats ml./100 ml./min-may be compared with the findings of other workers. Thus, Bradley and his co-workers (Bradley, Inglefinger, Bradley & Curry, 1945), using the bromsulphalein technique in conscious human subjects found a range of flow from about ml./100 g tissue/min, with a mean flow of about 100 ml./100 g tissue/mm. Considering the differences in subject and method, and the localized nature of the present observations, this may be regarded as reasonable agreement. The majority of published observations of liver blood flow were obtained in anaesthetized animals. Grindlay, Herrick & Mann (1941), using thermostromuhrs in the hepatic vein, hepatic artery and portal vein, report mean flow figures for the whole liver of ml./100 g/min. Their figures suggest, moreover, that anaesthesia has little or no effect on liver flow. The present work does not support such a conclusion. A drop of nearly 50 % in liver flow was invariably obtained following ether or pentobarbitone sodium anaesthesia. In this respect our findings are more in accord with those of Barcroft & Shore (1912), who reported blood flows in the livers of anaesthetized cats of from 33 3 to 48 ml./100 g/min. Grindlay et al. (1941) regard the circulation in the liver as highly variable and uneven, as regards both its spatial and temporal distribution. Thus, according to these workers, relatively large areas of liver are in a state of rest and relatively ischaemic at any given moment. The actively functioning parts, which are richly supplied with blood, are said to vary in size and location from time to time, according to the total activity. The present work gives no support to this view. If this concept of liver flow were true, it might be expected that measurements from small circumscribed areas such as we have been concerned with would show extreme variability. In fact this has not been observed. Observations continued for up to 2 weeks show no greater variation than from 75 to 90 ml./100 ml./min in any one recorder. Moreover, in the whole series of forty-eight rats, no single case showed a blood flow of less than 75 ml./100 ml./min, nor did any rat show a liver flow greater than 95 ml./ 100 ml./min. Our findings demonstrated, in fact, a remarkably even distribution of flow in the resting liver and a relatively narrow range of normal fluctuation. The present work failed to show any definite relation between fluctuations in liver flow and temperature fluctuations in the liver or brain. The anaesthetics studied produced a drop in blood flow, which again could not be related to the temperature effects. In the absence of blood-pressure records, however, it is

13 TEMPERATURE DISTRIBUTION AND LIVER BLOOD FLOW 201 impossible to state whether the effects were passive or whether they were due in part or in whole to primary vascular changes. SUMMARY 1. Methods are described for the thermoelectric measurement of temperature in the liver, brain and abdominal cavity of the conscious rat. The application of internal calorimetry to the recording of blood flow in the conscious rat liver is also described. 2. Mean temperatures in the conscious, resting rat were found to be liver = C, brain = 38-0 C, abdominal cavity = C. 3. Evidence is presented which suggests that the liver is the main organ of heat production in the abdomen, but that the brain is itself an independent centre of heat production. 4. Ether and pentobarbitone sodium were shown to produce a dramatic fall in temperature in all regions, which is presumed to be due to a depression of metabolic function mainly in the brain and liver. 5. The liver blood-flow figures suggest a mean figure of about 79 ml./100 ml. of liver tissue/min. No evidence was obtained to suggest uneven distribution of flow within the liver, nor to indicate great fluctuation from time to time. 6. Ether and pentobarbitone sodium were found to produce a fall in liver blood flow. The authors wish to express their gratitude to Prof. R. J. Brocklehurst and to Prof. H. S. Heller for their interest and advice, and to Mr C. J. Wilks for his valuable technical assistance. The work was aided by a grant from the Medical Research Council. REFERENCES Barcroft, J. & Shore, L. E. (1912). J. Physiol. 45, 296. Bradley, S. E., Inglefinger, F. J., Bradley, G. P. & Curry, J. J. (1945). J. clin. Invest. 24, 890. Chester, W. & Grayson, J. (1951). Nature, Lond., 168, 52. Federov, N. A. & Shur, E. I. (1942). Amer. J. Physiol. 137, 30. Feitelberg, S. & Lampl, H. (1935). Arch. exp. Path. Pharmak. 177, 726. Grayson, J. (1949). J. Physiol. 109, 53. Grayson, J. (1951a). Brit. med. J. ii, Grayson, J. (1951 b). J. Physiol. 114, 29 P. Grayson, J. (1951c). J. Physiol. 115, 29 P. Grindlay, J. H., Herrick, J. F. & Mann, F. C. (1941). Amer. J. Physial. 132, 489. Leslie, P. D. (1778). A Philosophical Inquiry into the Cause of Animal Heat. London.