The specific influence of carbon dioxide and carbamate compounds on the buffer power and Bohr effects in human haemoglobin solutions

1. Lymph from the lungs of lambs and sheep was found to enter both the right lymph duct and the thoracic duct. Right lymph duct flow was collected by constructing a venous sac, the venous tributaries of which were ligated but which the right lymph duct entered; thoracic duct flow was collected by cannulating the duct. Lymph from sites other than the lungs was excluded from the collections.

2. Measurements were made of the surface tension characteristics of lung extracts and of the liquid present in foetal lungs. These values were used together with gestational age and crown-rump length to designate the foetal lambs into mature and immature groups.

3. Lymph flow from the lungs averaged 0·99 ml./kg body wt./hr in immature foetal lambs, and 1·81 ml./kg/hr in mature foetal lambs before the start of ventilation. Lymph flow from the lungs of spontaneously delivered new-born lambs (mean age 51 hr) averaged 0·86 ml./kg/hr. In adult ewes right lymph duct flow averaged 0·11 ml./kg/hr and total lung lymph flow was estimated indirectly to be 0·33 ml./kg/hr. Calculated rates of protein flow in lung lymph (flow × protein concentration) were greater in foetal lambs than in adult sheep.

4. Total thoracic duct flow averaged 2·48 ml./kg/hr in immature foetal lambs, 5·30 ml./kg/hr in mature foetal lambs, 3·65 ml./kg/hr in new-born lambs, and 2·92 ml./kg/hr in adult ewes.

5. At the start of ventilation there was an increase in lymph flow from the lungs, which at 15-30 min reached a mean of 6·4 ml./kg/hr in mature lambs and 2·6 ml./kg/hr in immature lambs. At the same time the protein concentration of lymph decreased but the calculated protein flow increased.

6. The lungs of foetal lambs weighed more than the lungs of spontaneously delivered new-born lambs, and the difference could be accounted for by liquid which could be aspirated through the trachea of the foetal lamb. On ventilation of the lungs for 2 hr, without first allowing the escape of any lung liquid, lung weight measurements indicated that about 66% of the lung liquid had been taken up in mature lambs and about 50% in immature lambs.

7. It was concluded that the rate at which lymph is formed in the lungs is greater per kilogram body weight in foetal than in new-born lambs and greater in them than in ewes. The increase in lymph flow at the start of ventilation could account for the removal of about 40% of the liquid present in the lungs of the mature foetus and about 25% of the liquid in the lungs of the immature foetus.

     

The velocity of lymph flow in the canine thoracic duct

1. The velocity and pattern of movement of lymph in the thoracic duct of anaesthetized and conscious dogs has been studied by observing the movement of droplets of ultrafluid lipiodol in the duct.

2. The velocity of flow when anaesthetized varied from 0·1-2·0 cm/sec, to 5·0 cm/sec when conscious.

3. The pattern of flow was affected by respiration and the cardiac cycle. Most movement occurred at the end of inspiration.

4. The duct of five autopsy preparations was perfused with saline to assess the volume and velocity of flow produced by the level of pressure gradients previously observed in the duct. These studies show that the small gradients (2-5 mmHg) observed during life are more than sufficient to produce the normal volume and velocity of flow measured. The mean resistance of the duct was 0·5 mmHg/ml. min.

     

Distribution of chylomicrons and albumin in dog kidney

1. Under specified experimental conditions the distribution space of labelled chylomicrons in the kidney was 13·8 ± 0·9 ml./100 g. tissue. The assumption is supported that this provides a measure for the quantity of intravascular plasma constituents.

2. Values for red blood cells and albumin distribution spaces were 5·2 ± 0·6 and 20·2 ± 1·0 ml./100 g tissue, respectively, in the whole kidney. The ratio of tissue haematocrit over simultaneous arterial haematocrit averaged 0·56. The extravascular albumin fraction amounted to about 31·0% of the total albumin in the whole kidney.

3. A statistically significant correlation was demonstrated between osmotic urine/plasma (U/P) ratios (within the approximate limits of 0·6-1·8) and quantities of extravascular albumin in the medulla.

     

The relation of oxygen intake and velocity of walking and running,in competition walkers

1. The oxygen intake of four Olympic walkers was measured while walking and running at varying velocities on a treadmill at an altitude of 1800 m.2. The relation between O₂ intake and running at speeds between 8 km/hr and 21 km/hr was linear. The relation for walking at speeds up to 8 km/hr followed an upward concave curve. These findings were similar to results obtained at sea level by other investigators.3. For walking at speeds between 8 km/hr and 14·5 km/hr the relation of O₂ intake and velocity was a straight line having a slope twice that of running.4. Maximum O₂ intake in walking averaged 60·0 ml./kg/min (range 55·8-64·1 ml./kg/min) compared with 57·4 ml./kg/min (range 55·2-60·2 ml./kg/min) in running. An international class long distance runner serving as a control reached a maximum O₂ intake of 70 ml./kg/min.     

The origin of lipoprotein in the intestinal and hepatic lymph of unsuckled new-born calves

1. Experiments have been conducted to determine the origin and character of the lipid in thoracic duct lymph of new-born, unsuckled calves. This involved the collection and analysis of intestinal and hepatic lymph from two bile-fistulated and seven non-fistulated animals.

2. The output of total esterified fatty acid in intestinal and hepatic lymph in the unfed calf after recovery from the anaesthetic was about 0·6 and 0·025 g/hr, respectively.

3. Three lipoprotein fractions were obtained by ultracentrifugation of intestinal lymph samples. These appeared to correspond to very low- (d < 1·005), low- (1·2 > d < 1·005) and high- (d = 1·20) density lipoprotein of human serum. These lipoproteins contained approximately 40%, 50% and 10% respectively of the total lipid.

4. Very low-density lipoprotein was not found in blood serum or hepatic lymph and it was evident that very low-density lipoprotein and most of the low-density lipoprotein in intestinal lymph were derived from sources other than the capillary filtrate.

5. The output of total esterified fatty acid in intestinal lymph fell steadily during the course of an 11-16 hr period of bile deprivation to values 55% of those in comparable calves without bile fistulae. This was accompanied by a virtual disappearance of very low-density lipoprotein and a decrease in low-density lipoprotein of approximately 50%. These effects could not be attributed to starvation.

6. There was a general resemblance in fatty-acid composition between biliary lipid and the triglyceride of the lipoproteins, the predominant fatty acids being 16:0 and 18:1. The presence of appreciable levels of odd carbon number and branched-chain fatty acids were consistent with the transfer of significant amounts of free fatty acid from maternal blood to the foetus.

7. It is concluded that most of the lipid in thoracic-duct lymph of unfed, new-born calves is derived from the intestines and that the fatty acids of the very low-density lipoprotein in intestinal lymph arise from the absorption of biliary phospholipid.

     

Water uptake by Bufo melanostictus, as affected by osmotic gradients, vasopressin and temperature

1. The rate of water uptake across the skin was studied in the live toad, Bufo melanostictus. When toads were kept in distilled water at 29° C the uptake of water amounted to 16·9 ± 1·3 μl./cm²/hr; when bathed in sucrose or urea solutions, the water uptake diminished with increasing osmotic pressure. There was no water uptake observed when toads were kept in 200 m-osmolar sucrose or urea.

2. Intramuscular injections of vasopressin increased the rate of water uptake from distilled water. There was a good relation between doses and responses over various time intervals. A dose of 4 m-u. vasopressin/g body wt. doubled the rate of water uptake over a period of 1 hr. The same dose of vasopressin doubled the rate of water uptake when the toads were kept in solutions of sucrose or urea of different osmolarity.

3. The rate of water uptake when the toads were bathed in sodium chloride solutions was consistently 8 μl./cm²/hr greater than when bathed in sucrose or urea solutions of equal osmolarity. There was no water uptake when the sodium chloride solution was 285 m-osmolar.

4. Vasopressin (4 m-u./g) injected intramuscularly doubled the rate of water uptake from sodium chloride solutions of different osmolarity.

5. With solutions of potassium chloride, sodium nitrate, and potassium nitrate, in concentrations up to 150 m-osmoles/l., the rate of water uptake was found to be the same as with solutions of sodium chloride of the same osmolarity. Similarly, it was doubled by injection of vasopressin (4m-u./g).

6. The effect of temperature on the rate of water uptake before and after injection of vasopressin was investigated in toads kept in distilled water, sucrose, or sodium chloride solutions. For temperatures between 20 and 37° C, vasopressin (4 m-u./g) reduced the activation energy involved in the process of water uptake by 4000 cal.

7. The results agree with the view that water uptake follows a diffusion process which is facilitated by vasopressin, possibly as a result of increasing the size or number of available pores.

     

The effects of alteration of blood-volume on the concentration of circulating angiotensin in anaesthetized dogs

1. The blood-bathed organ technique was used to assay the concentration of angiotensin in the blood of anaesthetized dogs.

2. Alterations of blood volume caused inverse changes of angiotensin concentration owing to changes in the rate of generation of angiotensin which are probably due to changes of the rate of renin secretion.

3. Haemorrhage of 14-26 ml. blood/kg caused an increase of 0·25-1·5 μg/min in the rate of generation and an increase of 0·1-0·33 ng/ml. in the blood concentration of angiotensin.

4. The changes of angiotensin generation rate were not due to changes of renal arterial or venous pressure. They were abolished by blocking the renal nerves with lignocaine; they showed a consistent inverse correlation with central venous pressure but not with systemic arterial pressure.

5. It is concluded that changes of blood volume bring about changes of the rate of generation of angiotensin by a reflex mechanism the efferent limb of which involves the renal nerves. The afferent pathway remains to be elucidated, but the systemic baroceptors do not appear to be of primary importance.

6. The renin-angiotensin system is important in the homeostatic response to changes of blood volume.

     

The blood flow and oxygen consumption of brown adipose tissue in the new-born rabbit

1. A direct method for measuring venous outflow from brown adipose tissue in anaesthetized new-born rabbits is described.

2. During noradrenaline infusion the mean blood flow through brown adipose tissue increased from 87 to 360 ml./100 g tissue (wet wt.).min, and the mean rate of oxygen consumption of brown adipose tissue rose from 9·3 to 60 ml. O₂/100 g tissue.min.

3. During cold exposure the mean blood flow through brown adipose tissue increased from 90 to 304 ml./100 g tissue.min.

4. The mean cardiac output was 266 ml./kg body weight.min; during noradrenaline infusion it was 405 ml./kg body weight.min. At rest about one tenth, and during noradrenaline infusion about one quarter of the cardiac output went to brown adipose tissue.

5. It was calculated that most of the extra oxygen consumed during the metabolic response of the anaesthetized new-born rabbit to noradrenaline infusion or cold exposure was consumed by brown adipose tissue.

6. Hypoxia (breathing 10% O₂ in N₂) greatly reduced the increase in oxygen consumption but not the increase in blood flow in brown adipose tissue caused by noradrenaline infusion.

     

The clearance and antidiuretic potency of neurohypophysial hormones in man,and their plasma binding and stability

1. Bio-assay techniques have been used to measure plasma levels of neurohypophysial hormones in man, following either a single injection or a continuous infusion.2. The median half-life of oxytocin after a single injection of 2 u. was 3·2 min (2·0-5·7, 95% confidence limits); this increased significantly (P < 0·01) to 4·8 min (4·4-6·1) when the hormone was infused at a rate of 500 m-u./min. The vasopressins had appreciably longer half-lives. After a single injection of 1 or 1·5 u. 8-lysine vasopressin (LVP), the half-life was 5·7 min (3·6-6·0). Continuous infusions of the hormones at a rate of 120 m-u./min yielded half-lives of 5·5 min (5·0-7·1) for LVP, and 5·6 min (3·9-9·5) for 8-arginine vasopressin (AVP).3. The apparent volumes of distribution of the hormones were all of the order of two thirds the extracellular volume.4. In accordance with its shorter half-life, the clearance of oxytocin was greater than that of the vasopressins (1·5 l./min, compared with 1·0 l./min).5. The antidiuretic potencies of the hormones were studied in over-hydrated subjects, by measuring the rate of urine excretion following an I.V. injection. Duration of antidiuretic action increased in the order: oxytocin, LVP, AVP. A 5:1 mixture of oxytocin and AVP was not as long-lasting as AVP alone. 8·5% (4-22) of an administered dose of AVP was excreted in the urine, and this amount was significantly correlated with urine volume (r = +0·67, P < 0·05).6. Ultrafiltration of human plasma containing exogenous hormones showed that 30% (13-50) of AVP was bound, the degree of binding being independent of concentration over the range used (50-400 μ-u./ml.) In contrast, oxytocin was completely unbound.7. Exogenous oxytocin was more stable than exogenous AVP in human plasma. At 4° C there was no significant loss of oxytocin until 7 days, whereas 20% of AVP was inactivated in 2 days. At 37° C a 20% loss of AVP occurred within 4 hr, and a 50% loss within 24 hr; corresponding times for oxytocin were 24 and 48 hr.     

Circulatory responses of supine subjects to the exposure of parts of the body below the xiphisternum to subatmospheric pressure

1. Observations are reported on the effects of exposure of parts of the body below the level of the xiphisternum of supine subjects to a pressure 70 mm Hg below atmospheric for 1 min.

2. The stress on the circulation was greater than when parts below the iliac crests were similarly exposed. Heart rate increased by 15-20 beats/min, there was a sustained fall in arterial blood pressure, and forearm blood flow fell profoundly and in some subjects was reduced to below 0·1 ml./100 ml. min.

3. In arms that were sympathectomized, or had received an intraarterial infusion of an adrenergic blocking drug, the fall in forearm blood flow was much less and could be related to the fall in arterial pressure.

4. When the suction was released there was a brief overshoot of arterial blood pressure and brief cardiac slowing. Forearm blood flow rose to reach a peak some 15 sec after the release.

5. In the sympathectomized forearm on release of suction there was an immediate rise in blood flow which was proportionately much greater than the rise in arterial blood pressure.

6. This rise was not due to circulating vasodilator substances or to the activity of cholinergic vasodilator nerves. The possibility that it was the result of a change in the tone of the resistance vessels occurring in response to the sudden change in transmural pressure is discussed.

     

Transport of potassium at the blood—brain barrier

1. The pial surface of different regions of the central nervous system of the rabbit have been bathed with artificial cerebrospinal fluid (c.s.f.), containing different concentrations of potassium. The object has been to change the composition of the interstitial fluid with respect to this ion, where it is adjacent to subarachnoid c.s.f.

2. Two techniques, subarachnoid perfusion from the supracallosal space between the hemispheres to the cisterna magna and barbotage from the cisterna magna, have been used. If the artificial c.s.f. contains Evans Blue, the former procedure results in maximum staining of the pia and underlying nervous tissue of the pons-medulla and spinal cord. The latter procedure results in maximum staining of the medial and supero-lateral surfaces of the cerebral hemispheres, particularly anteriorly.

3. During subarachnoid perfusion at 0·06 ml./min with the potassium-free fluid, most regions of the brain took up significantly greater amounts of ⁴²K than was the case during perfusion with the fluids containing 3 and 10 m-equiv/l. For blue cerebral cortex, the tissue subjected directly to the inflowing fluid and showing the biggest differences, the ratios, c.p.m. per g brain/c.p.m. per ml. plasma, were 1·71 ± 0·12 (+44%), 1·19 ± 0·05 and 1·07 ± 0·08 (-10%) during perfusion with the fluids containing, 0, 3 and 10 m-equiv/l. respectively.

4. During barbotage, the uptake of ⁴²K into pons-medulla and spinal cord from blood plasma, the concentration in the latter being effectively kept near constant, was, at the end of 2 hr, greater when the fluid contained potassium, 0 m=-equiv/l. rather than 10 m-equiv/l. Thus the ratio, c.p.m per g brain/c.p.m. per ml. plasma was (0·99 ± 0·04 (+36%) as against 0·73 ± 0·05 for pons-medulla where the difference was greatest.

5. Simultaneous measurements of the entry of [¹⁴C]urea from blood to different regions of the central nervous system revealed no significant differences due to the differing concentrations of potassium imposed by either barbotage or subarachnoid perfusion. This appears to exclude a non-specific cause for the changes in ⁴²K uptake, an example of which might be a changing blood flow.

6. Reasons are given for supposing that the big increase in ⁴²K uptake due to the potassium-free fluid must be due to events occurring at the blood—brain barrier. This might be some form of interaction, possibly the single file effect, such that a low potassium concentration in the interstitial fluid potentiates ⁴²K influx across the blood—brain barrier. Alternatively it might be due to a low potassium concentration in this fluid greatly reducing active potassium movement from interstitial fluid to blood. The former explanation would conform neatly with the present results; but the latter would additionally be compatible with other evidence concerning the homoeostasis of potassium concentration in c.s.f. and the interstitial fluid of brain.

     

The effects of alteration of CO2 and pH on intestinal blood flow in the cat

1. The effect of alteration of arterial blood pH on intestinal blood flow in the cat has been determined under conditions of constant perfusion pressure.

2. Arterial blood pH was altered over the range 7·12-7·70 by infusion of acid and alkali. When end-tidal CO₂ was held constant, there was no change in intestinal blood flow.

3. When arterial blood pH was altered over the range 7·19-7·55 by the administration of CO₂ at constant respiratory volume and rate, flow increased with increasing CO₂.

4. The intestinal vascular bed was less responsive to noradrenaline at pH 7·2 than at pH 7·6. The change in sensitivity was evident when end-tidal CO₂ was controlled and depended therefore on a change in hydrogenion concentration.

5. The dilator effect of CO₂ did not depend upon alteration of sensitivity to noradrenaline since it was seen after adrenergic blockade.

     

Laboratory studies with the systemic trichononacide, metronidazole

Laboratory studies with the trichomonacidal agent, metronidazole, show that 66 strains of T. vaginalis were killed in three days by concentrations of 0·0625 μg./ml. to 1 μg./ml.     

The efficacy of closed-circuit extracorporeal filtration of thoracic duct lymph as a means of lymphocyte depletion

Thoracic duct-venous shunts were prepared in yearling calves. A lymph filtration apparatus was then inserted into the system, thus allowing for the removal of thoracic duct lymphocytes via closed-circuit extracorporeal filtration. Long term thoracic duct flow rates and lymphocyte concentrations averaged 20 litres per day and 22,000/mm³ respectively. Filtration proved very effective in removing cells from the thoracic duct lymph. Filtration periods of 9–11 days removed an average of nearly 2 × 10¹² lymphocytes. Such periods of cell removal decreased the thoracic duct cell concentration to nearly 10% of the original level. Six weeks following cessation of filtration, this level had risen to only 29%. It is concluded that closed-circuit extracorporeal filtration of thoracic duct lymph offers an important and effective new tool for achieving lymphocyte depletion.     

Quantitative determination of hepatitis B antigen by means of radial immunodiffusion

The method of radial immunodiffusion for measurement of hepatitis B antigen (HB ag) levels in sera of twenty and urines of three HB ag positive patients is described. In patients suffering from acute hepatitis, the level of HB ag in serum was 0·15–2·12 mg/ml (mean = 1·08±SD 0·69 mg/ml). In patients suffering from chronic hepatitis the level of HB ag in serum was 0·36–3·61 mg/ml (mean 2·56±SD 1·13 mg/ml). The highest levels of HB ag in serum, 2·62–5·12 mg/ml (mean 3·91±SD 0·90 mg/ml) were observed in symptomless HB ag carriers.

The amounts of HB ag excreted in urine, found in two chronic hepatitis patients and one HB ag carrier, were 13·2 mg, 46 mg and 82 mg/1000 ml of urine respectively.

     

Changes during eating in oxygen consumption, cardiac function and body fluids of sheep

1. A study was made of the changes taking place in O₂ consumption, cardiac function and the volume and composition of the body fluids of sheep while they consumed a meal of hay.

2. During eating P_{a, CO2} and P_{v, CO2} both increased, pH decreased and free plasma [HCO₃^-] increased. Venous haematocrit increased sharply at the beginning of the meal, and declined slowly after feed was removed.

3. Arterial P_O2 did not change significantly during eating. However P_{v, O2} fell slightly but significantly. The O₂ saturation of venous blood fell due to the decline in pH. Estimated CO₂ in arterial blood increased as a consequence of increased haemoglobin content. The net effect was to increase arteriovenous difference in O₂ content from 4·4 ml./100 ml. before eating to 6·0 ml./100 ml. at the end of the meal.

4. O₂ consumption increased about 60% during eating and fell rapidly thereafter. Heart rate followed a similar pattern. Cardiac output however increased only about 17%, from 6 to 7 l./min. Consequently stroke volume declined throughout the meal from 76 to 52 ml./beat.

5. Plasma volume, estimated from measurements of T-1824, declined sharply by about 300 ml. at the beginning of the meal and recovered slowly after feed was removed. Blood volume declined less because of a rise in circulating erythrocytes.

6. Extracellular fluid volume was estimated from measurements of thiocyanate and thiosulphate spaces. Thiocyanate space measurements were abandoned after thiocyanate was found to be concentrated in saliva. Considerable random variation occurred in measurements of changes in extracellular fluid from thiosulphate disappearance but the results did reveal a significant fall of 1000-1500 ml. in extracellular fluid volume during eating.

7. The significance of these interrelated changes is discussed in relation to the maintenance of homoeostasis during eating in the sheep.

     

The progressive pressor response to angiotensin in the rabbit

1. The threshold for any detectable rise of systemic arterial pressure during the prolonged intravenous administration of angiotensin to conscious rabbits was observed to be an infusion rate of 0·003-0·006 μg.kg^-1.min^-1.

2. At infusion rates between threshold and 0·04 μg.kg^-1.min^-1 the systemic arterial pressure rose progressively over a 3- to 7-day period to a plateau.

3. On stopping the angiotensin infusion the blood pressure fell rapidly back to its base line much faster than it rose during the infusion. The time taken to reach control values was approximately related to the duration of the infusion.

4. At infusion rates of about 0·05 μg.kg^-1.min^-1 the full rise of blood pressure developed within a few minutes, and could be sustained without change for many days. At higher rates the blood pressure diminished with time.

5. Diurnal fluctuations of blood pressure were often seen during prolonged infusions of angiotensin at low rates; and more rapid fluctuations of blood pressure over an hour or two were frequently encountered immediately after an infusion was turned off.

6. The possible role of angiotensin in producing chronic renal hypertension is discussed in the light of these observations.

     

Lymph node localization and whole body distribution of radioiodinated encephalitogenic polypeptide in guinea-pigs

A bovine encephalitogenic polypeptide (BEP) labelled with radioiodide retained its capacity to induce experimental encephalomyelitis (EAE). Guinea-pigs were injected with ¹²⁵I BEP in Freund's complete adjuvant (FCA), to study changes in the architecture and the distribution of radioactivity in draining lymph nodes, and the amount of radioactivity in various organs.

After injection of BEP in FCA the lymph node rapidly enlarged. Within 48 hr there was depletion of lymphocytes, the enlarging lymphoid follicles had become confluent and there was proliferation of large `epithelioid' cells throughout the node. At 5 days the lymph node architecture was disorganized and lymph follicles with germinal centres could not be recognized; similar but less pronounced changes were present in regional nodes. By contrast, after injection of flagellin in FCA, there were numerous lymphocytes, plasmablasts and pyroninophilic cells, germinal centres were prominent, and the architecture was preserved.

From 0·5 to 0·8% of the total injected radioactivity was concentrated in the popliteal lymph node 2–5 days after injection of ¹²⁵I BEP in FCA. No radioactivity was concentrated in the node after injection of ¹²⁵I BEP without FCA, and animals thus immunized did not develop encephalomyelitis.

The popliteal lymph node was examined by autoradiography after injection of ¹²⁵I BEP in FCA. At 24 hr radioactive encephalitogen associated with droplets of adjuvant was present mainly in the peripheral sinus and at 48 hr encephalitogen–adjuvant droplets were deposited randomly throughout cortex and medulla. These droplets appeared to represent sites where lymphoid cells acquired their capacity for pathogenic reactivity with their target antigen in the central nervous system.

     

Autoradiographic demonstration of inhomogeneous distribution of sodium in single oocytes of Bufo bufo

1. Autoradiography of frozen cells labelled with ²²Na has been used to locate a sequestered fraction of internal Na in the oocyte which exchanges very slowly or not at all with external Li.

2. Relative grain density in nucleus and cytoplasm, measured photometrically, was used as an indication of ²²Na distribution within the oocyte. In test experiments grain density fell to 50% within 19 μm of the edge of the section. Owing to the large diameter of the oocyte (> 600 μm) and its nucleus (> 200 μm), this resolution was adequate to determine cytoplasmic/nuclear (C/N) ratios of grain density.

3. In oocytes fully loaded with ²²Na, the mean C/N ratio was 0·92 ± 0·03 (n = 11). After 5 hr exchange in Li-substituted Na-free Ringer solution, the mean C/N ratio was 2·18 ± 0·04 (n = 11). After 5 hr exchange in Ringer solution as a control, the mean C/N ratio was 1·39 ± 0·18 (n = 7). The cytoplasm thus contained a fraction of ²²Na inexchangeable with Li, and more slowly exchangeable with Na than that in the nucleus.

4. The non-Li-exchangeable fraction of internal Na thus revealed appeared to be quantitatively similar to that already demonstrated by studies of ²²Na fluxes and of internal Na activity by means of Na-sensitive micro-electrodes.

     

Studies on the Mechanism of Shock: The Effect of Cocaine and Theophylline on the Temperature Response to Injury in the Cold-Acclimated Rat

The effects of cocaine and theophylline on the changes in core temperature, O₂ consumption and the rate of heat loss from the tail were studied in 20° and 3° acclimated rats during and after a 4-hr. period of bilateral hindlimb ischaemia at an environmental temperature of 20°.Cocaine (7 mg. base per kg. body wt. intravenously) had no effect on injured 20° acclimated rats but increased the core temperature in both injured and uninjured 3° acclimated ones. The changes in O₂ consumption were unaffected and heat loss from the tail decreased. Cocaine acted mainly by increasing peripheral vasoconstriction and so decreasing heat loss.Theophylline (90 mg. per kg. body wt. intraperitoneally), given 1 hr. before removal of the tourniquets, depressed the core temperature in 20° acclimated rats but increased it in 3° acclimated ones. Theophylline increased heat production in 3° acclimated rats, raising O₂ consumption and causing a maximal increase in heat loss from the tail. Whereas this increased heat loss could prevent a rise in the temperature of the uninjured it was insufficient to do so in the injured.Since previous work has shown that limb ischaemia causes a similar increase in adrenaline and noradrenaline secretion in 20° and 3° acclimated rats these results support the view that the difference between the responses to trauma in these 2 types of rat is due to the greater sensitivity of cold-acclimated rats to catecholamines.