In order to know the effect of the removal of both the suprarenals in rabbits upon their resistance to acetonitril the present investigations were undertaken. Acetonitril (Merck) was given intravenously, the minimum lethal dose was estimated for normal rabbits as 0.55 c. c. per kilo of body weight, and the maximum non-lethal dose, that is the maximum amount of the chemical which does not kill the animal, as 0.25 c. c. per kilo. When both the suprarenals were excised with an interval of one week and acetonitril was given one week after the last decapsulation, the resistance of the animals was reduced remarkably, 0.4 c. c. and 0.05 c. c. being estimated as the minimum lethal dose respectively the maximum non-lethal dose. When two weeks were allowed to elapse between both the decapsulations, with otherwise quite the same conditions related above, the resistance was decidedly greater than the above group, though on the other hand definitely smaller than the normal, the doses being noted as 0.5 c. c. and 0.1 c. c. The resistance of the animals, in which only the dummy operations were carried out with one-week interval and followed by acetonitril also with one-week interval, was further proved greater than the doubly decapsulated in the last mentioned manner. In them the minimum lethal dose was quite the same as in the normal, but the maximum non-lethal dose was a little smaller; the resistance of these animals was thus only a little inferior to the normal. The resistance to acetonitril of the rabbits surviving the double suprarenalectomy about three months or more was proved apparently quite the same as that of normal ones if only the minimum lethal dose be taken into account, but it is not quite the same judging from the maximum non-lethal dose. In these animals the latter was 0.15 c. c. per kilo, thus smaller not only than the normal ones but also than the animals with dummy operations. It may be noted by way of caution that the control experiments were run in parallel simultaneously with the principle. The resistance of rabbits to acetonitril one week after the unilateral suprarenalectomy or two weeks after the double splanchnictomy was detected as about the same as the normal, as far as the present experiments are concerned, but we do not assert this because of the incompleteness of these sets, especially of the latter set, of experiments. Through double suprarenalectomy the susceptibility of rabbits to acetonitril increased without a doubt, but it was of quite a minor grade, compared to the results obtained by Crivellari on rats. Some recovery of the diminished resistance to acetonitril of rabbits deprived of both the glands with lapse of time suggests some possible causal relationship existing between it and the compensatory hypertrophy of the accessory cortical tissue after removal of the main glands. This view suggests further the responsibility of the great reduction in cortical tissue for the diminished resistance to acetonitril of the doubly suprarenalectomized rabbits. For estimating the susceptibility or resistance of animals to some chemicals the determination of the maximum non-lethal dose can not only replace that of the minimum lethal dose, but also sometimes exceeds the latter in accuracy. To formulate again the results more briefly: Removal of both suprarenals elicits in rabbits an increase of the susceptibility to acetonitril, about 1.5 times of the minimum lethal dose of the normal and 5 times of the maximum non-lethal dose being recorded in the animals, deprived of one suprarenal two weeks previously and of the other one week previously. With lapse of time after the removal the susceptibility is apt to recover towards the initial, but three to nine months were proved insufficient to see the entire recovery. The maximum non-lethal dose was still small, though the minimum lethal dose was quite the same as with normal rabbits.
Resistance of rabbits, long surviving double suprarenalectomy, to nicotine, histamine, ephedrine and typhoid vaccine (in 0.5 per cent carbolic acid saline solution) was compared with that of normal rabbits. Adult, male animals of about the same weight were experimented on; they were fed and treated otherwise in quite the same manner, and poisoning with one and the same dosage of a chemical was run simultaneously on both kinds of rabbits, normal and decapsulated. Nicotine, histamine and ephedrine were dissolved in physiological saline solution of a certain quantity for each, regardless of amount of the chemical, and introduced into the ear vein always with exactly the same velocity. Typhoid vaccine was intraperitoneally injected; the toxicity of this matter is really largely due to the vehicle. The poisoning symptoms elicited by application of various dosages were closely observed, and the maximum non-lethal dose, that is the greatest dose which is poisonous to animals but does not kill them, and the minimum lethal dose were determined. The results are again summarized in Table XIII, together with the data on acetonitril.1) Resistance to such chemicals was indefinitely smaller in doubly suprarenoprived rabbits than in the normal controls, but the difference was never large in those rabbits long surviving double decapsulation, and the magnitude of diminution in resistance apparently depends at least largely upon the length of time allowed to elapse from the first and the second decapsulation till the injection, and the chemicals, under discussion, themselves have no significant bearing upon them, as far as our experiments are concerned. The present experiments were mainly undertaken about two months after the last decapsulation. We are fully aware that we could get more definite views in respect to this question provided the first and second decapsulation and injection were carried out invariably with definite spells between them. In fact the periods between were taken at random. That the regaining of resistance to toxines of the animals deprived of both suprarenals with lapse of time after decapsulation has some defmite relationship to the hypertrophy of the accessory cortical tissues has been properly alluded to by several experimentalists. In this respect it is worth while to review a work of Kojima23) on the compensatory hypertrophy of the fellow gland after a single decapsulation and of the accessories after double capsulation with the present data; some quantitative data are given there. There are some substances which are alleged to act incomparably excessively toxic to animals deprived of the suprarenals, as acetonitril (100 times) by Crivellari, 4) in contrast to nicotine, histamine, ete., typhoid vaccine (100 times) by Shiozawa, 20) who failed to adhere to Lewis24) in finding a considerably greater increase of susceptibility of rats to morphine through double decapsulation (400-500 times). It is a further question whether or not one can find various degrees of diminution in resistance of rabbits by applying various chemicals if they are administered only a few days after loss of both suprarenals. Finally the present data may be briefly recapitulated for the sake of convenience by saying that the sensitiveness of rabbits to nicotine, histamine, ephedrine, and typhoid vaccine (in 0.5 per cent carbolic acid saline solution) was not wholly identical but only a little inferior to that of normal, when tested about two, three months or somewhat later after double suprarenalectomy.
Aus vorliegenden Untersuchungen ergibt sick: 1. Das Blut von Kaninchen, Rind, Pferd und Hund weist kein Isoagglutinin auf. 2. Beim Schwein und Hammel kommt dagegen Isoagglutinin vor, und zwar kann man das Blut nach der Eigenschaft seiner Erythrozyten in 3 Gruppen unterscheiden. 3. Beim Huhn ist die Isoagglutinationsreaktion sicher zu beobachten, jedoch vermag man keine spezifische Ordnung aufzustellen. 4. Kaninchenblut weist ohne Ausnahme Kälteauto- and Kälteisoagglutinin in hohem Grade auf, jedoch ist durch Immunisierung mit Blutkörperchen derselben Tierspezies und mit der Emulsion von Meerschweinchenniere keine künstliche Erzeugung der Auto- und Isoagglutinine zu erzielen. 5. Rind, Pferd, Schwein, Hund, Hammel und Huhn haben Auto- und Isoagglutinin bei Kälte. Agglutinationserscheinungen treten beim Rind nur ausnahmsweise, beim Pferd, Hund und Hammel hingegen im allgemeinen in schwachem Grade auf. 6. Beim Meerschweinchen und bei der Kröte ist bei Wärme oder Kälte überhaupt keine Härnagglutination nachzuweisen.
1. Eine Ölemulsion holier Dispersität, in die Vene gebracht, ruft schon unmittelbar danach grosse Fettablagerung in der Leber hervor. Sehr Fein emulgierte Fettröpfchen gehen dabei grösstenteils durch den Lungenfilter glatt hindurch. 2. Bei schwächer dispergierten Emulsionen werden dagegen Fette sofort nach Infusion von der Lunge reichlich, jedoch von der Leber und Milz sehr viel weniger zurückgehalten. 3. Dieser in den Lungenkapillaren embolisch steckengebliebene Fettanteil wird mit der Zeit immer mehr zersplittert und wieder in den Kreislauf vorgeschleudert, was nachträgliche Fettdeponierung in den Körpergeweben, besonders reichlich in der Leber bedingt. 4. Die Ergebnisse der mit Ölemulsioneu verschiedener Dispersität vorgenommenen Versuche bestätigen nicht das spezifische Vermögen der Lunge, wohl aber das der Leber, aus dem Blutwege Fette an sich zu binden and zu retinieren. 5. Bei geeigneter Zusammensetzung können die Versuchstiere selbst ein nicht emulgiertes Ölgemisch auch intravenös ohne Lebensgefahr vertragen, während die gleiche Menge des Ölgemisches ohne Beimengung des Schutzkolloids augenblicklichen Tod herbeiführt.
On discussing the data above stated, it is obvious that the augmentation in the respiratory volume during CO2 inhalation is based on the accumulation of CO2 in the blood and tissues, because as is well known, the respiratory centre is very sensitive to the increased H-concentration in the blood. That the oxygen consumption is lowered by CO2 inhalation is presumably due to diminished oxidation of tissues caused by acidosis through CO2 inhalation. The fact, confirmed by Lehmann, 18) Chvostec, 19) Raeder, 20) Loewy and Münzer, 21) and Ito22) that in rabbits when the animals undergo an intravenous injection of hydrochlorid acid, the oxygen consumption diminishes, is accounted for by the acidosis. It is placed beyond doubt by the experiments of Ito, one of us (Hayasaka)23) and Dürr24) that an acidosis, deteriorating the oxidation in tissues, decreases the oxygen consumption. As already pointed out it is thought to be a strange phenomenon that CO2 output is appreciably decreased, in spite of profuse intake of CO2. But in Eppinger's25) experiments a dog (14 kilos body weight) showed after the inhalation of air containing 12% CO2 for 90 minutes an accumulation of 7.68 liters CO2, of which only 6% was exhausted in 1 hour after the cessation of CO2 inhalation, and an another dog (12.6 kilos body weight) during the inhalation of air containing 14.3% CO2 lasting 90 minutes, an accumulation of 9.01 liters CO2, of which only 19% was discharged in 1 hour thereafter. In brief, the majority of inspired CO2 has been retained in the tissues, that is, the latter have a considerable power of combination with CO2. This is in accordance with the fact observed by Stinzing, 26) that CO2 was evolved in an amount of about 180% from a muscle by boiling it. Thus, although the process, in which CO2 is combined with the tissues, is accounted for with difficulty, it has been illustrated by Eppinger25) that even the quantity of CO2 which is only physically dissolved in the human tissues, would amount to 25-30 liters, if the profuse water content of the tissues and its absorbent coefficient of CO2 at body temperature are taken into consideration. Thus, when we reflect on these presumptions, it is quite right that the carbon dioxide which is accumulated in the tissues after CO2 inhalation should be considerable in amount. In reviewing our data, the difference obtained by reducing CO2 output per minute from the sum of the amount of inspired CO2 and the physiologically produced CO2 amount per minute, i. e. the accumulated CO2 amount in the body per minute is culculated as 333-913c. c., as is shown in Table III. As above stated, through CO2 inhalation the oxygen consumption is decreased, but CO2 output is more intensively diminished, whereby it is quite natural that the respiratory quotient is lowered. The fact that the pulse rate is increased owing to CO2 inhalation can be regarded chiefly as a sign following the accelerated respiratory function, but may partly be provoked by the stimulation of the sympathetic nervous system due to the increased secretion of adrenaline, which results through acidosis aroused by the CO2 accumulation in the body, as Macleod27) has maintained. The evidence that the minute volume is augmented by CO2 inhalation falls in with the condition that the cardiac function ought to be accelerated in order to supply plenty of oxygen to make good the decreased oxidation of the tissues, which is presumed from the lowering of the oxygen consumption.
In man, inhalation of an air containing 5.3-6.8% CO2 for 5-7 minutes is followed by increase in the blood sugar content and decrease in the lactic acid content. Haemoglobin content is not changed or tends to be diminished, so that the blood concentration has tendency to dilution or does not undergo any appreciable modification. Serum-protein content is lessened in the majority of cases, but is sometimes augmented, its variation not running parallel to that in the haemoglobin content. Sodium chloride content in serum varies only slightly and irregularly. Attempts are made to account for these changes in the blood being brought about through CO2 inhalation.