THE EFFECT OF PAINTING THE PANCREAS WITH ADRENALIN UPON HYPERGLYCEMIA AND GLYCOSURIA

After Blum's discovery of the production of glycosuria by the subcutaneous injection of adrenal extract, Herter has the merit of having found that injection of adrenalin into the peritoneal cavity also produces glycosuria; this is an undeniable fact. Concerning Herter's claim that intraperitoneal injection gives a higher degree of glycosuria than subcutaneous or intravenous injection, we offer no comment since we have made no observations on the glycosuric effect of subcutaneous injection of adrenalin, while we have made only three experiments by intraperitoneal injection. The most we can predicate on the basis of the present experiments is that intraperitoneal injection of adrenalin produces a somewhat higher degree of glycosuria than could be anticipated. However, in an earlier study carried out several years ago we arrived at the conception that the more slowly adrenalin was absorbed from the tissues into the circulation, the greater was its glycosuric effect; hence an intramuscular injection, which in its effect is nearly equal to that of an intravenous injection, induced a glycosuria definitely smaller than that set up by a similar dose administered subcutaneously. Unless the absorption from the peritoneal cavity is shown to be different from the absorption from subcutaneous injections, there could be no reason to assume that the glycosuric effect of intraperitoneal injection is much greater than that of subcutaneous injection. We might add that our former experiments do not support Herter's view that subcutaneous injection of adrenalin yields only slight degrees of glycosuria, because it is largely oxidized before entering the circulation. A difference exists in the effects upon blood pressure and upon sugar production, depending upon the mode of administration of adrenalin. With regard to the sugar production, a subcutaneous injection has a definitely greater effect than an intravenous injection; with regard to the blood pressure effect, however, the opposite is true. Herter states that an intraperitoneal injection of adrenalin exerts a smaller effect upon blood pressure than an intravenous injection—a fact which Auer and Meltzer can confirm for the rabbit. Our experiments lead us to conclusions which do not conform to those of Herter. It will be recalled that Herter and his coworkers state first, that painting the pancreas causes a marked glycosuria and hyperglycemia, and, second, that the glycosuria and hyperglycemia produced by intraperitoneal injections are of pancreatic origin; that is, they are produced by the adrenalin's coming in contact with the pancreas. In our experiments tabulated in Table IV, in which the pancreas was isolated from the rest of the peritoneal cavity, the glycosuria was about one-third, and the rise in blood sugar about two-thirds that obtained by painting the unisolated pancreas. Hence two facts may be deduced: first, that the painting of the isolated pancreas produces only mild glycosuria and hyperglycemia, and, second, that the greater production of sugar observed after the painting of the unisolated pancreas cannot be of pancreatic origin. Indeed, our experiments point rather to the conclusion that the larger production of sugar after painting the unisolated pancreas is due to the fact that a large part of the adrenalin escapes to the peritoneum. The last mentioned view is supported by the statement of Herter and Wakeman that "applications to the kidney are apt to yield more sugar than similar application to the liver, intestine, spleen, or brain, but the glycosuria is less marked than after the pancreas has been painted." Emerson and one of us had shown that a dissolved substance painted upon a kidney with an intact membrane is incapable of penetrating the membrane and affecting the kidney, or even incapable of entering the circulation, except when the solution escapes to other parts of the peritoneum. It was this observation which led to the suggestion that the effects observed by Herter of painting the pancreas might have been due to the escape of adrenalin to the celiac ganglion. This point has not been directly tested, but several experiments were performed in which the adrenals were painted with the effect on sugar production apparently as intense as that obtained by painting the unisolated pancreas. However this may be, and whether the production of sugar after painting the unisolated pancreas is due to the escape of adrenalin to some definite organ covered by the peritoneum (celiac ganglion or adrenals) or whether the peritoneum as a whole is responsible for the sugar production, it appears that, when sugar production follows the intraperitoneal injection of adrenalin, it is not of pancreatic origin

THE RELATION OF THE RATE OF ABSORPTION OF ADRENALIN TO ITS GLYCOSURIC AND DIURETIC EFFECTS

Subcutaneous injections of adrenalin are, in contrast with its behavior in the production of the other effects of that drug, more favorable to the production of glycosuria in rabbits than intramuscular injections; the failures are fewer and the quantities of dextrose in the urine are generally larger. In general, as regards the stimulation of diuresis by adrenalin, a subcutaneous injection exerts generally a greater effect than an intramuscular one. Subcutaneous injections of a certain dose of adrenalin distributed over several areas are far less effective than the administration of that dose in a single injection; they fail frequently to produce any glycosuria, the quantity of dextrose in the urine, when present, being less, and the quantity of urine being generally diminished. Apparently the more slowly the injected adrenalin reaches the blood, the greater is its effect in producing glycosuria and generally, also, the greater its diuretic action

AN EXPERIMENTAL STUDY OF THE QUESTION OF ASPIRATION OF FOREIGN MATERIAL INTO THE AIR PASSAGES DURING INTRATRACHEAL INSUFFLATION

The foregoing experiments clearly justify the following conclusions :— Intratracheal insufflation protects the respiratory tract very efficiently against any invasion from the pharynx. The filling up of the pharynx with extraneous material, whether it be from the stomach or from the mouth, brings no danger to the trachea and bronchi. This holds true even if the animal is under deep anesthesia. On the other hand, the presence of a tube in the trachea or larynx without the protection of an effective recurrent air stream, definitely facilitates the entrance of foreign material from the pharynx into the trachea. Anesthesia, which removes the protective action of deglutition, greatly increases the danger from aspiration in these cases

THE STATUS OF RESPIRATION IN THE METHODS OF DIFFERENTIAL PRESSURE COMPARED WITH THAT UNDER THE METHOD OF INTRATRACHEAL INSUFFLATION

The maintenance of life of an individual with an open double pneumothorax under differential pressure depends essentially upon the normal position of the lower lobes of the lungs and their close approximation to the diaphragm, especially of the posterior parts of the lobes. A complete dislodgment of both lower lobes leads invariably to the death of the individual, which may occur in a very short time, or after fifteen to twenty-five minutes. In all cases the respiration is affected first; it slows almost at once and stops invariably before the heart. The result is the same whether the vagi are intact or both nerves are cut. Exceptionally, respiration may continue even after the separation of the lungs from the diaphragm, but only by having all the lobes well approximated to the thoracic walls. When by dislodgment of the lower lobes the respiration is stopped and the heart is feeble and slow, or stopped completely, it is rarely possible to restore life by artificial respiration or by other appropriate means. The extent of the exchange of gases occurring in normal respiration, with closed thoracic cavity, exceeds greatly the need for the maintenance of life, since normal respiration is provided with an abundance of factors of safety. Under differential pressure, however, life is carried on with an exchange of gases which amounts to a small fraction only of the extent of the exchange that takes place in normal respiration; respiration under differential pressure is, therefore, deprived of all factors of safety and is incapable of resisting the dangers of exceptional incidents. Deaths occurring in connection with the differential pressure have their cause essentially in this unguarded state of the function of respiration. Under tracheal insufflation, the function of respiration is surrounded with effective safeguards, at least as much as is normal respiration. Dislodgment of the lungs has no detrimental effect. After complete collapse of the lungs, capillary adhesions within the alveoli and the small bronchi become an additional obstacle to the redistension and respiration. Differential pressure holds this obstacle in abeyance. When the lungs become collapsed during an open pneumothorax, it should be kept in mind that the force which is required for redistension is greater than that which is sufficient to keep the lungs continually distended. At the beginning of a redistension, therefore, a higher pressure should be employed for a short time

THE CHARACTER OF THE PNEUMONIC LESIONS PRODUCED BY INTRABRONCHIAL INSUFFLATION OF VIRULENT STREPTOCOCCI

Comparing the pneumonic lesions produced by this very virulent streptococcus with those caused by a mildly virulent strain of the same organism, we find that with one exception the differences between them are only of a quantitative nature and not striking. There are the same intense leucocytic exudation into the alveoli and the leucocytic infiltration of the framework of the lungs. Macroscopically the pneumonia produced by the virulent organism was, as a rule, lobular in character. Occasionally, however, especially when large doses of the culture had been given, the gross appearance of the lesion gave the impression of a lobar pneumonia. But even in these cases the cut surface showed that the solid areas were separated by softer and lighter areas of aerated, congested, or edematous lung substance. Pleurisy was practically absent from the lungs in this series of experiments; only one case showed a narrow strip of fibrinous exudate on the pleura. Although in some instances large doses of the cultures were given and some dogs were permitted to live six or seven days, there was no mortality among the dogs in these experiments, just as there had been none among the animals experimented upon with the streptococcus of very low virulence. The course of the pneumonia caused by the virulent organism seemed to be somewhat longer than that produced by the less virulent one; areas of resolving pneumonia were found to persist on the sixth and seventh days after the injection, and in one such instance the solid focus contained viable organisms. There was some difference in the amount of fibrin present in the exudate caused by the two strains of streptococci. Although even in these experiments the amount of fibrin present was less than that found in the lesion produced by the virulent pneumococcus, it was perceptibly larger than the very small amount found in the lesions caused by the less virulent strain of streptococcus. It should be mentioned that there was no difference in the degree of phagocytosis observed in these two series of experiments. It was not marked in either case. One point of difference in the two series was noted: during the first forty-eight hours after insufflation of the virulent strain of streptococcus the blood of the animals obtained from the jugular vein during life and from the heart after death contained living organisms, while in the experiments with the slightly virulent streptococcus no living cocci were recovered from the blood. The virulence of the strain of streptococcus employed in the present investigation was, as has been pointed out, similar to that of the pneumococcus employed in the investigation of Lamar and Meltzer and in many of our own experiments, as far as mice were concerned, since both killed mice weighing fifteen grams in doses of 0.000,001 of a cubic centimeter in twenty-four to thirty-six hours. The findings in the lesions caused by these two organisms are comparable and therefore some deductions may be drawn regarding the similarity or dissimilarity of their actions. One of the first things we wish to bring out is the correction of our former statement regarding the presence of the cocci in the blood. As our new investigation shows, there is evidently no difference in this respect between the streptococcus and the pneumococcus. When both organisms are highly virulent they can be found in the circulating blood of the living dog or in the heart's blood of the dead dog during the first twenty-four or forty-eight hours after an intrabronchial insufflation. On the other hand, the present investigation rather confirms in a general way our first contention that the pneumonic lesions produced by the two different organisms differ distinctly in many ways. There is the difference in the mortality; even with fairly large quantities of the culture of the virulent streptococcus the mortality was nil in this series, although some of the dogs were kept alive for six and seven days. The mortality of the pneumococcus infection depends upon the quantity insufflated and may amount, as Lamar and Meltzer pointed out, to 16 per cent. The gross appearance of the lesion produced by the pneumococcus is, as frequently stated, that of a lobar pneumonia, frequently accompanied by a fibrinous exudate on the pleura. The gross appearance of the lesion produced even by a virulent streptococcus is, as a rule, that of a lobular pneumonia and is practically never accompanied by pleurisy. In the few instances in which large quantities of the streptococcus were given and the outward appearance of the lungs approached that of a lobar pneumonia, it was found that on section of the consolidated lung the solid foci proved to be separated by lighter areas of aerated, congested lung. In the lesions produced by the virulent streptococci the walls of the finer bronchi and the framework of the lung were markedly infiltrated with leucocytes, while in the lobar pneumonia produced by the pneumococcus the framework remained free from such infiltration. Finally there is the unmistakable difference in the amount of fibrin present in the alveolar exudate. While in the exudate of the lesion produced by the virulent streptococcus the amount was perceptibly larger than the insignificant amount present in the lesion caused by a slightly virulent strain, it is not to be compared with the large amount of fibrin which exists in the exudate of pneumococcus pneumonia. The several investigations which we have carried out seem to show conclusively that in general the streptococcus causes a lobular pneumonia which, besides the leucocytic intra-alveolar exudation, is characterized by a leucocytic infiltration of the lung framework, and that the pneumococcus causes a lobar pneumonia, which is practically free from leucocytic infiltration of the interstitial tissue of the lung. Furthermore, a virulent pneumococcus causes a lesion in which fibrin is a prominent element in the exudate and that element distinguishes the exudate sharply from the exudate of the lesion caused by a virulent streptococcus in which fibrin is present only in moderate amount. It distinguishes it in a still more striking manner from the exudates of the lesions caused by non-virulent pneumococci or streptococci, in which fibrin is present only in very small amounts. It seems that the formation of fibrin is connected in some specific way with the pneumococcus on the one hand, and with the virulence of the organism on the other. For even with the relatively small amounts of fibrin present in the exudates of lesions caused by the streptococcus there is a perceptible difference in the quantity according to the virulence of the organism. Whether fibrin is a means which enhances virulence, or whether it is a reaction product against it, our experiments so far do not entitle us to discuss

THE EFFECTS OF INTRASPINAL INJECTION OF MAGNESIUM SALTS UPON TETANUS

Intraspinal injections of magnesium sulphate, in doses which do not affect the respiratory centre or other vital function, are capable of abolishing completely all clonic convulsions and tonic contractions in cases of human tetanus, and experimental tetanus in monkeys. The relaxing effects of the injections may last twenty-four hours or longer. In experimental tetanus in monkeys early intraspinal injections of magnesium salts are capable of retarding the progress and development of the tetanic symptoms