THE CONSTRICTING INFLUENCE OF ADRENALIN UPON THE HUMAN CORONARY ARTERIES

1. Adrenalin causes a marked constriction of the human coronary artery, although it undoubtedly produces a relaxation in some mammals; e. g., calf, sheep, pig, etc. 2. The human coronary artery is probably provided with sympathetic vasoconstrictors. 3. If human blood-vessels are obtained in a warm condition within a few hours after death, they are often suitable for biological and pharmacological study.     

OBSERVATIONS WITH REGARD TO THE ACTION OF EPINEPHRIN ON THE CORONARY ARTERY

1. Excised rings of the coronary artery of the ox properly weighted react to epinephrin by dilatation. 2. This reaction of the ox coronary is not an active dilatation, but is in the nature of a sudden lowering from a high to a relatively low degree of tonus. The tonus is not, however, entirely abolished by epinephrin. 3. The degree of relaxation produced by epinephrin is not constant. It depends on several factors other than the concentration of epinephrin used. 4. It is possible to increase the sensitiveness of the coronary artery to epinephrin. 5. There is no evidence of any primary constrictor effect on the ox coronary from epinephrin in most dilute solutions, nor can the existence in this artery of any constrictor mechanism of sympathetic origin be determined by the excised ring method.     

THE QUESTION OF EPINEPHRIN IN THE CIRCULATION AND ITS RELATION TO BLOOD PRESSURE

1. The modified Meyer method here proposed, of parallel tests upon segments of surviving carotid and coronary arteries from the ox, is a satisfactory means for detecting epinephrin in complex body fluids like blood. 2. At the present time there is no evidence that epinephrin, in amounts sufficient to produce its physiological effects upon any hitherto used test objects, exists in the circulating blood, with the exception of blood from the suprarenal vein. 3. The examination of uncoagulated blood from six persons with high blood pressure has failed to show the presence of epinephrin or other constricting substances. 4. The constrictor substance in defibrinated blood and serum is not an epinephrin-like substance. In its point of action and its effects it is similar to barium chlorid. It is a direct stimulant to smooth muscle and seems to have no relation to the sympathetic innervation of muscle.     

EFFECT OF STIMULATION OF SENSORY NERVES UPON THE RATE OF LIBERATION OF EPINEPHRIN FROM THE ADRENALS

An attempt was made to determine whether stimulation of afferent nerves (sciatic and brachial) produced a detectable increase in the rate of liberation of epinephrin from the adrenals, as determined by testing adrenal vein blood on rabbit intestine and uterus segments. The result was negative.     

THE INFLUENCE OF CERTAIN FACTORS,ESPECIALLY EMOTIONAL DISTURBANCES,ON THE EPINEPHRIN CONTENT OF THE ADRENALS

1. No evidence has been obtained that in cats and dogs with the nerves of one adrenal cut, emotional disturbances cause depletion of the epinephrin store of the normally innervated adrenal as compared with its fellow. 2. The depletion of the epinephrin store in cats under morphine is not dependent upon so called morphine fright, since a similar depletion is found in dogs in which, as is known, morphine produces symptoms the reverse of those of fright. 3. The signs of morphine fright can all be elicited by administering morphine to a cat in which one adrenal has been removed and the nerve supply of the other cut, and in which accordingly no detectable liberation of epinephrin takes place. 4. The reactions of the denervated iris elicited by emotional disturbance, asphyxia, or etherization in a cat, one of whose adrenals has been removed and the nerves of the other cut, do not differ from these reactions in cats whose adrenals have not been interfered with. 5. The influence of postoperative edema of the adrenal in diminishing the epinephrin load, and the recuperation of the load after a time, have been studied in rabbits. 6. The diminution in the epinephrin store of the adrenals which follows operations on animals (postoperative depletion) has been studied. It is only in part associated with the anesthesia, since it may be as marked 6 or 8 hours after an operation lasting less than 1 hour as after 6 or 8 hours'' anesthesia without operation. 7. One adrenal was removed in rabbits and the epinephrin content of the remaining gland assayed at varying periods of time after removal of the first, the periods being longer than the time necessary for recovery from the postoperative depletion. In general, the second adrenal contained more epinephrin than the first, sometimes double the amount. 8. Marked depletion of the epinephrin store of innervated adrenals as compared with the corresponding denervated glands was seen in animals dead of infections of various kinds. 9. As shown by Elliott, diminution of the stock of epinephrin in the adrenal through electrical stimulation of the splanchnics is not easy to demonstrate, despite the fact that the liberation of epinephrin into the blood is notably increased by the stimulation. With short periods of stimulation, however, repeated over a long time at intervals just long enough to prevent fatigue, it has proved possible to demonstrate a distinct depletion.     

FIBRILLATION OF THE AURICLES: ITS EFFECTS UPON THE CIRCULATION

When the auricles fibrillate, the following effects are observed. 1. The arterial blood pressure may rise, fall, or remain stationary. Usually it falls. If it falls, it generally rises again towards or to the initial pressure. 2. The venous pressure changes are the reverse of the arterial. 3. The intestinal volume and the cardiac output changes are in the same direction as those of arterial blood pressure. 4. From these observations it may be concluded that the peripheral circulatory effects are purely passive. 5. The volume of the heart decreases except in instances where there is reason to believe that the circulation is failing. All the changes described in the foregoing paragraphs, and also the variations in blood pressure reactions which occur from time to time, are attributable to alterations in the rate of ventricular contraction. Similar, though perhaps less profound changes, are seen when the heart rate accelerates in like degree in response to regular induction shocks.     

ON THE INHIBITORY INFLUENCE OF EOSIN UPON SPORULATION

Sporulation of B. anthracis, B. subtilis, B. cereus, B. ruminatus, B. mesentericus, B. anthracoides and B. megatherium does not take place in an agar medium containing eosin "Gelb" in a concentration exceeding 0.5 per cent. In a concentration of 0.1 per cent. most of these bacteria fail to produce spores. The greatest sensitiveness is shown by B. cereus and B. mesentericus. In a bouillon medium sporulation is likewise inhibited by eosin, but after a longer time—seven weeks or more—sporulation still occurs where the concentration of the dye equals one-tenth per cent. Sporulation of B. tetani, B. anthracis symptomaticus, B. botulismus, B. œdema maligni, B. enteritidis sporogenes, and B. putrificus does not take place in a medium containing eosin "Gelb" in concentrations exceeding 0.03 per cent. With these organisms, no difference was noted in the final effect, depending on the medium employed. No permanent loss of power to produce spores ensues with the bacteria tested even after long sojourn in the eosinized media. It may be stated that on the whole the inhibitory action of eosin was more pronounced upon the anaerobic than upon the aerobic species of bacteria employed in these experiments.     

THE INFLUENCE OF CALCIUM CHLORIDE UPON EXPERIMENTAL BOTULISM

1. Calcium chloride given subcutaneously, intraperitoneally, or intravenously has been found to have no effect upon the production of botulism following the injection of Bacillus botulinus (Strain 80B) into the peritoneal cavity of guinea pigs. 2. Treatment of Bacillus botulinus with alcohol has been found markedly to decrease its toxicity for guinea pigs. This is in conformity with the work of Bronfenbrenner and Schlesinger. 3. Toxin-free spores of Bacillus botulinus have been found pathogenic for guinea pigs. 4. No prejudice as to possible results in rabbits should be based upon the above conclusions.     

THE INFLUENCE OF LECITHIN AND CHOLESTERIN UPON THE GROWTH OF TUMORS

1. Cholesterin, whether suspended in dilute alcohol or in sodium oleate solution, when injected directly into tumors causes a marked acceleration both of the primary and of the metastatic growth. 2. The acceleration of the growth of the primary tumor by cholesterin is most evident in the premetastatic stage. 3. Lecithin, when injected in the form of an aqueous emulsion directly into tumors, diminishes the tendency to form metastases, retards the metastatic growth when it does occur, and in some instances also retards the primary growth. 4. The retardation due to lecithin is most evident in the metastatic stage. 5. Simultaneous injection of M/6 strontium chloride solution into the tumors does not appreciably affect the action of the lecithin.     

THE INFLUENCE OF THE REDUCTION OF KIDNEY SUBSTANCE UPON NITROGENOUS METABOLISM

1. The removal of one half, two thirds and sometimes three quarters of the kidney substance in the dog causes no change in the general nitrogenous metabolism as determined by estimations of the total nitrogen, urea and ammonia elimination by the urine. 2. The removal of larger amounts, and sometimes of three quarters of the substance, leads to the metabolism condition of starvation. This, however, is apparently the result of the gastro-intestinal disturbance constantly associated with extensive kidney reduction and not of a disturbance of general nitrogenous metabolism. 3. The determination of the amount of fæcal nitrogen indicates that the gastro-intestinal disturbance is not due to diminished absorption; and except in one instance there was no evidence of its being due to an increased elimination of nitrogenous substances into the intestine. 4. These experiments do not support the theory that the kidney furnishes an internal secretion having an important influence on general nitrogenous metabolism. At least, if such a function exists, it is not disturbed by the removal of three quarters of the kidney substance. 5. The metabolism in excessive kidney reduction is that of inanition dependent on gastro-intestinal disturbances presumably due to faulty chemical correlation. In this connection further knowledge concerning the elimination into the intestine of toxic substances is desirable.     

THE INFLUENCE OF BIOTIN UPON SUSCEPTIBILITY TO MALARIA

Biotin-deficient chickens and ducks developed much more severe infections with Plasmodium lophurae than did non-deficient control animals. While a very mild degree of biotin deficiency sufficed to increase susceptibility, even an extreme degree of pantothenic acid deficiency had no effect. Biotin deficiency also increased the susceptibility of ducks to P. cathemerium. In animals infected with P. lophurae, the concentration of biotin in the plasma as well as in the red cells rose during the course of the infection, reached a peak at about the same time as the parasite number reached its peak, and then returned to normal as the infection subsided. While the administration of additional biotin to animals partially deficient in biotin could be considered a specific measure tending to lessen the severity of infection with P. lophurae, the injection of biotin into animals fed a diet adequate in this vitamin had no antimalarial effects, perhaps because the excess biotin was rapidly removed from the blood.     

ON THE INFLUENCE OF THE REACTION AND OF DESICCATION UPON OPSONINS

Opsonins reveal their maximum action in a medium of neutral reaction. No opsonization takes place in a serum which contains an amount of alkali corresponding to more than 1.6 c.c. of a 1/20 N. solution, or acid more than 0.5 c.c. of this concentration per 1 c.c. of serum. Of several normal blood serums titrated (lacmoid used as indicator) the average alkalinity was found to be equivalent to about 0.8 c.c. of 1/20 N. solution. The opsonic index obtained in the native serums is not the expression of the action of the whole content of opsonins, but only so much as the degree of optimum of the reaction permits to come into action. Estimation of the opsonic power should, therefore, be made in a medium of neutral reaction and in diluted serum. All serums have their opsonic power increased by diminishing the native alkalinity. Opsonins whose activity is suspended by an unfavorable reaction become immediately active as soon as the reaction is brought back to the neutral point, unless the acid or alkali employed approaches the strength of 1 N., at which point the alteration becomes permanent. Treatment of a serum with alcohol robs it of its opsonic power. The opsonic power of serum remains unaltered upon desiccation at 23° C. In the dry state opsonins are preserved for two years. The temperatures of 100°, 120°, 135° and 150° C. do not destroy opsonins of the dried serum. Complements of serum are also siccostabile and are preservable in that state for several months. Dry heat of 135° C. reduces but does not destroy the complementary power of the dried serum. The opsonins and complements of the dried serum regain their original thermolability when they are dissolved in a proper amount of water. Lastly, it may be emphasized that opsonins exhibit in their sensitiveness to reaction and resistance in the dry state to high temperatures certain properties characteristic of the ferments.     

THE INFLUENCE OF NITROGEN RETENTION UPON THE REGENERATION OF PLASMA PROTEINS

1. Because of the clinical observation that the capacity to form new plasma proteins is sometimes impaired in cases of nephritis (2), experiments were performed to determine whether the impaired function in the nephritic is related to nitrogen retention. 2. These experiments consisted of producing renal injury by injecting uranium nitrate into standard hypoproteinemic dogs and comparing the rate of blood plasma protein formation under these conditions of nitrogen retention with that in the uninjured dog. 3. Despite elevations in blood N.P.N. to more than ten times normal, no interference with plasma protein formation was observed. These elevations in N.P.N. affected principally the urea and undetermined fractions. 4. Neither elevation in N.P.N. nor proteinuria per se appears to have any effect upon plasma protein production. Possibly the deficient production of plasma proteins in the nephritic is related to a more general disturbance in metabolism in which the elevation in N.P.N. is secondary.