Maurice B. Visscher

STUDIES ON THE CIRCULATORY CHANGES IN THE DOG PRODUCED BY ENDOTOXIN FROM GRAM-NEGATIVE MICROORGANISMS

A clinical problem of increasing magnitude is the occurrence of hypotension in patients with bacteremia associated with the liberation of endotoxin from gram-negative microorganisms (1-3). Although the local vascular effects of endotoxin have been extensively studied in animals, particularly with reference to necrotizing effects on tumors (4, 5) and the Schwartzman reaction (6, 7), the hemodynamic alterations produced by these bacterial products remain unexplained. Endotoxins constitute a group of similar chemical substances identified as protein-polysaccharide complexes (8). In the course of a series of investigations reported elsewhere (9, 10), it was found that the pattern of the shock and the pathological changes in the gastrointestinal tract produced by the intravenous injection of endotoxins derived frotn Brucella melitensis, Escherichia coli, Serratia marcescens 1 and Salmonella typhosa 1

The energy metabolism of the heart in failure and the influence of drugs upon it

Abstract The failing heart has been shown to suffer first simply from a decrease in mechanical efficiency. The energy liberated at a given external diastolic volume remains the same, only the proportion which can be put to useful work falls off. There is in some instances in severe failure a decrease in the oxygen consumption of the heart held at constant external diastolic volume. The hydration of the myocardium under such circumstances has been measured and found to be sufficient to account for the falling off in energy liberation on the basis of the decrease in true mean fiber length when external volume only is kept constant. It is consequently still unnecessary to alter the generalization that initial fiber length governs energy liberation in the failing as well as in the normal heart, when chemical conditions are kept constant. The importance of the concept of the heart as a machine, doing work, with variable efficiency, has been stressed. Insufficient attention has been given in the past to the concept of efficiency in the physical sense as a criterion of the condition of the heart muscle. These studies appear to prove that myocardial failure consists, in essence, of an alteration of the energy-utilizing and not the energy-liberating mechanism. The machine is able to liberate energy, but it is unable to put it to useful work. The correction of this defect should be the physiological objective in the treatment of myocardial failure. The effects of several substances upon the heart muscle have been tested from this point of view. Histamine in effective doses decreases the oxygen consumption of the heart-lung preparation in spite of dilatation. This effect is associated with and presumably due to hydration. Cardiac failure following administration of sodium amytal is due entirely to a decrease in efficiency at constant external diastolic volume. Parathyroid extract increases the oxygen consumption and decreases the external efficiency of the heart. Several reputed cardiac tonics have little or no direct beneficial action on the heart. Coramine produces, instead, dilatation with decreased output and efficiency. Calcium increases the oxygen consumption and efficiency of the heart muscle at constant external diastolic volume. Glucosides of the digitalis series have the same action as calcium, but the maximum effect is delayed. It has been pointed out that these studies on the digitalis glucosides are significant chiefly in elucidating the mechanism of their action, but that a physiological rather than a toxicological assay of such substances has certain virtues. The methods employed in this study might properly be used in the study of the beneficial action of new agents on the failing heart.

Regular diurnal physiological variation in eosinophil levels in five stocks of mice.

Summary In 4 inbred strains and in one hybrid group of mice a regular diurnal variation of large magnitude in the circulating eosinophil count has been demonstrated. On the average, in these strains, the midnight count was less than one third of the morning level.

[Daily changes in 5-hydroxytryptamine concentration in mouse brain].

Summary ZBC mice, male or female, 5 or 7 weeks of age, were studied under conditions standardized for evaluation of 24-hour periodicity. A small but significant decrease in 5-HTA concentration of brain pools was noted prior to usual time of arousal. A sex difference in brain 5-HTA concentration also was recorded, the females exhibiting slightly higher values.

Canine Intestinal and Liver Weight Changes Induced by E. colt Endotoxin

Summary 1. Systemic arterial blood pressure response of the dog to injection of Es-cherichia coli endotoxin is characterized by a sudden precipitous drop, a partial recovery and a subsequent slower decline over a period of hours. 2. Utilizing a device for quantitatively estimating changes in weight of organs in vivo, an increase in liver weight of from 80 to 350 g has been noted within one to 2 minutes following injection of E. coli endotoxin. 3. Simultaneous increase in weight of small intestine of lesser magnitude (28 to 170 g) was noted at the same time and is believed to be due to back pressure from the liver. Increase in liver and intestinal weight were believed to be quantitatively sufficient to account for the hypotension observed. 4. A difference in reaction of the liver and intestine was noted. Whereas the liver returns to normal weight within 5 to 25 minutes, the small intestine continues to increase in weight reaching a maximum of from 196 to 770 g approximately one hour following endotoxin injection. 5. The secondary hypotension due to endotoxin is believed to be at least partially the result of loss of blood in the small intestine due to vascular damage in this organ.

The influence of insulin upon the mammalian heart.

WE have investigated the effects of preparations of insulin upon (A) the mechanical condition of the mammalian heart, in the heart-lung preparation and in the whole animal, and (B) the oxrygen consumption of the heart in the heart-lung preparation. No previous study has been made of the effects of insulin preparations upon the mechanical behaviour of the mammalian heart under such conditions as would exclude effects upon the rest of the circulatory system as well as upon other tissues of the body. Our attention was drawn to the subject by entirely unexpected observations while injecting insulin into the heart-lung preparation with the sole aim in view of measuring its oxygen consumption. The respiratory metabolism of the isolated heart under insulin has been studied by Burn and Dale(i), who found that there was sometimes an increase, and by P e s eric o (2) who found a random variation in either direction. The importance of the question of whether or not insulin actually hastens metabolism in active tissues, normal or diabetic, led us to re-investigate the problem with a better control upon the normal rate of metabolism, which the demonstration of the relation between diastolic ventricular volume and oxygen consumption by Starling and Visscher(3) enabled us to maintain.

Characterization of milk influence in spontaneous mammary carcinoma.

Previous studies 1 , 2 , 3 , 4 , 5 , 6 indicate the presence, in at least certain tissues of high cancer strain mice, of a substance or substances whose presence is essential to spontaneous mammary carcinoma. In these studies lactating mammary tissues inclusive of their contained milk have been brought into suspension and partial solution by micro-homogenization and the resulting fluid separated into several fractions by the use of an ultracentrifuge. Procedure. Fostered female C3H mice 1 month old were employed as test animals. Lactating breast tissues were obtained immediately after death by etherization, from high cancer C3H and A strain mice. The material was immediately homogenized with addition of between one and two times its volume of sterile distilled water. The resulting fluid was spun in the centrifuge at 15,000 rpm, giving a maximum accelerational force of 15,000 x g, for 30 minutes. Three layers resulted, a fatty top layer, designated as the fat fraction, a middle aqueous layer, the first supernatant fluid, and a bulky precipitate, the first sediment. The fat fraction was removed and employed as noted below. The aqueous layer was removed by suction without disturbing the sediment. The first supernatant fluid was then spun at 40,000 rpm, corresponding to 110,000 x g, for a period of 60 minutes. The final supernatant fluid was removed without disturbing the second sediment. The materials used for feeding or injection were (1) homogenized tissue, (2) fat fraction, (3) first sediment, (4) second sediment, and (5) final supernatant fluid. The amount of material of each fraction which was injected or fed was usually that which was obtained in that fraction from 1 g of original tissue.

The effects of alloxan and histamine on the permeability of the pulmonary alveolocapillary barrier to albumin

1. [131I]albumin transport from alveolus to perfusion fluid was evaluated in an isolated dog lung lobe preparation perfused at constant pressure with homologous plasma. The alveoli were filled with a 1:1 mixture of Ringer—Tyrode solution and plasma.

Occurrence of Endocarditis with Valvular Deformities in Dogs with Arteriovenous Fistulae.

Summary Observations have been reported in which after the creation of large arteriovenous fistulae in dogs endocarditis occurred without intentional introduction of bacteria. This result occurred in about 8 out of 10 dogs in which sufficiently large shunts existed for more than 4 weeks. Adrenal gland enlargement occurred following creation of a large fistula. Other concomitant findings have been reported and discussed.

Single Versus Multiple Gage Occupancy and Convulsion Frequency in C3H Mice.

Conclusions C3H male mice, singly housed and fed ordinary diets, show a high incidence of convulsions, associated chiefly with cage changing and weighing. When housed in pairs or larger groups the incidence of convulsions is low and the mortality negligible.