Normal Dog Plasma Research Articles

The comparison of erythropoietin activity in lymph and plasma.

Erythropoietin activity in lymph and plasma of normal and anemic dogs and sheep was tested. No erythropoietin activity in lymph from thoracic duct or renal lymph vessel in the normal animals was determined. In normovolemic anemic dogs the erythropoietin activity in plasma or lymph from thoracic duct was increased 4 and 8 h after bleeding. The rise of erythropoietin activity in the lymph did not differ from that of plasma.

Inositol production by the brain in normal and alloxan-diabetic dogs

It was found that there was no net uptake of inositol by CSF from plasma, indicating that the high concentration of inositol in the CSF relative to that in plasma of normal and diabetic dogs originates from inositol synthesized by brain. The inositol concentration and rate of efflux from the CSF were used to measure inositol turnover in CSF, and from this was calculated a minimum rate of inositol production by dog brain in vivo. There was no significant difference in the rate of inositol production by the brain (88 μmoles/kg brain/h) between the normal and alloxan-diabetic dog.

Studies on the role of phospholipids in the triglyceride cycle. II. Turnover of plasma phospholipids in ethionine-treated dogs.

AbstractThe disappearance of native labeled plasma phospholipids (nPLP32) was abruptly halted in the plasma of normal mongrel dogs shortly after givingdl‐ethionine by intraperitoneal injection. In other dogs, chronic feeding of ethionine over a period of three days prior to these measurements prolonged the turnover time of plasma phospholipids. This impairment in the turnover of plasma PL brought about by ethionine administration occurs regardless of sex differences in lipid metabolism or other physiological differences relating to the nutritional status of the animal. The amount of nPLP32 found in the liver at the end of the turnover experiments was also measured. These data suggest that phospholipid transport from plasma to liver is not impaired by ethionine. The possible significance of an ethionine‐induced choline deficiency which impairs transport of triglycerides and phospholipids from the liver to plasma is considered in regard to the role of phospholipids in the triglyceride cycle.

Factor VII deficiency in beagle dog plasma and its use in the assay of human factor VII.

DURING routine screening tests on a group of beagle dogs before a toxicological test, it was noted that several dogs showed a prolonging of the one-stage prothrombin time. Some of these dogs were found to be related (Fig. 1). The results of more detailed tests showed that intrinsic prothrombin activation was normal (Table 1) and that extrinsic prothrombin activation could be corrected by adding aliquots of normal human plasma or serum, normal dog plasma or serum, and Russell viper venom (Table 2). In addition, liver function tests were normal and the presence of an inhibitor was excluded (Table 3). Finally, factor VII activity assays, using congenitally deficient human plasma, confirmed that this factor specifically was reduced.

Factors influencing hematopoietic spleen colony formation in irradiated mice. II. The effect of foreign materials.

Normal dog plasma and serum, human, rat, and Swiss-Webster mouse plasma, phytohemagglutinin, sheep red cells, mumps and influenza vaccine, fibrinogen, and endotoxin injected before irradiation led to an increased number of endogenously derived spleen colonies in irradiated mice. Spleen weight and uptake of radioactive iron and iododeoxyuridine into such spleens were also increased. The relationship between these parameters of splenic hematopoiesis was unchanged by plasma injection suggesting that, while the number of colonies was increased, the composition of individual colonies was unchanged. This conclusion was supported by studies on plethoric mice in which splenic erythropoiesis is abolished. Increased splenic hematopoiesis was accompanied by an increase in the volume of packed red blood cells 10 days after irradiation. The total volume of plasma injected, the number of days of plasma injection preceding irradiation, and the route of administration were all important variables influencing the effect of plasma injections. Crude fractions of human albumin and gamma globulin, cortisol, C57BL (maternal) and DBA (paternal) mouse plasma, and isogeneic plasma were without effect. The ineffectiveness of isogeneic and closely related allogeneic plasma rendered unlikely the hypothesis that this effect represented the presence of homeostatic hematopoietic regulating factors in plasma. The increased hematopoiesis induced with plasma appeared to be limited to the spleen, for increased bone marrow hematopoiesis was not detected. Certain observations suggested that the effect of plasma may not be due to an antigenic or an inflammatory effect. From current observations, it was unclear whether the increased colonies induced by plasma were representative of expansion of the colony-forming cell pool or of increased efficiency of growth of the fraction surviving irradiation.

Total osmotic activity values for the synovial fluid and arterial plasma of normal humans, normal dogs and patients with joint effusions.

Total osmotic activity values for the synovial fluid and arterial plasma of normal humans, normal dogs and patients with joint effusions.

Role of a plasma factor in porphyrin biosynthesis.

SummaryEvidence is presented which indicates that there is present in the plasma of normal dogs a factor, possibly some type of plasma protein or a related substance, which inhibits in vitro biosynthesis of porphyrins from ALA. The amount of activity of this factor is decreased in the plasma of anemic phenylhydrazine-treated dogs. It is suggested that this plasma inhibitory factor may play a physiological role in regulating porphyrino-genesis.

An inhibitor of the lipolytic reaction from post-heparin plasma of normal dogs

A factor which was capable of inhibiting the hpolytic activity in vitro of the heparin-induced clearing factor lipase has been isolated from normal post-heparin plasma. Inhibition was found to be proportional to the concentration of the inhibitor and to the time during which the inhibitor was present in the reaction medium. Increased concentrations of substrate or enzyme did not alter the magnitude of inhibition. The action of the inhibitor appears to be of the non-competitive type.

INCREASED PLASMA LEVEL OF RENIN IN EXPERIMENTAL SECONDARY HYPERALDOSTERONISM.

Renal and peripheral venous plasma was prepared for assay of renin by the technique of Helmer and the formed angiotensin II was assayed for both pressor and steroidogenic activity. Both assays showed higher concentrations of renin in both renal and peripheral venous plasma from dogs with thoracic caval constriction than from normal dogs. The increase in aldosterone and corticosterone secretion by isolated adrenals in response to incubated plasma with its formed angiotensin II was qualitatively similar to that observed for synthetic angiotensin II. Thus, the steroid assay provided evidence that the final product formed for assay was angiotensin II. That the pressor activity in renal vein plasma was referable to a substance of renal origin is indicated by the lower level of activity in peripheral venous than in renal venous plasma and the fall in activity in peripheral venous plasma following nephrectomy. Further evidence for the validity of the assay for renin was obtained from studies of renin substrate. A large excess of renin substrate was found in normal dog plasma so that angiotensin II formed by incubation was not limited by substrate exhaustion. Also, the peripheral plasma level of renin substrate was essentially the same in dogs with thoracic caval constriction and in normal dogs.

Fibrinolysis and Fibrinogen Breakdown Products (Antithrombin VI) in Renal Venous Blood (RVB) in Dog

SummaryThe authors investigated fibrinolytic system of renal venous blood (RVB) peripheral venous blood (PVB) in normal dogs and in those with kidney injury produced by mercury chloride. An increase of fibrinolytic activity as well as a decrease of the level of plasminogen and fibrinogen were found in RVB plasma of normal dogs. An inhibition of the fibrinolytic activity was found in intoxicated dogs in both RVB and PVB plasmas, followed by an increase of plasminogen and fibrinogen levels. The occurence of fibrinogen breakdown products, antithrombin VI, was demonstrated in RVB plasma of normal dogs. It does not appear in RVB plasma of intoxicated dogs.On the basis of experimental results an important role of urokinase, secreted by the kidney into the general circulation is suggested as regards the maintenance of the coagulation and fibrinolysis balance in the organism as well as in the fibrinogen and plasminogen catabolism.It has been also concluded that the antithrombin VI, formed in the kidney circulation is a natural inhibitor of blood coagulation appearing in physiological conditions.

Inhibition of Aldosterone-Stimulating Activity of Hog and Dog Renin by the Plasma of Dogs Immunized with Hog Renin.

SummaryThe aldosterone-stimulating and 17-hydroxycorticoid-stimulating activity, as well as the pressor activity, of both hog and dog renin were inhibited when prior to injection into nephrectomized hypophysectomized assay dogs, the renin preparations were incubated with the plasma of dogs immunized with hog renin. Incubation with normal dog plasma had no effect on their activity.

Isolation and identification of 17 alpha-hydroxyprogesterone in adrenal venous plasma of normal dogs.

SummaryBy criteria of paper chromatography in several systems, ultraviolet and infrared spectrophotometry, 4 pregnene-17 α-ol-3.20, dione has been isolated and identified in adrenal vein blood of normal dogs given adrenocorticotropin intravenously. This steroid could not be detected in blood from the systemic circulation of dogs given adrenocorticotropin.The authors wish to express gratitude to Dr. Leo T. Samuels for helpful criticism and to Dr. Gunter Zweig, University of California, Pesticide Residue Research, Davis, Cal., for infrared analysis.

Plasma lactic dehydrogenase activity in experimental hemorragic shock.

Summary1. Marked elevations of plasma LDH activity in experimental hemorrhagic shock are described. An initial lag period is followed by a sharp rise to 15 to 50 times the original value. 2. Alterations of plasma LDH activity in shock bear a consistent relationship to such parameters of biological deterioration as rate of spontaneous return of blood from the reservoir to the animal (“taking up”) and reversibility to replacement transfusion. 3. Catheterization experiments in which consistent arterio-venous differences were demonstrated indicate that the sources of elevated plasma LDH activity are widespread and include liver, kidney and tissues of an extremity. 4. Electrophoretic separation of normal dog plasma reveals 4 enzymes with LDH activity. All 4 are elevated in plasma of dogs in shock. 5. Marked elevations of plasma GO-T, MDH and alkaline phosphatase were observed in dog plasma during hemorrhagic hypotension. No significant elevations in beta-glucuronidase, alpha-glucosidase, leucine aminopeptidase...

Acute circulatory collapse of the adrenalectomized dog following plasma infusion.

Adrenalectomized dogs maintained on desoxyeorticosterone acetate developed a fatal circulatory collapse when given normal dog plasma. They showed general restlessness, a rapid fall in blood pressure and cardiac index, a decline in central venous pressure and general prostration. Most dogs developed a bloody diarrhea and a minority showed edematous swelling of the face with itching. Animals with intact spleens exhibited marked hemoconcentration, splenectomized animals did not. Blood and plasma specific gravity determinations offered no evidence for gross plasma loss. Diphenhydramine prevented the collapse.

The pathogenesis of hemophilia; an experimental analysis of the anticephalin hypothesis in hemophilic dogs.

It has been possible to duplicate in the hemophilic dog four of the major experiments which have suggested in humans an "anticephalin" hypothesis for the pathogenesis of hemophilia. The experiments in the dog have been considerably extended, as compared with the human experiments, by a variety of techniques. I. Asbestos was placed in contact with hemophilic dog plasma, and the clotting time became shorter. When transfused, this plasma had no effect on the defective prothrombin utilization of hemophilic dogs, in contrast to untreated normal plasma. II. The ionic strength of native dog plasma and dog plasma citrated (38 per cent sodium citrate) then recalcified (0.2 M CaCl(2)) were calculated. The ionic strength of the native plasma was approximately 0.15 while that of the citrated plasma was approximately 0.21. Conductivity and freezing point determinations on the plasmas described above were consistent with the idea that the ionic strength of the citrated plasma was significantly higher. The biphasic dilution curve, to which much significance has been attached in arriving at the "anticephalin" hypothesis, can be produced readily in the dog. Diluting dog plasma with "iso-ionic" or "hyper-ionic" NaCl solution abolished the biphasic phenomenon. Dilution with distilled water exaggerated the biphasic curve. These experiments suggest that the biphasic curve is an artifact of uncontrolled ionic strength. III. The prothrombin utilization rates of undiluted whole hemophilic dog blood and hemophilic dog blood diluted 1:2 with 0.85 per cent NaCl were found to be the same. IV. Ether extraction of both normal and hemophilic dog plasma removed fibrinogen and reduced somewhat the concentration of prothrombin. In treated normal plasma AHF was reduced to the level of untreated hemophilic plasma, thus producing a quasi-hemophilic plasma. Defibrination and ether extraction of both normal and hemophilic dog plasma "generated" clotting activity which shortened the clotting time of hemophilic plasma and was active in the thromboplastin generation test. The activity "generated" by defibrination and ether extraction of dog plasma was adsorbed by a BaSO(4) suspension and shown, therefore, not to be the anti-hemophilic factor (AHF). Transfusion of ether-extracted normal or hemophilic dog plasma into hemophilic dogs had no effect on the prothrombin utilization rate, unlike untreated normal plasma which had a marked effect. Thus, four of the main lines of evidence supporting the "anticephalin" hypothesis were duplicated in the dog. However, by extending the experiments it was found that all were explainable on bases other than the presence of "anticephalin." Such an hypothesis is not necessary, therefore, to explain the pathogenesis of canine hemophilia. The apparent identity of hemophilia in the two species suggests that the hypothesis is also not applicable to humans.

Pressor and myotrophic activities of incubated plasma.

SummaryIncubation of normal human, dog or rat plasma at 37°C for 12 or 24 hours unmasks a pressor and myotrophic activity which is not due to known vasoactive substances.

Assay of antidiuretic substance in plasma of normal and diabetes insipidus dogs.

Assay of antidiuretic substance in plasma of normal and diabetes insipidus dogs.

Free and apparent amino acids in deproteinized plasma of normal and uremic (nephrectomized) dogs.

Summary1. Microbiological assay procedures were found to be applicable to the determination of free amino acids in depro-teinized plasma but only in the absence of interfering substances. The apparent (relative) values obtained in the presence of interfering substances were shown to be meaningful but only when determined over a wide range of concentration of plasma filtrates. 2. It was concluded that the concentration of some free amino acids (histidine, isoleucine, leucine, ly-sine, phenylalanine. proline, serine and val-ine) was not significantly different but that of some apparent amino acids was higher (ar-ginine and glycine) and others (methionine and threonine) lower in the deproteinized plasma of uremic (nephrectomized) compared to normal dogs.

Plasma enzyme activity in myocardial infarction in dog and man.

1. Increased plasma levels of transaminase as well as aldolase, isomerase and “malic acid dehydrogenase7' activity occurred in dogs after experimental myocardial infarction and in humans suffering from coronary occlusion. 2. Plasma levels of all enzymes were highest 24 hours after experimental myocardial embolization and had fallen rapidly at 48 hours. 3. Normal human values for plasma isomerase and “malic acid dehydrogenase” were significantly lower than those found in normal dog plasma, 4. In dogs following experimental myocardial embolization plasma transaminase, “malic acid dehydrogenase” and aldolase were increased to a greater extent than isomerase. In humans the plasma aldolase activity was comparatively less elevated than that of transaminase, “malic acid dehydrogenase” and isomerase. In both man and dog, coronary occlusion resulted in comparable increases of plasma transaminase and “malic acid dehydrogenase” activity. In dogs with coronary embolism, there was a reversible decrease in coronary flow myocardial oxygen usage, coronary vascular resistance as well as an early reversible negative pyruvate balance. At 24 hours the coronary flow and myocardial oxygen usage had returned to normal. 5. The negative myocardial pyruvate balance appeared to be an immediate response of an hypoxic myocardium. In contrast, the release of enzymes into the plasma was correlated with muscle necrosis. 6. A rapid and simple method is described for the determination of “malic acid dehydrogenase” activity in plasma.

Protein-lipid relationships innormal dog plasma: application of Cohn method 10.

Although Cohn's microfractionation method number 10 was specifically devised to meet the conditions of protein concentration and distribution in human plasma, it is shown in this contribution that it may be applied to studies of canine plasma. Essentially all of the lipids of plasma are recovered in Fractions IV + V + VI and I + III. Only negligible amounts appear in Fraction II. Electrophoretic studies proved that the lipoproteins of Fraction IV + V + VI have the mobility of alpha globulins and those in Fraction I + III have the mobility of beta globulins.