Effect of lymph removal during drainage of the thoracic lymph duct on the development of disseminated intravascular coagulation syndrome

The experiments on 25 dogs have shown a considerable decrease in the consumption of clotting factors and reduced hyperfibrinolysis with the onset of disseminated intravascular coagulation syndrome in animals poisoned with acetic essence (2 ml/kg).     

Naturally Occurring Canine Nephrotic Syndrome is a Potentially Hypercoagulable State

Fourteen dogs with naturally occurring nephrotic syndrome were evaluated for abnormalities in the hemostatic system. Histopathologic diagnoses included 8 dogs with membraneous glomerulonephritis, 1 dog with acute glomerulon-ephritis, 2 dogs with idiopathic glomerulopathy, and 2 dogs with amyloidosis. The coagulation protein assays performed included concentrations of factors V, VII, VIII: C, IX, X, fibrinogen (I), anti-thrombin III, and plasminogen. Thrombocyte counts were also performed. All of these analytes were significantly elevated (P < 0.05) with the exception of ATIΠ which was significantly decreased (P < 0.05). Five of the dogs had histologic evidence and 1 dog had angiographic evidence of thrombosis and thromboembolism. Naturally occurring canine nephrotic syndrome thus represents a potentially hypercoagulable state and may serve as a valuable model in the study of certain components of the human disease.     

Model of disseminated intravascular coagulation

Vascular-thrombocytic and plasma hemostasis was studied in dogs after blood loss (40--50 ml/kg weight) and subsequent hypervolemic (60--65 ml/kg weight) transfusion of homologous (from 3 donors) platelet and leukocyte rich in plasma. After a short phase of hypercoagulation all the tested dogs displayed hypocoagulation accompanied by a decrease in the count of platelets and a fall of their aggregation function, prolongation of bleeding time, diminution of capillary wall resistance, a decrease of plasma fibrinogen concentration and factor XIII activity, and by a rise of blood fibrinolytic activity. The data obtained show the development of the acute disseminated intravascular coagulation syndrome (DIC). DIC model is porposed on the basis of the results obtained.     

Automated synthetic substrate assays for coagulopathies of dogs

Automated synthetic substrate assays for factors II and VII in the extrinsic coagulation pathway have been developed in our laboratory. In both kinetic assays, p-nitroaniline (pNA) was cleaved from the substrate and measured spectrophotometrically at 405 nm. Plasma samples from 5-8 month old beagle dogs were analyzed for factors II and VII, and also for prothrombin times. A subpopulation considered abnormal (prothrombin times greater than 8 seconds) had slightly elevated factor II levels, but extremely low factor VII levels, relative to the normal group. Therefore, the prolonged prothrombin times of this abnormal group can now be confidently attributed to their decreased factor VII levels. The known genetic predisposition of beagle dogs to factor VII deficiency supports this conclusion. Thus, synthetic substrates are useful for the measurement of coagulation factors in dogs, and permit ready automation of the assay.     

Dynamics of contraction of the left and right ventricles of the heart (according to kinetocardiography data) in the development of renovascular hypertension in dogs of various ages]

Kinetocardiograms of the left and the right ventricles of the heart were recorded in puppies and adult dogs during development in them of experimental renovascular hypertension. Development of hypertension in adult dogs led to the shortening of ejection period, and in puppies--to its prolongation. The vector analysis of kinetocardiograms demonstrated in adult dogs the appearance of the syndrome of hypodynamics of the left ventricle replaced later by the syndrome of high diastolic pressure. In the puppies' left ventricle there appeared the phasic syndrome of high diastolic pressure replaced by the syndrome of stenosis of the exit tract. The phasic structure of the cycle of the right ventricle is characterized by the appearance of the syndrome of hyperdynamia detectable earlier in adult dogs.     

Changes in hemolymphocoagulation in acute arterial occlusive diseases of the lower extremity

In the present, on the 20 mongrel dogs, the authors studied the changes of coagulation in the blood and lymph in acute occlusion of thigh artery. The results of research show that during the development of pathological process the hypercoagulation displacements were observed in the blood-vascular and in lymphatic links of humoral transport. Increase in coagulation of lymph is one of the possible reasons of difficulty for lymph drainage++ of the injured organ.     

Experimental therapy of disseminated intravascular coagulation by streptokinase administration

Disseminated intravascular coagulation was induced in dogs by infusion of tissue thrombokinase. Its course was followed by coagulation tests, determination of the rate of microthrombosis, and measurement of organ functions and oxygen consumption. The therapeutic result of streptokinase administration at an early stage of pathological changes is demonstrated by improvement of the disturbed organ functions and oxygen supply as well as by the decrease in plasma-haemoglobin level. When streptokinase was administered at an advanced stage of organ damages, they remained irreversible, although repatency of the microvasculature had been reached.     

Hospitalized dogs recovery from naturally occurring heatstroke; does serum heat shock protein 72 can provide prognostic biomarker?

Heatstroke is a serious illness in dogs characterized by core temperatures above 41 °C with central nervous system dysfunction. Experimental heatstroke models have tried to correlate biomarker levels with the severity of the syndrome. Serum heat shock protein (eHSP70) levels were recently evaluated as a biomarker of heat tolerance and acclimation, their role as a marker of heatstroke is inconclusive. Here, we monitored eHSP70 levels in correlation with systemic biomarkers in 30 naturally occurring canine heatstroke cases. Thirty dogs diagnosed with environmental (33 %) or exertional (66 %) heatstroke admitted to hospital (0–14 h post-injury) were tested for biomarkers of organ damage and coagulation parameters. eHSP70 levels were measured upon admission and 4, 12, and 24 h later (T1, T2, and T3, respectively). No differences were found between exertional and environmental heatstroke cases. The eHSP profile demonstrated an inverted bell shape, with the lowest levels at the 12 h time point. A positive correlation between eHSP70, lactate, and aPPT was also noted at T2 in all the dogs in the study. Twenty-four h after presentation, eHSP70 levels returned to those measured upon admission, this change was only significant in the survivors. The obtained results suggest that eHSP72 level profile may be predictive of survival.     

The role of leukotoxin (9,10-epoxy-12-octadecenoate) in the genesis of coagulation abnormalities

This study was designed to clarify whether or not leukotoxin (9, 10-epoxy-12-octadecenoate), which is biosynthesized by neutrophils, might be involved in the genesis of coagulating abnormalities. Twelve dogs were divided into 2 groups. In the test group (n = 6), 100 mumol/kg of leukotoxin was injected intravenously, and in the control group (n = 6), 100 mumol/kg of linoleate was injected. In each group, a series of blood samples were collected and used for coagulation studies. After the end of the experimental period, a histological study was performed on organs removed from the dogs. In the leukotoxin group, fibrin and fibrinogen degradation products (FDP) was increased time-dependently. Fibrinogen was decreased, and prothrombin time and activated partial thromboplastin time were prolonged in parallel with the increase in FDP. A decrease in number of platelets was also observed. Intravascular coagulation was observed in sections of lung. These data were compatible with a diagnosis of disseminated intravascular coagulation (DIC). No significant changes in these parameters were observed in the linoleate group. Leukotoxin has been confirmed to show antifungal and antibacterial activity, and its production might be a defensive response to infection. Over-production of leukotoxin associated with severe infection might therefore account for infection-induced DIC.     

THE ANTIPROTEOLYTIC ACTIVITY OF SERUM : II. PHYSIOLOGICAL SIGNIFICANCE. THE INFLUENCE OF PURIFIED TRYPSIN INHIBITOR ON THE COAGULATION OF THE BLOOD

1. Serum antitrypsin and pancreatic trypsin inhibitor inhibited the coagulation of plasma in vitro. 2. This could be largely prevented by trypsin. 3. The anticoagulant action of the trypsin inhibitor was apparently due to its antiprothrombic action. It had no appreciable antithrombic action. 4. Examination of the blood of two hemophiliacs indicated that the prolonged coagulation time of their blood is not due to an excess of trypsin inhibitor. 5. Examination of the blood of heparinized dogs indicated that heparin does not appreciably contribute to the antiproteolytic activity of the serum.     

Temporary normalization of blood sugar, in a totally pancreatectomized dog, after placing an artificial insulin distributor]

Islets of Langerhans were stablished in the spaces between 9 synthetic hollowfibers in a "bio-artificial insulin distributor" which was implanted in the carotid artery of totally pancreatectomized dogs. Normo-glycemia was restored after 4 hours. The major problem encountered was coagulation in the fibers. Presently, this limits the prolonged utilization of this system.     

Replacement therapy of acquired antithrombin III deficiency in experimental nephrotic syndrome

The influence of antithrombin III on hemostasis and renal function was studied in experiments on rats with nephrotic syndrome. The development of nephrotic syndrome was accompanied by the activation of blood coagulation and appearance of acquired antithrombin III deficiency due to its loss with the urine. The replacement therapy by bovine antithrombin III at a dose of 25 U/kg a day for 10 days decreased the signs of excessive thrombinogenesis in experimental animals and increased the amount of thrombin-antithrombin III complexes in the blood flow. The activation of coagulation in rats with nephrotic syndrome predominantly induced the disturbances of the excretory renal function which could be efficiently corrected by antithrombin III.     

Genetic cause of X-linked Alport syndrome in a family of domestic dogs

Alport syndrome is a hereditary disease of type IV (basement membrane) collagens that occurs spontaneously in humans and dogs. In the human, X-linked Alport syndrome (XLAS) is caused by mutations in COL4A5, resulting in absence of type IV collagen alpha5 chains from the glomerular basement membrane (GBM) of affected individuals. The consequence of this defect is progressive renal failure, for which the only available treatments are dialysis and transplantation. Recent studies support the prospect of gene transfer therapy for Alport syndrome, but further development of required technologies and demonstration of safety and efficacy must be accomplished in a suitable animal model. We previously identified and have propagated a family of mixed-breed dogs with an inherited nephropathy that exhibits the clinical, immunohistochemical, pathological, and ultrastructural features of human XLAS. To identify the causative mutation, COL4A5 cDNAs from normal and affected dogs were sequenced in their entirety. Sequence analyses revealed a 10-bp deletion in exon 9 of affected dogs. This deletion causes a frame-shift that results in a premature stop codon in exon 10. Characterization of the causative mutation was followed by development of an allele-specific test for identification of dogs in this kindred that are destined to develop XLAS.     

Comparative studies of measuring condition of activated partial thromboplastin time and contact factors in experimental animals

For establishing the optimal incubation time (OIT) for measurement of the activated partial thromboplastin time (APTT) in dogs, rabbits, guinea pigs, rats and mice, we determined the shortest clotting time of the plasma from each animal species and compared them with that of human plasma. The OIT for APTT determination was 15 to 30 sec in guinea pigs, rats and mice and 5 to 10 minutes in dogs and rabbits. The mouse APTT (about 30 sec) with the OIT thus determined was similar to human APTT, and relatively longer than APTT in other animal species (10-20 sec). To elucidate the mechanism of the species differences in OIT, we examined the plasma of each animal species for the activity of the contact factors such as factor XII, factor XI, high molecular weight kininogen (HMWK) and prekallikrein (PK) and their effect on the coagulation of contact factor-deficient plasma. The total activity of contact factors was higher in dogs and guinea pigs and lower in rabbits and mice than that in humans. Species difference with the factor XII, Factor XI and HMWK was noted in clotting time but not in OIT. These results suggest that the species difference in OIT for APTT is probably due to difference in activity of the plasma contact factors and in the mode of coagulation for each contact factor.     

Bench to bedside: targeting coagulation and fibrinolysis in acute lung injury

Substantial progress has been made in understanding the contribution of alterations in coagulation and fibrinolysis to the pathogenesis of acute lung injury (ALI). Findings from mouse, rat, baboon, and human studies indicate that alterations in coagulation and fibrinolysis may be of major pathogenetic importance in ALI and other inflammatory conditions in the lung including pneumonia, sepsis, and ventilator-induced lung injury. Therapies targeted at both activation of coagulation through the extrinsic coagulation cascade and modulation of coagulation through the protein C system have the potential to favorably impact clinical ALI/acute respiratory distress syndrome.     

Coronary arteriolar vasoconstriction to angiotensin II is augmented in prediabetic metabolic syndrome via activation of AT1 receptors

The metabolic syndrome is associated with activation of the renin-angiotensin system. However, whether the coronary vascular response to ANG II is altered under this condition is unknown. Experiments were conducted in control and chronically high-fat-fed dogs with the prediabetic metabolic syndrome both in vitro (isolated coronary arterioles, 60-110 microm) and in vivo (anesthetized and conscious). We found that plasma renin activity and ANG II levels are elevated in high-fat-fed dogs and that this increase in ANG II is associated with a significant increase in ANG II-mediated coronary vasoconstriction in isolated coronary arterioles and in anesthetized open-chest dogs. The vasoconstriction to ANG II is abolished by ANG II type 1 (AT1) receptor blockade. In conscious chronically instrumented dogs, AT1 receptor blockade with telmisartan improved the balance between coronary blood flow and myocardial oxygen consumption in the high-fat-fed dogs but not in normal control dogs, i.e., the relationship between coronary venous Po2 and myocardial oxygen consumption was shifted upward, toward normal control values. Quantitative assessment of coronary arteriolar AT1 and ANG II type 2 (AT2) receptor mRNA levels by real-time PCR revealed no significant difference between normal control and high-fat-fed dogs; however, Western blot analysis showed a significant increase in AT1 receptor protein level with no change in AT2 receptor protein density. These findings indicate that AT1 receptor-mediated coronary constriction is augmented in the prediabetic metabolic syndrome and contributes to impaired control of coronary blood flow via increases in circulating ANG II and/or coronary arteriolar AT1 receptor density.     

脓毒症致凝血异常发生机制的研究进展

脓毒症是由感染引起的全身炎症反应综合征,其病情凶险,死亡率高。凝血异常是脓毒症的主要特点之一,是多方面因素共同作用的结果。在脓毒症的发生发展过程中,炎症因子既可以激活凝血级联反应又可以抑制抗凝系统和纤维蛋白溶解系统,最终导致其凝血活性增强,炎症诱导的凝血紊乱进一步促进和加重炎症反应。而脓毒症患者的高凝状态可导致静脉血栓栓塞甚至DIC的发生,引起了研究者们的广泛关注。本文将就脓毒症致凝血异常发生机制的研究进展做一综述。     

Ultrastructural manifestations of pulmonary thrombohemorrhagic syndrome in endotoxic shock

In electron microscopic investigation in the initial period of endotoxin shock in rats, rabbits and dogs there are haemorrhages and microthrombi with precipitation of fibrin. In intermediate period of shock signs of intravascular coagulation predominate and on the stage of late endotoxemia qualitatively new sign of destruction is interstitial fibrosis. Involving of coagulative link completes and enhances microcirculatory changes in the lungs and promotes formation of acute lung insufficiency.     

Counteracting clotting in sepsis

The complexity of factors that regulate bleeding and coagulation has long confounded researchers. Andrew Wei and Shaun Jackson help clear the air by examining clinical findings pointing to a mechanistic basis for a common bleeding disorder, immune thrombocytopenic purpura. Mark Kahn tackles two research studies that could lead to improved therapies for a coagulation syndrome that hits people with severe sepsis.