The Effect of Exocrine Pancreas Stimulation on the Coagulation and Fibrinolytic System in Dogs

1973 ◽  
Vol 29 (03) ◽  
pp. 603-609
Author(s):  
A Gabryelewicz ◽  
J Prokopowicz ◽  
W Szalaj ◽  
N Wolosowicz ◽  
W Laszewicz ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Prothrombin Time ◽  
Fibrinolytic Activity ◽  
Exocrine Pancreas ◽  
Blood Platelet ◽  
Fibrinolytic System

SummaryThe coagulation and fibrinolytic systems have been investigated in the dogs treated intravenously with secretin, pancreozymin and CCK.There was significant shortening of plastic and glass clotting times, a fall in blood platelet numbers, prolongation of the prothrombin time, and a transitory inhibition of plasma euglobulin fibrinolytic activity. The greatest changes were found after CCK.It should be stressed that the peak changes were earlier and more intense when morphine was given with the hormones.In the authors’ opinion the present findings support the supposition concerning the role of enzymatic toxemia in hemostatic disturbances seen in acute pancreatitis.

Platelet-Activating Factor Mediates Pancreatic Function Derangement in Caerulein-Induced Pancreatitis in Rats

1994 ◽  
Vol 87 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Ricardo Alonso ◽  
Angel Montero ◽  
Miguel Arévalo ◽  
Luis J. García ◽  
Concepción Sánchez-Vicente ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Platelet Activating Factor ◽  
Blood Platelet ◽  
Pancreatic Tissue ◽  
Portal Blood ◽  
Blood Levels ◽  
Inflammatory Infiltration ◽  
Subcutaneous Injections ◽  
Protein Output

1. We have assessed the role of platelet-activating factor in caerulein-induced acute pancreatitis (four subcutaneous injections of caerulein at a dose of 20 μg/kg) by measuring platelet-activating factor levels in portal blood, pancreatic tissue and peritoneal exudate in rats with and without pancreatitis. 2. We have also observed the effect of the platelet-activating factor antagonist, BN-52021, on the hyper-amylasaemia and exocrine pancreatic secretion impairment associated with pancreatitis. 3. In rats with pancreatitis the basal pancreatic flow rate was increased (1.63 ± 0.41 versus 0.25 ± 0.03 μl/min). Total protein output was similar in both untreated (5.98 ± 1.93 μg/min) and caerulein-injected (6.5 ± 2.0 μg/min) animals. Amylase output was lower in rats with pancreatitis (19.6 ± 4.8 μ-units/min) than in controls (39.4 ± 16.6 μ-units/min). 4. Caerulein-treated animals had significantly higher serum amylase levels than untreated animals. BN-52021 significantly reduced the caerulein-induced hyperamylasaemia. 5. Portal blood platelet-activating factor levels increased in rats with pancreatitis and in rats infused with cholecystokinin. Rats injected with caerulein and BN-52021 had portal blood levels of platelet-activating factor that were lower than those with pancreatitis. 6. Morphological derangements associated with pancreatitis (inflammatory infiltration and cell vacuolization) were also markedly reduced in BN-52021-treated animals. 7. The results of this study suggest that platelet-activating factor is involved in the development of caerulein-induced acute pancreatitis in rats.

Influence of Dicoumarol Derivatives on Plasma Fibrinolytic System

1959 ◽  
Vol 03 (02) ◽  
pp. 279-285 ◽  
Author(s):  
Marta Niewiarowska ◽  
Zenon Wegrzynowicz
Keyword(s):  
Single Dose ◽  
Prothrombin Time ◽  
Anticoagulant Therapy ◽  
Clinical Evaluation ◽  
Fibrinolytic Activity ◽  
Coronary Thrombosis ◽  
Fibrinolytic System ◽  
Number Of Patients ◽  
Anticoagulant Drugs

SummaryThe influence of some coumarine derivatives (anticoagulant drugs: pelentan [tromexan], sintrom, marcoumar) on plasma fibrinolytic activity has been investigated. The cases studied included a number of patients with coronary thrombosis treated in long-term anticoagulant therapy and rabbits treated with a single dose of the drug.The anticoagulants have no significant effect either on fibrinogen or plasminogen level. All of the above mentioned drugs cause a prolongation of the euglobulin fibrinolysis time and an increase of the antiplasmin level. These two changes may be correlated to the prolongation of the prothrombin time.The authors suggest that the described phenomena may be useful for biological and clinical evaluation of anticoagulant drugs.

TAFI Meets the Sticky Ends

2001 ◽  
Vol 85 (01) ◽  
pp. 1-2 ◽  
Author(s):  
Nuala Booth
Keyword(s):  
Fibrinolytic Activity ◽  
Potential Role ◽  
Thromboembolic Disease ◽  
Fibrinolytic System ◽  
The Other ◽  
Pivotal Role ◽  
Plasmin Activity ◽  
Carboxypeptidase B ◽  
Fibrinolysis Inhibitor

SummaryThe coagulation and fibrinolytic system are often considered as separate entities, despite the obvious connection that one produces fibrin, the substrate for the other. A potent example of a more subtle and yet important connection lies in thrombin’s ability to generate an inhibitor of fibrinolysis. This exemplifies the pivotal role of thrombin in haemostasis, a consequence of its broad range of activities. Thrombin activates the zymogen form of a basic carboxypeptidase, generating an active enzyme called carboxypeptidase U, carboxypeptidase R, plasma carboxypeptidase B or TAFIa, thrombin activable fibrinolysis inhibitor (reviewed in 1-4; references from the reviews are not cited here). The activated carboxypeptidase removes C-terminal basic residues from fibrin. C-terminal Lys residues are key to binding t-PA and plasminogen, and thus to generating plasmin activity, a mechanism by which partially-lysed fibrin amplifies plasmin formation. The removal of these C-terminal Lys residues therefore decreases local fibrinolytic activity (Fig. 1). Several recent studies, two of which appear in this issue of Thrombosis and Haemostasis (5, 6), add to our knowledge of this activity and its potential role in thromboembolic disease.

Tissue Plasminogen Activator in Human Megakaryocytes and Platelets: Immunocytochemical Localization, Immunoblotting and Zymographic Analysis

1988 ◽  
Vol 59 (03) ◽  
pp. 529-534 ◽  
Author(s):  
C Jeanneau ◽  
Y Sultan
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Blood Platelets ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Sds Page ◽  
Tissue Plasminogen ◽  
Zymographic Analysis

SummaryTwo approaches were used to identify and characterize the presence of tissue plasminogen activator (t-PA) in megakaryocytes and platelets. We investigated the fibrinolytic activity of human megakaryocytes (MK) and platelets. The presence of t-PA antigen in megakaryocytes and platelets was demonstrated using immunocytochemical techniques and polyclonal or monoclonal antibodies specific for t-PA. When cells were applied to fibrin plates, lysis zones developed around isolated human megakaryocytes, whereas no fibrinolytic activity appeared when either intact washed platelets or platelet lysate were deposited. After SDS-PAGE of platelet and MK extracts (Triton X-100) immunoblotting and peroxidase staining identified t-PA antigen in several bands. Zymographic analysis of SDS-PAGE carried out on fibrin film overlays identified one or two zones corresponding to free or complexed t-PA. These results indicate that t-PA is present in platelets as well as in the precursor cells, however, in platelets, t-PA may not be immediately available for plasminogen activation and fibrin degradation. From our findings and from previous work of others, it appears that platelets may either activate or inhibit the fibrinolytic system. Therefore the conditions of plasminogen activation by platelet t-PA and plasmin inhibition by platelet α2-antiplasmin or other inhibitors have to be precised before the role of platelets in clot dissolution is understood.The physiological role of platelets in fibrinolysis and clot dissolution remains unclear. In 1953, the antifibrinolytic activity of blood platelets was demonstrated (1) and in the early 1960’s a fibrinolytic activity, increasing with platelet concentration in the experimental system, was shown (2, 3). In 1979, it was demonstrated that metabolically active platelets were necessary for platelets to play a role in the fibrinolytic system (4). More recently it was established by Plow and Collen (5) that the specific plasmin inhibitor, α2-antiplasmin is a constituent of platelet α-granules.In the present study, we investigated the fibrinolytic components and activity of human megakaryocytes and platelets, using zymographic and immunochemical techniques. We report here our observations that human megakaryocytes and platelets contain tissue plasminogen (t-PA) which possesses fibrinolytic activity.

A New Hypothesis: Possible Mechanisms in the Involvement of the Increased Plasminogen Activator Activity in Branching Regions of the Aorta in the Initiation of Atherosclerosis

1980 ◽  
Vol 43 (02) ◽  
pp. 141-146 ◽  
Author(s):  
A Smokovitis
Keyword(s):  
Plasminogen Activator ◽  
Early Life ◽  
Fibrinolytic Activity ◽  
Atherosclerotic Lesion ◽  
Protective Role ◽  
Fibrinolytic System ◽  
Actual Role ◽  
Plasminogen Activator Activity ◽  
New Hypothesis

SummaryBranching regions of the aorta are predilection regions for atherosclerosis. The intima in the branching regions of the normal aorta shows a constantly increased plasminogen activator activity from early life. At these areas, the endothelium is also damaged, it shows increased permeability, etc. The constantly increased plasminogen activator activity (local plasmin production) might play a protective role or on the contrary might participate in the initiation of atherosclerosis at the branching regions through a number of proved or suggested mechanisms.No matter what the actual role of the locally increased plasminogen activator activity in the initiation of atherosclerosis is, the role of the fibrinolytic system in the progression of the atherosclerotic lesion seems to be clear. There is an accumulation of evidence that the impaired fibrinolytic activity in atherosclerotics participates in the progression and the complications of the disease.

Differential Role of Components of the Fibrinolytic System in the Formation and Removal of Thrombus Induced by Endothelial Injury

1999 ◽  
Vol 81 (04) ◽  
pp. 601-604 ◽  
Author(s):  
Hiroyuki Matsuno ◽  
Osamu Kozawa ◽  
Masayuki Niwa ◽  
Shigeru Ueshima ◽  
Osamu Matsuo ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Thrombus Formation ◽  
Endothelial Injury ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Clot Lysis ◽  
Wild Type ◽  
Type Plasminogen Activator ◽  
Pai 1

SummaryThe role of fibrinolytic system components in thrombus formation and removal in vivo was investigated in groups of six mice deficient in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), or plasminogen activator inhibitor-1 (PAI-1) (u-PA-/-, t-PA-/- or PAI-1-/-, respectively) or of their wild type controls (u-PA+/+, t-PA+/+ or PAI-1+/+). Thrombus was induced in the murine carotid artery by endothelial injury using the photochemical reaction between rose bengal and green light (540 nm). Blood flow was continuously monitored for 90 min on day 0 and for 20 min on days 1, 2 and 3. The times to occlusion after the initiation of endothelial injury in u-PA+/+, t-PA+/+ or PAI-1+/+ mice were 9.4 ± 1.3, 9.8 ± 1.1 or 9.7 ± 1.6 min, respectively. u-PA-/- and t-PA-/- mice were indistinguishable from controls, whereas that of PAI-1-/- mice were significantly prolonged (18.4 ± 3.7 min). Occlusion persisted for the initial 90 min observation period in 10 of 18 wild type mice and was followed by cyclic reflow and reocclusion in the remaining 8 mice. At day 1, persistent occlusion was observed in 1 wild type mouse, 8 mice had cyclic reflow and reocclusion and 9 mice had persistent reflow. At day 2, all injured arteries had persistent reflow. Persistent occlusion for 90 min on day 0 was observed in 3 u-PA-/-, in all t-PA-/- mice at day 1 and in 2 of the t-PA-/-mice at day 2 (p <0.01 versus wild type mice). Persistent patency was observed in all PAI-1-/- mice at day 1 and in 5 of the 6 u-PA-/- mice at day 2 (both p <0.05 versus wild type mice). In conclusion, t-PA increases the rate of clot lysis after endothelial injury, PAI-1 reduces the time to occlusion and delays clot lysis, whereas u-PA has little effect on thrombus formation and spontaneous lysis.

Effect of Dipyridamole on Spontaneous Platelet Aggregation in Whole Blood Decreases with the Time After Venepuncture: Evidence for the Role of ADP

1987 ◽  
Vol 58 (02) ◽  
pp. 744-748 ◽  
Author(s):  
A R Saniabadi ◽  
G D O Lowe ◽  
J C Barbenel ◽  
C D Forbes
Keyword(s):  
Platelet Aggregation ◽  
Correlation Coefficient ◽  
Whole Blood ◽  
Blood Platelet ◽  
Inhibitory Effect ◽  
Time Interval ◽  
Adp Receptor ◽  
Spontaneous Platelet Aggregation

SummarySpontaneous platelet aggregation (SPA) was studied in human whole blood at 3, 5, 10, 20, 30, 40 and 60 minutes after venepuncture. Using a whole blood platelet counter, SPA was quantified by measuring the fall in single platelet count upon rollermixing aliquots of citrated blood at 37° C. The extent of SPA increased with the time after venepuncture, with a correlation coefficient of 0.819. The inhibitory effect of dipyridamole (Dipy) on SPA was studied: (a) 10 μM at each time interval; (b) 0.5-100 μM at 3 and 30 minutes and (c) 15 μM in combination with 100 μM adenosine, 8 μM 2-chloroadenosine (2ClAd, an ADP receptor blocker) and 50 μM aspirin. There was a rapid decrease in the inhibitory effect of Dipy with the time after venepuncture; the correlation coefficient was -0.533. At all the concentrations studied, Dipy was more effective at 3 minutes than at 30 minutes after venepuncture. A combination of Dipy with adenosine, 2ClAd or aspirin was a more effective inhibitor of SPA than either drug alone. However, when 15 μM Dipy and 10 μM Ad were added together, the inhibitory effect of Dipy was not increased significantly, suggesting that Dipy inhibits platelet aggregation independent of Ad. The increase in SPA with the time after venepuncture was abolished when blood was taken directly into the anticoagulant containing 5 μM 2ClAd. It is suggested that ADP released from the red blood cells is responsible for the increased platelet aggregability with the time after venepuncture and makes a serious contribution to the artifacts of in vitro platelet function studies.

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

On the Fibrinolytic System in Aged Rats, and Its Reactivity to Endotoxin and Cytokines

1992 ◽  
Vol 67 (06) ◽  
pp. 697-701 ◽  
Author(s):  
J J Emeis ◽  
A Brouwer ◽  
R J Barelds ◽  
M A Horan ◽  
S K Durham ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
High Dose ◽  
Base Line ◽  
Aged Rats ◽  
Tissue Type Plasminogen Activator ◽  
Young Rats ◽  
Type Plasminogen Activator

SummaryAged rats are more susceptible to endotoxin-induced effects, including microthrombosis and platelet aggregation, than are young rats. To investigate whether changes in the fibrinolytic system might be involved, we investigated the fibrinolytic activity in plasma euglobulin fractions and tissues (lung and heart) of young (6-months old) and aged (24-months old) rats under baseline conditions and after challenge with endotoxin. Aged rats had lower plasma levels of tissue-type plasminogen activator (t-PA) and of urokinase-type PA (u-PA) activity. PA inhibitor (PAI) activity was higher in the plasma of aged rats, as was t-PA activity in lung and heart.Rats were treated with either a low dose (1 μg/kg) or a high dose (10 mg/kg) of endotoxin. Both treatments induced a transient phase of increased blood fibrinolytic activity, as evidenced by higher levels of tissue-type plasminogen activator (t-PA) activity and decreased levels of PA inhibitor (PAI) activity. Over time, the fibrinolytic activity decreased, probably due to increased levels of PA inhibitor.Both the early increase in t-PA activity, and the subsequent increase in PAI activity, were more pronounced in the aged rats, as compared with the younger rats, after the high dose of endotoxin. The aged rats also responded to an injection of interleukin-1β or tumor necrosis factor-α with a larger increase of PAI activity than did the younger rats.Together the data suggest that, compared to young rats, aged rats have a decreased base-line plasma fibrinolytic activity, while their fibrinolytic system is more responsive to challenge by endotoxin and cytokines.

Fibrinolytic Activity of Cerebro-Spinal Fluid and the Development of Artificial Cerebral Haematomas in Dogs

1969 ◽  
Vol 21 (02) ◽  
pp. 294-303 ◽  
Author(s):  
H Mihara ◽  
T Fujii ◽  
S Okamoto
Keyword(s):  
Cerebrospinal Fluid ◽  
Carboxylic Acid ◽  
Fibrinolytic Activity ◽  
Clinical Implications ◽  
Trans Form ◽  
Plate Method ◽  
Blood Samples ◽  
Fibrin Plate ◽  
The Brain

SummaryBlood was injected into the brains of dogs to produce artificial haematomas, and paraffin injected to produce intracerebral paraffin masses. Cerebrospinal fluid (CSF) and peripheral blood samples were withdrawn at regular intervals and their fibrinolytic activities estimated by the fibrin plate method. Trans-form aminomethylcyclohexane-carboxylic acid (t-AMCHA) was administered to some individuals. Genera] relationships were found between changes in CSF fibrinolytic activity, area of tissue damage and survival time. t-AMCHA was clearly beneficial to those animals given a programme of administration. Tissue activator was extracted from the brain tissue after death or sacrifice for haematoma examination. The possible role of tissue activator in relation to haematoma development, and clinical implications of the results, are discussed.

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