EFFECTS OF VASOPRESSIN AND ADRENALINE ON FIBRINOLYSIS: SYNERGISTIC OR ADDITIVE?

1987 ◽  
Author(s):  
P J Grant ◽  
P G Wiles ◽  
M Boothby ◽  
J A Davies ◽  
C R M Prentice
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Saline Infusion ◽  
Low Doses ◽  
Additive Effects ◽  
Plasma Adrenaline ◽  
Normal Volunteers ◽  
Plasminogen Activator Activity ◽  
Lysis Time

Vasopressin (aVP) andadrenalineboth enhance plasminogenactivator activity when infused at low doses in man and probably act asphysiological regulators of fibrinolysis under certain conditions. Therelative contributions of these hormones to changes in fibrinolysis are unknown. This study was carried out to investigate whether aVP and adrenaline act synergistically on plasminogen activator in man. Four normal volunteers were infused with (1) aVP (1. OU/h), (2) adrenaline (420 μg/h), (3) aVP and adrenaline and(4) 0.9% saline for 1h. Saline (0.9%) wasinfused for 30 min before and afterinfusion. There was a minimum of 2 weeks between infusions andthe subjects were not aware of the contentsof the infusate. Samples were takenafter 30 min saline infusion and every 30 min for 1 1/2h foreuglobulinclot lysis time (ECLT), factor VIII:C, aVP and adrenaline. During (1) and (3) plasma aVP rose from (median)0.9 pg/ml to 13.2 pg/ml after 1h. During (2) and (4) plasma aVP remained constant at 0.9 pg/ml. Plasma adrenaline rose from 0.21nmol/1 to 0.62 nmol/1 after 1h during (2) and (3) and remained unchanged at 0.20 nmol/1 during(1) and (4). Plasminogen activator activity (106 /ECLT2 ) rose (%) from 100 to 150% at 1h during adrenalineinfusion,(p < 0.05), 100 to 148% during aVP (p < 0.05), 100 to 252% (p < 0.05) when both wereinfused and from 100 to 123% (N. S) during saline infusion. Factor VIII remained unchanged. The results indicate that at low physiological concentrations, aVP and adrenaline have additive effects on fibrinolysis but are probably not synergistic. This is consistent with the view that aVP and adrenaline mediate this response by different receptors.

Effects of physiological concentrations of vasopressin on haemostatic function in man

1985 ◽  
Vol 69 (4) ◽  
pp. 471-476 ◽  
Author(s):  
P. J. Grant ◽  
J. A. Davies ◽  
G. M. Tate ◽  
M. Boothby ◽  
C. R. M. Prentice
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Generation Time ◽  
Plasma Concentrations ◽  
Plasminogen Activator Activity ◽  
Lysis Time ◽  
Coagulation Mechanism ◽  
Coagulant Activity ◽  
Euglobulin Lysis Time ◽  
Ristocetin Cofactor

1. Plasma concentrations of vasopressin (aVP) attained under conditions of stress were simulated by infusing four volunteers with 0.25, 0.5, 1.0 and 2.0 pressor units of aVP over 1 h (units/h). Three subjects had all four infusions and one received only 1.0 unit/h. 2. Blood samples were taken for assay of factor VIII coagulant activity (FVIIIC), factor VIII related antigen (FVIIIRAg), the ristocetin cofactor (FVIIIRiCof), euglobulin lysis time (ELT) and aVP concentrations before infusion (time 0) and every 20 min for 80 min. Fibrinopeptide A (FPA) generation time was measured at time 0, 60 and 80 min. 3. At infusion rates of 0.25 unit/h median aVP levels peaked at 6.5 pg/ml and there was no change in haemostatic function. At 0.5 unit/h aVP levels peaked at 16.0 pg/ml, there was no change in FVIII or FPA generation time, and plasminogen activator activity (106/ELT2) rose from 100 to 400 units. At 1.0 unit/h, aVP levels rose to 25.4 pg/ml, FVIIIC rose by 160% and activator activity from 87 to 360 units. At 2.0 units/h, aVP concentrations reached 83 pg/ml, there was an increase in all modalities of FVIII and activator activity rose from 251 to 452 units. FPA generation time shortened and circulating plasma levels of FPA were increased. 4. There was a highly significant correlation between the percentage increases in all three components of FVIII and plasma aVP levels (FVIIIC: r = 0.87, P < 0.0001; FVIIIRAg: r = 0.61, P < 0.0001; FVIIIRiCof: r = 0.80, P < 0.0001) and between the increase in plasminogen activator activity and aVP levels (r = 0.56, P < 0.0001). 5. The results indicate that plasma concentrations of aVP comparable with those attained during stress cause a rise in FVIII, an increase in plasma activator activity and effects on FPA generation consistent with low-level activation of the coagulation mechanism. Endogenous vasopressin could mediate alterations in haemostatic function known to accompany events such as surgical operations.

THE EFFECTS OF PHYSIOLOGICAL CONCENTRATIONS OF VASOPRESSIN ON COMPONENTS OF THE FIBRINOLYTIC PATHWAY

1987 ◽  
Author(s):  
H Hariman ◽  
J R Hughes ◽  
P J Grant ◽  
J A Davies
Keyword(s):  
Plasminogen Activator ◽  
Generation Time ◽  
Venous Blood ◽  
Normal Subjects ◽  
Saline Infusion ◽  
Tissue Type ◽  
Clot Lysis ◽  
Plasminogen Activator Activity ◽  
Plasma Factor

Evidence from studies in man suggests that vasopressin (aVP) at physiological concentrations activates the coagulation pathway, increases plasminogen activator activity and may have a role in the regulation of haemostasis under conditions of physical stress. Infusion of aVP in normal subjects increases plasma factor VIII concentrations and shortens the euglobulin clot lysis time (ECLT), but the mechanisms involved in these changes and their haemostatic significance are unclear. The aims of this study were to investigate the effects of aVP on the fibrinolytic pathway and to evaluate whether thrombin or plasmin are generated in vivo by aVP. After 30 min 0.9% saline infusion, vasopressin (20iu in 250ml 0.9% saline) was infused at 2.0 u/h for 1h in 9 normal subjects to achieve plasma aVP concentrations comparable to those attained during stress. Venous blood samples were taken before saline infusion (time 0) and every 30 min for 2h for assay of aVP, activated partial thromboplastin time (APTT), fibrinopeptide A (FPA), FPA generation time, FPBB15-42 ECLT, tissue-type plasminogen activator (t-PA) and t-PA inhibition. Plasma aVP rose frcm 0.5 pg/ml at time 0 to (median) 70.7 pg/ml at 90 min. The APTT shortened from 43.8 ± 1.9 to 34.4 ± 1.6 (SEM) seconds (p < 0.001) at 90 min. Plasma FPA and the FPA generation time remained unchanged (p > 0.05). Plasminogen activator activity rose from 36.4 ± 15.2 to 587.5 ± 206.6 units (p < 0.005), t-PA increased frcm 229.8 ± 20.4 to 1107.4 ± 224.1 ml.U/ml (p < 0.005) and t-PA inhibition fell frcm 7.9 ± 1.1 to 3.9 ± 0.9 I.U/ml (p < 0.05) in response to the aVP infusion. FPB815-42 increased frcm a baseline value of 1.7 ± 0.4 to 2.2 ± 0.7 pmol/ml after 90 min (p < 0.05). The results suggest the effects of aVP on fibrinolysis are due to an increase in t-PA and decrease in t-PA inhibition. The increase in FPBB 15-42 with no change in FPA supports the hypothesis that plasmin was generated by non-fibrin dependent pathways.

Plasminogen activator activity and plasma-coagulum lysis measured by use of optimized fibrin gel structure preformed in microtiter plates

1995 ◽  
Vol 41 (7) ◽  
pp. 979-985 ◽  
Author(s):  
J Sidelmann ◽  
J Jespersen ◽  
J Gram
Keyword(s):  
Plasminogen Activator ◽  
Reference Interval ◽  
Spectroscopic Studies ◽  
Tissue Type ◽  
Response Curves ◽  
Fibrin Gel ◽  
Plasminogen Activator Activity ◽  
Microtiter Plates ◽  
Lysis Time ◽  
The Difference

Abstract We introduce a new fibrin plate assay performed in microtiter plates. By means of spectroscopic studies we optimized the structure of the fibrin gel and then used the optimized fibrin gel to determine plasminogen activator activity. Plasminogen activator solutions were applied on top of the fibrin gel, and the absorbance of the gel was recorded at 405 nm. After incubation for 17 h at 25 degrees C, the absorbance was measured again. The difference in absorbance was proportional to the concentration of plasminogen activator, such that the dose-response curves were linear when the difference in absorbance was plotted as a function of the logarithmic concentration of plasminogen activator. We assayed both tissue-type and urokinase-type plasminogen activator activity. The intraassay CV was &lt; 4.7% (n = 20); the interassay CV was &lt; 3.1% (n = 15). Using the optimized procedure, we modified the assay for determination of plasma-coagulum lysis time in human plasma. We established a reference interval for lysis time in apparently healthy subjects of 75 to 201 ks. Patients with deep vein thrombosis showed significantly (P = 0.013) higher values.

VASOPRESSIN AND THE REGULATION OF FIBRINOLYSIS: HAEMOSTATIC RESPONSES TO HYPOTENSION IN THE ABSENCE OF ADRENALINE RELEASE

1987 ◽  
Author(s):  
K K Hampton ◽  
P J Grant ◽  
M Boothby ◽  
J A Davies ◽  
C R M Prentice
Keyword(s):  
Blood Pressure ◽  
Plasminogen Activator ◽  
Postural Hypotension ◽  
Autonomic Failure ◽  
Plasma Concentrations ◽  
Mean Blood Pressure ◽  
Plasma Adrenaline ◽  
Plasminogen Activator Activity ◽  
Adrenaline Release ◽  
Lying Down

Vasopressin (aVP) infusions resulting in plasma concentrations that simulate those during stress cause increases in factor VIII (EVTII) and plasminogen activator activity (PAA). During apcmorphine induced nausea and abdominal surgery similar increases in aVP are associated with elevated FVIII and PAA suggesting aVP is a mediator of haemostatic function. However during stress there is release of adrenaline which has similar effects on haemostasis. The aim of this study was to investigate the effects of endogenous aVP release on haemostasis in patients with postural hypotension (a potent stimulus to aVP release) due to autonomic neuropathy who have absent circulating adrenaline. The study was performed in i) three patients with progressive autonomic failure (PAF) who release aVP but not adrenaline ii) three patients with PAF with multi-system atrophy (MSA, the Shy-Drager syndrome) who have deficient release of both aVP and adrenaline. After lying down overnight patients stood for 2 minutes on 3 occasions at 1 hour intervals. Samples were taken for aVP, adrenaline, ECLT and FVIII. In PAF mean blood; pressure fell from 108 lying to 47 irmHg standing. Pulse did not change. aVP rose from 1.2 lying to 56 pg/ml standing. Plasma adrenaline was sub-normal throughout. Median PAA (106 /ECLT2 ) lying was 92 and rose on standing to 376 units and correlated with plasma aVP (r = 0.87, p < 0.0001). In PAF with MSA mean blood pressure fell from 107 lying to 61 irmHg standing. aVP levels did not change and adrenaline remained below normal. PAA rose from a median 30 lying to 87 units standing. No change in FVIII was observed in either group. The results suggest that aVP regulates plasminogen activator activity in the absence of adrenaline. The lack of a rise in FVIII suggests that circulating adrenaline may be necessary for aVP to exert an effect on FVIII concentrations.

Haemostatic responses and vasopressin release during colonoscopy in man

1991 ◽  
Vol 81 (2) ◽  
pp. 257-260 ◽  
Author(s):  
K. K. Hampton ◽  
P. J. Grant ◽  
J. Primrose ◽  
H. G. Dean ◽  
J. A. Davies ◽  
...  
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Plasma Concentrations ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Plasminogen Activator Activity ◽  
Plasma Vasopressin ◽  
Type Plasminogen Activator ◽  
Coagulant Activity ◽  
Von Willebrand

1. During major abdominal surgery there are increases in Factor VIII and plasminogen activator activity, associated with elevated plasma concentrations of vasopressin, of a magnitude shown to affect haemostasis. 2. To investigate the mechanisms involved in the haemostatic response to surgery, 12 patients undergoing fibre-optic colonoscopy were studied, of which six had a complete and six had an incomplete examination. 3. Venous blood samples were taken before, during and after the procedure for assay of plasma vasopressin, adrenaline and noradrenaline concentrations, Factor VIII coagulant activity, von Willebrand factor antigen level, euglobulin clot lysis time, tissue-type plasminogen activator activity and tissue-type plasminogen activator inhibition. 4. In the six patients who underwent a complete procedure the median plasma vasopressin concentration rose from 0.6 pg/ml to 153 pg/ml during colonoscopy. Factor VIII coagulant activity rose from 0.9 to 2.4 i.u./ml and von Willebrand factor antigen level rose from 139 to 224%. Plasminogen activator activity increased from 20 to 144 units and tissue-type plasminogen activator activity rose from 107 to 1338 m-i.u./ml, whereas tissue-type plasminogen activator inhibition fell from 4.8 to 1.0 i.u./ml. 5. In the six patients in whom a limited procedure was performed, there were no changes in haemostatic function or in plasma vasopressin concentration. Plasma concentrations of adrenaline and noradrenaline did not change in either group. 6. The results indicate that vasopressin regulates the intrinsic coagulation pathway and fibrinolytic system in the absence of adrenaline release.

APC Resistance and other Haemostatic Variables during Pregnancy and Puerperium

1999 ◽  
Vol 81 (04) ◽  
pp. 527-531 ◽  
Author(s):  
U. Kjellberg ◽  
N.-E. Andersson ◽  
S. Rosén ◽  
L. Tengborn ◽  
M. Hellgren
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Protein C ◽  
Activated Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Reference Level ◽  
Soluble Fibrin ◽  
Prothrombin Fragment ◽  
D Dimer

SummaryForty-eight healthy pregnant women were studied prospectively and longitudinally. Blood sampling was performed at 10-15, 23-25, 32-34 and 38-40 weeks of gestation, within one week and at eight weeks postpartum. Classic and modified activated protein C ratio decreased as pregnancy progressed. In the third trimester 92% of the ratios measured with the classic test were above the lower reference level whereas all modified test ratios were normal. Slight activation of blood coagulation was shown with increased levels of prothrombin fragment 1+2, soluble fibrin and D-dimer. Fibrinogen, factor VIII and plasminogen activator inhibitor type 1 and type 2 increased. Protein S and tissue plasminogen activator activity decreased. Protein C remained unchanged. No correlation was found between the decrease in classic APC ratio and changes in factor VIII, fibrinogen, protein S, prothrombin fragment 1+2 or soluble fibrin, nor between the increase in soluble fibrin and changes in prothrombin fragment 1+2, fibrinogen and D-dimer.

Influence of Moderate and Strenuous Daily Physical Activity on Fibrinolytic Activity of Blood: Possibility of Plasminogen Activator Stores Depletion

1979 ◽  
Vol 41 (04) ◽  
pp. 745-755 ◽  
Author(s):  
Dušan Keber ◽  
Mojca Stegnar ◽  
Irena Keber ◽  
Bojan Accetto
Keyword(s):  
Physical Activity ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Regular Physical Activity ◽  
Clot Lysis ◽  
Moderate Activity ◽  
Lysis Time ◽  
Strenuous Activity ◽  
Activity Measurements ◽  
Clot Lysis Time

SummaryFibrinolysis was studied in 10 alpinists during regular physical activity of different intensity. Blood was sampled at rest and after exposure to submaximal workload on the treadmill on three occasions: before and after 6 months physical conditioning (moderate physical activity), and after 6 weeks of an alpinistic expedition (strenuous physical activity). Measurements included submaximal working capacity, fibrinogen, euglobulin clot lysis time (ELT), whole plasma clot lysis time, and estimations derived from ELT - percent increase in fibrinolytic activity after exercise (RFS), and absolute increase in fibrinolytic activity after exercise (PAR).Regular moderate activity increased the resting level of ELT, but strenuous activity decreased is. After each treadmill testing, a marked increase in fibrinolytic activity was observed. RFS was unaltered at all three testings. PAR increased after moderate activity, but decreased after strenuous activity.The results indicate that regular physical activity can lead from enhanced to decreased resting activity of plasminogen activator in blood. It is presumed that increased release of activator during prolonged stress causes partial depletion of endothelial stores with the consequence of decreased activator activity in the blood.

No Evidence for Short-Term Regulation of Plasminogen Activator Inhibitor Activity by Insulin in Man

1992 ◽  
Vol 67 (01) ◽  
pp. 117-120 ◽  
Author(s):  
Helena Vuorinen-Markkola ◽  
llpo Puhakainen ◽  
Hannele Yki-Järvinen
Keyword(s):  
Plasminogen Activator ◽  
Plasma Glucose ◽  
Serum Triglyceride ◽  
Plasminogen Activator Inhibitor ◽  
Saline Infusion ◽  
Serum Triglycerides ◽  
Serum Free ◽  
Free Insulin ◽  
Activator Inhibitor ◽  
Pai 1

SummaryIn crossectional studies a positive correlation has been found between circulating insulin, triglycerides and plasminogen activator inhibitor (PAI-1) activity. To directly examine the effect of insulin on PAI-1 activity in vivo, we determined the response of PAI-1 activity in 17 normal subjects to acute hyperinsulinemia (serum free insulin 92 ± 8 mU/l) during maintenance of normoglycemia (plasma glucose 5.1 ± 0.1 mmol/l). In 12 matched control subjects PAI-1 activity was measured during infusion of saline (serum free insulin 3.6 ± 0.3 mU/l, plasma glucose 5.2 ± 0.1 mmol/l). Plasma PAI-1 activity decreased during the insulin infusion from 9.0 α 1.4 to 5.6 α 0.8 U/ml (p <0.01), and during saline infusion from 7.0 ± 1.4 to 4.3 ± 0.6 U/ml (p <0.05). Serum triglyceride concentrations decreased from 1.09 ± 0.20 to 0.76 ± 0.09 mmol/l (p < 0.001) during hyperinsulinemia but remained unchanged during the saline infusion (1.04 ± 0.11 vs. 1.02 ± 0.12 mmol/l, NS). We conclude that insulin does not acutely change plasma PAI-1 activity, and that acute insulin-induced changes in serum triglycerides occur independently from those of PAI-1 activity.

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.

Ontogenesis of Tissue Plasminogen Activator in the Human

1971 ◽  
Vol 25 (03) ◽  
pp. 469-480 ◽  
Author(s):  
B Åstedt ◽  
M Pandolfi
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Vena Cava ◽  
Vasa Vasorum ◽  
Moderate Activity ◽  
Foetal Development ◽  
Plasminogen Activator Activity ◽  
Stage Of Development ◽  
Tissue Plasminogen ◽  
Enzyme Pattern

SummaryThe ontogenesis of tissue plasminogen activator in various tissues was studied in 10 embryos and 58 foetuses with a histochemical method.The first appearance of activator activity was seen in a 4-weeks old embryo. At 8-9 weeks it was seen in the eye, meninges, heart, lungs, kidney and vena cava. In the foetal heart high activity was found in the coronary vessels, which can be regarded as the vasa vasorum of the heart. In the lungs a moderate activity increased at 24 weeks of age, when vascularisation increases more rapidly. Intense activity was seen in the highly vascularized corneoscleral junction of the eye later involved in the drainage of aqueous humor.In the kidney the activity could be related to the vessels, while no activity was seen in the glomeruli, the collecting system or the pelvis. In the vessels the activator activity was fairly high. No activity was seen in any stage of development of the liver.The plasminogen activator activity may be of importance for maintaining the foetomaternal circulation and micro-circulation in rapidly growing foetal organs. In the embryo the enzyme pattern is dominated by protein synthetizing enzymes. During foetal development the enzyme pattern changes owing to supervention of enzymes necessary for the function of the various organs. Plasminogen activator belongs to this latter group. The appearance of plasminogen activator activity may therefore be regarded mainly as a sign of functional maturity of the foetal organs.

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