Some Factors Influencing Metabolism and Distribution of Fibrinogen in Man and Rabbits

1977 ◽  
Vol 37 (02) ◽  
pp. 243-252
Author(s):  
Yi-Hsiang Chen ◽  
E. B Reeve

SummaryTo shed some light on the homeostatic regulation of plasma fibrinogen, metabolic studies were made in healthy females, and in normal, thyroidectomized, and thyroxine-treated rabbits. In females, compared with normal males, plasma fibrinogen concentration, plasma and interstitial fibrinogen decreased consequent to an increased fractional catabolic rate and a normal fibrinogen synthesis rate. The interstitial/plasma fibrinogen ratio remained unchanged. In normal rabbits, with increasing body weight fractional catabolic rate and catabolic rate decreased, while fibrinogen concentration and plasma fibrinogen remained constant owing to a simultaneous decrease in fibrinogen synthesis. In addition, fractional transcapillary transfer rate and transcapillary flux also decreased resulting in a shrinkage of interstitial fibrinogen. Thyroidectomy and thyroxine-injection markedly altered fibrinogen metabolism: thyroid hormone accelerated fibrinogen catabolism but also stimulated synthesis. The net result was an increase in plasma fibrinogen and fibrinogen concentration. The interstitial/plasma fibrinogen ratio decreased in thyroxine-treated, and increased in thyroidectomized animals. This study defines the variations of the fibrinogen system parameters in these physiologic and pathologic conditions, and illustrates some patterns of alterations in fibrinogen metabolism.

1978 ◽  
Vol 39 (01) ◽  
pp. 039-045 ◽  
Author(s):  
Y Takeda ◽  
T Takeuchi

Summary10 healthy female subjects and 15 female patients with essential hypertension were studied with respect to fibrinogen metabolism in a steady state. Autologous I-125-labeled fibrinogen (I-125-fibrinogen) was used as a tracer. Comparison of the results showed that plasma volume, t½ of plasma I-125-fibrinogen and fractional catabolic rate (j3p) of plasma fibrinogen were not appreciably different in both groups of subjects, but plasma fibrinogen concentration, and catabolic flux of (synthesis rate) were significantly higher in hypertensive subjects, whereas extravascular fibrinogen and fractional transcapillary transfer rate (j1) of were significantly decreased in the patients. Further analyses of the data in both groups showed that there were significant correlations between diastolic blood pressure (P) and j1 with a regression equation of j1 = e−0.0285P, between 1 and between and j1 with a regression equation of 1. These results indicate that the observed decrease of j1 triggered the transition from normal to pathological steady state and is responsible for the altered metabolism and distribution of fibrinogen in hypertensive subjects.


1974 ◽  
Vol 32 (02/03) ◽  
pp. 292-305 ◽  
Author(s):  
M Grün ◽  
H Liehr ◽  
D Brunswig ◽  
H Thiel

SummaryThe fibrinogen synthesis rate in patients with cirrhosis of the liver is enhanced. To confirm this, both experimental and clinical investigations were carried out. The fibrinogen synthesis rate was studied, using the incorporation rate of 14-C-Leucine into thrombin clottable plasma protein in the setting of experimental portal hypertension caused by gradual occlusion of the portal vein. Under these conditions the plasma distribution space increased to 148% of the control (day 6). This was dependent on the amount of the portocaval shunt volume. While plasma fibrinogen concentration remained unaltered, the plasma fibrinogen pool increased to 154% of the controls. At the same time, the fibrinogen synthesis rate increased to 159%. In relation to liver weight per 100 gm body weight the rate of synthesis was much more enhanced (211 % of control). During the decline to normal plasma volume, due to a decrease of portocaval shunt volume, the fibrinogen synthesis was inhibited (61% of control).Under clinical conditions in patients with cirrhosis and portal hypertension, the pathophysiological state is in important aspects comparable to the experimental model. A group of 28 patients with cirrhosis was investigated from the same point of view. In these patients the plasma volume and the plasma fibrinogen pool was markedly increased, depending again on the portocaval shunt volume but not on the portal pressure. From these data it is concluded that in patients with cirrhosis fibrinogen synthesis is enhanced.


1970 ◽  
Vol 38 (1) ◽  
pp. 111-121 ◽  
Author(s):  
E. Regoeczi

1. Fibrinogen catabolism was studied in ten rabbits before and after suddenly elevating the intravascular pool by injecting a single dose of homologous fibrinogen equivalent to 18–83% of the corresponding protein already present in this pool. Of the two metabolic tracers used, [131I]fibrinogen was injected 3–4 days before and [125I]fibrinogen at the time of introducing the change. 2. Analysis of total body as well as of the circulating radioactivities indicated that the excess protein did not affect the fractional catabolic rate constant, thus permitting the conclusion that fibrinogen catabolism closely follows a first order kinetic reaction. In some animals a fraction of the injected fibrinogen shifted to extravascular sites and altered the pool ratio. Elimination of the excess protein took about 5 days and was accompanied by changes in the synthesis rate of fibrinogen.


1978 ◽  
Vol 39 (01) ◽  
pp. 032-038
Author(s):  
Ingo Mahn ◽  
Richard-Mathias Moeller ◽  
Gert Müller-Berghaus

Summary16 nón-pregnant female and 19 pregnant rabbits were injected with purified rabbit 125I-fibrinogen in order to study the catabolism of fibrinogen before and after delivery. The half-life time (T ½) of the clottable 125I-radioactivity in pregnant rabbits during the last third of gestation was 27.3 ± 5.3 hr in comparison to 54.4 ± 3.7 hr in non-pregnant rabbits. After delivery, T ½ returned to normal values of 47.9 ± 10.9 hr. The fractional catabolic rate (FCR) of the clottable 125I-radioactivity was 67.1% × d−1 ± 8.6 before and 41.6% × d−1 after delivery whereas FCR in non-pregnant rabbits amounted to 44.7% × d−1 ± 4.8. These figures demonstrate a pronounced increase in fibrinogen catabolism during the last third of gestation in pregnant rabbits and a normalization immediately after delivery. Although in pregnant rabbits the elimination of fibrinogen from the circulating blood was pronouncedly increased, the plasma fibrinogen concentration did not change. Only after delivery did the fibrinogen concentration increase when the fibrinogen catabolism had already normalized.


1978 ◽  
Vol 40 (01) ◽  
pp. 118-127 ◽  
Author(s):  
Y Takeda ◽  
H Arai

SummaryStudies were made of the effects of heparin, typhoid vaccine and thrombophlebitis on factor X (F.X) metabolism in dogs, using 125-labelled F.X (125I-F.X) as a tracer. 10 healthy male dogs were used for control study and 5 male dogs were used for each of other studies. Plasma F.X concentration was measured by a solid-phase radioimmunoassay. In the control dogs, the plasma F.X concentration was 2.4 ± 0.2 (SD) mg per dl, the plasma F.X (x) was 1.2 ± 0.1(SD) mg per kg, the halflife of plasma 125I-F.X(t½) was 0.5 ± 0.01 (SD) days, the fractional catabolic rate (j3p) was 2.4 ± 0.1 (SD) per day and the catabolic flur (J3pX) (synthesis rate) was 2.9 ± 0.7 (SD) mg per kg per day. These results were not appreciably altered in heparinized dogs. However, a single intravenous injection of 2 ml typhoid vaccine caused a shortened t½ of 0.38 ± 0.01 (SD) days and a decrease of plasma F.X concentration to 1.3 ± 0.13 (SD) mg per dl. Studies in heparinized dogs showed similar effects of typhoid vaccine. Next, thrombophlebitis was produced by a previous method and its effects on F.X metabolism were studied. No detectable alterations of F.X metabolism were found. These results indicate that in health most F. X is directly catabolized without the formation of activated F.X (F.Xa), that the observed effects of typhoid vaccine are mostly due to an acceleration of the direct catabolism of F.X without F.Xa formation and finally that localized thrombophlebitis has no appreciable effects on F.X metabolism.


1972 ◽  
Vol 27 (02) ◽  
pp. 319-336 ◽  
Author(s):  
G. N. Tytgat ◽  
D. Collen ◽  
L. S. Oei ◽  
B. Van Damme

SummaryThe metabolism of dog fibrinogen, labelled with radioactive iodine was studied in 16 healthy dogs on 28 occasions, in 12 dogs with CCl4-induced chronic liver damage and in 5 dogs with interruption of the hepatoportal blood flow by occlusion of the portal vein.Results in healthy control dogs were: plasma volume 48±12 ml/kg ; plasma fibrinogen concentration 316±102 mg%; total plasma fibrinogen pool 168±42 mg/kg, representing 0.72±0.08 of the total body pool; fibrinogen half-life 2.54±0.23 day; fractional catabolic rate 0.39±0.05 of the plasma pool per day; absolute catabolic rate 58±25 mg/kg per day.Results in dogs with CCl4-induced liver damage were: plasma volume 46 ± 12 ml/kg ; plasma fibrinogen concentration 334±97 mg%; total plasma fibrinogen pool 152±55 mg/kg, representing 0.70±0.04 of the total body pool; fibrinogen half-life 2.15±0.26 days; fractional catabolic rate 0.47±0.06 of the plasma pool per day; absolute catabolic rate 71±21 mg/kg per day.Results in dogs with longstanding portal vein occlusion were: plasma volume 41 ±8 ml/kg; plasma fibrinogen concentration 330±23 mg%; total plasma fibrinogen pool 142±36 mg/kg, representing 0.70±0.06 of the total body pool; fibrinogen half-life 2.60 ±0.36 days; fractional catabolic rate 0.40 ±0.04 of the plasma pool per day; absolute catabolic rate 56±14 mg/kg per day.A significant difference between control dogs and dogs with liver disease was observed for the fibrinogen half-life and the fractional catabolic rate. All fibrinogen turnover data in dogs with portal vein occlusion were comparable to control values.Heparinization did not influence the fibrinogen half-life in most of the control dogs and in the dogs with portal vein occlusion ; however in 2 control dogs, a prolongation of their rather short fibrinogen survival occurred during anticoagulation. In contrast, a general trend towards prolongation and occasionally normalization of the fibrinogen life span during heparinization was observed in the dogs with liver damage, supporting the concept of accelerated fibrinogen consumption by a process of disseminated intravascular coagulation in liver disease.


1980 ◽  
Vol 44 (03) ◽  
pp. 146-149 ◽  
Author(s):  
Nicole Ardaillou ◽  
Jeannine Yvart ◽  
Philippe Le Bras ◽  
Marie-José Larrieu

SummaryThe catabolism of human fragment D, (FgD), obtained by plasmin digestion of fibrinogen has been investigated in normal subjects and patients with liver cirrhosis and the results compared with those obtained for fibrinogen (Fg). Fg was labelled with I-125 and Fg D with I-131 using the chloramine T method. The plasma disappearance curves of both labelled proteins fitted a two exponential curve. In controls the plasma clearance rate of Fg D was greater than that of Fg as shown by the marked difference between the half-lives of these two tracers: 8,9 and 83,5 hours for Fg D and Fg respectively. The fractional catabolic rate of Fg D was 3.38 times the plasma pool per day. In nine patients with liver cirrhosis, catabolism of Fg was not modified. In contrast, catabolism of Fg D was significantly reduced with a half life of 13.0 hours and a low fractional catabolic rate. These results suggest the role of the liver in the catabolism of Fg D in man.


1974 ◽  
Vol 31 (03) ◽  
pp. 395-402 ◽  
Author(s):  
V Bocci ◽  
T Conti ◽  
M Muscettola ◽  
A Pacini ◽  
G. P Pessina

SummaryRabbit fibrinogen digest products (FDP) have been separated by Pevikon block electrophoresis yielding fragments D, E and other unidentified FDP.The fragments were injected into rabbits. Surprisingly, as little as 4.3 mg of fragment D elicited a significant increase in plasma fibrinogen concentration 24 hr after injection. The stimulating activity of fragment D is at least 10-fold higher than that of fragment E.


2009 ◽  
Vol 94 (12) ◽  
pp. 4891-4897 ◽  
Author(s):  
Laurence Duvillard ◽  
Guillaume Dautin ◽  
Emmanuel Florentin ◽  
Aline Jeannin ◽  
Jean-Paul Pais de Barros ◽  
...  

Context: The impact of estrogen plus progestin as an oral contraceptive on high density lipoprotein (HDL) apolipoprotein (apo) AI metabolism in humans is poorly understood. Objectives: This study was designed to measure the in vivo effect of Moneva (30 μg ethinylestradiol, 75 μg gestodene) on HDL apoAI production rate and fractional catabolic rate. Design: Using 13C-leucine, we performed two kinetic studies in the fed state in 10 normolipidemic young women, before and 3 months after beginning Moneva. Results: On Moneva, serum triglycerides increased by 12% (P = 0.03) in the fed state, whereas low-density lipoprotein and HDL cholesterol remained unchanged. HDL apoAI pool size and production rate were increased by 9.2% (67.3 ± 7.1 vs. 61.6 ± 6.7 mg · kg−1; P = 0.05) and 26.5% (14.3 ± 2.7 vs. 11.3 ± 2.2 mg · kg−1 · d−1; P = 0.02), respectively. HDL apoAI fractional catabolic rate was not significantly modified. Three-month treatment by Moneva induced a shift of HDL size distribution from HDL2 toward HDL3 (HDL3 = 51.5 ± 8.1 vs. 46.5 ± 9.2% of total HDL; P = 0.02) and an increase in the proportion of apoAI among HDL components (38.8 ± 4.3 vs. 34.4 ± 2.8%; P = 0.01). Conclusion: Oral contraception by estrogen plus progestin induces changes in HDL apoAI metabolism characterized by an increase in production rate and pool size, with a higher proportion of HDL3 particles. Whether or not these changes are beneficial to prevent atherosclerosis has to be explored further.


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