lncrease of Tissue Plasminogen Activator in Limbs During Venous Occlusion : A Simple Haemodynamic Model

Summary

Venous occlusion of a limb is an established procedure for increasing the venous plasma concentration of tissue plasminogen activator (t-PA). In this paper a simple haemodynamic model was developed to describe the venous plasma t-PA concentration as a function of haemodynamic parameters and the local release rate of t-PA during venous occlusion of the limb. The venous plasma pool of a limb was regarded as a single well-mixed compartment with a constant input rate of t-PA. The intravascular volume, blood flow and total limb volume of the upper extremity were also measured in three healthy subjects in order to characterise the haemodynamics during venous occlusion. Venous occlusion was shown to cause such an intense decrease of blood flow through the limb that the postocclusion increase in concentration of t-PA need not be explained by an increased release rate of t-PA but could be attributed merely to the diminished dilution of the venous compartment by inflowing arterial plasma. According to our model and haemodynamic measurements, the significant differences in the postocclusion concentration of t-PA between the arrn and leg can be explained by different local release rates of t-PA.

• References

• 1 Wiman B, Mellbring G, Ralnby M. Plasminogen activator release during venous stasis and exercise as determined by a new specific assay. Clin Chim Acta 1983; 127: 279-288
• 2 Booth NA, Walker E, Maughan R, Bennet B. Plasminogen activator in normal subjects after exercise and venous occlusion: t-PA circulates as complexes with C1-inhibitor and PAI-1. Blood 1987; 69: 1600-4
• 3 Keber D. Mechanism of tissue plasminogen activator release during venous occlusion. Fibrinolysis 1988; 2 Suppl (Suppl. 02) 96-103
• 4 Todd AS. The hystological localisation of fibrinolysin activator. J Pathol Bacteriol 1959; 78: 281-3
• 5 Todd AS. Endothelium and fibrinolysis. Bibl Anat 1973; 12: 98-105
• 6 Nilson I, Wallen R, Melnbring G. In vivo metabolism of tissue-type plasminogen activator. Scand J Haematol 1984; 33: 49-53
• 7 Brommer EJ P, Derkx FH M, Schalekamp MA D H, Dooijewaard G, Klaauw MM. Renal and hepatic handling of endogenous tissuetype plasminogen activator (t-PA) and its inhibitor in man. Thromb Haemostas 1988; 59: 404-4ll
• 8 Smith TD, Richards P. A simple kit for the preparation of Tc-99mlabelled red blood cells. J Nucl Med 1976; 17: 126-132
• 9 Da Rocha AF G. The liver. In: Textbook of Nuclear Medicine. Volume II: Clinical Applications Harbert J, Da Rocha AF G. eds Lea and Febiger; Philadelphia, PA: 1984: 245-277
• 10 Secker-Walker RH. The respiratory system. In: Textbook of Nuclear Medicine. Volume II: Clinical Applications Harbert J, Da Rocha AF G. eds Lea and Febiger; Philadelphia, PA: 1984: 311-79
• 11 Ranby M, Bergsdorf N, Nilsson T, Melbring G, Winbald B, Bucht G. Age dependance of tissue plasminogen activator concentration in plasma, as studied by an improved enzyme linked immunosorbent assay. Clin Chem 1986; 32: 2160-2165
• 12 Witzleb E. Functions of the vascular system. In: Human Physiology Schmidt RR, Thews G. eds Springer Verlag Berlin, Heidelberg; New York: 1983: 396-455
• 13 Kruithof EK O, Nicoloso G, Bachmann E. Plasminogen activator inhibitor-i: Development of a radioimmunoassay and observations on its plasma concentration after venous occlusion and platelet aggregation. Blood 1987; 70: 1645-53
• 14 Keber D, Stegnar M, Kluft C. Different tissue plasminogen activator release in the arm and leg during venous occlusion is equalized after DDAVP infusion. Thromb Haemostas 1990; 63: 72-5