PDF herunterladen
Thromb Haemost 1997; 78(03): 1150-1156
DOI: 10.1055/s-0038-1657702
Rapid Communication
Schattauer GmbH Stuttgart

An Experimental Multiple-Organ Model for the Study of Regional Net Release/Uptake Rates of Tissue-type Plasminogen Activator in the Intact Pig

Christina Jern
1   The Heart and Lung Institute, Clinical Experimental Research Laboratory, Goteborg University, Göteborg
2   The Institute of Clinical Neuroscience, Department of Neurology, Göteborg University, Göteborg
,
Heléne Seeman-Lodding
3   The Dept of Anesthesiology, Sahlgrenska University Hospital, Göteborg University, Göteborg
,
Bjӧrn Biber
4   The Dept of Anesthesiology, Umeå University Hospital, Umeå, Sweden
,
Ola Winsӧ
3   The Dept of Anesthesiology, Sahlgrenska University Hospital, Göteborg University, Göteborg
,
Sverker Jern
1   The Heart and Lung Institute, Clinical Experimental Research Laboratory, Goteborg University, Göteborg
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 24. 1997

Accepted after revision 12. Mai 1997

Publikationsdatum:
12. Juli 2018 (online)

Auch verfügbar auf
  als PDF herunterladen  Lizenzen und Reprints

Summary

Experimental data indicate large between-organs variations in rates of synthesis of tissue-type plasminogen activator (t-PA), which may reflect important differences in the capacity for constitutive and stimulated t-PA release from the vascular endothelium. In this report we describe a new multiple-organ experimental in vivo model for simultaneous determinations of net release/uptake rates of t-PA across the coronary, splanchnic, pulmonary, and hepatic vascular beds. In eleven intact anesthetized pigs, blood samples were obtained simultaneously from the proximal aorta, coronary sinus, pulmonary artery, and portal and hepatic veins. Plasma flows were monitored separately for each vascular region. Total plasma t-PA was determined by ELISA with a porcine t-PA standard. Regional net release/uptake rates were defined as the product of arteriovenous concentration gradients and local plasma flows. The net release of t-PA across the splanchnic vascular bed was very high, with a mean output of 1,919 ng total t-PA X min-1 (corresponding to 90 ng per min and 100 g tissue). The net coronary t-PA release was 68 ng X min-1 (30 ng X min-1 X 100 g"1)- Pulmonary net fluxes of t-PA were variable without any significant net t-PA release. The net hepatic uptake rate was 4,855 ng X min-1 (436 ng X min-1 X 100 g-1). Net trans-organ changes of active t-PA mirrored those of total t-PA. The results demonstrate marked regional differences in net release rates of t-PA in vivo. The experimental model we present offers new possibilities for evaluation of regional secretion patterns in the intact animal.

 

  • References

  • 1 Emeis JJ. Mechanisms involved in short-term changes in blood levels of tissue-type plasminogen activator. in: Tissue-type Plasminogen Activator (t-PA): Physiological and Clinical Aspects. Kluft C. ed. Boca Raton; CRC Press: 1988. 02. pp. 21-35
    Suche in Google Scholar
  • 2 Prowse CV, MacGregor IR. Regulation of the plasminogen activator level in blood. in: Tissue-type Plasminogen Activator (t-PA): Physiological and Clinical Aspects. Kluft C. ed. Boca Raton; CRC Press: 1988. 02. pp. 49-65
    Suche in Google Scholar
  • 3 Wun T-C, Capuano A. Spontaneous fibrinolysis in whole human plasma. Identification of tissue activator-related protein as the major plasminogen activator causing spontaneous activity in vitro. J Biol Chem 1985; 260: 5061-5066
    PubMedSuche in Google Scholar
  • 4 Jem C, Selin L, Jem S. In vivo release of tissue-type plasminogen activator across the human forearm during mental stress. Thromb Haemost 1994; 72: 285-291
    Thieme ConnectPubMedSuche in Google Scholar
  • 5 Jem S, Selin L, Bergbrant A, Jem C. Release of tissue-type plasminogen activator in response to muscarinic receptor stimulation in human forearm. Thromb Haemost 1994; 72: 588-94
    Thieme ConnectPubMedSuche in Google Scholar
  • 6 Jem C, Bjӧrkman J-A, Jem S. Sympathetic stimulation markedly enhances tissue-type plasminogen activator release across the coronary vasculature. Circulation 1996; 94: 1-241 (1408A).
    CrossrefPubMedSuche in Google Scholar
  • 7 Keber D, Blinc A, Fettich J. Increase of tissue plasminogen activator in limbs during venous occlusion: a simple hemodynamic model. Thromb Haemost 1990; 64: 433-437
    Thieme ConnectPubMedSuche in Google Scholar
  • 8 Emeis JJ. Regulation of the acute release of tissue-type plasminogen activator from endothelium by coagulation products. in: Plasminogen activation in fibrinolysis in tissue remodeling, and in development. Brakman P, vKluft C. (eds). Ann NY Acad Sci. 1992. 667. 249-258
    Suche in Google Scholar
  • 9 Padro T, van denHoogen, Emeis JJ. Distribution of tissue-type plasminogen activator (activity and antigen) in rat tissues. Blood Coagulation Fibrinolysis 1990; 01: 601-608
    PubMedSuche in Google Scholar
  • 10 van den Eijnden-SchrauwenY, Kooistra T, de VriesREM, Emeis JJ. Studies on the acute release of tissue-type plasminogen activator from human endothelial cells in vitro and in rats in vivo: evidence of a dynamic storage pool. Blood 1995; 85: 3510-3517
    PubMedSuche in Google Scholar
  • 11 van HinsberghVWM. Regulation of the synthesis and secretion of plasminogen activators by endothelial cells. Haemostasis 1988; 18: 307-327
    PubMedSuche in Google Scholar
  • 12 Bålfors E, Häggmark S, Ariola Jr S, Biber B, Pontén J, Reiz S. In vitro analysis of thermal transport in coronary sinus thermodilution catheters. Clin Physiol 1983; 03: 469-476
    CrossrefPubMedSuche in Google Scholar
  • 13 Aneman A, Pontén J, Fändriks L, Eisenhofer G, Friberg P, Biber B. Splanchnic and renal sympathetic activity in relation to hemodynamics during isofluran administration in pigs. Anesth Analg 1995; 80: 135-142
    PubMedSuche in Google Scholar
  • 14 Rånby M, Nguyen G, Scarabin PY, Samama M. Immunoreactivity of tissue plasminogen activator and of its inhibitor complexes. Thromb Haemost 1989; 61: 409-414
    Thieme ConnectPubMedSuche in Google Scholar
  • 15 Pohl G, Jӧmvall H, Kok P, Wallen P. Porcine tissue plasminogen activator. Immunoaffmity purification, structural properties and glycosylation pattern. FEBS 1986; 205: 92-96
    CrossrefPubMedSuche in Google Scholar
  • 16 Wallen P, Bergsdorf N, Rånby M. Purification and identification of two structural variants of porcine tissue plasminogen activator by affinity adsorption on fibrin. Biochim Biophys Acta 1982; 719: 318-328
    CrossrefPubMedSuche in Google Scholar
  • 17 Wiman B, Mellbring G, Rånby M. Plasminogen activator release during venous stasis and exercise as demonstrated by a new specific assay. Clin ChimActa 1983; 127: 279-288
    CrossrefPubMedSuche in Google Scholar
  • 18 Rånby M, Sundell IB, Nilsson TK. Blood collection in strong acidic citrate anticoagulant used in a study of dietary influence on basal t-PA activity. Thromb Haemost 1989; 61: 511-516
    Thieme ConnectPubMedSuche in Google Scholar
  • 19 Huisman LGM, Meijer P, van GriensvenJ, Kluft C. Evaluation of the specificity of antigen assays for plasminogen activator inhibitor 1: comparison of two new commercial kits. Fibrinolysis 1992; 06 (Suppl. 03) 87-88
    PubMedSuche in Google Scholar
  • 20 Simpson AJ, Booth NA, Moore NR, Bennet B. The platelet and plasma pools of plasminogen activator inhibitor (PAI-1) vary independently in disease. Br J Haematol 1990; 75: 543-548
    CrossrefPubMedSuche in Google Scholar
  • 21 Rijken D. Plasminogen activators and plasminogen activator inhibitors: biochemical aspects. Ballière’s Clinical Haematology 1995; 08: 291-312
    PubMedSuche in Google Scholar
  • 22 Chandler WL, Loo SC, Momin D. Adrenergic stimulation of regional plasminogen activator release in rabbits. Thromb Haemost 1992; 68: 545-549
    Thieme ConnectPubMedSuche in Google Scholar
  • 23 Valén G, Eriksson E, Risberg B, Vaage J. Fibrinolysis during cardiac surgery. Release of tissue plasminogen activator in arterial and coronary sinus blood. Eur J Cardiothorac Surg 1994; 08: 324-330
    CrossrefPubMedSuche in Google Scholar
  • 24 Eliasson M, Evrin P-E, Lundblad D, Asplund K, Rånby M. Influence of gender, age and sampling time on plasma fibrinolytic variables and fibrinogen. Fibrinolysis 1993; 07: 316-323
    PubMedSuche in Google Scholar
  • 25 Rahr HB, Sorensen JV, Larsen JF, Svendsen JensenF, Bredahl C. Plasminogen activators and plasminogen activator inhibitor in portal blood from patients with and without gastric malignancy. Scand J Gastroenterol 1996; 31: 170-174
    CrossrefPubMedSuche in Google Scholar
  • 26 Gough SCL, Smyllie J, Sheldon J, Rice PJS, Grant PJ. The anatomical distribution of plasma fibrinolytic activity in man during cardiac catheterization. Thromb Haemost 1992; 68: 442-447
    Thieme ConnectPubMedSuche in Google Scholar
  • 27 Chandler WL, Levy WC, Stratton JR. The circulatory regulation of TPA and UPA secretion, clearance, and inhibition during exercise and during the infusion of isoproterenol and phenylephrine. Circulation 1995; 92: 2984-2994
    CrossrefPubMedSuche in Google Scholar
  • 28 Loskutoff DJ, Sawdey M, Keeton M. Schneiderman. Regulation of PAI-1 gene expression in vivo. Thromb Haemost 1993; 70: 135-137
    Thieme ConnectPubMedSuche in Google Scholar
  • 29 Chomiki N, Henry M, Alessi MC, Anfosso F, Juhan-Vague I. Plasminogen activator inhibitor-1 expression in human liver and healthy or atherosclerotic vessel walls. Thromb Haemost 1994; 72: 44-53
    PubMedSuche in Google Scholar
  • 30 Hart DA. Hepatic regulation of fibrinolysis in normal and disease states. in: Fibrinolysis in disease. Molecular and hemovascular aspects of fibrinolysis. Glas-Greenwalt P. ed. Boca Raton; CRC Press: 1995. pp 43-54
    Suche in Google Scholar
  • 31 Mattsson C. Turnover and clearance of t-PA. in: Tissue-type Plasminogen Activator (t-PA): Physiological and Clinical Aspects. Kluft C, ed. Boca RatonFL. CRC Press: 1988. 02. pp. 37-48
    Suche in Google Scholar
  • 32 Otter M, Kuiper J, van BerkelThJC, Rijken DC. Mechanisms of tissue-type plasminogen activator (tPA) clearance by the liver. Ann NY Acad Sci 1992; 667: 431-442
    CrossrefPubMedSuche in Google Scholar
  • 33 Brommer EJP, Derkx FHM, Schalekamp MADH, Dooijewaard G, vd KlaauwMM. Renal and hepatic handling of endogenous tissue-type plasminogen activator (t-PA) and its inhibitor in man. Thromb Haemost 1988; 59: 404-411
    Thieme ConnectPubMedSuche in Google Scholar
  • 34 Juhan-Vague I, Chandler WL, Aillaud MF, Alessi MC, Vague P, Henderson P. Humans clear active t-PA faster than t-PA/PAI-1 complex. Fibrinolysis 1996; 10 (Suppl. 03) 102 (A342)
    PubMedSuche in Google Scholar
  • 35 Wing LR, Hawksworth GM, Bennet BBooth. Clearance of t-PA, PAI-1 and t-PA-PAI-1 complex in an isolated perfused rat liver system. J Lab Clin Med 1991; 117: 109-114
    PubMedSuche in Google Scholar
  • 36 Kuiper J, Otter M, Voorschuur AH, van ZonneveldAJ, Rijken DC, van BerkelThJC. Characterization of the interaction of a complex of tissue- type plasminogen activator and plasminogen activator inhibitor type 1 with rat liver cells. Thromb Haemost 1995; 74: 1298-1304
    Thieme ConnectPubMedSuche in Google Scholar
  • 37 Brommer EJP. The level of extrinsic plasminogen activator (t-PA) during clotting as a determinant of the rate of fibrinolysis: Inefficiency of activators added afterwards. Thromb Res 1984; 34: 109-115
    CrossrefPubMedSuche in Google Scholar
  • 38 Fox KAA, Robison AK, Knabb RM, Rosamond TL, Sobel BE, Bergmann SR. Prevention of coronary thrombosis with subthrombolytic doses of tissue-type plasminogen activator. Circulation 1985; 72: 1346-1354
    CrossrefPubMedSuche in Google Scholar