Intracoronary β2 receptor activation induces dynamic local t-PA release in the pig

Summary

To investigate β₂-adrenergic agonist-mediated effects on coronary fluxes of local fibrinolytic factors, healthy anaesthetised and instrumented pigs (n=10) were studied during infusion of isoprenaline (IPR) into the left main coronary artery. Coronary net fluxes of total t-PA antigen, active t-PA and total PAI-1 antigen were determined at baseline and at 3, 5, 7 and 10 minutes of IPR infusion. During IPR, net release of total t-PA increased in a biphasic pattern with transiently high levels at 3 (+440 %) and 7 minutes (+620%) and returned towards baseline at 10 minutes. Net coronary release of active t-PA increased with maximum levels at 3 minutes (+50%). Baseline coronary net flux of total PAI –1 showed a decrease which was most pronounced at 10 minutes. To conclude, a fast β₂agonist-mediated local release of t-PA into the coronary vasculature was demonstrated. For total t-PA, this response was characterised by a biphasic release profile.

Keywords

Tissue-type plasminogen activator - plasminogen activator inhibitor - porcine - coronary circulation - β₂-adrenergic agonism

• References

• 1 Emeis JJ. Regulation of the acute release of tissue-type plasminogen activator from the endothelium by coagulation activation products. Ann N Y Acad Sci 1992; 667: 249-58.
• 2 Kooistra T, Schrauwen Y, Arts J. et al Regulation of endothelial cell t-PA synthesis and release. Int J Hematol 1994; 59 (04) 233-55.
• 3 Jern C, Selin L, Jern S. In vivo release of tissue-type plasminogen activator across the human forearm during mental stress. Thromb Haemost 1994; 72 (02) 285-91.
• 4 Jern C, Selin L, Tengborn L. et al Sympathoadrenal activation and muscarinic receptor stimulation induce acute release of tissue-type plasminogen activator but not von Willebrand factor across the human forearm. Thromb Haemost 1997; 78 (02) 887-91.
• 5 Chandler WL, Levy WC, Stratton JR. The circulatory regulation of T-PA and UPA secretion, clearance, and inhibition during exercise and during the infusion of isoproterenol and phenylephrine. Circulation 1995; 92 (10) 2984-94.
• 6 Stein CM, Brown N, Vaughan DE. et al Regulation of local tissue-type plasminogen activator release by endothelium-dependent and endothelium-independent agonists in human vasculature. J Am Coll Cardiol 1998; 32 (01) 117-22.
• 7 von Kanel R, Dimsdale JE. Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo. Eur J Haematol 2000; 65 (06) 357-69.
• 8 Seeman-Lodding H, Häggmark S, Jern C. et al Aortic cross-clamping influences regional net release and uptake rates of tissue-type plasminogen activator in pigs. Acta Anaesthesiol Scand 1997; 41 (09) 1114-23.
• 9 Seeman-Lodding H, Häggmark S, Jern C. et al Systemic levels and preportal organ release of tissue-type plasminogen activator are enhanced by PEEP int the pig. Acta Anaesthesiol Scand 1999; 43 (06) 623-33.
• 10 Österlund B, Holmgren A, Häggmark S. et al Surgical stress induces acute coronary release of tissue-type plasminogen activator in the pig. Acta Anaesthesiol Scand 2000; 44 (10) 1226-31.
• 11 Österlund B, Andersson B, Häggmark S. et al Myocardial ischemia induces coronary t-PA release in the pig. Acta Anaesthesiol Scand 2002; 46 (03) 271-8.
• 12 Jern C, BjÖrkman J-A, Jern S. Sympathetic stimulation markedly enhancestissue-type plasminogen activator release across the coronary vasculature. Circulation 1996; 94 (I-241) 1408A.
• 13 Rånby M, Nguyen G, Scarabin PY. et al Immunoreactivity of tissue plasminogen activator and of its inhibitor complexes. Biochemical and multicenter validation of a two site immunosorbent assay. Thromb Haemost 1989; 61 (03) 409-14.
• 14 Jern C, Seeman-Lodding H, Biber B. et al An experimental multiple-organ model for the study of regional net release/uptake rates of tissue-type plasminogen activator in the intact pig. Thromb Haemost 1997; 78 (03) 1150-6.
• 15 Huisman L.G.M, Meijer P, van Griensven J, Kluft C. Evaluation of the specificity of antigen assays for plasminogen activator inhibitor 1: comparison of two new commercial kits. Fibrinolysis 1992; 6 (03) (Suppl) 87-8.
• 16 Gough SC, Smyllie J, Sheldon T. et al The anatomical distribution of plasma fibrinolytic activity in man during cardiac catheterisation. Thromb Haemost 1992; 68 (04) 442-7.
• 17 Rosenfeld BA, Nguyen ND, Sung I, Faraday N. Neuroendocrine stress hormones do not recreate the postoperative hypercoagulable state. Anesth Analg 1998; 86 (03) 640-5.
• 18 von Kanel R, Mills PJ, Fainman C. et al Effects of psychological stress and psychiatric disorders on blood coagulation and fibrinoly-sis: a biobehavioral pathway to coronary artery disease?. Psychosom Med 2001; 63 (04) 531-44.
• 19 Winnerkvist A, Wiman B, Valen G. et al Release of tissue plasminogen activator during reperfusion after different times of ischaemia in isolated, perfused rat hearts. Thromb Res 1996; 82 (06) 533-42.
• 20 Winnerkvist A, Wiman B, Valen G. et al Oxidative stress and release of tissue plasmi-nogen activator in isolated rat hearts. Thromb Res 1997; 85 (03) 245-57.
• 21 Jern C, Eriksson E, Tengborn L. et al Changes of plasma coagulation and fibrinoly-sis in response to mental stress. Thromb Haemost 1989; 62 (02) 767-71.
• 22 Larsson PT, Wiman B, Olsson G. et al Influence of metoprolol treatment on sympa-tho-adrenal activation of fibrinolysis. Thromb Haemost 1990; 63 (03) 482-7.
• 23 Chandler WL, Levy WC, Veith RC. et al A kinetic model of the circulatory regulation of tissue plasminogen activator during exercise, epinephrine infusion, and endurance training. Blood 1993; 81 (12) 3293-302.
• 24 Stein CM, Nelson R, He HB. et al Norepinephrine release in the human forearm: effects of epinephrine. Hypertension 1997; 30 (05) 1078-84.
• 25 Hegeman RJ, van den Eijnden-Schrauwen Y, Emeis JJ. Adenosine 3’: 5’-cyclic monophosphate induces regulated secretion of tissuetype plasminogen activator and von Willebrand factor from cultured human endothelial cells. Thromb Haemost 1998; 79 (04) 853-8.
• 26 Wall U. In vivo studies on local release of tissue-type plasminogen activator from the vascular endothelium. Thesis, Gothenburg University: Sweden; 1997
• 27 Newby DE. Intracoronary infusions and the assessment of coronary blood flow in clinical studies. Heart 2000; 84 (02) 118-20.
• 28 Minai K, Matsumoto T, Horie H. et al Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation: effects of angiotensin-converting enzyme inhibitors. J Am Coll Cardiol 2001; 37 (06) 1565-70.
• 29 Newby DE, McLeod AL, Uren NG. et al Impaired coronary tissue plasminogen activator release is associated with coronary therosclerosis and cigarette smoking: direct link between endothelial dysfunction and atherothrombosis. Circulation 2001; 103 (15) 1936-41.
• 30 Sjogren LS, Gan L, Doroudi R. et al Fluid shear stress increases the intra-cellular storage pool of tissue-type plasminogen activator in intact human conduit vessels. Thromb Haemost 2000; 84 (02) 291-8.
• 31 Sjogren LS, Doroudi R, Gan L. et al Elevated intraluminal pressure inhibits vascular tissue plasminogen activator secretion and downregulates its gene expression. Hypertension 2000; 35 (04) 1002-8.
• 32 Jern S, Selin L, Bergbrant A. et al Release of tissue-type plasminogen activator in response to muscarinic receptor stimulation in human forearm. Thromb Haemost 1994; 72 (04) 588-94.
• 33 Gossinger HD, Speiser W, Siostrzonek P. et al Pacing-induced myocardial ischemia does not affect the endothelial release of coagulant and fibrinolytic factors into the coronary circulation. Clin Cardiol 1991; 14 (03) 250-6.