Abstract
Thrombolytic therapy may be hampered by the resistance of thrombi to dissolution with plasminogen activators and by reocclusion following successful thrombolysis. A number of adjuvant treatments are being evaluated to overcome resistance to lysis, to acceleraterecanalization, and to prevent reocclusion. These include potent antiplatelet agents such as combinations of thromboxane A2 and serotonin receptor antagonists, substances with combined thromboxane synthase inhibitor/prostaglandin endoperoxide receptor antagonist action,antiplatelet glycoprotein (GP) IIb/IIIa monoclonal antibodies, or RGD-containing polypeptides. Alternatively, potent specific thrombin inhibitors such as hirudin or argatroban are being explored as superior agents to heparin for the acceleration and persistence of lysis with plasminogen activators. While it is clear that compounds with antithrombin or antiplatelet properties may enhance and sustain the action of thrombolytic agents, their optimal use and potential (hemorrhagic) side effects remain to be further explored. However, optimized thrombolytic therapy will eventually consist of potentspecific plasminogen activators in combination with conjunctive anticoagulants and/or antiplatelet agents.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Collen, D., Stump, D.C., and Gold, H.K. (1988) ‘Thrombolytic therapy’, Ann. Rev. Med. 39, 405–423.
Collen, D. (1990) ‘Coronary thrombolysis: streptokinase or recombinant tissue-type plasminogen activator ?’, Ann. Int. Med. 112, 529–538.
Chesebro, J.H., Knatterud, G., and Braunwald, E. (1988) ‘Correspondence section. Thrombolytic therapy’, N. Engl. J. Med. 319, 1544–1545.
Gold, H.K., Leinbach, R.C., Palacios, I.F., Yasuda, T., Block, P.C., Buckley, M.J., Akins, C.W., Daggett, W.M., and Austen, W.G. (1983) ‘Coronary reocclusion after selective administration of streptokinase’, Circulation 68, I50–I54.
Johns, J.A., Gold, H.K., Leinbach, R.C., Yasuda, T., Gimple, L.W., Werner, W., Finkelstein, D.B., Newell, J.B., Ziskind, A.A., and Collen, D. (1988) ‘Prevention of coronary artery reocclusion and reduction in late coronary artery stenosis after thrombolytic therapy in patients with acute myocardial infarction. A randomized study of maintenance infusion of recombinant human tissue-type plasminogen activator’, Circulation 78, 546–556.
Raynaud, P. and Desveaux, B. (1988) ‘Réocclusion après traitement par l’Actilyse’, Arch. Mal Coeur 81, 25–32.
Chesebro, J.H., Knatterud, G., Roberts, R., Borer, J., Cohen, L.S., Dalen, J., Dodge, H.T., Francis, C.K., Hillis, D., Ludbrook, P., Markis, J.E., Mueller, H., Passamani, E.R., Powers, E.R., Rao, A.K., Robertson, T., Ross, A., Ryan, T.J., Sobel, B.E., Willerson, J., Williams, D.O., Zaret, B.L., and Braunwald, E. (1987) ‘Thrombolysis in myocardial infarction (TIMI) trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge’, Circulation 76, 142–154.
Rovelli, F., De Vita, C., Feruglio, G.A., Lotto, A., Selvini, A., Tognoni, G., and GISSI investigators, (1987) ‘GISSI trial: early results and late follow-up’, J. Am. Coll. Cardiol. 10, 33B–39B.
ISIS-2 (Second International Study of Infarct Survival) and Collaborative Group, (1988) ‘Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2’, Lancet 2, 349–360.
Wilcox, R.G., von der Lippe, G., Olsson, C.G., Jensen, G., Skene, A.M., and Hampton, J.R. (1988) ‘Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction. Anglo-Scandinavian Study of Early Thrombolysis (ASSET)’, Lancet 2, 525–530.
Yasuda, T., Gold, H.K., Fallon, J.T., Leinbach, R.C., Garabedian, H.D., Guerrero, J.L., and Collen, D. (1989) ‘A canine model of coronary artery thrombosis with superimposed high grade stenosis for the investigation of rethrombosis after thrombolysis’, J. Am. Coll. Cardiol. 13, 1409–1414.
Friedman, M. and Van den Bovenkamp, G.J. (1966) ‘The pathogenesis of a coronary thrombus’, Am. J. Pathol. 48, 19–44.
Jang, I.K., Gold, H.K., Ziskind, A.A., Fallon, J.T., Holt, R.E., Leinbach, R.C., May, J.W., and Collen, D. (1989) ‘Differential sensitivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator (rt-PA). A possible explanation for resistance to coronary thrombolysis’, Circulation 79, 920–928.
Yasuda, T., Gold, H.K., Leinbach, R.C., Saito, T., Guerrero, J.L., Jang, I.K., Holt, R., Fallon, J.T., and Collen, D. (1990) ‘Lysis of plasminogen activator-resistant platelet-rich coronary artery thrombus with combined bolus injection of recombinant tissue-type plasminogen activator and anti-platelet GPIIb/IIIa antibody’, J. Am. Coll. Cardiol. 16, 1728–1735.
Yasuda, T., Gold, H.K., Fallon, J.T., Leinbach, R.C., Guerrero, L., Scudder, L.S., Kanke, M., Shealy, D., Ross, M.J., Collen, D., and Coller, B.S. (1988) ‘Monoclonal antibody against the platelet glycoprotein (GP) IIb/IIIa receptor prevents coronary artery reocclusion after reperfusion with recombinant tissue-type plasminogen activator in dogs’, J. Clin. Invest. 81, 1284–1291.
Gold, H.K., Coller, B.S., Yasuda, T., Saito, T., Fallon, J.T., Guerrero, J.L., Leinbach, R.C., Ziskind, A.A., and Collen, D. (1988) ‘Rapid and sustained coronary artery recanalization with combined bolus injection of recombinant tissue-type plasminogen activator and monoclonal antiplatelet GPIIb/IIIa antibody in a canine preparation’, Circulation 77, 670–677.
Yasuda, T., Gold, H.K., Yaoita, H., Leinbach, R.C., Guerrero, J.L., Jang, I.K., Holt, R., Fallon, J.T., and Collen, D. (1990) ‘Comparative effects of aspirin, a synthetic thrombin inhibitor and a monoclonal antiplatelet GPIIb/IIIa antibody on coronary artery reperfusion, reocclusion and bleeding with recombinant tissue-type plasminogen activator in a canine preparation’, J. Am. Coll. Cardiol. 16, 714–722.
Davies, M.J. and Thomas, A.C. (1985) ‘Plaque fissuring - the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina’, Br. Heart J. 53, 363–373.
De Wood, M.A., Spores, J., Notske, R., Lowell, T., Mouser, T., Burroughs, R., Golden, M.S., and Lang, H.T. (1980) ‘Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction’, N. Engl. J. Med. 303, 897–902.
Fuster, V., Badimon, L., Badimon, J. Adams, P.C. Turitto, V., and Chesebro, J.H. (1987) ‘Drugs interfering with platelet functions: mechanisms and clinical relevance’, in M. Verstraete, J. Vermylen, R. Lijnen and J. Arnout (eds.), Trombosis and Haemostasis, Leuven University Press, Leuven, Belgium, pp. 349–418.
Loscalzo, J. and Vaughan, D.E. (1987) ‘Tissue plasminogen activator promotes platelet disaggregation in plasma’, J. Clin. Invest. 79, 1749–1755.
The TIMI Study Group, (1985) ‘Special Report. The thrombolysis in Myocardial Infarction (TIMI) Trial’, N. Engl. J. Med. 312, 932–936.
Verstraete, M., Bernard, R., Bory, M., Brower, R.W., Collen, D., de Bono, D.P., Erbel, R., Huhamnn, W., Lennane, R.J., Lubsen, J., Mathey, D., Meyer, J., Michels, H.R., Rutsch, W., Schartl, M., Schmidt, W., Uebis, R., and von Essen, R. (1985) ‘Randomised trial of intravenous recombinant tissue-type plasminogen activator versus intravenous streptokinase in acute myocardial infarction’, Lancet 1, 842–847.
Gold, H.K., Leinbach, R.C., Garabedian, H.D., Yasuda, T., Johns, J.A., Grossbard, E.B., Palacios, I., and Collen, D. (1986) ‘Acute coronary reocclusion after thrombolysis with recombinant human tissue-type plasminogen activator: prevention by a maintenance infusion’, Circulation 73, 347–352.
Harrison, D.G., Ferguson, D.W., Collins, S.M., Skorton, D.J., Ericksen, E.E., Kioschos, J.M., Marcus, M.L., and White, C.W. (1984) ‘Rethrombosis after reperfusion with streptokinase: importance of geometry of residual lesions’, Circulation 69, 991–999.
Gold, H.K., Cowley, M.J., Palacios, I.F., Vetrovec, G.W., Akins, C.W., Block, P.C., and Leinbach, R.C. (1984) ‘Combined intracoronary streptokinase and coronary angioplasty during acute myocardial infarction’, Am. J. Cardiol. 53, 122C–125C.
Folts, J.D., Crowell Jr., E.B., and Rowe, G.G. (1976) ‘Platelet aggregation in partially obstructed vessels and its elimination with aspirin’, Circulation 54, 365–370.
Gallagher, K.P., Folts, J.D., and Rowe, G.G. (1978) ‘Comparison of coronary arteriograms with direct measurements of stenosed coronary arteries in dogs’, Am. Heart J. 95, 338–347.
Aiken, J.W., Shebuski, R.J., Miller, O.V., Gorman, R.R. (1981) ‘Endogenous prostacyclin constributes to the efficacy of a thromboxane synthetase inhibitor for preventing coronary artery thrombolysis’, J. Pharmacol. Exp. Ther. 219, 299–308.
Schumacher, W.A., Lee, E.C., and Lucchesi, B.R. (1985) ‘Augmentation of streptokinase-induced thrombolysis by heparin and prostacyclin’, J. Cardiovasc. Pharmacol. 7, 299–308.
Fitzgerald, D.J., Wright, F., and FitzGerald, G.A. (1989) ‘Increased thromboxane biosynthesis during coronary thrombolysis. Evidence that platelet activation and thromboxane A2 modulate the response to tissue-type plasminogen activator in vivo’, Circ. Res. 65, 83–94.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Gold, H.K. et al. (1991). Adjuvant Agents to Enhance and Sustain Reperfusion with t-PA: Studies in Experimental Dog Models. In: Herman, A.G. (eds) Antithrombotics. Developments in Cardiovascular Medicine, vol 126. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3484-2_13
Download citation
DOI: https://doi.org/10.1007/978-94-011-3484-2_13
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-5540-6
Online ISBN: 978-94-011-3484-2
eBook Packages: Springer Book Archive