Tissue-type plasminogen activator is a naturally occurring, clot-selective activator of fibrinolysis. We recently reported that human tissue-type plasminogen activator isolated from a Bowes-melanoma-tissue-culture supernate lysed coronary thrombi in dogs without depleting circulating fibrinogen or alpha 2-antiplasmin, in contrast to the case with streptokinase and urokinase. In the present study coronary thrombolysis, confirmed angiographically, was induced within 19 to 50 minutes with intravenous or intracoronary tissue-type plasminogen activator in six of seven patients with evolving myocardial infarction. Circulating fibrinogen, plasminogen, and alpha 2-antiplasmin were not depleted by this agent, in contrast to the case in the two patients subsequently given streptokinase. In the one patient in whom lysis was not inducible with tissue-type plasminogen activator, it was also not inducible with streptokinase. These observations indicate that clot-selective coronary thrombolysis can be induced in patients with evolving myocardial infarction by means of tissue-type plasminogen activator, without concomitant induction of a systemic lytic state. Definition of its therapeutic benefit must await greater availability of the agent and the performance of appropriate clinical trials.
This article has been cited by other articles:
Collen, D., Lijnen, H.R.
(2009). The Tissue-Type Plasminogen Activator Story. Arterioscler. Thromb. Vasc. Bio.
29: 1151-1155
[Abstract][Full Text]
Dauerman, H. L., Sobel, B. E.
(2003). Synergistic treatment of ST-segmentelevation myocardial infarction with pharmacoinvasive recanalization. J Am Coll Cardiol
42: 646-651
[Abstract][Full Text]
Ohman, E. M., Harrington, R. A., Cannon, C. P., Agnelli, G., Cairns, J. A., Kennedy, J.W.
(2001). Intravenous Thrombolysis in Acute Myocardial Infarction. Chest
119
: 253S-277S
[Full Text]
Zhang, Y.-L., Hervio, L., Strandberg, L., Madison, E. L.
(1999). Distinct Contributions of Residue 192 to the Specificity of Coagulation and Fibrinolytic Serine Proteases. J. Biol. Chem.
274: 7153-7156
[Abstract][Full Text]
Tachias, K., Madison, E. L.
(1997). Variants of Tissue-type Plasminogen Activator That Display Extraordinary Resistance to Inhibition by the Serpin Plasminogen Activator Inhibitor Type 1. J. Biol. Chem.
272: 14580-14585
[Abstract][Full Text]
Collen, D.
(1996). Fibrin-Selective Thrombolytic Therapy for Acute Myocardial Infarction. Circulation
93: 857-865
[Full Text]
Meehan Carr, J., Bovill, E. G., Tracy, R. P., Mankowski, M., Mann, K. G., McDonagh, J.
(1996). Changes in Fibrinogen After rt-PA Administration. CLIN APPL THROMB HEMOST
2: 43-50
[Abstract]
Tomaru, T., Uchida, Y., Sonoki, H., Tsukamoto, M., Sugimoto, T.
(1989). The Thrombolytic Effects of Native Tissue-Type Plasminogen Activator (AK-124) on Experimental Canine Coronary Thrombosis. ANGIOLOGY
40: 429-435
[Abstract]
Carlson, S. E., Aldrich, M. S., Greenberg, H. S., Topol, E. J.
(1988). Intracerebral Hemorrhage Complicating Intravenous Tissue Plasminogen Activator Treatment. Arch Neurol
45: 1070-1073
[Abstract]
Snyder, R. W., Lambrou, F. H., Williams, G. A.
(1987). Intraocular Fibrinolysis With Recombinant Human Tissue Plasminogen Activator: Experimental Treatment in a Rabbit Model. Arch Ophthalmol
105: 1277-1280
[Abstract]
Salem, B. I., Gowda, S., Haikal, M.
(1987). Reduced In-Hospital Mortality Following Intracoronary Streptokinase Treatment of Acute Myocardial Infarction. VASC ENDOVASCULAR SURG
21: 215-219
[Abstract]
SMITH, B., KENNEDY, J. W.
(1987). Thrombolysis in the Treatment of Acute Transmural Myocardial Infarction. ANN INTERN MED
106: 414-420
[Abstract]
Zwerner, P. L., Gore, J. M.
(1986). Analytic Review: Thrombolytic Therapy in Acute Myocardial Infarction. J Intensive Care Med
1: 302-318
[Abstract]
Curl, G. R., Jakubowski, J. A., Nabseth, D. C., Bush, H. L. Jr
(1986). Efficacy of Tissue Plasminogen Activator and Urokinase in a Canine Model of Prosthetic Graft Thrombosis. Arch Surg
121: 782-788
[Abstract]
MARDER, V. J., ROTHBARD, R. L., FITZPATRICK, P. G., FRANCIS, C. W.
(1986). Rapid Lysis of Coronary Artery Thrombi with Anisoylated Plasminogen: Streptokinase Activator Complex: Treatment by Bolus Intravenous Injection. ANN INTERN MED
104: 304-310
[Abstract]
VAN DE WERF, F., NOBUHARA, M., COLLEN, D.
(1986). Coronary Thrombolysis with Human Single-Chain, Urokinase-Type Plasminogen Activator (Pro-Urokinase) in Patients with Acute Myocardial Infarction. ANN INTERN MED
104: 345-348
[Abstract]
Jaffe, A. S., Sobel, B. E.
(1986). Thrombolysis With Tissue-Type Plasminogen Activator in Acute Myocardial Infarction: Potentials and Pitfalls. JAMA
255: 237-239
[Abstract]
Vehar, G.A., Spellman, M.W., Keyt, B.A., Ferguson, C.K., Keck, R.G., Chloupek, R.C., Harris, R., Bennett, W.F., Builder, S.E., Hancock, W.S.
(1986). Characterization Studies of Human Tissue-type Plasminogen Activator Produced by Recombinant DNA Technology. Cold Spring Harb Symp Quant Biol
51: 551-562
[Abstract]
TOPOL, E. J., BELL, W. R., WEISFELDT, M. L.
(1985). Coronary Thrombolysis with Recombinant Tissue-Type Plasminogen Activator: A Hematologic and Pharmacologic Study. ANN INTERN MED
103: 837-843
[Abstract]
(1985). Thrombolysis for Evolving Myocardial Infarction. ANN INTERN MED
103: 463-469
[Abstract]
Wei, J. Y., Markis, J. E., Malagold, M., Grossman, W.
(1985). Time Course of Serum Cardiac Enzymes After Intracoronary Thrombolytic Therapy: Creatine Kinase, Creatine Kinase MB Isozyme, Lactate Dehydrogenase, and Serum Glutamic-Oxaloacetic Transaminase. Arch Intern Med
145: 1596-1600
[Abstract]
Dunn, M. I., Dreiling, R. J.
(1985). Streptokinase. Arch Intern Med
145: 1381-1383
[Abstract]
BOUNAMEAUX, H., VERMYLEN, J., DESIRE, C.
(1985). Thrombolytic Treatment with Recombinant Tissue-Type Plasminogen Activator in a Patient with Massive Pulmonary Embolism. ANN INTERN MED
103: 64-65
[Abstract]