Circulation, Vol 77, 660-669, Copyright © 1988 by American Heart Association
CL Lucore and BE Sobel
To delineate interactions of infused tissue-type plasminogen activator
(t-PA) with inhibitors in plasma and their impact on fibrinolytic activity,
serial plasma samples from patients with acute myocardial infarction and
from normal rabbits given infusions of t-PA were assayed for t-PA antigen,
activity of "fast acting" plasminogen activator inhibitor (PAI-1), and the
presence and nature of t-PA-inhibitor complexes. In patients, endogenous
t-PA circulated predominantly as a 100 kilodalton (kDa) complex with PAI-1,
as verified by immunoprecipitation. During infusions, t-PA circulated not
only as free t-PA (55 kDa) but also in complexes with PAI-1 (100 kDa),
alpha 2- antiplasmin (110 kDa), and C1-esterase inhibitor (170 kDa). After
termination of infusions, levels of free t-PA declined, while inhibitor
complexes remained prominent. Free PAI-1 activity, assayed
spectrophotometrically, was markedly elevated in the 24 hr interval after
infusion of t-PA in 47% of patients with infarction. The specific activity
of t-PA during infusions was 0.4 IU/ng or greater. However, during the 3 hr
interval after infusions in patients, specific activity declined in
association with prominence of t-PA complexes, predominantly with PAI-1.
Infusions of t-PA in normal rabbits did not result in reactive increases in
PAI-1 activity or in the t-PA-PAI-1 complex. After infusions, t-PA was
associated predominantly with alpha 2-antiplasmin and C1-esterase inhibitor
rather than PAI-1. t-PA inhibitor complexes were seen despite immediate
acidification of whole blood, indicating that they were present in
vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Interactions of tissue-type plasminogen activator with plasma inhibitors and their pharmacologic implications
Cardiovascular Division, Washington University School of Medicine, St. Louis, MO 63110.
This article has been cited by other articles:
 |
|
 |
|
  C. R. Weiler and R. G. Van Dellen Genetic Test Indications and Interpretations in Patients With Hereditary Angioedema Mayo Clin. Proc., July 1, 2006; 81(7): 958 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sakamoto, H. Ogawa, K. Takazoe, M. Yoshimura, H. Shimomura, Y. Moriyama, H. Arai, and K. Okajima Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase: Comparison with unfractionated heparin J. Am. Coll. Cardiol., October 15, 2003; 42(8): 1389 - 1394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. J. Brown, S. Kumar, C. A. Painter, and D. E. Vaughan ACE Inhibition Versus Angiotensin Type 1 Receptor Antagonism: Differential Effects on PAI-1 Over Time Hypertension, December 1, 2002; 40(6): 859 - 865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L. Chandler, M. L. Jascur, and P. J. Henderson Measurement of Different Forms of Tissue Plasminogen Activator in Plasma Clin. Chem., January 1, 2000; 46(1): 38 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brown, M. Agirbasli, and D. E. Vaughan Comparative Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Antagonism on Plasma Fibrinolytic Balance in Humans Hypertension, August 1, 1999; 34(2): 285 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhu, P. Carmeliet, and W. P. Fay Plasminogen Activator Inhibitor-1 Is a Major Determinant of Arterial Thrombolysis Resistance Circulation, June 15, 1999; 99(23): 3050 - 3055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Reed and A. K. Houng The Contribution of Activated Factor XIII to Fibrinolytic Resistance in Experimental Pulmonary Embolism Circulation, January 19, 1999; 99(2): 299 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E Newby, R. A Wright, P. Dawson, C. A Ludlam, N. A Boon, K. A.A Fox, and D. J Webb The L-arginine/nitric oxide pathway contributes to the acute release of tissue plasminogen activator in vivo in man Cardiovasc Res, May 1, 1998; 38(2): 485 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Genser, P. Lechleitner, J. Maier, F. Dienstl, E. Artner-Dworzak, B. Puschendorf, and J. Mair Rebound increase of plasminogen activator inhibitor type 1 after cessation of thrombolytic treatment for acute myocardial infarction is independent of type of plasminogen activator used Clin. Chem., February 1, 1998; 44(2): 209 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Schneider, M. A. Ricci, D. J. Taatjes, P. Q. Baumann, J. C. Reese, B. J. Leavitt, P. M. Absher, and B. E. Sobel Changes in Arterial Expression of Fibrinolytic System Proteins in Atherogenesis Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3294 - 3301. [Abstract] [Full Text]
|
|
|
|
|
|
D. E. Vaughan, J.-L. Rouleau, P. M. Ridker, J. M. O. Arnold, F. J. Menapace, and M. A. Pfeffer Effects of Ramipril on Plasma Fibrinolytic Balance in Patients With Acute Anterior Myocardial Infarction Circulation, July 15, 1997; 96(2): 442 - 447. [Abstract] [Full Text]
|
|
|
|
|
|
A. N. Butte, A. K. Houng, I.-K. Jang, and G. L. Reed {alpha}2-Antiplasmin Causes Thrombi to Resist Fibrinolysis Induced by Tissue Plasminogen Activator in Experimental Pulmonary Embolism Circulation, April 1, 1997; 95(7): 1886 - 1891. [Abstract] [Full Text]
|
|
|
|
|
|
H. M. Hoffmeister, M. Jur, H. P. Wendel, W. Heller, and L. Seipel Alterations of Coagulation and Fibrinolytic and Kallikrein-Kinin Systems in the Acute and Postacute Phases in Patients With Unstable Angina Pectoris Circulation, May 15, 1995; 91(10): 2520 - 2527. [Abstract] [Full Text]
|
|
|
|
|
|
P. B. Kurnik Circadian Variation in the Efficacy of Tissue-Type Plasminogen Activator Circulation, March 1, 1995; 91(5): 1341 - 1346. [Abstract] [Full Text]
|
|