Alterations in the fibrinolytic system components during acute myocardial infarction

Abstract

The purpose of this study was to evaluate the changes in tissue-plasminogen activator (t-PA), plasminogen activator inhibitor - type 1 (PAI-1) and D-dimer (DD) antigen plasma levels in acute myocardial infarction (AMI) patients after thrombolytic therapy with two different thrombolytic agents, rt-PA or acetyl-streptokinase and to find out any correlation between the plasma t-PA, PAI-1 and DD levels with the infarct size as it is estimated from the peak of serum CPK levels. The plasma antigen levels of t-PA, PAI-1 and DD were measured by the enzyme immunoassay method (Stago), in 57 consecutive patients (M = 46, F = 11, mean age 55.6 +/- 8.8 years) and in 25 normal subjects (M = 18, F = 7, mean age 54.0 +/- 5.5 years). In 47 out of the 57 patients who were treated successfully with 100 mg of rt-PA (26 patients) or with 1.5 MU 21 of acetyl-streptokinase, as well as in 10 patients who were not treated, samples were obtained again 4 and 24 hours after the end of thrombolytic therapy or admission, respectively. During the acute phase of myocardial infarction the t-PA, PAI-1 and DD antigen plasma levels were significantly higher than in healthy people. There were no significant changes in the t-PA, PAI-1 and DD plasma levels of the patients who were not treated with a thrombolytic agent. We found a significant elevation of t-PA (p < 0.001), PAI-1 (p < 0.05) and DD (p < 0.001) after 4 hours in comparison with the baseline (at presentation, before therapy). After 24 hours the t-PA and DD plasma levels remained significantly higher (p < 0.001) while the PAI-1 plasma levels returned to the pre-therapy levels. There were no significantly different changes in the t-PA, PAI-1 and DD plasma levels of either group of patients, treated with rt-PA or acetyl-streptokinase while the t-PA and PAI-1 levels were positively correlated with infarct size as estimated from peak serum CPK levels.

Admission Levels of C-Reactive Protein and Plasminogen Activator Inhibitor-1 in Patients With Acute Myocardial Infarction With and Without Cardiogenic Shock or Heart Failure on Admission

“…The authors have explained these results by the time lag of 6 hours in the hepatic synthesis of CRP, 4) by the association of CRP elevation with preinfarction unstable angina pectoris accompanied by silent myocardial ischemia, which acts as ischemic preconditioning, and by the inductive effect of inflammation on expression of angiogenic growth factors associated with reduced infarct size and on endogenous production of nitrous oxide, which protects myocardium from reperfusion injury. 40) On the other hand, also consistent with our results, both basal levels of PAI-1 in the population-based studies 41,42) and its acute-phase levels including those assessed on admission in the clinical studies [10][11][12][13] have been shown to be elevated in AMI patients. However, the mechanisms behind this association is unclear.…”

“…16) Concerning this last issue, among the factors associated with the occurrence of LVD after AMI, the presence of diabetes 45,46) and larger enzymatic infarct size 31,32) have also been shown to be associated with increased levels of PAI-1 in this setting. 10,13) Therefore, it is not possible to conclude that our finding of an association between higher PAI-1 levels and the occurrence of CS in AMI patients is merely due to a pre-existing medical condition or severity of the ongoing disease process. However, in a number of experimental studies, PAI-1 has been proposed to play an important role in ventricular remodelling after AMI.…”

“…8,9) In these studies, it has also been shown that this measurement of CRP is associated with short-and long-term outcomes in CS patients. 8,9) On the other hand, admission levels of plasminogen activator inhibitor-1 (PAI-1), which is a key regulator of the fibrinolytic system, have also been shown to be elevated [10][11][12][13] and associated with adverse outcomes 10,12,14) in AMI patients. However, studies on the relationship between the admission PAI-1 levels and left ventricular (LV) functional status in AMI patients are scarce.…”

Effects of Extracellular DNA on Plasminogen Activation and Fibrinolysis

“…High levels of PAI-1 inhibit the fibrinolytic system and promote thrombosis and uncontrolled fibrin deposition (38,39). The level of PAI-1 strongly correlates with the size of myocardial infarction (40) and unfavorable outcomes in severe multiple organ failure in sepsis, disseminated intravascular coagulation (41)(42)(43)(44), and pleural injury (26). It has been unclear as to whether there is a molecular mechanism that connects physiological effects of high levels of EC DNA and PAI-1 to the fibrinolytic system.…”

Modulation of Serpin Reaction through Stabilization of Transient Intermediate by Ligands Bound to α-Helix F

“…High levels of PAI-1 inhibit the fibrinolytic system by preventing the formation of plasmin from plasminogen and promote thrombosis (6, 7). An elevated concentration of PAI-1 correlates with an increased rate of ischemic arterial disease (8) as follows: atherosclerosis, angina pectoris (9 -14), and myocardial infarction (15)(16)(17)(18)(19)(20)(21)(22), as well as with deep vein thrombosis and disseminated intravascular coagulation (23-25). Because complete inactivation of PAI-1 is not lifethreatening (26 -28), the development of new approaches to the therapeutic neutralization of PAI-1 is a subject of many studies (for review see Refs.…”