Changes in Plasminogen Activator Inhibitor 1 and Tissue-Type Plasminogen Activator during Exercise in Patients with Coronary Artery Disease

Abstract

As depressed fibrinolysis is implicated in the pathogenesis of coronary artery disease, we have studied the activation of fibrinolysis during maximal, symptom-limited exercise in a group of 68 men. After exercise they were divided, according to their coronary angiography and exercise ²⁰¹T1 emission computed tomography results, into three groups. Group 1: persons with normal exercise ²⁰¹T1 emission computed tomography results and no underlying diseases who served as controls; group 2: patients with coronary artery disease without exercise-induced myocardial ischemia, and group 3: patients with coronary artery disease with transient, exercise-induced myocardial ischemia. Before and at peak exercise we measured the plasminogen activator activity (PAA) in the euglobulin fraction of plasma by an amidolytic method and the concentrations of tissue plasminogen activator (t-PA), activator-inhibitor complex – plasminogen activator inhibitor 1 (PAI-1) complexed with t-PA -and total PAI-1 by enzyme immunoassay. The concentration of free PAI-1 in plasma was calculated by subtraction of the concentration of activator-inhibitor complex from that of total PAI-1. Under basal conditions, group 3 had significantly higher free and total PAI-1 levels than group 1. There were no statistically significant differences between the three groups in PAA, t-PA, and activator-inhibitor complex levels. At peak exercise, group 1 showed the highest release of t-PA accompanied with highest increases in PAA as well as in activator-inhibitor complex, the proportion of released t-PA antigen not bound to PAI-1 being highest in group 1. Free PAI-1 decreased significantly, but there were no differences between individual groups. Our results indicate that increased PAI-1 levels in plasma and decreased release of t-PA from endothelial stores play a role in impairment of fibrinolysis in coronary artery disease. These disturbances are more pronounced in patients who develop myocardial ischemia during exercise.

Serum Vaspin Concentrations in Human Obesity and Type 2 Diabetes

“…Moreover, elevated vaspin concentrations after 4 weeks of intensive physical training might represent a transient adaptation mechanism because competitive sportsmen with long-term physical training had significantly lower vaspin serum concentration than untrained age-and BMI-matched control subjects. The potential (22), diet, and physical training (23,24). These results, together with our data on circulating vaspin, suggest that protease inhibitors either play a causative role in the development of obesity and metabolic disorders or that they are at least biomarkers for these diseases.…”

Safety and Implementation of Exercise Testing and Training After Coronary Stenting in Patients With Acute Myocardial Infarction.

“…21 In addition, the counteractive increase in fibrinolytic activity seen during exercise in healthy subjects is deficient in patients with coronary artery disease. 22 As a result of this imbalance between the coagulation and fibrinolytic systems, patients with coronary artery disease are at increased risk for an acute coronary event during acute strenuous exercise. 15 These findings, together with a few case reports of thrombotic coronary occlusion after coronary stenting, [12][13][14] have raised concern about the potential increase in the risk of acute coronary event associated with ETT and ECR in patients after coronary stenting for AMI.…”

Fibrinolytic activity is not dependent upon exercise mode in post-myocardial infarction patients

“…Several previous studies have shown that ®brinolytic activity increases during acute exercise in CAD patients, but the exercise-induced increase is reduced compared with subjects without CAD (Aznar et al 1988;Estelles et al 1985;Rydzewski et al 1990). …”

“…However, several studies have shown mean increases in t-PA activity of less than 100% in CAD patients (Aznar et al 1988;Estelles et al 1985;Rydzewski et al 1990), whereas the increases in subjects without CAD are usually between 250 and 350% (Aznar et al 1988;Estelles et al 1985;Rydzewski et al 1990; . This would suggest that our CAD patients exhibited increases in t-PA activity (approximately 300%) with exercise similar to those shown to occur in normal controls in other studies.…”

“…The mechanism linking reduced ®brinolytic activity to CAD is probably associated with problems of formation and/or removal of intrinsic thrombi, since most myocardial infarctions (MI) are caused by thrombosis (DeWood et al 1980). Reductions in ®brinolytic activity can be the result of decreased levels of tissue plasminogen activator (t-PA) released from the vascular endothelium (Ranby and Brandstrom 1988) and/or increased levels of its speci®c inhibitor, plasminogen activator inhibitor-1(PAI-1) (Jansson et al 1993;Rydzewski et al 1990). Subsequently, it has been well documented that CAD patients exhibit increased PAI-1 activity (Hamsten et al 1985;Speiser et al 1990), and that their ability to increase t-PA activity in response to a ®brinolytic stressor, such as venous occlusion, is reduced (Francis et al 1988;Hamsten 1995).…”