Fibrinolytic response to acute exercise in patients with peripheral arterial disease

Purpose: Elevations in tissue plasminogen activator (tPA) are postulated to protect against atherothrombotic events during exercise. However, fibrinolytic response to repetitive bouts of symptom-limited exercise is unknown in peripheral arterial disease (PAD) patients, a population with impaired fibrinolysis and increased risk for ischemic events. The purpose of the present study was to evaluate the fibrinolytic response to repetitive bouts of symptom-limited exercise in PAD patients. Methods: Nine (8 male, 1 female) patients with Fontaine State II PAD were studied. Fasting blood samples for determination of tPA and plasminogen activator inhibitor (PAI-1) were obtained into an acidified citrate solution via an indwelling venous catheter before, immediately after, 30 min after, and 60 min after submaximal treadmill walking. Patients walked intermittently at 65% of maximal intensity achieved on a previous graded exercise test until 30 min of exercise was achieved. Results: Exercise increased tPA activity by 180% (0.5 ± 0.16 IU·mL^-1 baseline, 1.4 ± 1.2 IU·mL^-1 postexercise), and decreased PAI-1 activity by 40% (20.6 ± 5.5 AU·mL^-1 baseline, 11.8 ± 6.2 AU·mL^-1 postexercise), without changing tPA or PAI-1 antigen. Notably, plasma tPA activity levels 1 h after exercise remained elevated by 80%, whereas PAI-1 activity remained decreased by 49%. The decrease in PAI-1 significantly (P < 0.05) correlated with oxygen uptake (VO₂) during submaximal exercise (r = -0.77). Conclusion: These findings demonstrate that repetitive bouts of symptom-limited exercise produce a substantial improvement in the fibrinolytic profile of PAD patients, which persists at least 1 h after exercise cessation.