A single bout of walking exercise enhances endogenous fibrinolysis in stroke patients.

PURPOSE: Impaired endogenous fibrinolysis is an important predictor for increased risk of stroke and myocardial infarction. Acute exercise can enhance fibrinolysis, primarily by stimulating short-term increases in plasma tissue plasminogen activator (tPA), which is postulated to protect against atherothrombotic events. No prior studies have examined the fibrinolytic response to exercise in stroke survivors despite their high risk for recurrent stroke and myocardial infarction. The purpose of this study was to assess the fibrinolytic response to acute submaximal exercise in chronic hemiparetic stroke patients. METHODS: Eighteen (16 men, 2 women) untrained stroke patients with chronic hemiparetic gait deficits volunteered for participation in this single session exercise study. Fasting blood samples for determination of tPA and plasminogen activator inhibitor (PAI-1) enzyme activities were obtained before, immediately after, and 60 min after submaximal treadmill walking. Patients walked at 60% maximal heart rate reserve (low-moderate intensity) for a cumulative total of 20 min. RESULTS: The exercise bout increased tPA activity by 79% (P < 0.01) and decreased PAI-1 activity by 18% (P < 0.01). At 1 h after completing the walking exercise, plasma tPA activity levels were still significantly elevated (43%,P < 0.01), and PAI-1 activity levels were 25% lower (P < 0.01) than baseline. CONCLUSIONS: These findings demonstrate that a single bout of aerobic walking exercise can improve fibrinolysis profiles in chronic stroke patients. Significant increases in endogenous tPA and reductions in PAI-1 activity persist for at least 1 h after exercise cessation. The implications are that alterations in physical activity during the day may modify clot lysing potential, thereby affecting atherothrombotic risk.

External pneumatic compression does not increase urokinase plasminogen activator after abdominal surgery.

External pneumatic compression (EPC) devices prevent lower extremity deep venous thrombosis (DVT) by reducing stasis. There is a widely held belief that they also enhance endogenous fibrinolysis; however, recent studies of tissue plasminogen activator (the primary activator of fibrinolysis) and plasminogen activator inhibitor-1 (the primary inhibitor of fibrinolysis) failed to confirm this. The hypothesis of this study was that EPC devices increase the level of urokinase plasminogen activator (uPA), a second activator of fibrinolysis. This was a prospective trial in which 44 subjects who underwent major abdominal surgery were randomized to receive unfractionated heparin injections, thigh-length sequential EPC devices, or both for DVT prophylaxis. Prophylaxis was begun immediately before surgical incision and continued until postoperative day 5 or discharge. Venous blood samples were collected from an antecubital vein for measurement of systemic uPA levels and from the common femoral vein for measurement of regional uPA levels. Samples were collected the day before surgery, after induction of anesthesia but before surgical incision, and on postoperative days 1, 3, and 5. uPA levels (ng/mL) were measured with an enzyme-linked immunoassay. Baseline uPA levels (0.41 to 0.56 ng/mL; P >.05, analysis of variance with repeated measures) were similar among the three groups. uPA levels did not change after surgery in systemic or regional blood samples in any group. There were no significant differences in systemic or regional uPA levels in the groups treated with EPC devices relative to those treated with heparin at any time point (P >.05, analysis of variance with repeated measures). Enhancement of fibrinolysis with EPC devices remains unproven; the findings reported here suggest that effective DVT prophylaxis can only be assured when the devices are used in a manner that reduces venous stasis.

Exercise training enhances endogenous fibrinolysis in peripheral arterial disease.

PURPOSE: Acute clinical events resulting from atherosclerosis (myocardial infarction, stroke) are associated with impaired endogenous fibrinolysis, the system by which the body lyses inappropriately formed thrombus. Endurance exercise training improves fibrinolysis in normal subjects and those with coronary artery disease. The hypothesis of this study was that exercise training would improve fibrinolysis in subjects with peripheral arterial disease (PAD). METHODS AND RESULTS: Twenty-one men with intermittent claudication (IC-EX) underwent treadmill exercise training for 6 months. Twenty age-matched male subjects with IC were followed for the same period (IC-NONEX). Fibrinolytic activity was measured prior to entry into exercise or "usual care," and at the completion of the study period. Fibrinolysis was quantified by measurement of the activity levels of tissue plasminogen activator (tPA, the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1), using an amidolytic method. Fibrinolysis, quantified as increased PAI-1 activity, was reduced in both claudicant groups relative to healthy controls at baseline. After 6 months of exercise, subjects in the IC-EX group experienced significant improvements in fibrinolytic activity, manifested as a 23% decrease in PAI-1 activity and a 28% increase in tPA activity. No changes occurred in the IC-NONEX group. In the IC-EX group, subjects with the highest initial PAI-1 values experienced the greatest decreases in PAI-1 activity and thus the greatest benefit from exercise. CONCLUSIONS: Patients with PAD have impaired fibrinolytic activity, manifested primarily as increases in the inhibitor of fibrinolysis, PAI-1. Six months of exercise training reduced these impairments, and may serve as an intervention to reduce cardiovascular mortality and morbidity in these patients.

The effect of external pneumatic compression on regional fibrinolysis in a prospective randomized trial.

INTRODUCTION: External pneumatic compression devices (EPC) prevent deep venous thrombosis (DVT) by reducing lower extremity venous stasis. Early studies suggested they also enhance fibrinolytic activity; however, in a recent study, EPC had no effect on systemic fibrinolysis in patients undergoing abdominal surgery. The hypothesis of this study was that EPCs enhance regional fibrinolysis in these subjects. METHODS: Forty-five patients (44 male, one female; mean age, 67 years) undergoing major abdominal surgery (35 bowel procedures, 10 aortic reconstructions) were prospectively randomized to one of three groups for DVT prophylaxis: subcutaneous heparin injections (HEP), thigh-length sequential EPC devices (EPC), or both (HEP+EPC). Prophylaxis was begun immediately before surgical incision and continued until postoperative day 5 or patient discharge. Venous blood samples were collected from the common femoral vein for measurement of regional fibrinolysis after induction of anesthesia but before initiation of prophylaxis, and on postoperative days 1, 3, and 5. A baseline sample was collected the day before surgery. Fibrinolysis was quantified with measurement of the activities of tissue plasminogen activator (tPA; the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1) with amidolytic technique. RESULTS: tPA activity in all groups was normal at baseline; baseline PAI-1 activity was elevated. Within each prophylaxis group, no significant changes occurred in either tPA or PAI-1 activities after induction of anesthesia or after surgery compared with before surgery (P >.05, analysis of variance with repeated measures). No changes occurred between postoperative samples and after anesthesia within each group. No significant enhancement of fibrinolysis, manifested as either increased tPA activity or decreased PAI-1 activity, occurred in either EPC group compared with the HEP group at any time point (P >.05, analysis of variance with repeated measures). No differences were noted when surgery was performed for malignant disease versus nonmalignant disease. CONCLUSION: In this study, enhanced regional fibrinolysis in the lower extremities could not be detected with the use of EPCs, as measured with tPA and PAI-1 activity in common femoral venous blood samples. EPC devices do not appear to prevent DVT with fibrinolytic enhancement; effective and safe prophylaxis is provided only when the devices are used in a manner that reduces lower extremity venous stasis.