Paul R. Nagelkirk

Exercise-Induced Changes in Coagulation and Fibrinolysis in Healthy Populations and Patients with Cardiovascular Disease

This review highlights the clinical significance of coagulation and fibrinolytic responses, and adaptations in healthy individuals and patients with cardiovascular disease (CVD). Much of the review focuses on indicators of the potential for coagulation and fibrinolysis. The terms ‘coagulation potential’ and ‘fibrinolytic potential’ are used frequently, as much of the literature in the area of exercise haemostasis evaluates factors that reflect an increased potential for coagulation, while coagulation per se, may or may not be occurring. Similarly, fibrinolysis is definitively the lysis of inappropriate or excessive blood clot, which may or may not be occurring when the enzymes that stimulate fibrinolysis are activated. Nevertheless, markers of coagulation and fibrinolytic potential are associated with CVD, ischaemic events, and cardiovascular mortality. Additionally, fibrinolytic potential is associated with other established CVD risk factors. Ischaemic events triggered by physical exertion are more likely to occur due to an occlusive thrombus, suggesting the exercise-induced responses related to haemostasis are of clinical significance.The magnitude of increase in coagulation potential, platelet aggregation and fibrinolysis appears to be primarily determined by exercise intensity. Patients with CVD may also have a larger increase in coagulation potential during acute exercise than healthy individuals. Additionally, the magnitude of the fibrinolytic response is largely related to the resting fibrinolytic profile of the individual. In particular, high resting plasminogen activator inhibitor-1 may diminish the magnitude of tissue plasminogen activator response during acute exercise. Therefore, acute responses to exercise may increase the risk of ischaemic event. However, chronic aerobic exercise training may decrease coagulation potential and increase fibrinolytic potential in both healthy individuals and CVD patients. Due to the aforementioned importance of resting fibrinolysis on the fibrinolytic response to exercise, chronic aerobic exercise training may cause favourable adaptations that could contribute to decreased risk for ischaemic event, both at rest and during physical exertion.

Temporal changes in tPA and PAI-1 after maximal exercise.

PURPOSEnAlthough fibrinolysis increases with acute exercise, it decreases rapidly during the postexercise period. Therefore, the time point at which blood samples are collected postexercise could affect reported tissue plasminogen activator (t-PA) and/or plasminogen activator inhibitor-1 (PAI-1) levels. The purpose of this study was to determine the time course of t-PA and PAI-1 changes after acute maximal exercise.nnnMETHODSnEight healthy males performed a graded maximal exercise test on a treadmill. Venous blood samples were collected using an indwelling catheter before exercise and at 1, 2, 4, 6, 8, and 10 min postexercise. Mean differences in t-PA activity, t-PA antigen, and PAI-1 activity at each time point were assessed using a repeated measures ANOVA. Post hoc means comparisons were performed by contrasting the 1-min postexercise value against all other time points.nnnRESULTSnBoth t-PA activity and t-PA antigen significantly increased from pre- to postexercise (P < 0.05). t-PA activity did not change from 1 to 2 min postexercise but decreased significantly at 4 min postexercise. Likewise, t-PA antigen remained elevated from 1 to 2 min postexercise but decreased at 4 min postexercise. PAI-1 decreased from pre- to postexercise but did not change during the 10-min postexercise period.nnnCONCLUSIONnTo accurately evaluate the t-PA response to acute exercise, blood samples should be collected within 2 min after the cessation of exercise.

Changes in von Willebrand factor and fibrinolysis following a post-exercise cool-down

Abstract The purpose of this study was to determine the effect of a post-exercise active cool-down on von Willebrand factor and fibrinolysis. Ten subjects performed two maximal oxygen uptake (V̇O2max) tests followed by a 10-min passive (PC) or an active (AC) cool-down. Blood samples were obtained pre-exercise, post-exercise, post-PC/AC, and 1xa0h post-exercise and analyzed for von Willebrand factor antigen (vWf:Ag), tissue plasminogen activator (tPA) antigen and activity and plasminogen activator inhibitor-1 (PAI-1) activity. Data were analyzed using repeated measures analysis of variance. No significant differences were found betweennV̇O2max tests for treadmill time, V̇O2max, respiratory exchange ratio, maximal heart rate, or maximal blood lactate concentration. vWf:Ag was significantly elevated (P<0.05) following PC [198.4 (18.3)% normal] versus AC [174.5 (15.6)% normal] and remained elevated 1-h post-exercise [179.4 (16.4)% normal for PC vs 158.6 (13.8)% normal for AC]. There were no differences between tests for tPA or PAI-1 activity, although tPA antigen was significantly elevated following PC versus AC (P <0.05). Following the cool-down, hematocrit was higher (P <0.05) for the PC test [48.90 (0.36)] compared with AC [47.43 (0.51)]. An AC reduces post-exercise vWf:Ag and tPA antigen without affecting tPA or PAI-1 activity.

Regulating oxygen uptake during high-intensity exercise using heart rate and rating of perceived exertion.

PURPOSEnThe purpose of this study was to comparatively evaluate the use of heart rate (HR) or rating of perceived exertion (RPE) in eliminating the slow component of oxygen uptake (.VO2) during high-intensity aerobic exercise.nnnMETHODSnNine sedentary males (age = 23.9 +/- 4.6 yr, height = 177.4 +/- 10.1 cm, weight = 75.28 +/- 12.95 kg) completed three 15-min submaximal exercise cycle ergometer tests based on: 1) constant power output (PO) corresponding to 75% .VO2max (PO75), 2) HR corresponding with 75% .VO2max (HR75), and 3) RPE response corresponding with 75% .VO2max (RPE75). .VO2, HR, RPE, and blood lactate concentration [La-] were measured during all tests. Data were analyzed using repeated measures analysis of variance, and post hoc means comparisons were performed using a Fishers LSD test.nnnRESULTSnEnd-exercise .VO2 was significantly higher than the respective 3-min .VO2 for the PO75 and RPE75 tests, but not the HR75 test. End-exercise .VO2 was significantly greater for the PO75 test than both the RPE75 and HR75 tests, but there was no significant difference between end-exercise .VO2 for the RPE75 and HR75 tests. End-exercise HR and RPE were significantly higher for the PO75 test than both the RPE75 and HR75 tests. There were no significant differences between the RPE75 and HR75 tests for end-exercise HR or end-exercise RPE.nnnCONCLUSIONnResults suggest using both HR and RPE are effective at reducing the slow component of .VO2 that occurs during high-intensity exercise.

Age and aerobic training status effects on plasma and skeletal muscle tPA and PAI-1

IntroductionReductions in fibrinolytic potential occur with both aging and physical inactivity and are associated with an increased cardiovascular disease risk. Plasmin, the enzyme responsible for the enzymatic degradation of fibrin clots, is activated by tissue plasminogen activator (tPA), while plasminogen activator inhibitor-1 (PAI-1) inhibits its activation. Currently, fibrinolysis research focuses almost exclusively on changes within the plasma. However, tPA and PAI-1 are expressed by human skeletal muscle (SM). Currently, no studies have focused on changes in SM fibrinolytic activity with regard to aging and aerobic fitness.PurposeThe purpose of this study was to cross-sectionally evaluate effects of age and aerobic fitness on tPA and PAI-1 expressions and activity in SM.MethodsTwenty-six male subjects were categorized into the following groups: (1) young aerobically trained (nxa0=xa08); (2) older aerobically trained (nxa0=xa06); (3) young aerobically untrained (nxa0=xa07); and (4) older aerobically untrained (nxa0=xa05). Muscle biopsies were obtained from each subject. SM tPA activity was assessed using gel zymography and SM tPA and PAI-1 expressions were assessed using RT-PCR.ResultsTrained subjects had higher SM tPA activity compared to untrained (25.3xa0±xa02.4xa0×xa0103 vs. 21.5xa0±xa05.6xa0×xa0103xa0pixels, respectively; pxa0=xa00.03) with no effect observed for age. VO2 max and SM tPA activity were also significantly correlated (rxa0=xa00.42; pxa0<xa00.04). SM tPA expression was higher in older participants, but no effect of fitness level was observed. No differences were observed for PAI-1 expression in SM.ConclusionsHigher levels of aerobic fitness are associated with increased fibrinolytic activity in SM.