Christopher J. Womack

Improved walking economy in patients with peripheral arterial occlusive disease

The effect of exercise rehabilitation on the oxygen cost of ambulation in patients with peripheral arterial occlusive disease (PAOD) was evaluated with specific emphasis on the effects of exercise rehabilitation on the slow component of VO2. Because the slow component of VO2 represents an increase in VO2 despite constant-intensity exercise, it can profoundly affect the relative energy cost of exercise in individuals with a low functional capacity. Twenty-six patients with intermittent claudication performed treadmill walking at 2.0 mph/0% grade for 20 min or until maximal claudication pain before and after 4 months of rehabilitation. The slow component of VO2 during the treadmill test was defined as the difference between the end-exercise VO2 and the VO2 observed at minute 3. Ankle/brachial systolic pressure index (ABI) was measured before and immediately following the exercise test. Rehabilitation consisted of 3 d x wk(-1) of treadmill walking for 15-30 min at 60-70% of VO2peak. The slow component of VO2 and end-exercise VO2 at pretraining (0.75 +/- 0.90 and 11.12 +/- 2.10 mL x kg[-1] x min[-1]) were significantly reduced after 4 months of exercise rehabilitation (-0.07 +/- 1.11 and 10.07 +/- 1.80 mL x kg[-1] x min[-1]; P < 0.05). Exercise rehabilitation also significantly (P < 0.05) increased the post-exercise ABI (pre-rehabilitation = 0.36 +/- 0.26, post-rehabilitation = 0.43 +/- 0.25). These data suggest that 4 months of exercise rehabilitation: 1) improves walking economy in PAOD patients because of a decreased slow component of VO2, and 2) increases post-exercise ABI.

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.

Exercise training decreases the growth hormone (GH) response to acute constant-load exercise

To assess the influence of exercise training on the growth hormone (GH) response to acute exercise, six untrained males completed a 20-min, high-intensity, constant-load exercise test prior to and after 3 and 6 wk of training (the absolute power output (PO) during each test remained constant x PO = 182.5 +/- 29.5 W). Training increased (pre- vs post-training) oxygen uptake (VO2) at lactate threshold (1.57 +/- 0.33 L.min-1 vs 1.97 +/- 0.24 L.min-1 P < or = 0.05). VO2 at 2.5 mM blood lactate concentration ([HLa]) (1.83 +/- 0.38 L.min-1 vs 2.33 +/- 0.38 L.min-1, P < or = 0.05), and VO2peak (3.15 +/- 0.54 L.min-1 vs 3.41 +/- 0.47 L.min-1, P < or = 0.05). Power output at the lactate threshold (PO-LT) increased with training from 103 +/- 28 to 132 +/- 23W (P < or = 0.05). Integrated GH concentration (20 min exercise + 45 min recovery) (microgram.L-1 x min) after 3 wk (138 +/- 106) and 6 wk (130 +/- 145) were significantly lower (P < or = 0.05) than pre-training (238 +/- 145). Plasma epinephrine and norepinephrine responses to training were similar to the GH response (EPI-pre-training = 2447 +/- 1110; week 3 = 1046 +/- 144; week 6 = 955 +/- 322 pmol.L-1; P < or = 0.05; NE pre-training = 23.0 +/- 5.2; week 3 = 13.4 +/- 4.8; week 6 = 12.1 +/- 6.8 nmol.L-1; P < or = 0.05). These data indicate that the GH and catecholamine response to a constant-load exercise stimulus are reduced within the first 3 wk of exercise training and support the hypothesis that a critical threshold of exercise intensity must be reached to stimulate GH release.

Effects of a maximal exercise test on neurocognitive function

Objective: To examine the effects of a maximal exercise test on cognitive function in recreational athletes. Design: A repeated-measures design was used to compare baseline with post-cognitive function and fatigue symptoms after a maximal exercise test. Setting: Division 1 American Midwestern University, (Michigan State University, Michigan, USA). Participants: 102 male and female recreational athletes. Intervention: Participants in the experimental group (n = 54) were asked to perform a maximal treadmill exercise test to maximal oxygen uptake (VO2 max). Participants in the control group were asked to rest for 15 min. Main outcome measurements: All participants were administered a neuropsychological test battery called Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) before and after exercise to measure neurocognitive function and fatigue symptoms. Results: Results revealed a significant group (control, experimental)×time (baseline, post-test 1, post-test 2) interaction for verbal memory composite scores (p = 0.025). Specifically, verbal memory composite scores decreased in the experimental group from baseline to post-test 1 (p = 0.00). These values returned to baseline 3 days after the Vo2 max test (p = 0.00). Further analysis on verbal memory composite scores demonstrated significant differences on immediate recall memory (p = 0.00) and delayed recall memory (p = 0.00). No significant differences were observed for visual memory (p = 0.54), motor processing speed (p = 0.68) and reaction time (p = 0.44) composite scores between the experimental and control groups. Conclusion: The results of this study suggest that a maximal exercise test attenuated a limiting effect on cognitive function. When utilising a neuropsychological test battery to evaluate a patient who has sustained a head injury, the test should not be administered immediately after a practice or a game session.

The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine

BackgroundAlthough caffeine supplementation improves performance, the ergogenic effect is variable. The cause(s) of this variability are unknown. A (C/A) single nucleotide polymorphism at intron 1 of the cytochrome P450 (CYP1A2) gene influences caffeine metabolism and clinical outcomes from caffeine ingestion. The purpose of this study was to determine if this polymorphism influences the ergogenic effect of caffeine supplementation.MethodsThirty-five trained male cyclists (age = 25.0 ± 7.3 yrs, height = 178.2 ± 8.8 cm, weight = 74.3 ± 8.8 kg, VO2max = 59.35 ± 9.72 ml·kg-1·min-1) participated in two computer-simulated 40-kilometer time trials on a cycle ergometer. Each test was performed one hour following ingestion of 6 mg·kg-1 of anhydrous caffeine or a placebo administered in double-blind fashion. DNA was obtained from whole blood samples and genotyped using restriction fragment length polymorphism-polymerase chain reaction. Participants were classified as AA homozygotes (N = 16) or C allele carriers (N = 19). The effects of treatment (caffeine, placebo) and the treatment × genotype interaction were assessed using Repeated Measures Analysis of Variance.ResultsCaffeine supplementation reduced 40 kilometer time by a greater (p < 0.05) magnitude in AA homozygotes (4.9%; caffeine = 72.4 ± 4.2 min, placebo = 76.1 ± 5.8 min) as compared to C allele carriers (1.8%; caffeine = 70.9 ± 4.3 min, placebo = 72.2 ± 4.2 min).ConclusionsResults suggest that individuals homozygous for the A allele of this polymorphism may have a larger ergogenic effect following caffeine ingestion.

Relationship Between Free-Living Daily Physical Activity and Peripheral Circulation in Patients with Intermittent Claudication:

The purpose of this study was to determine the relationship between free-living daily physical activity and peripheral circulation under resting, reactive hyperemia, and maximal exercise conditions in peripheral arterial occlusive disease (PAOD) patients with intermittent claudication. Sixty-one PAOD patients (age=70 ±6 years, ankle/brachial index [ABI] =0.57 ±0.24) were recruited from the Vascular Clinic at the Baltimore Veterans Affairs Medical Center and from radio and newspaper advertise ments. Free-living daily physical activity was measured as the energy expenditure of physical activity (EEPA), determined from doubly labeled water and indirect calorimetry. Patients also were characterized on ankle/brachial index, calf blood flow, calf transcutaneous oxygen tension (TcPO2), and calf transcutaneous heating power (TcHP). ABI and calf blood flow served as markers of the macrocirculation of the lower extremity, while TcPO2 and TcHP served as markers of the microcirculation. The clau dication patients were sedentary, reflected by a mean EEPA value of 486 ±274 kcal/day. EEPA was related to calf TcHP at rest (282 ±24 mW; r=-0.413, p=0.002), after postoc clusion reactive hyperemia (275 ±22 mW; r=-0.381, p=0.004), and after maximal exercise (276 ±20 mW; r=-0.461, p<0.001). ABI, calf blood flow, and calf TcPO2 were not related to EEPA under any condition. In conclusion, higher levels of free-living daily physical activity were associated with better microcirculation of the calf musculature in older PAOD patients with intermittent claudication.

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 (VO(2)) 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.

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.

Hemostatic responses to resistance training in patients with coronary artery disease.

PURPOSE This study was undertaken to evaluate changes in coagulation and fibrinolytic responses to an acute bout of resistance training in patients with coronary artery disease. METHODS Fourteen low-to-moderate risk men (mean age, 57.6 +/- 9 years; body mass index, 26.7 +/- 4.0 kg/m) with known coronary artery disease participated in this study. All subjects were recruited from the hospitals outpatient cardiac rehabilitation program and none were participating in a resistance training exercise program at the time. Using 8 different resistance training devices, each subject performed 1 set of 10 repetitions to volitional fatigue, resting 1 minute between sets. Blood samples (5 mL) were drawn preexercise, immediate postexercise, and 1 hour postexercise in the seated position. All values were corrected for plasma volume changes. Alterations in von Willebrand Factor antigen, tissue plasminogen activator antigen, and plasminogen activator inhibitor-1 activity were analyzed using repeated measures analysis of variance. RESULTS Although von Willebrand Factor antigen remained unchanged from preexercise values, tissue plasminogen activator antigen and plasminogen activator inhibitor-1 activity increased and decreased, respectively, in the immediate postexercise recovery period. Moreover, the latter reduction persisted at 1 hour postexercise. CONCLUSION An acute bout of resistance training improves fibrinolytic potential in men with coronary artery disease, without elevating thrombotic potential. These data support the safety of resistance training in this population when contemporary prescriptive guidelines are used.

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

PURPOSE Although 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. METHODS Eight 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. RESULTS Both 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. CONCLUSION To accurately evaluate the t-PA response to acute exercise, blood samples should be collected within 2 min after the cessation of exercise.