Both atenolol and propranolol blunt the fibrinolytic response to exercise but not resting fibrinolytic potential.

This randomized, double-blind trial found that tissue plasminogen activator activity increased and plasminogen activator inhibitor-1 activity decreased significantly more with exercise during placebo treatment than during treatment with beta blockade. These results suggest that beta blockade blunts the fibrinolytic response to maximal exercise.

Factors affecting fibrinolytic potential: cardiovascular fitness, body composition, and lipoprotein(a).

The purpose of the study was to determine the factors that affect basal (resting) and poststressor fibrinolytic activity or potential. Variables of interest included cardiovascular fitness (maximal oxygen consumption [Vo2max]), body fat, body mass index (BMI), and lipids/lipoproteins, including lipoprotein(a) [Lp(a)]. Blood was collected from 46 middle-aged men before and after a maximal exercise test. Pearson and Spearman correlation coefficients were calculated to determine associations between the variables of interest and tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities in the basal state and after stimulation with maximal exercise. Multiple regression analyses were also conducted to determine independent predictors of the fibrinolytic variables. Maximal exercise produced significant increases in t-PA activity and decreases in PAI-1 activity. Postexercise t-PA activity was inversely related to basal PAI-1 activity (r = -.34). Vo2max was positively correlated with t-PA activity (basal, r = .39; postexercise, r = .67) and inversely related to PAI-1 activity (basal, r = -.41; postexercise, r = -.42). Body fat was correlated with postexercise t-PA activity (r = -.60) and both basal and postexercise PAI-1 activity (r = .42), but the correlation with basal t-PA activity was not significant (P = .058). Postexercise t-PA activity was positively correlated (r = .37) with high-density lipoprotein cholesterol (HDL-C) and negatively correlated (r = -.42) with low-density lipoprotein cholesterol (LDL-C). Basal PAI-1 activity was negatively correlated with HDL-C (r = -.37), Lp(a) was not correlated with any fibrinolytic variable or fitness. Multiple regression analyses showed that Vo2max was an independent predictor of both basal and postexercise t-PA activity (R2 = .16 and .34, respectively). Triglyceride (TG) levels and Vo2max were significant independent predictors of PAI-1 activity (R2 = .31). In conclusion, cardiovascular fitness was a strong independent predictor of fibrinolytic potential. In addition, poststressor measures of fibrinolytic potential may provide more information about the fibrinolytic system than basal values.

Effects of maximal exercise and venous occlusion on fibrinolytic activity in physically active and inactive men.

The purposes of this study were to 1) characterize changes in fibrinolytic activity in response to maximal exercise and 5-min venous occlusion and 2) compare responses in men of various habitual physical activity levels. Tissue plasminogen activator (TPA) activity and plasminogen activator inhibitor 1 (PAI-1) activity were measured in 15 inactive, 15 regularly active, and 15 highly active men. Data were analyzed using a three-way analysis of variance with repeated measures. Pretest TPA activity was similar among groups. TPA activity increased postexercise with higher values seen in the active groups (P < 0.001). The highly active group also significantly increased TPA activity postvenous occlusion (P < 0.01). Pretest PAI-1 activity was different among groups, with the inactive group showing the highest activity and the highly active group the lowest (P < 0.05). PAI-1 activity decreased with exercise (P < 0.01) but did not change with venous occlusion. In conclusion, active men exhibited greater changes in fibrinolytic activity with maximal exercise and venous occlusion than inactive men. This enhanced fibrinolytic activity may be an important mechanism mediating the cardioprotective effect provided by regular physical activity.

Estrogen replacement therapy and coagulation: relationship to lipid and lipoprotein changes.

OBJECTIVE: To examine the relationship of estrogen-induced changes in lipids and lipoproteins with alterations in the coagulation system. METHODS: Coagulation and lipid indices were measured in 31 postmenopausal women, ages 40-60 years, after a 3-month course of 0.625-mg conjugated equine estrogen. We analyzed changes in variables from baseline to 3 months using t tests for paired samples or the Wilcoxon matched-pairs signed-rank test. RESULTS: Unopposed estrogen replacement therapy produced statistically significant decreases in antithrombin-III antigen (P = .006) and activity (P = .001) and total protein S (P = .003) and a significant increase in protein C antigen (P = .017). C4b-binding protein also decreased significantly from baseline to 3 months (P < .001). Mean fibrinogen level decreased by 18.2 mg/dL, not a statistically significant change (P = .213). Estrogen produced the expected statistically significant changes in lipids and lipoproteins. Several correlations between changes in lipids and lipoproteins and coagulation indices were statistically significant. Protein C antigen and activity changes correlated directly with high-density lipoprotein cholesterol changes (r = .52, P < or = .005; r = .38, P < or = .05; respectively), and protein C antigen also correlated directly with increases in apoprotein A-I (r = .54, P < or = .005). Triglyceride changes correlated directly with changes in protein C antigen (r = .36, P < or = .05) and activity (r = .49, P < or = .005) and inversely with C4b-binding protein (r = -.58, P < or = .01). Apoprotein B was correlated with free protein S (r = .48, P < or = .01). CONCLUSIONS: Although several estrogen-induced changes may decrease atherosclerotic potential and hypercoagulability, others may promote coagulability. These divergent effects may be manipulated pharmacologically by other estrogen compounds or by the addition of various progestins.

Effects of exercise intensity, duration, and time of day on fibrinolytic activity in physically active men.

The purposes of this investigation were to determine: 1) whether the fibrinolytic responses to acute, submaximal exercise were best related to intensity, duration, or total caloric expenditure; and 2) whether the time of day exercise is performed affects the fibrinolytic response. Twelve physically active men (mean age = 34.8 +/- 4.0 yr) performed four 30-min exercise sessions: 50% VO2max, a.m. and p.m., and 80% VO2max, a.m. and p.m. Blood samples were analyzed for tissue plasminogen activator (TPA) activity and plasminogen activator inhibitor-1 (PAI-1) activity. Data were analyzed using a three-way ANOVA with repeated measures. TPA activity: preexercise TPA did not differ among the four sessions. TPA increased with exercise in all sessions except the 50% a.m. session. Exercise at 80% increased TPA more than 50% (P < 0.001) and evening sessions increased TPA more than morning sessions (P < 0.05). PAI-1 activity: preexercise PAI-1 activity was higher during the morning than evening and significantly decreased with exercise in all sessions except the 50% p.m. session. It was concluded that changes in fibrinolytic activity appear to be influenced primarily by exercise intensity rather than duration or total caloric expenditure. Additionally, time of day of exercise performance significantly influenced fibrinolytic activity.

Effect of a single session of exercise on lipoprotein(a).

Lipoprotein(a) (Lp(a)) is bound to apolipoprotein B-100 by disulfide linkage and is associated in the upper density range of low density lipoprotein cholesterol. Persons with elevated concentrations of Lp(a) are regarded as having an increased risk for premature coronary artery disease. Although many studies exist evaluating the effects of a single session of exercise on lipids and lipoproteins, little information is available concerning the effects of exercise on Lp(a). Therefore, the purpose of this study was to determine the effects of a single exercise session on plasma Lp(a). Twelve physically active men completed two 30-min submaximal treadmill exercise sessions: low intensity (LI, 50% VO2max) and high intensity (HI, 80% VO2max). Blood samples were obtained immediately before and after exercise. Total cholesterol (LI: before 4.22 +/- 0.26, after 4.24 +/- 0.28; HI: before 4.24 +/- 0.31, after 4.11 +/- 0.28 mmol.l-1, mean +/- SE) and triglyceride (LI: before 1.14 +/- 0.16, after 1.06 +/- 0.16; HI: before 1.12 +/- 0.19, after 1.21 +/- 0.19 mmol.l-1) concentrations did not differ immediately after either exercise session, nor did Lp(a) concentrations differ immediately after either exercise session (LI: before 4.1 +/- 2.2, after 4.0 +/- 2.1: HI: before 3.9 +/- 2.2, after 3.7 +/- 2.0 mg.dl-1). These results suggest that neither a low nor a high intensity exercise session lasting 30 min in duration has an immediate effect on plasma Lp(a).

Physiological responses to weight-loss intervention in inactive obese African-American and Caucasian women.

BACKGROUND: The physiological responses of inactive obese premenopausal African-American and Caucasian women to the identical exercise training and behavior modification program were compared. METHODS: Inactive obese (96.1+/- 2.9 kg, BMI=34.8 +/- 0.7 kg/m2, % body fat=46.0 +/- 0.8; mean +/- SEM) premenopausal (36 +/- 2 yrs) African-American (n=10) and Caucasian (n=19) women were included. Resting metabolic rate (RMR), respiratory exchange ratio (RER), and maximal aerobic power (VO2max) were measured by indirect calorimetry, and body composition by plethysmography. Resting and maximal heart rates, blood glucose and lipids, and blood pressure were also measured. Treatment consisted of a 13-week diet and exercise behavior modification program. Group mean comparisons were made with a Student's "t"-test or an ANCOVA, which controlled for individual differences in body mass and lean body mass (LBM). Significance was set at p<0.05. RESULTS: Initially, the groups were not significantly different in height, mass, BMI, age, % body fat, fat mass, LBM, girth measurements, RMR, RER, VO2max, blood pressure, or cholesterol profile. The number of weeks completed, number of exercise sessions completed, total minutes of exercise for the entire intervention, average minutes of daily exercise, and total estimated exercise energy expenditure were all similar between groups. Furthermore, both groups reported similar dietary compliance. Both groups reduced body mass, BMI, LBM, girth measurements, and increased VO2max (mlO2 x kg-1 x min-1) significantly and similarly. CONCLUSIONS: African-American and Caucasian women respond the same physiologically to weight loss intervention. The higher prevalence in obesity for African-American women is not due to a different physiological response to diet and exercise.

Fibrinolytic responses to moderate intensity exercise. Comparison of physically active and inactive men.

The purposes of this study were to compare fibrinolytic responses to moderate intensity exercise in physically active and inactive men and during morning and evening exercise. Fourteen physically inactive men (mean age, 34.7 +/- 4.0 years) and 12 regularly active men (34.8 +/- 4.0 years) performed two exercise sessions, morning and evening, at 50% of maximal oxygen consumption. Tissue plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1) activity were measured before and after exercise. Data were analyzed using a three-way ANOVA with repeated measures. TPA activity increased with exercise in both groups, although the active group demonstrated greater increases than the inactive group. Postexercise TPA activity was greater with evening than morning exercise. The inactive group exhibited greater PAI-1 activity than the active group. PAI-1 activity was higher during the morning than evening but did not change with exercise for either group. We conclude that moderate intensity exercise increases TPA activity in physically active and inactive men, with greater increases seen in active men, particularly during evening exercise. Moderate intensity exercise does not appear to affect PAI-1 activity. The lower PAI-1 activity in active men may be one mechanism whereby regular physical activity lowers the risk for coronary artery disease.

The suprapharmacologic dosing of antithrombin concentrate for Staphylococcus aureus-induced disseminated intravascular coagulation in guinea pigs: substantial reduction in mortality and morbidity.

An animal model of gram-positive septicemia was developed to evaluate the effects of antithrombin (AT) concentrates on morbidity, mortality, and laboratory consequences of disseminated intravascular coagulation (DIC). DIC was induced in guinea pigs by infusing Staphylococcus aureus (SA) isolated from blood cultures of patients with DIC (DIC-SA) or without DIC (non-DIC-SA). The non-DIC-SA animals and animals infused with sterile saline served as controls. Varying doses of AT were administered either 30 minutes or 24 hours after infusion of SA. DIC was confirmed within 4 hours by changes in prothrombin time, activated partial thromboplastin time, fibrinogen, fibrinogen-fibrin degradation products, and AT activity. Clinical bleeding was also evident. Mortality of untreated DIC-SA animals was 36% within 24 hours and up to 75% by 72 hours. Intervention with any dose of AT between 125 and 1,000 IU/kg 30 minutes after DIC-SA infusion was associated with 100% survival (P < or = .05 in the 250 IU/kg group) and sustained increases in AT activity and fibrinogen concentrations (P < or = .05). When AT was administered in combination with low molecular weight heparin (LMWH) or if LMWH was adminstered alone, mortality from DIC-SA was slightly, but not significantly reduced compared with untreated DIC-SA. Gross hemorrhage was observed premortem and at autopsy in all of the DIC-SA animals but in substantially fewer animals that received AT (P < or = .001 in the 250, 500, and 1,000 IU/kg groups). In contrast, groups treated with LMWH, alone or with AT, experienced hemorrhage and appeared to develop pathologic DIC. Fibrin formation in end-organs was detected in all guinea pigs in the untreated DIC-SA group and in the groups treated with 125 IU/kg AT and LMWH alone. AT doses between 250 and 1,000 IU/kg administered 30 minutes after DIC-SA infusion prevented fibrin formation in end-organs (P < or = .001 in the 250 and 1,000 IU/kg groups). AT administered 24 hours after DIC-SA could not reverse pre-existing histopathologic evidence of DIC but favorably affected survival, which reached statistical significance in the 1,000 IU/kg AT group (P < or = .025). In summary, suprapharmacologic doses of AT concentrate significantly decreased morbidity and mortality and ameliorated adverse changes in laboratory measures induced by DIC-SA in this guinea pig model and were not associated with untoward hemorrhagic complications. These findings provide justification for studying the use of AT therapy in patients with DIC-SA.

Differences in resting metabolic rates of inactive obese African-American and Caucasian women.

OBJECTIVE: To compare resting metabolic rates (RMR) of African-American (n = 25) and Caucasian (n = 22) premenopausal (35+/-1 y, Mean +/- s.e.m.) women who are obese (95.2+/-2.9 kg, body mass index (BMI) = 34.7+/-0.9, % body fat = 45.2+/-0.9), inactive and free from metabolic disorders or medications that would affect heart rate or RMR. MEASUREMENTS: RMR and respiratory exchange ratio (RER) by indirect calorimetry, body composition by plethysmography, maximal aerobic capacity (VO2max) and girth measurements. RESULTS: Group mean comparisons were made with a Student's t-test or an ANCOVA, which controlled for individual differences in body weight and lean body mass (LBM). Significance was set at P < 0.05. Groups were not significantly different in age, height, weight, BMI, % body fat, fat mass, RER, VO2max, resting heart rate, maximal heart rate; or chest, waist, hip, arm, thigh or calf circumferences. After adjusting for body weight, RMR (I O2/min) for African-Americans (0.254+/-0.007) was significantly lower (9%) than for Caucasians (0.277+/-0.008). After RMR (I O2/min) was adjusted for LBM, an even larger difference (-12%) persisted for African-Americans (0.250+/-0.008) compared to Caucasians (0.281+/-0.008). Predicted RMR (kJ/d) for the African-Americans was the same as measured RMR, whereas Caucasian women expended about 13% more energy than predicted. When controlling for LBM, the partial correlation between VO2max and RMR was r=0.51 when VO2max was expressed as I/min, and r=0.56 when VO2max was expressed as ml O2/kg/min, both highly significant (P < 0.000). CONCLUSION: The lower prevalence of obesity in Caucasian women may be due in part to a higher RMR as well as an under estimation of RMR in weight control therapy. Fitness level (VO2max) as well as LBM are significant predictors of RMR for both races.

Fibrinolytic activity is similar in physically active men with and without a history of myocardial infarction.

The purpose of this study was to evaluate fibrinolytic potential at rest and after a fibrinolytic stressor in men with a history of myocardial infarction (MI) compared with an age- and activity-matched group of men without coronary artery disease (CAD). All men were currently enrolled in exercise programs. Tissue-type plasminogen activator (TPA) and plasminogen activator inhibitor 1 (PAI-1) activity and antigen levels were measured at rest and after a maximal exercise test. A 2 x 2 (group x time) ANOVA with repeated measures was used to evaluate fibrinolytic potential. Bivariate regressions were conducted to evaluate relations between fibrinolytic potential and maximal oxygen uptake (VO2max). Age was similar between groups (CAD, 57.5 +/- 6.6; non-CAD, 58.1 +/- 7.3 years); however, VO2max was higher in non-CAD subjects (36.2 +/- 6.2 vs 27.5 +/- 5.9 mL.kg-1.min-1). Mean +/- SEM resting TPA and PAI-1 activities were similar between CAD and non-CAD subjects (TPA, 2.8 +/- 0.2 vs 2.8 +/- 0.2 IU/mL; PAI-1, 15.9 +/- 3.1 vs 13.1 +/- 4.1 AU/mL). Both groups showed similar significant increases in TPA activity with exercise (P < .05), and postexercise TPA activity was also similar (CAD, 9.1 +/- 2.0 IU/mL; non-CAD, 11.7 +/- 2.6 IU/mL). Both groups also showed similar significant decreases in PAI-1 activity with exercise (P < .05) and no differences in postexercise PAI-1 activity (CAD, 13.2 +/- 2.5 AU/mL; non-CAD, 10.4 +/- 3.6 AU/mL). Significantly higher resting TPA antigen levels were seen in CAD (14.8 ng/mL) than non-CAD (10.2 ng/mL) subjects (P < .05), but neither group showed significant changes with exercise (CAD, 12.9 ng/mL; non-CAD, 11.8 ng/mL). Resting PAI-1 antigen was similar in the two groups (CAD, 71.4 ng/mL; non-CAD, 74.2 ng/mL) and did not significantly change with exercise (CAD, 77.9 ng/mL; non-CAD, 72.3 ng/mL). VO2max was positively correlated with postexercise TPA activity (r = .52, P < .05) and negatively correlated with resting TPA antigen (r = -.43, P < .05). Resting TPA antigen was also directly correlated with body mass index (r = .63, P < .05). The finding that functional fibrinolytic activity was not different in physically active men with and without CAD contrasts with previous reports. This suggests that matching subjects on the bases of age and habitual physical activity status and controlling exercise intensity are important factors to consider when evaluating fibrinolytic potential.

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

In this study we investigated possible differences in fibrinolytic activity in cardiac patients while they performed treadmill and cycle ergometry. Thirteen post-myocardial infarction patients completed two maximal exercise tests on treadmill and cycle ergometers. Blood was collected before and after each exercise test and was analyzed for the fibrinolytic variables, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activity, and lactate. Maximal oxygen uptake, heart rate, and ventilation were greater (P < 0.05) on the treadmill than during cycle ergometry, however, blood lactate was similar between modes. t-PA activity significantly increased with exercise (P < 0.05) and there was a trend toward a reduction in PAI-1 activity with exercise, but this did not reach statistical significance. The fibrinolytic responses to maximal exercise did not differ between the two modes of exercise studied. Therefore, exercise intensity, but not the mode of exercise, appeared to be the primary determinant of the fibrinolytic response to acute exercise in these patients.

Hemostatic responses to maximal exercise in oral contraceptive users.

OBJECTIVE: This study examined the effect of exercise on markers of fibrinolysis and coagulation in users and nonusers of oral contraceptives. STUDY DESIGN: Fourteen oral contraceptive users and 14 nonusers performed a maximal exercise test on a cycle ergometer. Blood samples were collected before and immediately after the completion of the test. A repeated-measures analysis of variance was used for statistical analysis with values considered significant at P =.05. RESULTS: Acute maximal exercise resulted in significant increases in tissue plasminogen activator activity in both groups. There was a trend toward a smaller increase in tissue plasminogen activator activity in oral contraceptive users, but the difference between groups was not statistically significant. Plasminogen activator inhibitor 1 activity was reduced with exercise in both groups but with a significantly greater decrease observed in the nonusers (P <.0001). Prothrombin fragment 1+2 was significantly higher (P <.0001) in the oral contraceptive group but did not change with exercise. Epinephrine levels before and after exercise were similar between the 2 groups, but postexercise norepinephrine concentrations were significantly lower (P =.026) in the oral contraceptive users. CONCLUSION: These data suggest that oral contraceptive use blunts the fibrinolytic response to exercise. This, together with increased coagulation activation in oral contraceptive users, may alter the hemostatic balance during exercise.