Echocardiographic Doppler evaluation of left ventricular diastolic filling in older, highly trained male endurance athletes

Previously published data have suggested that endurance training does not retard the normative aging impairment of early left ventricular diastolic filling (LVDF). Those studies, suggesting no effect of exercise training, have not examined highly trained endurance athletes or their LVDF responses after exercise. We therefore compared LVDF characteristics in a group of older highly trained endurance athletes (n = 12, mean age 69 years, range 65-75) and a group of sedentary control subjects (n = 12, mean age 69 years, range 65-73) with no cardiovascular disease. For all subjects, M-mode and Doppler echocardiographic data were obtained at rest. After baseline studies, subjects underwent graded, maximal cardiopulmonary treadmill exercise testing using a modified Balke protocol. Breath-by-breath respiratory gas analysis and peak exercise oxygen consumption (VO(2)max) measurements were obtained. Immediately after exercise and at 3-6 minutes into recovery, repeat Doppler echocardiographic data were obtained for determination of LVDF parameters. VO(2)max (44 +/-6.3 vs 27+/-4.2 ml/kg/min, P<0.001), oxygen consumption at anaerobic threshold (35+/-5.4 vs 24+/-3.8 ml/kg/min, P<0.001), exercise duration (24+/-3 vs 12+/-6 minutes, P<0.001), and left ventricular mass index (61+/-13 vs 51+/-7.8 kg/m(2), P<0.05) were greater in endurance athletes than in sedentary control subjects, whereas body mass index was lower (22+/-1.7 vs 26+/-3.4 kg/m(2), P<0.001). No differences in any of the LVDF characteristics were observed between the groups with the exception of a trend toward a lower atrial filling fraction at rest in the endurance athlete group versus the control subjects (P = 0.07). High-intensity endurance exercise training promotes exceptional peak exercise oxygen consumption and cardiovascular stamina but does not appear to alter normative aging effects on left ventricular diastolic function.     

Effects of aerobic exercise training in community-based subjects aged 80 and older: a pilot study

OBJECTIVES: To assess the ability of sedentary, frail subjects aged 80 and older to train in a community-based exercise program and to evaluate clinical factors that predict improvements in peak oxygen consumption (VO2peak). DESIGN: Pretest, posttest. SETTING: Charlestown Retirement Community, Catonsville, Maryland PARTICIPANTS: Twenty-two (11 male, 11 female; mean age +/- standard deviation = 84 +/- 4.0, range 80-92) self-referred. INTERVENTION: Six months of moderate-intensity aerobic exercise training, two to three sessions/week, 20 to 30 minutes per session. Training modes included treadmill walking and/or stationary cycling. MEASUREMENTS: Baseline and follow-up maximal exercise treadmill tests (ETTs) with electrocardiogram monitoring and respiratory gas analysis. RESULTS: Six months of aerobic exercise training resulted in significant increases (mean +/- standard deviation) in ETT duration (11.9 +/- 3.3 vs 15.9 +/- 4.3 minutes; P =.01), VO2peak (1.23 +/- 0.37 vs 1.31 +/- 0.36 L/min; P =.04), and oxygen pulse (9.3 +/- 2.8 vs 10.1 +/- 3.2; P =.03). Mean heart rate was significantly lower during submaximal ETT stages 1 through 4 (P <.05), and resting systolic blood pressure decreased (146 +/- 18 vs 133 +/- 14 mmHg; P =.01) after training. Multiple regression analysis indicated that baseline VO2peak (r = 0.75, P =.002) and the total amount of time spent in exercise training (r = 0.55, P =.008) were independent predictors of the training-related improvements in VO2peak. CONCLUSION: Subjects aged 80 and older can increase aerobic capacity and reduce systolic blood pressure in a community-based exercise program of moderate intensity. The most important predictors of change in VO2peak were baseline VO2peak and the time spent in exercise training. Subjects with a lower baseline VO2peak had the greatest improvements in VO2peak after training.     

Coronary flow reserve of the angiographically normal left anterior descending coronary artery in patients with remote coronary artery disease

Coronary artery disease (CAD) has been suggested to alter coronary flow reserve (CFR; the ratio between hyperemic and baseline coronary flow velocities) not only in territories supplied by stenotic arteries but also in angiographically normal, remote regions. However, few data exist regarding the left anterior descending (LAD) coronary artery as the normal index artery. The influence of remote CAD on CFR of the angiographically normal LAD was evaluated with transthoracic Doppler ultrasound to measure CFR in the LAD during 90 seconds of venous adenosine infusion (140 microg/kg/min) in 122 subjects who were assigned to 1 group; group 1 comprised 49 controls without angiographically detectable CAD, and group 2 consisted of 73 patients with an angiographically normal LAD and remote CAD. Group 2 was divided into 4 subgroups: 16 patients with previous remote percutaneous coronary intervention (group 2A); 13 patients with significant remote stenosis (group 2B); 23 patients with previous remote myocardial infarction and percutaneous coronary intervention (group 2C); and 21 patients with previous remote myocardial infarction but no percutaneous coronary intervention (group 2D). CFR in the LAD was not significantly different in groups 1 and 2 (3.08 +/- 0.61 and 3.03 +/- 0.69, respectively, p = NS). Decreased ejection fraction and increased wall motion score index in patients with remote CAD (p < 0.00001) and multivessel CAD did not affect CFR in the LAD (group 2A 3.18 +/- 0.77; group 2B 3.05 +/- 0.65; group 2C 3.07 +/- 0.79; group 2D 2.86 +/- 0.50, respectively; F = 0.63, p = NS). In conclusion, CFR of an angiographically normal LAD is preserved in patients with remote CAD, even in the presence of previous remote myocardial infarction and wall motion abnormalities.     

Fitness, training, and the growth hormone-->insulin-like growth factor I axis in prepubertal girls

We recently demonstrated that a brief endurance type training program led to increases in thigh muscle mass and peak oxygen uptake (VO(2)) in prepubertal girls. In this study, we examined the effect of training on the GH-->insulin-like growth factor I (GH-->IGF-I) axis, a system known to be involved both in the process of growth and development and in the response to exercise. Healthy girls (mean age 9.17 +/- 0.10 yr old) volunteered for the study and were randomized to control (n = 20) and training groups (n = 19) for 5 weeks. Peak VO(2), thigh muscle volume, and blood samples [for IGF-I, IGF-binding proteins (IGFBP)-1 to -6, and GHBP] were measured. At baseline, IGF-I was significantly correlated with both peak VO(2) (r = 0.44, P < 0.02) and muscle volume (r = 0.58, P < 0.004). IGFBP-1 was negatively correlated with muscle volume (r = -0.71, P < 0.0001), as was IGFBP-2. IGFBP-4 and -5 were significantly correlated with muscle volume. We found a threshold value of body mass index percentile (by age) of about 71, above which systematic changes in GHBP, IGFBP-1, and peak VO(2) per kilogram were noted, suggesting decreases in the following: 1) GH function, 2) insulin sensitivity, and 3) fitness. Following the training intervention, IGF-I increased in control (19.4 +/- 9.6%, P < 0.05) but not trained subjects, and both IGFBP-3 and GHBP decreased in the training group (-4.2 +/- 3.1% and -9.9 +/- 3.8%, respectively, P < 0.05). Fitness in prepubertal girls is associated with an activated GH-->IGF-I axis, but, paradoxically, early in a training program, children first pass through what appears to be a neuroendocrine state more consistent with catabolism.     

Cardiac contributions to exercise training responses in patients with chronic heart failure: a strain imaging study

The improvement of exercise capacity due to exercise training in heart failure has been associated with peripheral adaptation, but the contribution of cardiac responses is less clear. We sought the extent to which the improvement of functional capacity in patients undergoing exercise training for heart failure was related to myocardial performance. Thirty-seven patients (35 men, age 64 +/- 11) with symptomatic heart failure and left ventricular ejection fraction < or = 35% (29 +/- 9%) were studied during a 16-week exercise training program. LV function was assessed by resting and exercise 2D-echocardiography, tissue Doppler derived myocardial strain, and strain rate. Peak oxygen consumption (VO2) and LV function were measured at baseline and follow-up, and the contribution of LV function at baseline and its response to training to the change of each parameter was sought. Baseline peak VO2 (12.4 +/- 4.6) increased by 9% at 8 weeks (13.5 +/- 4.2, P = 0.26), and by 21% at 16 weeks (15.0 +/- 4.9, P < 0.001). Although there were no overall changes in myocardial parameters in this study, change in peak VO2 at 16 weeks was significantly correlated with baseline strain (r = 0.51, P = 0.003) and the improvement of strain at 8 weeks (r = 0.44, P = 0.01), independent of baseline functional capacity and clinical variables. Thus, change in peak VO2 following 16 weeks exercise training is related to myocardial function at baseline.     

Central and peripheral adaptations after 12 weeks of exercise training in post-coronary artery bypass surgery patients.

PURPOSE: Training adaptations in patients with coronary artery disease (CAD) have been reported previously, but little is known about central and peripheral adaptations in those recovering from coronary artery bypass graft surgery (CABG). The purpose of this study was to examine the effects of 12 weeks of endurance exercise training on exercise performance and left ventricular and peripheral vascular reserve in a group of uncomplicated CABG patients. METHODS: Thirty-one patients were recruited and began training 8 to 10 weeks after uncomplicated CABG. Patients underwent progressive exercise training consisting of walking and jogging, at 75% to 80% maximal oxygen intake (VO2max). Measures of left ventricular function included ejection fraction (EF), ventricular volumes, and the pressure volume ratio, an index of contractility. Peak ischemic exercise calf blood flow and vascular conductance was determined using strain-gauge plethysmography. Maximal oxygen intake and submaximal blood lactate concentration also was determined. RESULTS: A significant improvement in VO2max (1497 +/- 60 mL/min versus 1691 +/- 71 mL/min) was observed after training. This change was accompanied by an increase in the EF during submaximal exercise (60 +/- 3% versus 63 +/- 2% at 40% VO2max; 61 +/- 3% versus 64 +/- 3% at 70% VO2max) (P < 0.05), and the change in EF from rest to exercise (delta EF). No changes were observed for ventricular volumes during exercise, although there was a trend for a higher stroke volume at 70% VO2max. A significant increase (18%) was observed for peak ischemic exercise calf blood flow and vascular conductance. In addition, submaximal blood lactate concentration was lower after training. CONCLUSIONS: These data indicate that exercise training for 12 weeks in patients recovering from CABG can elicit significant improvements in functional capacity that, for the most part, are secondary to peripheral adaptations, with limited support for improvement in left ventricular function.     

Exercise-induced human coronary collateral function: quantitative assessment during acute coronary occlusions

In 50 patients undergoing percutaneous transluminal coronary angioplasty because of chronic angina pectoris, a collateral flow index (CFI) was determined at the start and the end of two 1-min coronary occlusions, randomly accompanied by a resting state or a 3-min dynamic handgrip exercise (DHE). CFI expressing collateral flow relative to normal antegrade flow was determined by simultaneous coronary occlusive pressure, mean aortic pressure and central venous pressure measurements. When comparing CFI without and with DHE at the start as well as at the end of balloon occlusions, a significant increase was observed with DHE (overall p < 0.0001); start: 0.18 +/- 0.12 vs. 0.22 +/- 0.13, respectively (p = 0.01); end of occlusion: 0.21 +/- 0.14 vs. 0.25 +/- 0.14, respectively (p = 0.007).     

Regular exercise training compared with percutaneous intervention leads to a reduction of inflammatory markers and cardiovascular events in patients with coronary artery disease

BACKGROUND: Chronic vascular inflammation may trigger ischemic events whereas regular physical exercise training (ET) has shown to be cardioprotective in patients with coronary artery disease (CAD). We investigated the impact of 2 years regular ET versus percutaneous intervention (PCI) on chronic inflammation and cardiovascular events. METHODS AND RESULTS: A total of 101 male patients with stable CAD and an indication for revascularization were prospectively randomized to regular ET (n=51) or PCI with stentimplantation (n=50). High-sensitive C-reactive protein and interleukin-6, exercise capacity and ischemic endpoints were analyzed at baseline and after 2 years. At 2 years maximal oxygen consumption (VO2 max) increased by 10% in the ET group (23.3+/-0.6 to 25.7+/-1.0 ml O2/kg/min; P=0.0171 versus baseline) versus 7% in the PCI group (22.3+/-0.8 to 23.9+/-1.2 ml O2/kg/min; P=0.4248). In a subgroup of patients, high-sensitive C-reactive protein levels and interleukin-6 levels were significantly reduced after ET by 41 and 18%, respectively, whereas no relevant changes were observed in the PCI group. Event-free survival rates after 24 months were 78% (ET) versus 62% (PCI) (P=0.039). CONCLUSION: In patients with stable coronary artery disease, regular physical exercise is associated with a reduction of inflammatory markers and ischemic events.     

Effect of long-term exercise on regional myocardial function and coronary collateral development after gradual coronary artery occlusion in pigs

The effect of myocardial ischemia, induced by long-term exercise, on regional myocardial function and coronary collateral development was examined in pigs after gradual occlusion of the left circumflex coronary artery (LCx) with an ameroid occluder. Thirty days after surgery, regional myocardial function and blood flow were assessed during exercise in 22 pigs separated into exercise (n = 12) and sedentary groups (n = 10). The exercise group trained on a treadmill for 25 +/- 1 days, 30-50 min/day, at heart rates of 210-220 beats/min. After 5 weeks, another exercise test was performed. In the exercise group, after training, we observed an improvement in systolic wall thickening, expressed as a percentage of rest, in the collateral-dependent LCx region from 64 +/- 8% to 87 +/- 6% (p less than 0.01) at moderate exercise levels (220 beats/min) and from 45 +/- 7% to 73 +/- 7% (p less than 0.01) at severe exercise levels (265 beats/min). Transmural myocardial blood flow in the LCx region expressed as a ratio of flow in the nonoccluded region of the left ventricle also increased significantly (p less than 0.01) during severe exercise after 5 weeks. The sedentary group showed an improvement in systolic wall thickening in the LCx region during moderate exercise compared with the initial exercise test (p less than 0.05) but no significant change in systolic wall thickening or myocardial blood flow ratios during severe exercise after 5 weeks. We conclude that long-term exercise after gradual LCx coronary artery occlusion in pigs improves myocardial function and coronary collateral reserve in collateral-dependent myocardium during exercise.     

Effects of a supervised home-based aerobic and progressive resistance training regimen in women infected with human immunodeficiency virus: a randomized trial

BACKGROUND: Women infected with human immunodeficiency virus (HIV) increasingly demonstrate abnormalities in fat distribution and metabolism; however, the effects of a home-based exercise regimen in this group have not been investigated. METHODS: We conducted a 16-week randomized intervention study of a supervised home-based progressive resistance training and aerobic exercise program in 40 HIV-infected women with increased waist-hip ratio and self-reported fat redistribution. Cross-sectional muscle area and muscle attenuation were measured by computed tomography. Cardiorespiratory fitness was determined by calculated maximum oxygen consumption (VO2max) and strength by 1-repetition maximum. RESULTS: Cardiorespiratory fitness (VO2max) was markedly lower at baseline (median [95% confidence interval], 15.4 [8.3-25.2] mL x kg(-1) x min(-1)) than reported values for healthy female subjects (26-35 mL x kg(-1) x min(-1)). Subjects randomized to exercise had significant improvement in mean +/- SEM VO2max (1.5 +/- 0.8 vs -2.5 +/- 1.6 mL x kg(-1) x min(-1); P<.001) and endurance (1.0 +/- 0.3 vs -0.6 +/- 0.3 minute; P<.001). Strength increased at the knee extensors, pectoralis, knee flexors, shoulder abductors, ankle plantar flexors, and elbow flexors (all P<.001). Total muscle area (6 +/- 1 vs 2 +/- 1 cm2; P = .02) and attenuation (2 +/- 1 vs -1 +/- 1 Hounsfield unit; P = .03) increased in the exercise group. No significant difference was seen in lipid levels, blood pressure, or abdominal visceral fat between the groups, but subjects randomized to exercise reported improved energy and appearance. CONCLUSIONS: A 16-week, supervised, home-based exercise regimen improved measures of physical fitness in HIV-infected women. The effects on strength were most significant, but improvements in cardiorespiratory fitness, endurance, and body composition were also seen.     

Training in dogs with normal coronary arteries: lack of effect on collateral development

STUDY OBJECTIVE - The aim of the study was to investigate the effect of exercise training on coronary collateral development in a normal heart animal model. DESIGN - Dogs with normal hearts were fitted with balloon occluders around the left circumflex coronary artery. Haemodynamic variables and myocardial blood flow (using radioactive microspheres) were measured during 1 min circumflex occlusions at rest and during exercise, before and after a 12 week exercise programme. Resting measurements were also made after 4 weeks. SUBJECTS - Trained subjects were 10 one year old beagles; eight beagles served as sedentary controls. Although measurements were made in all dogs at 4 weeks, four trained and three control animals died during the experiment because of complications, so the data reported at 12 weeks are derived from six trained and five sedentary animals. Except during the few occasions when the left circumflex artery was transiently occluded to allow measurement of collateral flow, all coronary arteries were patent and without impediment to normal flow. MEASUREMENTS and RESULTS - Measurements of haemodynamic variables and coronary blood flow were made at the start and repeated at 4 weeks (resting measurements only) and 12 weeks of exercise training. Initial resting circumflex collateral flow was 0.26(SEM 0.05) cm3.g-1.min-1 in the training group and 0.23(0.03) in the control group (NS). The ratio of ischaemic to normal blood flow was 0.16(0.02) in both groups. At 4 weeks there were no changes in either group. At 12 weeks the ischaemic to normal blood flow ratio had increased in both trained and sedentary dogs to 0.24(0.05) and 0.26(0.06) respectively, but the trend over the 12 week period was not significant. The decline in cardiac output and dramatic increase in left atrial pressure during combined coronary occlusion and exercise were comparable in both groups at weeks 1 and 12. CONCLUSIONS - Exercise does not accelerate the development of coronary collaterals in dogs with normal coronary arteries.     

Vasoconstriction of canine coronary collateral vessels with vasopressin limits blood flow to collateral-dependent myocardium during exercise

This study was performed to test the hypothesis that active constriction of coronary collateral vessels can worsen hypoperfusion of collateral-dependent myocardium during exercise. Studies were performed in seven adult mongrel dogs in which intermittent followed by permanent occlusion of the left circumflex coronary artery produced an area of collateral-dependent myocardium without gross evidence of infarct. Myocardial blood flow was determined with microspheres while measurement of aortic and distal coronary pressures allowed calculation of collateral and small vessel resistance at rest and during treadmill exercise. The ability of collateral vessel constriction to limit blood flow was assessed by infusion of vasopressin during exercise. During control conditions, blood flow in the collateral zone underwent a subnormal increase during exercise in comparison with the normal zone (1.74 +/- 0.27 versus 2.50 +/- 0.40 ml/min/g, respectively, p less than 0.05). Infusion of vasopressin in a dose that caused no change in normal zone flow (0.01 microgram/kg/min i.v.) produced a 30 +/- 5% further decrease in flow to the collateral zone (p less than 0.01). This decrease in collateral zone flow resulted from a 48 +/- 14% increase in transcollateral resistance in response to vasopressin infusion (p less than 0.01), as well as a 40 +/- 9% increase in small vessel resistance in the collateral zone (p less than 0.01). These data demonstrate that active constriction of both collateral vessels and coronary resistance vessels can contribute to hypoperfusion of collateral-dependent myocardium during exercise.     

Effect of enhanced external counterpulsation on resting oxygen uptake in patients having previous coronary revascularization and in healthy volunteers

This study analyzed the acute effects of enhanced external counterpulsation (EECP) on oxygen uptake (VO2) at rest in adults with symptomatic coronary artery disease (CAD) compared with healthy volunteers. EECP therapy increases exercise tolerance in patients with refractory angina pectoris. This may be attributed, at least in part, to a training effect, but measurement of VO2 during an EECP treatment session has not been previously reported. We measured VO2 continuously in 20 adults during a single treatment session of EECP, including 10 subjects with previous coronary revascularization who were referred for EECP therapy for refractory angina, and 10 healthy, sedentary volunteers. VO2 was measured for 10 minutes before EECP, during a 30-minute EECP treatment session, and for 10 minutes after cessation of EECP treatment. Patients with CAD were older (65.9 +/- 12 vs 38.5 +/- 7 years, p = 0.002) and had a higher body mass index (32.0 +/- 10.0 vs 25.5 +/- 3.0 kg/m2, p = 0.027) and percent body fat (37 +/- 7% vs 21+/-9%, p = 0.006). VO2 at rest, although slightly lower in the CAD group, was not significantly different (2.75 +/- 0.54 vs 3.19 +/- 0.51 ml/kg/min, p = 0.09). The 2 groups demonstrated a small, sustained increase in VO2 during EECP treatment (CAD +0.66 +/- 0.56 ml/kg/min, p < 0.005; healthy +0.72 +/- 0.40 ml/kg/min, p < 0.001; CAD vs healthy, p = 0.13), which returned to baseline levels during recovery. In conclusion, VO2 at rest is increased to the same degree during an EECP treatment session in healthy subjects and symptomatic patients with CAD. This effect may contribute to the increased exercise tolerance of patients with refractory angina after receiving EECP therapy.     

Exercise-induced silent myocardial ischemia and future cardiac events in healthy, sedentary, middle-aged and older men.

OBJECTIVES: Before men older than age 45 participate in vigorous exercise programs, the American Heart Association and the American College of Sports Medicine recommend they undergo a screening maximal exercise treadmill test. We examined the predictive value for subsequent cardiac events of exercise-induced silent myocardial ischemia (SI) during the exercise treadmill test in healthy, sedentary, obese, middle-aged and older men recruited for research studies. DESIGN: A cohort study with 7 years of follow-up. SETTING: Out-patient research at a tertiary hospital. PARTICIPANTS: 170 healthy, sedentary, obese, middle-aged and older (ages 45-79 years) men with no prior history of coronary artery disease (CAD) recruited for research studies. MEASUREMENTS: Cardiac risk factors, exercise-induced SI (ST segment depression on the electrocardiogram during a maximal exercise treadmill test), maximal aerobic capacity (VO2max), and 7- year follow-up data on incident CAD. RESULTS: At baseline, 37 of the men (22%) had exercise-induced SI on their treadmill tests. Seven-year follow-up data was obtained in 97% of the patients. In the interim, 31 men had cardiac endpoints (sudden cardiac death, myocardial infarction, angioplasty, coronary artery bypass graft surgery, angina), and four had noncardiac deaths. Seventeen of the 37 men (46%) with exercise-induced SI on their baseline exercise tests had cardiac endpoints compared with 14 of 133 (11%) men with normal exercise tests (P < .001). Compared with the men with no cardiac endpoints, the men with subsequent cardiac endpoints were older (63 +/- 1 vs 58 +/- 1 years, mean +/- SEM, P < .001) and had a lower maximal aerobic capacity (VO2max) (24 +/- 1 vs 29 +/- 1 mL/kg/min, P < .001). In Cox proportional hazards analysis, exercise-induced SI and a low VO2max were independent predictors of subsequent cardiac endpoints. CONCLUSION: In a healthy population of obese, sedentary, middle-aged and older men, exercise-induced SI and low VO2max were predictors of incident CAD. This suggests that exercise treadmill testing is beneficial in assessing risk for future cardiac events in obese, sedentary individuals.     

A comparison of longitudinal changes in aerobic fitness in older endurance athletes and sedentary men

OBJECTIVES: To compare the longitudinal changes in maximal aerobic capacity (VO2max) in healthy middle aged and older athletes and sedentary men. DESIGN: A cohort study with mean follow-up of 8.7 years (range 4.0-12.8). SETTING: Outpatient research at a tertiary hospital. PARTICIPANTS: Forty-two healthy, middle aged, and older athletes (initial age 64 +/- 1 year) and 47 healthy sedentary men of comparable age recruited for research studies. MEASUREMENTS: VO2max during a maximal treadmill test. RESULTS: At baseline, the cross-sectional rates of decline in VO2max with age (slope) were virtually identical in the athletes and sedentary men (-0.42 versus -0.43 mL x kg(-1) x min(-1) x year(-1)). At follow-up, the VO2max had declined by 11.9 +/- 1.1 mL x kg(-1) x min(-1) (22%) in the athletes, a crude average rate of -1.4 +/- 0.14 mL x kg(-1)x min(-1) x year(-1). By comparison, the VO2max declined by 4.4 +/- 0.6 mL x kg(-1) x min(-1) (14%) in the sedentary men, a crude average rate of change of -0.48 +/- 0.07 mL x kg(-1) x min(-1) x year(-1). Therefore, the observed absolute rate of longitudinal decline in VO2max in the athletes was triple that of the sedentary men (P= .001) and significantly greater than the decline predicted by their baseline cross-sectional data (P= .001). Post hoc analyses of the longitudinal data in the athletes based on the training regimens over the follow-up period demonstrated that the seven individuals who continued to train vigorously ("high training") had no significant decline in VO2max (0.28% change in VO2max per year). By contrast, the VO2max declined by 2.6% per year in the "moderate training" group (N=21), 4.6% per year in the "low training" group (N=13), and 4.7% per year in the two individuals who developed cardiovascular disease. CONCLUSION: The longitudinal decline in VO2max in older male endurance athletes is highly dependent upon the continued magnitude of the training stimulus. The majority of the athletes reduced their training levels over time, resulting in longitudinal reductions in VO2max two to three times as large as those predicted by cross-sectional analyses or those observed longitudinally in their sedentary peers.     

Effect of mild endurance exercise training and pravastatin on peripheral vasodilatation of forearm resistance vessels in patients with coronary artery disease.

BACKGROUND: Improved endothelial function may contribute to the beneficial effects of cholesterol lowering therapy in patients with coronary artery disease (CAD), but results of the effect of statin therapy on endothelial function are disparate in these patients. Exercise training has been reported to improve endothelial function of patients at risk of or with established CAD. The goal of the study was to compare the effect of mild exercise training or statin therapy on forearm endothelial function in CAD patients with average cholesterol levels. DESIGN AND METHODS: Twenty-eight sedentary male patients with angiographically documented CAD and average pretreatment total plasma cholesterol levels (5.1+/-0.9 mmol/l) aged 42-75 years were included. They were randomly assigned in a 2 : 1 order to either statin therapy (pravastatin, 40 mg daily) or exercise training therapy (mild endurance exercise three or more times a week). The effects of 10 weeks of either treatment on endothelium-dependent and independent vasodilation of forearm resistance vessels was assessed by plethysmography. Cardiopulmonary exercise testing was performed at baseline and after 10 weeks. RESULTS: Ten weeks of pravastatin therapy significantly reduced low-density lipoprotein cholesterol (from 3.8+/-0.6 to 3.1+/-0.6 mmol/l at study end, P=0.04) and the ratio of total to high-density lipoprotein cholesterol (from 4.9+/-0.8 to 3.7+/-0.7 mmol/l, P=0.002). Exercise training did not significantly modify the lipid profile. Peak oxygen consumption, maximal achieved workload and exercise duration tended to improve in the exercise training group but remained unchanged in the pravastatin-treated group. Neither 10 weeks of pravastatin nor mild endurance exercise training improved endothelium-dependent or independent vasomotor function in forearm resistance vessels. CONCLUSIONS: In patients with CAD and average cholesterol levels, 10 weeks of treatment with mild endurance exercise training or with pravastatin failed to improve endothelium-dependent or independent vasomotor function in forearm resistance vessels.     

Presence of asymmetric dimethylarginine gradients across high-grade lesions in patients with coronary artery disease

BACKGROUND: Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is a systemic marker of endothelial dysfunction. Although experimental evidence indicates that asymmetric dimethylarginine may play an important role in atherogenesis, local asymmetric dimethylarginine levels have not been measured in vivo. OBJECTIVES: We sought to determine whether: (i) asymmetric dimethylarginine is elevated locally at sites of coronary lesions, (ii) systemic asymmetric dimethylarginine concentrations correlate with local levels, and (iii) percutaneous coronary intervention produces immediate local asymmetric dimethylarginine elevation. METHODS: In patients undergoing percutaneous coronary intervention (n=15), blood samples were obtained from a peripheral venous site, the coronary ostium proximal to the lesion and the coronary vessel distal to the lesion, before percutaneous coronary intervention. Samples were also obtained distal to the coronary lesion immediately after percutaneous coronary intervention and from the peripheral venous line 24 h after percutaneous coronary intervention. RESULTS: Asymmetric dimethylarginine gradients were present across the coronary bed: local asymmetric dimethylarginine (micromol/l) was significantly higher distal to coronary lesions compared with proximally (2.39+/-1.27 vs. 1.52+/-0.68, P=0.005), and to systemic venous levels (2.39+/-1.27 vs. 1.17+/-0.72, P=0.001). Local asymmetric dimethylarginine did not increase immediately after percutaneous coronary intervention (1.88+/-0.89 vs. 2.39+/-1.27, P=0.11). Peripheral venous percutaneous coronary intervention levels 24 h after percutaneous coronary intervention were similar to baseline values (1.17+/-1.2 vs. 1.17+/-0.72, P=0.98). CONCLUSION: Asymmetric dimethylarginine gradients exist across coronary lesions, suggesting asymmetric dimethylarginine release at the plaque site. Local asymmetric dimethylarginine accumulation may contribute to the endothelial dysfunction associated with high-grade coronary lesions. Peripheral asymmetric dimethylarginine is a marker of generalized endothelial dysfunction, but our findings highlight its limitation in detecting focal injury.     

Coronary collateral perfusion in patients with coronary artery disease: effect of metoprolol.

BACKGROUND: The use of ultrathin Doppler angioplasty guidewires has made it possible to measure collateral flow quantitatively. Pharmacologic interventions have been shown to influence collateral flow and, thus, to affect myocardial ischaemia. METHODS: Twenty-five patients with coronary artery disease undergoing PTCA were included in the present analysis. Coronary flow velocities were measured in the ipsilateral (n = 25) and contralateral (n = 6; two Doppler wires) vessels during PTCA with and without i.v. adenosine (140 microg/kg.min) before and 3 min after 5 mg metoprolol i.v., respectively. The ipsilateral Doppler wire was positioned distal to the stenosis, whereas the distal end of the contralateral wire was in an angiographically normal vessel. The flow signals of the ipsilateral wire were used to calculate the collateral flow index (CFI). CFI was defined as the ratio of flow velocity during balloon inflation divided by resting flow. RESULTS: Heart rate and mean aortic pressure decreased slightly (ns) after i.v. metoprolol. The collateral flow index was 0.25+/-0.12 (one fourth of the resting coronary flow) during the first PTCA and 0.27+/-0.14 (ns versus first PTCA) during the second PTCA, but decreased with metoprolol to 0.16+/-0.08 (p<0.0001 vs. baseline) during the third PTCA. CONCLUSIONS: Coronary collateral flow increased slightly but not significantly during maximal vasodilatation with adenosine but decreased in 23 of 25 patients after i.v. metoprolol. Thus, there is a reduction in coronary collateral flow with metoprolol, probably due to an increase in coronary collateral resistance or a reduction in oxygen demand.     

Assessment of coronary flow reserve using digital angiography before and after successful percutaneous transluminal coronary angioplasty

Important alterations of coronary blood flow and coronary flow reserve occur during percutaneous transluminal coronary angioplasty (PTCA). This study evaluated these alterations using digital subtraction angiography. Coronary flow reserve was determined before and after successful PTCA in 20 patients with 1-vessel coronary artery disease (CAD). Ten other patients with angiographically normal coronary arteries, normal exercise electrocardiographic responses and normal cardiac structure also were evaluated. Coronary flow reserve was calculated as the ratio of papavarine-induced hyperemic flow to basal flow. Flow reserve for the stenotic artery in patients who underwent PTCA was 1.6 +/- 0.2 (mean +/- standard error of the mean) (range 0.9 to 3.9, n = 20). After successful PTCA, flow reserve for this artery increased to 3.1 +/- 0.2 (range 1.7 to 5.2, n = 20) (p less than 0.0001 vs before PTCA). Flow reserve for adjacent nonstenotic, nondilated arteries was 2.6 +/- 0.2 (range 1.4 to 4.5, n = 13). Coronary flow reserve in the stenotic arteries before PTCA was far below normal. In addition, both successfully dilated arteries and nondilated, nonstenotic arteries in these patients with CAD had flow reserve values smaller than those in the patients with normal arteries (4.8 +/- 0.6, range 2.3 to 12.6, n =22) (p less than 0.01). These findings suggest that digital angiographic determinations of coronary flow reserve can reveal important alterations of individual artery vasodilatory capacity. The data suggest that although an epicardial coronary in a patient with CAD may appear angiographically normal, flow reserve remains impaired due to abnormalities as yet undefined.