Reversal of exertional hypotension by prolonged exercise training in selected patients with ischemic heart disease

The effect of prolonged intense endurance exercise training on exertional hypotension was investigated in 16 patients with coronary artery disease who had a 10 mm Hg or greater fall in systolic blood pressure (SBP) during progressive exercise testing. Training consisted of walking, running, or cycling at 50% to 60% of peak oxygen uptake (peak VO2) for 30 min 3 days per week for an initial 3 months and was followed by an additional 9 months of similar exercise performed at 70% to 90% of peak VO2 for 50 to 60 min 5 days per week. The 1 year program resulted in a 41% increase in peak VO2 and lower heart rate and blood pressure responses to submaximal work. Before conditioning, SBP attained a maximal value of 162 +/- 5 mm Hg but fell 21 +/- 3 mm Hg, to 141 +/- 7 mm Hg, at peak effort (p less than .01). After training, maximal SBP was achieved at a faster heart rate (157 +/- 5 vs 132 +/- 6 beats/min; p less than .001) and was 7.4% higher (174 +/- 6 vs 162 +/- 5 mm Hg; p less than .005), while SBP at peak exercise had increased by 21% (171 +/- 6 vs 141 +/- 7 mm Hg; p less than .001) and ST segment depression was slightly reduced. Left ventricular ejection fraction (LVEF) before training declined from 56 +/- 4% at rest to 52 +/- 3% at peak exercise (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlates and prognostic implication of exercise capacity in chronic congestive heart failure

Previous studies have shown poor correlations between exercise tolerance and measurements of left ventricular (LV) function during rest in patients with congestive heart failure (CHF). To further evaluate the determinants of exercise tolerance and their relation to prognosis, we performed rest and exercise hemodynamic measurements and blood pool scintigraphy in 27 patients with CHF. All patients were treated with digitalis and diuretic drugs, but not vasodilator drugs. Exercise capacity was assessed by maximal oxygen consumption (VO2max) during upright bicycle ergometry. Both right ventricular (RV) and LV ejection fractions were measured by radionuclide techniques, and arterial, right atrial and pulmonary artery pressures, cardiac output, and derived hemodynamic indexes were determined. As a group, patients with severely impaired exercise tolerance (group 1, VO2max less than 10 ml/min/kg) had significantly higher rest pulmonary capillary wedge and right atrial pressures (30 +/- 4 vs 23 +/- 6 and 12 +/- 4 vs 7 +/- 2 mm Hg, respectively) than those with a VO2max of 10 to 18 ml/min/kg (group 2). They also had lower LV and RV ejection fractions (16 +/- 4% vs 21 +/- 4% and 19 +/- 12% vs 27 +/- 7%, respectively). However, overlap among individual patients was considerable, and only pulmonary capillary wedge pressure at rest correlated significantly (r = 0.69, p less than 0.001) with VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of levels of cigarette smoke exposure on symptom-limited spiroergometry

Previous investigations demonstrated reduced exposure to selected cigarette smoke constituents in adult smokers switching from conventional cigarettes (CC) to an electrically heated cigarette smoking system (EHCSS). This study investigated whether reduced exposure and no smoking (NS) would improve exercise performance. In a 3-period crossover study, 18 male adult smokers (age, 43.6+/-5.3 years) of CC were randomized to smoke CC (tar, 11 mg; nicotine, 0.8 mg; carbon monoxide, 11 mg), to use EHCSS (tar, 3 mg; nicotine, 0.2 mg; carbon monoxide, 0.4 mg [Federal Trade Commission method]), or to NS for 3 days before performing symptom-limited spiroergometry. NS and EHCSS vs CC resulted in less severe dyspnea (NS, 44.4% [P<.01 vs CC;] EHCSS, 50% [P=.03 vs CC;] CC, 88.9%), higher working capacity (NS, 2.92+/-0.4 W/kg [P=.06 vs CC;] ECHSS, 2.92+/-0.4 W/kg [P=.04 vs CC;] CC, 2.86+/-0.5 W/kg), higher peak oxygen uptake (NS, 2694+/-466 mL O(2)/min [P=.08 vs CC;] EHCSS, 2830+/-606 mL O(2)/min [P=.03 vs CC;] CC, 2682+/-492 mL O(2)/min), higher anaerobic threshold (NS, 1324+/-306 mL O(2)/min; EHCSS, 1396+/-312 mL O(2)/min [P=.03 vs CC;] CC, 1315+/-290 mL O(2)/min), and higher maximum rate-pressure product (NS, 30.1+/-2.7 x 10(3) mm Hg/min; EHCSS, 2.8 x 10(3) mm Hg/min [P<.01 vs CC;] CC, 30.7+/-29.2+/-3.6 x 10(3) mm Hg/min) indicating that reduced exposure from tobacco smoke and NS for 3 days may improve cardiovascular function as detected by symptom-limited spiroergometry.     

Incremental prognostic value of exercise hemodynamic variables in chronic congestive heart failure secondary to coronary artery disease or to dilated cardiomyopathy

To determine the prognostic value of hemodynamic variables at rest and during exercise, 49 patients with chronic congestive heart failure undergoing hemodynamic evaluation at rest and during symptom-limited exercise were followed for 1 year. One-year mortality rate was 33%. On univariate analysis, nonsurvivors differed significantly from survivors in pulmonary arterial wedge pressure at rest (22 +/- 10 vs 15 +/- 10 mm Hg; p = 0.01) and during exercise (32 +/- 9 vs 24 +/- 9 mm Hg; p = 0.003), stroke work index at rest (19 +/- 6 vs 25 +/- 9 g-m/m2; p = 0.03) and during exercise (20 +/- 7 vs 32 +/- 14 g-m/m2; p = 0.001) and exercise-induced increment in stroke work index (0.5 +/- 0.4 vs 7 +/- 8 g-m/m2; p = 0.004), but not with respect to left ventricular ejection fraction, exercise duration, peak oxygen consumption or peak left ventricular hydraulic power. Patients with a peak exercise stroke work index less than 20 g-m/m2 had a 66% mortality rate compared with a mortality rate of 13% in patients with a peak exercise stroke work index greater than 20 g-m/m2 (p = 0.0001). Multiple logistic regression analysis identified pulmonary arterial wedge pressure at rest and peak exercise stroke work index as the only independent predictors of mortality. A receiver-operating characteristic curve analysis revealed that peak exercise stroke work index provided significant incremental prognostic information over the resting hemodynamic variables.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amlodipine increases nitric oxide production in exhaled air during exercise in patients with essential hypertension

BACKGROUND: Endothelial production of nitric oxide (NO) is attenuated in patients with essential hypertension. We investigated whether treatment with amlodipine increased exhaled NO output (VNO) at rest and during exercise in patients with essential hypertension. METHODS: We studied the effect of amlodipine in seven untreated hypertensive patients. Cardiopulmonary exercise testing and NO measurement of exhaled air were performed on these patients before and after 2 months of amlodipine treatment. RESULTS: Amlodipine decreased blood pressure (BP) both at rest and during exercise (at rest: 147.1 +/- 6.4 [SEM]/89.9 +/- 4.4 v 133.6 +/- 5.4/82.7 +/- 3.9 mm Hg, P <.05; at peak exercise: 224.9 +/- 8.0/113.1 +/- 5.3 v 207.0 +/- 6.0/100.7 +/- 5.0 mm Hg, P <.05) without affecting heart rate (at rest: 67.6 +/- 3.9 v 70.4 +/- 4.5 beats/min, P =.33; peak exercise: 146.4 +/- 7.4 v 144.0 +/- 7.2 beats/min, P =.49). Amlodipine did not affect minute ventilation (VE) at rest or during exercise. It did not alter anaerobic threshold, peak oxygen uptake (peak VO(2)), or peak workload. However, after amlodipine treatment, VNO was significantly greater both at rest (130.8 +/- 19.4 v 180.4 +/- 24.8 nL/min, P <.05) and at peak exercise (380.0 +/- 47.5 v 582.6 +/- 74.3 nL/min, P <.05). CONCLUSIONS: Amlodipine increased NO production, at least in the pulmonary circulation, in patients with essential hypertension. In addition to its antihypertensive effect, the enhancement of NO production by amlodipine in the vasculature of other organs may contribute to its beneficial effects on the cardiovascular system.     

Exercise performance in patients with uncomplicated essential hypertension. Effects of nifedipine-induced acute blood pressure reduction.

In untreated patients with uncomplicated essential hypertension, exercise induces an abnormal increase in blood pressure; the influences of this increase on exercise were evaluated by a cardiopulmonary exercise test (CPX) performed in control conditions (step 1) and during acute blood pressure reduction (step 2). Patients were classified as (1) normotensive (resting diastolic blood pressure [BPd] less than 90 mm Hg; n = 14), (2) mildly hypertensive (BPd of 90 to 104 mm Hg; n = 9), and (3) moderately to severely hypertensive (BPd greater than or equal to 105 mm Hg; n = 16). For the three groups, peak mean blood pressure during exercise was 125 +/- 5 mm Hg (mean +/- SEM), 144 +/- 3 mm Hg (p less than 0.01 vs normotensive), and 161 +/- 4 mm Hg (p less than 0.01 vs normotensive and p less than 0.01 vs mild hypertension), respectively. Oxygen consumption (VO2) at peak exercise and at ventilatory anaerobic threshold was 26.1 +/- 1.1 and 17.2 +/- 0.5 ml/min/kg, 25.4 +/- 1.1 and 16.9 +/- 0.8 ml/min/kg, and 26.4 +/- 1.3 and 17.5 +/- 1.2 ml/min/kg in normotensive subjects, those with mild hypertension, and those with moderate to severe hypertension, respectively. Fourteen normotensive subjects, six with mild hypertension, and nine with moderate to severe hypertension participated to step 2 (nifedipine vs placebo, double-blind crossover). Nifedipine reduced blood pressure at rest and at peak exercise in those with hypertension. Peak exercise VO2 was unaffected by nifedipine in both normotensive subjects and those with hypertension. With nifedipine, ventilatory anaerobic threshold occurred earlier and at a lower VO2 in mild and in moderate to severe hypertension (delta VO2 = -1.9 and -2.4 ml/min/kg, respectively). These findings might be due to nifedipine-induced redistribution of blood flow during exercise and might be the reason for the complaint of weakness after blood pressure reduction in hypertensive subjects.     

Pulmonary pressure-flow relation as a determinant factor of exercise capacity and symptoms in patients with regurgitant valvular heart disease

BACKGROUND: Exertional dyspnea is a frequent limiting symptom in patients with chronic heart failure. Furthermore, dyspnea and a plateau in VO(2) (oxygen consumption) at peak exercise often co-exist in chronic heart failure, especially in patients with severe regurgitant valvular heart disease (RVHD), their relevance to hemodynamics and subjective symptoms during exercise have not been fully understood. OBJECTIVES: The purpose of this study was to examine the determinant factor of exercise capacity in patients with RVHD. METHODS: We performed a symptom-limited cardiopulmonary exercise test using a sitting cycle ergometer with right heart catheterization in 20 patients with severe RVHD. VO(2) and hemodynamics were measured at rest and during exercise, and symptomatic end-point at peak exercise was evaluated by using Borg's score. RESULTS: Of the 20 patients, 11 attained a plateau in VO(2) at peak exercise (Group 1). At peak exercise, pulmonary arterial pressure (PAP) was higher, and cardiac output (CO) and VO(2) were lower in Group 1 than in patients without a plateau in VO(2) (Group 2) (mean PAP: 60+/-10 vs. 48+/-9 mm Hg, P=0.05; CO: 8.3+/-2.6 vs. 11.2+/-2.6 l/min, P=0.01; VO(2): 1059+/-259 vs. 1359+/-328 ml/min, P=0.01). In Group 1, 6 patients complaining of dyspnea rather than leg fatigue at peak exercise had lower CO (7.1+/-1.8 vs. 9.7+/-3.0 l/min, P=0.05) and higher slope of mean PAP-CO relation (P-Q slope) (10.6+/-3.6 vs. 5.4+/-1.7, P=0.01), compared with the other 5 patients with leg fatigue. CONCLUSIONS: Development of pulmonary hypertension during exercise is the important limiting factor for exercise capacity in patients with RVHD. The limitation of increase in CO concomitant with pulmonary hypertension could be an important factor in the appearance of dyspnea.     

Gas exchange during maximal upper extremity exercise

STUDY OBJECTIVE: to characterize gas exchange and cardiopulmonary performance during maximal progressive arm crank exercise. DESIGN: Cardiopulmonary variables were measured and arterial blood gases were determined in blood samples obtained from an indwelling radial arterial catheter during arm crank exercise (34 watts/min). Arm crank exercise was compared to maximal leg exercise performed by a different but comparable group of subjects from a previous study. PARTICIPANTS: 19 healthy young (mean +/- SEM: 20 +/- 1 yr) black males. RESULTS: Peak arm crank exercise resulted in lower values compared to peak leg exercise for: power (129 +/- 2 vs 253 +/- 10 W), VO2 (2.17 +/- 0.04 vs 3.26 +/- 0.14 L/min); VCO2 (2.9 +/- 0.11 vs 4.32 +/- 0.17 L/min); HR (168 +/- 3 vs 189 +/- 3 beats/min); AT (1.15 +/- 0.05 vs 1.83 +/- 0.07 L/min); and VE (101 +/- 2 vs 144 +/- 8 L/min), respectively. Arm crank exercise (baseline vs peak) elicited an impressive improvement in PaO2 (85 +/- 1 to 97 +/- 1 mm Hg), no change in SaO2 (96 +/- 0.2 to 96 +/- 0.2 percent), no significant increase in P(A-a)O2 (3 +/- 0.7 to 5 +/- 0.9 mm Hg) and an appropriate trending decrease in VD/VT (0.22 +/- 0.01 to 0.17 +/- 0.01). Peak arm crank values were significantly different from peak cycle exercise for PaO2 (82 +/- 2.2 mm Hg), SaO2 (93 +/- 0.4 percent), P(A-a)O2 (21 +/- 1.9 mm Hg) and VD/VT (0.08 +/- 0.01). At comparable levels of VO2 for arm crank and cycle exercise (2.17 +/- 0.04 vs 2.26 +/- 0.08 L/min), significant differences were observed for PaO2 (97 +/- 1.4 vs 81 +/- 1.9 mm Hg); SaO2 (96 +/- 0.2 vs 94 +/- 0.4 percent); P(A-a)O2 (5 +/- 0.9 vs 14 +/- 1.5 mm Hg); and VD/VT (0.17 +/- 0.01 vs 0.08 +/- 0.01), respectively. CONCLUSIONS: Maximal arm crank exercise represents a submaximal cardiopulmonary stress compared to maximal leg exercise. The differences in gas exchange observed at peak exercise between arm crank and leg exercise for the most part reflect the lower VO2 achieved. However, the persistence of these gas exchange differences even at a comparable level of VO2 suggests that factors other than VO2 may be operative. These factors may include differences in alveolar ventilation, CO2 production, ventilation-perfusion inequality, diffusion, and control of breathing.     

Value of the Bruce protocol to determine peak exercise oxygen consumption in patients evaluated for cardiac transplantation

BACKGROUND: Peak exercise oxygen consumption (peak VO2) is an important discriminator of survival in patients with systolic heart failure and is used to select ambulatory patients for transplantation. The major trials assessing the relationship between peak VO2 and survival have used a variety of low-level exercise protocols. It is unknown how peak VO2 measured in this patient population by the more vigorous Bruce treadmill protocol compares with that obtained on less intense protocols. METHODS: We studied 15 patients (50 +/- 12 years old) with severe heart failure (left ventricular ejection fraction 23.5% +/- 8.6%). Patients randomly performed 3 exercise tests with the Bruce treadmill, modified Naughton treadmill, and modified bicycle protocols within 14 days. To determine the ability of this patient population to perform the Bruce protocol, we also retrospectively analyzed the ability of 84 patients to perform this test on their initial evaluations at our center. RESULTS: All patients reached the anaerobic threshold (AT) on all 3 protocols. The Bruce and modified Naughton treadmill protocols resulted in similar peak VO2 percent predicted peak VO2, and VO2 at AT values (17.7 +/- 3.8 mL/kg/min, 57.2% +/- 21.1% and 15.4 +/- 4.1 mL/kg/min vs 18.0 +/- 4.7 mL/kg/min, 58.1% +/- 22.5% and 15.6 +/- 4.4 mL/kg/min, respectively). Peak VO2 and VO2 at AT on both treadmill protocols were higher than those obtained with bicycle testing (15.3 +/- 3.1 and 11.8 +/- 3.0 mL/kg/min, P <.05). Exercise duration was shorter with the Bruce and bicycle protocols (6.2 +/- 2.2 and 6.7 +/- 2.4 minutes, respectively) compared with the modified Naughton protocol (9.7 +/- 4.3 minutes, both P <.005). In addition, 79 of the 84 patients (94%) evaluated were able to complete the Bruce protocol and reach AT. CONCLUSIONS: The Bruce protocol was more time efficient than the modified Naughton protocol and yielded similar peak VO2, percent predicted peak VO2, and VO2 at AT values. Bicycle exercise may underestimate peak VO2 values. The form of exercise should be considered when assessing peak VO2 criteria for transplant listing.     

Reliability of isokinetic strength and aerobic power testing for patients with chronic heart failure

PURPOSE: The objective of this study was to assess the reliability of testing skeletal muscle strength and peak aerobic power in a clinical population of patients with chronic heart failure (CHF). METHODS: Thirty-three patients with CHF (New York Heart Association (NYHA) Functional Class 2.3 +/- 0.5; left ventricular ejection fraction 27% +/- 7%; age 65 +/- 9 years; 28:5 male-female ratio) underwent two identical series of tests (T1 and T2), 1 week apart, for strength and endurance of the muscle groups responsible for knee extension/flexion and elbow extension/flexion. The patients also underwent two graded exercise tests on a bicycle ergometer to measure peak oxygen consumption (VO(2peak)). Three months later, 18 of the patients underwent a third test (T3) for each of the measures. Means were compared using MANOVA with repeated measures for strength and endurance, and ANOVA with repeated measures for VO(2peak). RESULTS: Combining data for all four movement patterns, the expression of strength increased from T1 to T2 by 12% +/- 25% (P <.001; intraclass correlation coefficient [ICC] = 0.89). Correspondingly, endurance increased by 13% +/- 23% (P =.004; ICC = 0.87). Peak oxygen consumption was not significantly different (16.2 +/- 0.8 and 16.1 +/- 0.8 mL.kg(-1).min(-1) for T1 and T2, respectively; P =.686; ICC = 0.91). There were no significant differences between T2 and T3 for strength (2% +/- 17%; P =.736; ICC = 0.92) or muscle endurance (-1% +/- 15%; P =.812; ICC = 0.96), but VO(2peak) decreased from 16.7 +/- 1.2 to 14.9 +/- 0.9 mL.kg(-1).min(-1) (-10% +/- 18%; P =.021; ICC = 0.89). CONCLUSIONS: These data suggest that in a population of patients with CHF, a familiarization trial for skeletal muscle strength testing is necessary. Although familiarization is not required for assessing oxygen consumption as a single measurement, VO(2peak) declined markedly in the 3-month period for which these patients were followed. Internal consistency within patients was high for the second and third strength trials and the first and second tests of VO(2peak).     

Cardiorespiratory responses to exercise training after orthotopic cardiac transplantation

We have tested the feasibility and effectiveness of a 2 year (average 16 +/- 7 months) walk/jog exercise program on 36 male orthotopic cardiac transplant patients (21 to 57 years old) seen initially 2 to 23 months after surgery. Comparison of initial exercise test results with those in 45 age-matched normal men showed the patients to have a lesser lean body mass (56 +/- 7 vs 63 +/- 8 kg, p less than .001), with a higher resting heart rate (104 +/- 12 vs 77 +/- 14 beats/min, p less than .001) and systolic (138 +/- 16 vs 129 +/- 17 mm Hg, p less than .001) and diastolic (95 +/- 14 vs 84 +/- 10 mm Hg, p less than .001) blood pressures. Peak power output was less than normal (101 +/- 27 vs 219 +/- 41 W, p less than .001), as was peak heart rate (136 +/- 15 vs 176 +/- 13 beats/min, p less than .001), peak oxygen intake (VO2max) (22 +/- 5 vs 34 +/- 6 ml.kg.min-1, p less than .001), and absolute anaerobic threshold (1.18 +/- 0.40 vs 2.04 +/- 0.40 liters.min-1, p less than .001). Peak ventilatory equivalent was higher (48 +/- 9 vs 37 +/- 61.1-1, p less than .001). Cardiac output (Q), as estimated by the CO2 rebreathing method, was slightly above normal at rest (p less than .01), but below normal at two submaximal work rates. The group's average weekly training distance was 24 km, with eight highly compliant patients progressing to 32 km or more weekly. After training, lean tissue increased (+2.4 +/- 3.1 kg, p less than .001), and resting values were reduced for heart rate (-4 +/- 11 beats/min, p less than .05), systolic (-13 +/- 20 mm Hg, p less than .001), and diastolic (-9 +/- 17 mm Hg, p less than .001) blood pressures. There were significant reductions in submaximal values for minute ventilation (VE), ratings of perceived exertion, and diastolic blood pressure at equivalent workloads. Peak values increased for power output (+49 +/- 34 W, p less than .001), VO2max (+4.0 +/- 6.0 ml.kg.min-1, p less than .001), VE (+20 +/- 20 l.min-1, p less than .001), and heart rate (+13 +/- 17 beats/min, p less than .001), and decreased for diastolic blood pressure (-8 +/- 15 mm Hg, p less than .001).(ABSTRACT TRUNCATED AT 400 WORDS)     

Sleep apnea syndrome and diastolic blood pressure elevation during exercise

BACKGROUND: Several studies assessing the role of obstructive sleep apnea syndrome (OSAS) as an independent risk factor for hypertension have produced conflicting results. Although the sleep apnea syndrome is associated with hypertension, there are no references regarding the blood pressure response of normotensive OSAS patients during exercise. STUDY OBJECTIVES: The aim of this study was to investigate the relationship between diastolic blood pressure (DBP) response during exercise and the severity of OSAS. METHODS: We performed exercise testing a day after polysomnography in 17 normotensive males who were admitted for the first time because of OSAS and in 10 normal subjects who were members of the same families. During maximal incremental exercise test (bicycle ergometry) oxygen consumption (VO(2)) and the DBP were estimated at rest and at peak exercise. VO(2) was also measured when DBP were 100 and 110 mm Hg. RESULTS: At peak exercise DBP was significantly higher in OSAS patients (115.3 +/- 9.2 mm Hg) than in normal subjects (101 +/- 8.4 mm Hg, p < 0.01). OSAS patients reached a DBP of 110 mm Hg with a significantly lower VO(2) than normal subjects (1,881.5 +/- 703.4 vs. 1,972.3 +/- 108.6 ml/min, p = 0.045). VO(2) was not different between the two groups at a DBP of 100 mm Hg (1,211.2 +/- 371.7 vs. 1,536.6 +/- 267.2 ml/min, p = 0.089) but OSAS patients had a significantly lower heart rate than normals (111.2 +/- 13 vs. 118.6 +/- 27.6, p = 0.009). None of the aspects of quality of life, according to the Nottingham Health Profile Questionnaire, Part 1, were significantly different between patients and normal subjects. CONCLUSIONS: Normotensive OSAS patients develop DBP elevation at an earlier stage during exercise compared to normal subjects. This hypertensive response was not correlated with the severity (apnea-hypopnea index, oxygen desaturation parameters) of OSAS. DBP elevation could be a limiting factor of physical performance in this group of patients.     

Plasma endothelin-1 levels and clinical correlates in patients with chronic heart failure

BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, and patients with chronic heart failure (CHF) are reported to have high plasma ET-1 levels. The aim of this study was to investigate the relation between plasma ET-1 levels and clinical correlates in patients with CHF. The effects of maximal exercise on plasma ET-1 levels were also investigated. METHODS: Plasma concentrations of ET-1, norepinephrine, and atrial and brain natriuretic peptide (ANP and BNP) both at rest and after maximal cardiopulmonary exercise test were determined in 100 patients with CHF (60 +/- 12 years, New York Heart Association [NYHA] class I-III, left ventricular ejection fraction [LVEF]=36 +/- 8%, peak oxygen uptake [VO2] = 18.2 +/- 5.0 mL/min/kg) and 27 controls. RESULTS: Patients with NYHA class II and III CHF had higher ET-1 levels (controls, NYHA class I, II, III: 2.1 +/- 0.6, 2.1 +/- 1.0, 2.6 +/- 0.9, 3.4 +/- 0.8 pg/mL, analysis of variance P <.0001). Maximal exercise did not alter ET-1 levels in controls or in each CHF subgroup. When all CHF patients were analyzed together, cardiothoracic ratio (P<.01), peak VO2 (P<.001), plasma norepinephrine (P<.01), plasma ANP (P<.01), and plasma BNP (P<.001) were significantly related with resting ET-1 levels on univariate analysis. Multivariate analysis revealed peak VO2 and plasma BNP levels showed an independent and significant relationship with the resting plasma ET-1 levels. CONCLUSIONS: Resting ET-1 levels were increased in symptomatic patients with CHF, and maximal exercise did not increase ET-1 levels. Peak VO2 and plasma BNP levels were independently associated with resting plasma ET-1 levels in patients with CHF.     

Acute moderate-intensity exercise induces vasodilation through an increase in nitric oxide bioavailiability in humans

BACKGROUND: Long-term moderate-intensity exercise augments endothelium-dependent vasodilation through an increase in nitric oxide (NO) production. The purpose of this study was to determine the effects of different intensities of acute exercise on hemodynamics in humans. METHODS: We evaluated forearm blood flow (FBF) responses to different intensities of exercise (mild, 25% maximum oxygen consumption [VO2max]; moderate, 50% VO2max; and high, 75% VO2max; bicycle ergometer, for 30 min) in eight healthy young men. The FBF was measured by using a strain-gauge plethysmography. RESULTS: After exercise began, moderate-intensity exercise, but not mild-intensity exercise, promptly increased FBF from 2.8+/-1.1 mL/min/100 mL to a plateau at 5.4+/-1.6 mL/min/100 mL at 5 min (P<.01) and increased mean arterial pressure from 84.7+/-11.8 mm Hg to a plateau at 125.7+/-14.3 mm Hg at 5 min (P<.01). Moderate-intensity exercise decreased forearm vascular resistance (FVR) from 29.2+/-5.4 to 16.8+/-3.2 mm Hg/mL/min/100 mL tissue (P<.01). The administration of NG-monomethyl-L-arginine, an NO synthase inhibitor, abolished moderate exercise-induced augmentation of vasodilation. Although we were not able to measure FBF during high-intensity exercise because of large body motion, high-intensity exercise markedly increased mean arterial pressure from 82.6+/-12.2 to 146.8+/-19.8 mm Hg. High-intensity exercise, but not mild-intensity or moderate-intensity exercise, increased plasma concentration of 8-isoprostane, an index of oxidative stress, from 24.1+/-10.8 to 40.2+/-16.7 pg/mL (P<.05) at 10 min after the end of exercise. CONCLUSIONS: These findings suggest that acute moderate-intensity exercise induces vasodilation through an increase in NO bioavailability in humans and that high-intensity exercise increases oxidative stress.     

Neurohormonal determinants of peak oxygen uptake in patients with chronic heart failure

Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. This study determined whether peak oxygen uptake (VO2) can be predicted by the degree of neurohormonal and cytokine activations in CHF. Plasma norepinephrine. epinephrine, renin-angiotensin system activity, ANP, BNP, and serum interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were measured in 84 CHF patients (age, 59 +/- 1 years, LVEF, 36 +/- 1%) and 34 controls. Maximal cardiopulmonary exercise testing was performed. Peak VO2 (Controls vs CHF: 27.8 +/- 1.3 vs 18.2 +/- 0.5 mL/min/kg, P < 0.0001) was lower in CHF. Patients with CHF had increased plasma norepinephrine (211 +/- 11 vs 315 +/- 24 pg/mL), renin activity (1.2 +/- 0.2 vs 6.2 +/- 1.1 ng/mL/hr), ANP (22 +/- 3 vs 72 +/- 7 pg/mL), and BNP levels (18 +/- 3 vs 200 +/- 25 pg/mL) (all P < 0.01). Serum IL-6 (1.1 0.1 vs 2.4 +/- 0.3 pg/mL) and TNF-alpha (2.7 +/- 0.2 vs 4.0 +/- 0.3 pg/mL) levels were higher in CHF (both P < 0.001). Univariate analysis revealed that age (P < 0.001), cardiothoracic ratio (P < 0.001), norepinephrine (P < 0.0001), ANP (P < 0.001), BNP (P < 0.01), and log IL-6 (P < 0.05) were significantly related with peak VO2. Stepwise regression analysis indicated that plasma norepinephrine and ANP emerged as significant determinants of peak VO2, independent of patient age (overall R = 0.61, P < 0.0001). In summary, patients with CHF exhibited activation of neurohormones and proinflammatory cytokines. Among the elevated hormonal and cytokine markers, plasma norepinephrine and ANP levels were independent predictors of exercise capacity.     

Oxygen transport and oxygen consumption during supplemental oxygen administration in patients with chronic obstructive pulmonary disease

PURPOSE: Oxygen consumption (VO2) is independent of oxygen delivery (DO2) above a critical level of DO2. VO2 may become dependent on DO2 when oxygen demand exceeds oxygen supply. We studied DO2 VO2, and exercise capacity in 12 stable, ambulatory patients with chronic obstructive pulmonary disease (COPD) receiving ambient air and 26% oxygen to ascertain whether VO2 is dependent on DO2 in this patient sample. PATIENTS AND METHODS: An exercise protocol consisting of a symptom-limited, low-level treadmill test with progressive increments in workload was performed twice, once with patients breathing ambient air and once with patients breathing 26% oxygen. Expired gas, arterial and mixed venous blood values, and recordings of systemic and pulmonary artery pressures were obtained after a 10-minute period of rest (while standing) and during the last minute of each three-minute exercise level. RESULTS: Five patients had an increase in exercise capacity, defined as an increase in the maximal VO2 greater than 25%, using supplemental oxygen. In these patients, oxygen delivery increased from 10.9 +/- 3.4 to 13.8 +/- 4.7 mL/minute/kg (p = 0.008) at rest and from 16.2 +/- 5.0 to 24.7 +/- 2.7 mL/minute/kg (p = 0.046) during exercise with supplemental oxygen administration. VO2 increased from 0.329 +/- 0.065 to 0.436 +/- 0.109 L/minute (p = 0.029) at rest and from 0.776 +/- 0.275 to 1.119 +/- 0.482 L/minute (p = 0.048) during exercise. Three of these five patients had an arterial oxygen pressure greater than 55 mm Hg at rest. Seven patients had little or no increase in exercise capacity with supplemental oxygen. This patient group had no increase in VO2 at rest. The DO2 failed to increase at rest despite an increase in arterial oxygen content because of a reduction in cardiac output. CONCLUSION: These data demonstrate that DO2 may fail to increase in some patients with COPD and resting or exertional hypoxemia when supplemental oxygen is administered because of a reduction in cardiac output; that patients who fail to increase their DO2 are less likely to increase exercise capacity; and that some stable, ambulatory patients with COPD who do not qualify for supplemental oxygen at rest by current standards may have inadequate DO2 to meet physiologic needs.     

Use of cardiopulmonary exercise testing with hemodynamic monitoring in the prognostic assessment of ambulatory patients with chronic heart failure

OBJECTIVES: We studied whether direct assessment of the hemodynamic response to exercise could improve the prognostic evaluation of patients with heart failure (HF) and identify those in whom the main cause of the reduced functional capacity is related to extracardiac factors. BACKGROUND: Peak exercise oxygen consumption (VO2) is one of the main prognostic variables in patients with HF, but it is influenced also by many extracardiac factors. METHODS: Bicycle cardiopulmonary exercise testing with hemodynamic monitoring was performed, in addition to clinical evaluation and radionuclide ventriculography, in 219 consecutive patients with chronic HF (left ventricular ejection fraction, 22 +/- 7%; peak VO2, 14.2 +/- 4.4 ml/kg/min). RESULTS: During a follow-up of 19 +/- 25 months, 32 patients died and 6 underwent urgent transplantation with a 71% cumulative major event-free 2-year survival. Peak exercise stroke work index (SWI) was the most powerful prognostic variable selected by Cox multivariate analysis, followed by serum sodium and left ventricular ejection fraction, for one-year survival, and peak VO2 and serum sodium for two-year survival. Two-year survival was 54% in the patients with peak exercise SWI < or = 30 g x m/m2 versus 91% in those with a SWI >30 g x m/m2 (p < 0.0001). A significant percentage of patients (41%) had a normal cardiac output response to exercise with an excellent two-year survival (87% vs. 58% in the others) despite a relatively low peak VO2 (15.1 +/- 4.7 ml/kg/min). CONCLUSIONS: Direct assessment of exercise hemodynamics in patients with HF provides additive independent prognostic information, compared to traditional noninvasive data.     

Relation between central and peripheral hemodynamics during exercise in patients with chronic heart failure. Muscle blood flow is reduced with maintenance of arterial perfusion pressure

We studied the central hemodynamic, leg blood flow, and metabolic responses to maximal upright bicycle exercise in 30 patients with chronic heart failure attributable to severe left ventricular dysfunction (ejection fraction, 24 +/- 8%) and in 12 normal subjects. At peak exercise, patients demonstrated reduced oxygen consumption (15.1 +/- 4.8 vs. 32.1 +/- 9.9 ml/kg/min, p less than 0.001), cardiac output (8.7 +/- 3.2 vs. 18.6 +/- 4.4 l/min, p less than 0.001), and mean systemic arterial blood pressure (116 +/- 15 vs. 135 +/- 13 mm Hg, p less than 0.01) compared with normal subjects. Leg blood flow was decreased in patients versus normal subjects at rest and matched submaximal work rates and maximal exercise (2.1 +/- 1.9 vs. 6.4 +/- 1.4 l/min, all p less than 0.01). Mean systemic arterial blood pressure was no different in the two groups at rest or at matched submaximal work rates, whereas leg vascular resistance was higher in patients compared with normal subjects at rest, submaximal, and maximal exercise (all p less than 0.01). Although nonleg blood flow was decreased at rest in patients, it did not decrease significantly during exercise in either group. Peak exercise leg blood flow was related to peak exercise cardiac output in patients (r = 0.66, p less than 0.01) and normal subjects (r = 0.67, p less than 0.01). In patients, leg vascular resistance was not related to mean arterial blood pressure, pulmonary capillary wedge pressure, arterial catecholamines, arterial lactate, or femoral venous pH at rest or during exercise. Compared with normal subjects during submaximal exercise, patients demonstrated increased leg oxygen extraction and lactate production accompanied by decreased leg oxygen consumption. Thus, in patients with chronic heart failure compared with normal subjects, skeletal muscle perfusion is decreased at rest and during submaximal and maximal exercise, and local vascular resistance is increased. Our data indicate that nonleg blood flow and arterial blood pressure were preferentially maintained during exercise at the expense of leg hypoperfusion in our patients. This was associated with decreased leg oxygen utilization and increased leg oxygen extraction when compared to normal subjects, providing further evidence that reduced perfusion of skeletal muscle is important in causing early anaerobic skeletal muscle metabolism during exercise in subjects with this disorder.(ABSTRACT TRUNCATED AT 400 WORDS)     

Determinants of delayed improvement in exercise capacity after percutaneous transvenous mitral commissurotomy

BACKGROUND: Percutaneous transvenous mitral commissurotomy (PTMC) results in short-term hemodynamic and symptomatic improvements. We have previously shown that the immediate symptomatic relief is related to the improvement in excessive exercise ventilation. The exercise capacity, however, does not improve in the short term but does improve gradually over several months. The pathophysiologic basis for the delayed improvement in exercise capacity has not been fully evaluated. METHODS: To elucidate the determinants of improvement in exercise capacity late after PTMC, maximal ergometer exercise with respiratory gas analysis and exercise hemodynamic measurements were performed in 22 patients with symptomatic mitral stenosis before, immediately after, and 7 months after PTMC. RESULTS: Mitral valve area increased from 0.9 +/- 0.2 cm(2) to 1.7 +/- 0.4 cm(2) after PTMC (P <.01). Significant improvements were observed in symptoms, cardiac output at peak exercise (6.6 +/- 1.5 L/min vs 8.6 +/- 1.9 L/min, P <.01), and mean pulmonary artery pressure at peak exercise (54.1 +/- 15.6 mm Hg vs 42.3 +/- 9.5 mm Hg, P <.01) immediately after PTMC. Excessive exercise ventilation, as assessed by the slope of the regression line between expired minute ventilation and carbon dioxide output (VE-VCo(2)), decreased significantly from 38.2 +/- 8.2 to 33.3 +/- 4.9 (P <.01). There were no significant changes in peak oxygen uptake (from 17.5 +/- 3.2 mL/kg per minute to 17.9 +/- 3.6 mL/kg per minute) immediately after PTMC. At 7 months, improved mitral valve area, symptoms, cardiac output at peak exercise, mean pulmonary artery pressure at peak exercise, and VE-VCo(2) were unchanged compared with values immediate after PTMC. Significant improvement was observed in peak oxygen uptake (19.7 +/- 3.0 mL/kg per minute [P <.01 compared with pre-PTMC or immediate post-PTMC values]). The increase in exercise cardiac output or the decrease in pulmonary artery pressure was not correlated with the late improvement in peak oxygen uptake. The short- or long-term improvements in VE-VCo(2), however, were significantly correlated with the late improvement in peak oxygen uptake. CONCLUSIONS: Our results suggest that ventilatory improvement, not increased exercise cardiac output, contributed at least in part to the late improvement in exercise capacity after PTMC.     

Peak cardiac power measured noninvasively with a bioreactance technique is a predictor of adverse outcomes in patients with advanced heart failure

Peak oxygen consumption (VO(2) ) during cardiopulmonary exercise testing (CPET) is a powerful predictor of survival, providing an indirect assessment of cardiac output (CO). Noninvasive indices of CO derived from bioreactance methodology would add significantly to peak VO(2) as a means of risk-stratifying patients with heart failure. In this study, 127 patients (53 ± 14 years of age, 66% male) with heart failure and an average ejection fraction of 31% ± 15% underwent symptom-limited CPET using a bicycle ergometer while measuring CO noninvasively by a bioreactance technique. Peak cardiac power was derived from the product of the peak mean arterial blood pressure and CO divided by 451. Follow-up averaged 404 ± 179 days (median, 366 days) to assess endpoints including death (n=3), heart transplant (n=10), or left ventricular assisted device implantation (n=2). Peak VO(2) and peak power had similar areas under the curve (0.77 and 0.76), which increased to 0.83 when combined. Kaplan-Meier cumulative survival curves demonstrated different outcomes in the subgroup with a VO(2) <14 mL/kg/min when stratified by a cardiac power above or below 1.5 W (92.2% vs 82.1% at 1 year and 81.6% vs 58.3% at last follow-up, P=.02 by log-rank test). Among patients with heart failure, peak cardiac power measured with bioreactance methodology and peak VO(2) had similar associations with adverse outcomes and peak power added independent prognostic information to peak VO(2) in those with advanced disease (eg, VO(2) <14 mL/kg/min).