Maximal ventilation at rest and exercise in patients with chronic pulmonary disease

74 subjects of different ages: normal children, 19 boys (A) and 7 girls (C) aged between 11 and 15 years; asthmatic boys (n = 7, group B) and girls (n = 7, group D), with similar ages; normal male adult subjects (n = 10, group E) and pulmonary patients with restrictive (n = 8, group G) or obstructive (n = 16, group F) ventilatory impairment, were submitted to measurements of vital capacity (VC), forced expiratory volume in 1 s, (FEV1), maximal voluntary ventilation (MVV), maximal peak expiratory (PEF) and inspiratory (PIF) flows at rest, and two maximal exercise stress tests in which the ventilation at maximal exercise (MEV) were retained. Indirect MVV was obtained by multiplying the FEV1 by 35 and 37.5. The correlation coefficients between MVV and VC, FEV1, PEF and PIF were always as high as r greater than 0.76. (p less than 0.001), with a discrepancy between the calculated and measured MVV. The average ratio MVV/FEV1 always exceeds 39 and is much higher in groups B, C and G. The mean percent values of the ratio MEV/MVV were 0.63 in normal men and 0.74 in normal boys. In patients, this ratio is higher than in adult normals: F = 0.81 and G = 0.88, and is not due to methodological errors, but seems to correspond to several physiological features playing only a role during exercise (MEV). This work shows the difficulty in predicting correctly the MVV at rest and in assessing the ventilatory reserve during maximal exercise in chronic pulmonary patients.     

Effects of aging, gender, and physical training on peripheral vascular function

BACKGROUND. Blood pressure and total peripheral resistance increase with age. However, the effect of age on vasodilatory capacity has not been characterized. METHODS AND RESULTS. To delineate the effects of aging, gender, and physical training on peripheral vascular function, we measured blood pressure during submaximal and maximal treadmill exercise and measured blood pressure, calf blood flow, and calf conductance (blood flow/mean blood pressure) at rest and during maximal hyperemia in 58 healthy sedentary subjects (men aged 25 +/- 5 and 65 +/- 3 years and women aged 27 +/- 5 and 65 +/- 4 years) and in 52 endurance exercise-trained subjects (men aged 30 +/- 3 and 65 +/- 4 years and women aged 27 +/- 3 and 65 +/- 3 years). Systolic and mean blood pressures were higher at rest, during maximal calf hyperemia, and during submaximal exercise of the same intensity in the older than in the younger subjects of the same gender and exercise training status (p less than 0.01). The magnitude of the age-related effect on blood pressure during exercise was greater in women than in men (p less than 0.01). Diastolic blood pressure during submaximal exercise was also higher in the older than in the younger subjects (p less than 0.05) but not in women treated with estrogen replacement. In contrast, systolic and mean blood pressures during submaximal work were lower in physically conditioned subjects than in sedentary age- and gender-matched subjects (p less than 0.05) but not in older women. Increased age was associated with reduced maximal calf conductance in women (p less than 0.01) but not in men. However, calf vasodilatory capacity was higher in trained than in untrained subjects (p less than 0.01), regardless of age and gender. There was a significant inverse relation between maximal calf conductance and systolic, diastolic, and mean blood pressures during submaximal exercise (r = -0.31 to -0.53, p less than 0.01) and a direct relation between maximal calf conductance and maximal oxygen uptake (r = 0.66, p less than 0.0001). CONCLUSIONS. Thus, for healthy subjects between the ages of 25 and 65 years, there is an interactive effect between age and gender and an independent effect of physical training on peripheral vascular function.     

Ventilatory and P0.1 response to hypercapnia in quadriplegia.

Unlike individuals with comparable degrees of respiratory muscle weakness from other causes, quadriplegic patients have a blunted ventilatory and P0.1 response to hypercapnia. This suggests that the diminished response in quadriplegia is due, in part, to an alteration in respiratory drive. We measured the hypercapnic response in 9 subjects with chronic quadriplegia (Q) and 8 normal controls (N). Ventilatory muscle strength, maximum voluntary ventilation (MVV), and lung volumes were measured in all subjects. The ventilatory response (HCVR) in Q was significantly less than in N (0.73 +/- 0.37 vs 2.95 +/- 0.4 L.min-1.mmHg-1; P less than 0.001), even when normalized for indices of respiratory muscle performance (e.g., vital capacity, MVV). There was no significant change in the HCVR in Q after the administration of naloxone. We also serially studied 2 subjects with acute quadriplegia, and found that despite progressive improvement in respiratory muscle performance, there was no accompanying increase in the response to hypercapnia. These data suggest that muscle weakness alone cannot explain the blunted hypercapnic response in quadriplegia, and are consistent with the hypothesis that these subjects have a reduced ventilatory drive.     

Exercise-related changes in serum catecholamines and potassium: effect of sustained exercise above and below lactate threshold

Plasma potassium and catecholamines exhibit rapid shifts during exercise testing, particularly when exercise intensity exceeds lactate threshold. To assess changes that may occur during sustained exercise, we studied 10 healthy men to determine the effect of 20 minutes of exercise at 25 W above lactate threshold (ALT) and 20 minutes of exercise at 25 W below lactate threshold (BLT). Both conditions showed elevation of catecholamines at end exercise compared to baseline, but catecholamine levels ALT were significantly higher than the levels BLT (2270 +/- 190 versus 900 +/- 230 pg/ml norepinephrine, p less than 0.001; 509 +/- 69 versus 150 +/- 18 pg/ml epinephrine, p less than 0.001). This difference persisted at 2 minutes of recovery (1620 +/- 130 versus 590 +/- 60 pg/ml norepinephrine, p less than 0.001; 216 +/- 31 versus 98 +/- 16 pg/ml epinephrine, p less than 0.001). Both conditions resulted in a significant elevation in potassium at end exercise compared to baseline, but the potassium levels ALT were significantly higher than the levels BLT (1.1 +/- 0.1 mEq/L versus 0.5 +/- 0.1 mEq/L, p less than 0.001. The fall in potassium in the immediate post-exercise period was significantly greater following exercise ALT (-0.8 +/- 0.1 mEq/L versus -0.2 +/- 0.1 mEq/L, p less than 0.001). Thus sustained exercise slightly ALT resulted in a significant potassium flux and very elevated catecholamine levels. Avoiding these metabolic stresses by exercising BLT may decrease chances for exercise-related arrhythmia or other cardiac dysfunction in susceptible patients.     

Progressive mechanical ventilatory constraints with aging.

To investigate the progressive nature of mechanical ventilatory constraints with aging, we studied 20 young (age 39 +/- 3 yr), 14 senior (70 +/- 2 yr), and 11 elderly (88 +/- 2 yr) men and women during exercise. All subjects had normal pulmonary function and performed graded cycle ergometry to exhaustion. Minute ventilation (V E), lung volume, and expiratory airflow limitation (EAFL) were measured during each 1-min increment in work rate. Data were analyzed by two-way analysis of variance (ANOVA; age x gender) at rest, ventilatory threshold (VTh), and peak exercise. If an interaction was present, each gender was analyzed with a one-way ANOVA. Aging resulted in an increased V E for a given submaximal work rate, although V E during peak exercise was lowest in the elderly group (p < 0.01). End-expiratory lung volume (EELV, % of TLC) in men increased progressively with age and all groups were different at VTh (p < 0.01) and peak exercise (p < 0.01). In women, EELV (% of TLC) also increased with aging, the senior and elderly subjects had a greater EELV at VTh (p < 0.01) and peak exercise (p < 0.01) than the young group. Additionally, the normal decrease in EELV during the early stages of exercise was not observed in elderly subjects. End-inspiratory lung volume (EILV) also progressively increased with aging; senior and elderly subjects had a higher EILV at rest (p < 0.05), VTh (p < 0.01), and peak exercise (p < 0.01) than young subjects. EAFL (% of VT) increased with aging; elderly subjects experienced greater EAFL at rest (p < 0.05), VTh (p < 0.01), and peak exercise (p < 0.01) than both young and senior subjects. We conclude that mechanical ventilatory constraints are progressive with aging, elderly subjects demonstrating marked mechanical ventilatory constraints during exercise. The impact of these constraints on exercise tolerance cannot be determined from this investigation and remains unclear.     

Exercise test variables of a population with maximal bicycle exercise test

The aim of the study was to establish reference values for appraising the circulatory response of men and women to age-predicted maximal heart rate (220-age) exercise testing. The data of exercise testing have been analysed in 942 subjects (608 men and 334 women). Under exercise testing the mean maximal heart rate was 177/min in both sexes. Increase in heart rate per minute of exercise was 5.59 +/- 1.93 in men, 9.00 +/- 4.94 in women. At the peak of exercise test, systolic blood pressure was considerably higher in men than in women (188.96 +/- 27.98 vs. 171.66 +/- 28.46 mmHg; p much less than 0.0001). The average working capacity was 1.7 W/kg among men and 1.31 W/kg among women. The duration of exercise testing time was significantly longer in men than in women (918.6 + 269.4 vs. 578.4 +/- 193.2 s; p less than 0.0001). Reference values for testing time are given according to sex and age with due consideration of body weight and height.     

Pulmonary function responses of older men and women to ozone exposure

The pulmonary function of 8 men and 8 women (51 to 76 years of age), all nonsmokers, was measured before and after 2-h exposures to filtered air (FA) and 0.45 ppm ozone (O3). The subjects alternated 20-min periods of rest and 20-min periods of cycle ergometer exercise at a workload predetermined to elicit a ventilatory minute ventilation (VE) of approximately 25 L/min (BTPS). Functional residual capacity (FRC) was determined pre- and post-exposure. Forced vital capacity (FVC) was determined before and after exposure, and 5 min after each exercise period. Ventilatory minute volume (VE) was measured during the last 2 min of each exercise period, and heart rate was monitored throughout each exposure. The pulmonary function data were evaluated as the percentage change from pre- to post-exposure to partially remove the effect of differences between men and women in absolute lung volume. There were no statistically significant (p greater than 0.05) differences between the responses of men and women to FA or O3 exposure. There were no significant (p greater than 0.05) changes in any variable consequent to FA exposure. Exposure to O3 induced significant (p less than 0.01) decrements in FVC, FEV1.0, and FEV3.0 at post-exposure compared to pre-exposure. Ozone exposure induced no significant (p greater than 0.05) effect on FEF25-75% or FEF75%. Men had a significantly (p less than 0.05) higher mean exercise VE than women (27.9 +/- 0.29 L vs. 25.4 +/- 0.8 L; mean +/- SD). Since the men and women had similar decrements in pulmonary function, even though the women inhaled less O3, the data suggest that women may be somewhat more responsive to O3 than men. We also compared the responses of our older subjects with those of young men and women that we studied with the same protocol, and with published results of other investigators who have studied young men and women. This comparison suggests that older individuals may be less responsive to O3 than young individuals.     

Closed-loop control of respiratory drive using pressure-support ventilation: target drive ventilation

By using diaphragm electrical activity (multiple-array esophageal electrode) as an index of respiratory drive, and allowing such activity above or below a preset target range to indicate an increased or reduced demand for ventilatory assistance (target drive ventilation), we evaluated whether the level of pressure-support ventilation can be automatically adjusted in response to exercise-induced changes in ventilatory demand. Eleven healthy individuals breathed through a circuit (18 cm H2O/L/second inspiratory resistance at 1 L/second flow; 0.5-1.0 L/second expiratory flow limitation) connected to a modified ventilator. Subjects breathed for 6-minute periods at rest and during 20 and 40 W of bicycle exercise, with and without target drive ventilation (the target was set to 60% of the increase in diaphragm electrical activity observed between rest and 20 W of unassisted exercise). With target drive ventilation during exercise, the level of pressure-support ventilation was automatically increased, reaching 13.3 +/- 4.0 and 20.3 +/- 2.8 cm H2O during 20- and 40-W exercise, respectively, whereas diaphragm electrical activity was reduced to a level within the target range. Both diaphragmatic pressure-time product and end-tidal CO2 were significantly reduced with target drive ventilation at the end of the 20- (p < 0.01) and 40-W (p < 0.001) exercise periods. Minute ventilation was not altered. These results demonstrate that target drive ventilation can automatically adjust pressure-support ventilation, maintaining a constant neural drive and compensating for changes in respiratory demand.     

Respiratory response and ventilatory muscle recruitment during arm elevation in normal subjects.

Despite the fact that the arms are used extensively in daily life and that some of the muscles of the shoulder girdle share both a respiratory and a positional function for the arms, surprisingly little is known about the respiratory response to unsupported upper extremity activity. To determine the respiratory consequences of simple arm elevation during tidal breathing, we measured minute ventilation (VE), tidal volume (VT), respiratory rate (f), heart rate (HR), oxygen uptake (VO2), and carbon dioxide production (VCO2) in 22 normal subjects seated with arms elevated in front of them to shoulder level (AE) for 2 min and down at the sides (AD) for the same time period. The sequence was randomized. Compared with AD, during AE there were significant increases in VO2 (336 +/- 18 vs 289 +/- 14 ml/min, p less than 0.001), VCO2 (315 +/- 23 vs 245 +/- 16 ml/min, p less than 0.001), HR (84 +/- 6 vs 73 +/- 4 beats/min, p less than 0.05), VE (11.5 +/- 0.9 vs 9.3 +/- 0.6 L/min, p less than 0.001), and VT (868 +/- 66 vs 721 +/- 48 ml, p less than 0.001). In 11 subjects, breath-by-breath metabolic and ventilatory parameters were studied with AD for 2 min, AE for 2 min, and with AD for 3 min while also recording gastric (Pg), pleural (Ppl), and transdiaphragmatic pressures (Pdi). With AE, there was a significant increase in Pg at end inspiration (PgI, 15.4 +/- 3.2 vs 11.9 +/- 2.7 cm H2O, p less than 0.01) and in Pdi (26.5 +/- 3.4 vs 21.4 +/- 2.4 cm H2O, p less than 0.01) with no change in Pg at end expiration (PgE) or in Ppl. The increases in VO2, VCO2, VE, and VT during arm elevation persisted for 2 min after arm lowering, whereas Pgi and Pdi abruptly dropped as the arms were lowered. We conclude that simple arm elevation during tidal breathing results in significant increases in metabolic and ventilatory requirements. These increased demands are associated with higher PgI and Pdi suggesting an increased diaphragmatic contribution to the generation of ventilatory pressures. The sudden drop in Pg with arm lowering indicate a change in ventilatory muscle and or torso recruitment independent of the metabolic drive and ventilatory needs. These findings may help explain the limitation that has been reported in some normal subjects and in many patients with lung disease during unsupported upper extremity activity.     

Role of respiratory function in exercise limitation in chronic heart failure

OBJECTIVE: To test the hypothesis that respiratory function contributes to limit maximal exercise performance in patients with chronic heart failure by using the technique of dead space loading during exercise. DESIGN: Blinded subjects underwent two maximal incremental exercise tests in random order on an upright bicycle ergometer: one with and one without added dead space. SETTING:: Tertiary-care university teaching hospital. SUBJECTS: Seven patients with stable chronic heart failure (mean +/- SEM left ventricular ejection fraction, 27 +/- 3%). RESULTS: Subjects were able to significantly increase their peak minute ventilation during exercise with added dead space when compared with control exercise (57.4 +/- 5.9 vs 50.0 +/- 5.6 L/min; p < 0.05). Peak oxygen uptake, workload, heart rate, and exercise duration were not significantly different between the added dead space and control tests. Breathing pattern was significantly deeper and slower at matched levels of ventilation during exercise with added dead space. CONCLUSION: Because patients with chronic heart failure had significant ventilatory reserve at the end of exercise and were able to further increase their maximal minute ventilation, we conclude that respiratory function does not contribute to limitation of exercise in patients with chronic heart failure.     

Effects of cardiac transplantation on ventilatory response to exercise.

Patients with heart failure frequently exhibit an excessive ventilatory response to exercise, which is acutely unaltered by therapeutic interventions. To investigate whether these ventilatory responses resolve after cardiac transplantation, 15 ambulatory patients with severe heart failure underwent exercise testing with measurement of respiratory gases before and 1.4 +/- 0.6 years [corrected] after transplantation. Ventilatory response was also measured in 7 age-matched, sedentary control subjects. Left ventricular ejection fraction at rest and hemodynamic measurements were obtained before and after transplantation in all patients. After transplantation, ejection fraction at rest increased from 16 +/- 6 to 56 +/- 10%, pulmonary capillary wedge pressure declined from 26 +/- 8 to 12 +/- 5 mm Hg, and cardiac index increased from 1.7 +/- 0.5 to 2.8 +/- 0.5 liters/min/m2 (all p less than 0.001). Peak oxygen consumption increased from 11.8 +/- 1.9 to 19.2 +/- 3.1 ml/kg/min (p less than 0.001), but remained significantly lower than that in control subjects (33.4 +/- 6.9 ml/kg/min; p less than 0.01). Minute ventilation (VE) was significantly reduced after transplantation, but excessive compared with normal values. Ventilation at a carbon dioxide production of 1 liter/min decreased significantly after cardiac transplantation (52.1 +/- 7.9 to 38.8 +/- 3.8 liters; p less than 0.01), but remained elevated when contrasted to that in control subjects (31.4 +/- 3.4 liters; p less than 0.05). Ventilatory response to exercise is significantly improved after cardiac transplantation; however, VE remains excessive. This may reflect an attenuated cardiac output response to exercise, abnormal intrapulmonary pressures or persistent deconditioning.     

Effects of aerobic training on exercise tolerance and echocardiographic dimensions in untrained postmenopausal women

The cardiovascular effects of physical training were evaluated in a controlled trial involving 32 healthy, untrained, postmenopausal women. The subjects were randomly assigned to an aerobic exercise training program or a control group. The exercise group participated in at least three 40-minute supervised sessions per week for 8 months. Twenty-five subjects completed the study: eight in the control group and 17 in the training group. The training group had a significant increase over the training period in maximal oxygen consumption (27.3 +/- 4.6 ml/kg/min vs 30.8 +/- 5.4 ml/kg/min, p less than 0.05) and maximal treadmill exercise duration (9.8 +/- 2.6 minutes vs 11.3 +/- 2.2 minutes; p less than 0.05). The control group had no significant change in maximal treadmill exercise duration (9.0 +/- 1.2 minutes vs 9.2 +/- 1.4 minutes) but had a slight increase in maximal oxygen consumption (23.7 +/- 3.4 ml/kg/min vs 24.4 +/- 4.1 ml/kg/min, p less than 0.05). The training group had significant increases in M-mode echocardiographic left ventricular end-diastolic dimension (4.6 +/- 0.6 cm vs 4.8 +/- 0.4 cm, p less than 0.05) and calculated left ventricular ejection fraction (0.66 +/- 0.14 vs 0.74 +/- 0.12, p less than 0.05). M-mode echocardiograms demonstrated no significant change in left ventricular dimensions or wall thickness in the control group. In this group of untrained postmenopausal women, a training effect was associated with enhanced resting left ventricular ejection fraction and increased resting left ventricular end-diastolic dimension.     

Effects of hydralazine on mouth occlusion pressure and ventilatory response to hypercapnia in patients with chronic obstructive pulmonary disease and pulmonary hypertension

Hydralazine has been shown to increase minute ventilation (VE) in patients with chronic obstructive pulmonary disease and pulmonary hypertension. The mechanism by which hydralazine produces this effect has not been defined. We investigated the effects of orally administered hydralazine on hypercapnic ventilatory response (delta VE/delta PaCO2) and central respiratory drive (delta P0.1/delta PaCO2) as well as the effects on hemodynamics, ventilation, and gas exchange in 10 male patients (mean age, 59 +/- 2 yr). The patients had a severe degree of chronic air-flow obstruction (FEV1, 1.07 +/- 0.08 L) and mild pulmonary hypertension (mean pulmonary artery pressure, 25 +/- 4 mm Hg). After hydralazine, the slope of delta VE/delta PaCO2 increased by 177% (p less than 0.005), and the slope of delta P0.1/delta PaCO2 increased by 145% (p less than 0.05). Resting ventilation increased from 14.8 +/- 1.0 to 17.1 +/- 1.4 L/min (p less than 0.02), primarily as a result of increased respiratory frequency. After hydralazine, PaO2 increased from 66 +/- 4 to 70 +/- 3 mm Hg (p less than 0.05) at rest and from 54 +/- 3 to 59 +/- 3 mm Hg (p less than 0.02) during exercise. PaCO2 decreased from 46 +/- 3 to 42 +/- 3 mm Hg (p less than 0.001) at rest and from 50 +/- 3 to 45 +/- 3 mm Hg (p less than 0.001) during exercise. No change was seen in the dead space to tidal volume ratio or the degree of venous admixture. Mean pulmonary artery pressure and total pulmonary resistance both at rest and during exercise were unchanged after hydralazine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Breathing route during sleep

Nasal obstruction has been associated with apneic episodes during sleep. However, the normal distribution of nasal and oral air flow while asleep has not been investigated. To determine the normal route of ventilation during sleep, we studied 7 healthy men and 7 healthy women using a sealed face mask that mechanically separated nasal and oral air flow. Standard sleep staging techniques were employed. The subjects slept 297 +/- 29 (SEM) min, with a mean of 197 +/- 15 min of ventilation recorded. Ventilation was decreased during sleep as has been previously demonstrated. However, during sleep, we found that men breathed a greater percentage of total ventilation through the mouth (29.0 +/- 8.2%) than did women (5.0 +/- 1.0%, p less than 0.02). The same trend applied during wakefulness but did not reach significance (p = 0.06). Although none was symptomatic, 4 subjects, all men, had more than 3 apneas per hour. These 4 men had a greater percentage of mouth ventilation (37.3 +/- 19.0%) than did the other 10 subjects with few or no apneas (8.1 +/- 2.7%, p less than 0.02). It was also noted that increasing age in men was associated with an increasing percentage of mouth ventilation (r = 0.83 p less than 0.03) but this relationship was not observed in women. We conclude that mouth breathing may be associated with apneas during sleep and that breathing through the mouth occurs commonly in men, particularly in those who are older. This suggests that nasal breathing may be important in the maintenance of ventilatory rhythmicity during sleep.     

Plasma hypoxanthine and exercise

During exercise, ATP is converted to ADP and AMP to supply energy for muscular contraction. It is then regenerated via various pathways of intermediary metabolism. However, with high levels of exercise, net ATP degradation in muscle occurs. In exercise and other clinical situations, adenine nucleotide degradation leads to an accumulation of degradative purine products including hypoxanthine. In an effort to monitor events of energy metabolism, we examined plasma hypoxanthine levels at various exercise intensities. Peak plasma hypoxanthine levels after maximal exercise (18.9 +/- 2.6 microM, mean +/- SEM) were significantly greater than resting levels (1.1 +/- 0.1 microM; p less than 0.001). Hypoxanthine levels after steady state exercise at 52, 76, and 97% of ventilatory threshold did not exceed resting levels. However, plasma hypoxanthine rose significantly after exercise at 124% of ventilatory threshold (6.3 +/- 1.0 microM; p less than 0.01) and at 152% of ventilatory threshold (17.0 +/- 3.6 microM; p less than 0.001). Exercise at subventilatory threshold intensity (74% of ventilatory threshold) for a prolonged time period, such that total work equaled that performed at 152% of ventilatory threshold, did not elevate hypoxanthine levels (0.46 +/- 0.1 microM) above resting values. We conclude that elevation of plasma hypoxanthine levels occur during exercise at intensities that exceed the ventilatory threshold and indicate that net adenine nucleotide degradation has occurred.     

Effects of beta-blocker therapy on ventilatory responses to exercise in patients with heart failure

BACKGROUND: Ventilatory efficiency is the increase in ventilation relative to carbon dioxide production during exercise. Congestive heart failure (CHF) is associated with decreased ventilatory efficiency. beta-blockers improve hemodynamics, prolong survival, and improve functional class in patients with CHF, though peak exercise performance may not improve. We hypothesized beta-blockers increase ventilatory efficiency in patients with CHF. METHODS AND RESULTS: The study group comprised 614 subjects with left ventricular ejection fraction < or = 40% referred for cardiopulmonary exercise testing. Clinical and exercise data were reviewed and recorded. For comparison, subjects were divided into those treated with beta-blockers (n = 195) and those not treated (n = 419). Subjects on beta-blockers had lower minute ventilation (12 +/- 4 versus 14 +/- 4 L/min, P < .001) at rest, which remained lower during submaximal and maximal exercise, by 4 and 6 L/min, respectively (P = .001). Ventilatory efficiency was increased in subjects treated with beta-blockers at submaximal (32 +/- 6 versus 34 +/- 7, P = .002) and maximal (34 +/- 7 versus 37 +/- 10, P = .005) exercise. Differences between treatment subgroups remained significant by covariate analysis; beta-blockers were also independently associated with decreased minute ventilation by multiple regression. CONCLUSION: Beta-blockers may be associated with increased ventilatory efficiency in CHF patients, which may contribute to improved functional class and quality of life.     

Diastolic function in hypertrophic cardiomyopathy: relation to exercise capacity.

Doppler echocardiography was used to assess diastolic function in 40 patients with hypertrophic cardiomyopathy and to relate it to the patients' symptoms, anaerobic threshold and maximal oxygen consumption during cardiopulmonary exercise testing. The patients had a smaller early (E wave) (p less than 0.01), higher late (A wave) (p less than 0.05) mitral diastolic flow velocity, larger A/E ratio (p less than 0.01), longer isovolumetric relaxation time and E wave duration (p less than 0.001) and slower deceleration rate of the E wave (p less than 0.001) than 40 age- and gender-matched normal subjects. In the patients with hypertrophic cardiomyopathy, maximal oxygen consumption and anaerobic threshold were, respectively, 26.3 +/- 9.2 and 21.1 +/- 6.1 ml/kg per min compared with 47 (range 39 to 68) (p less than 0.01) and 41 (range 27 to 58) ml/kg per min (p less than 0.01) in normal subjects. There was no relation between Doppler indexes and symptoms but symptomatic patients had lower maximal oxygen consumption and anaerobic threshold compared with asymptomatic patients (21.4 +/- 7 vs. 30.7 +/- 10, p less than 0.001 and 18.6 +/- 4.7 vs. 23.1 +/- 5.7, respectively, p less than 0.001). In conclusion, Doppler echocardiography can identify abnormalities of left ventricular filling in patients with hypertrophic cardiomyopathy. However, these indexes measured at rest do not correspond to the patient's professed symptomatic status or exercise capacity measured objectively. Conversely, cardiopulmonary exercise testing reveals a depressed maximal oxygen consumption and anaerobic threshold even in the least symptomatic patients.     

Ventilatory mechanisms of exercise intolerance in chronic heart failure.

Mechanisms that have been suggested to underlie the abnormal ventilatory response to exercise in patients with chronic congestive heart failure (CHF) include high pulmonary pressures, ventilation-perfusion mismatching, early metabolic acidosis, and abnormal respiratory control. To evaluate the role that ventilation and gas exchange play in limiting exercise capacity in patients with CHF, data from 33 patients with CHF and 34 normal subjects of similar age who underwent maximal exercise testing were analyzed. Maximal oxygen uptake was higher among normal subjects (31.7 +/- 6 ml/kg/min) than among patients with CHF (17.7 +/- 4 ml/kg/min; p less than 0.001). The ventilatory equivalent for oxygen, expressed as a percentage of maximal oxygen uptake, was 25% to 35% higher among patients with CHF compared with normal subjects throughout exercise (p less than 0.01). A steeper component effect of ventilation on maximal oxygen uptake was observed among normal subjects compared with patients with CHF, which suggests that a significant portion of ventilation in CHF is wasted. Maximal oxygen uptake was inversely related to the ratio of maximal estimated ventilatory dead space to maximal tidal volume (VD/VT) in both groups (r = -0.73, p less than 0.001). Any given oxygen uptake at high levels of exercise among patients with CHF was accompanied by a higher VD/VT, lower tidal volume, and higher respiratory rate compared with normal subjects (p less than 0.01). Relative hyperventilation in patients with CHF started at the beginning of exercise and was observed both below and above the ventilatory threshold, which suggests that the excess ventilation was not directly related to earlier than normal metabolic acidosis. Thus abnormal ventilatory mechanisms contribute to exercise intolerance in CHF, and excess ventilation is associated with both a higher physiologic dead space and an abnormal breathing pattern. The high dead space is most likely due to ventilation-perfusion mismatching in the lungs, which is related to poor cardiac output, and the abnormal breathing pattern appears to be an effort to reduce the elevated work of breathing that is caused by high pulmonary pressures and poor lung compliance.     

Augmented ventilatory response to exercise in pulmonary hypertension

The ventilatory response to submaximal exercise, defined as the slope of minute ventilation over carbon dioxide production (VE/VCO2), was determined in 12 normal subjects, ten patients with pulmonary hypertension before and after heart-lung transplantation, and eight patients following heart transplantation. Patients with pulmonary hypertension show an augmented ventilatory response compared to normal subjects (pulmonary hypertension [mean, 57.7 +/- 6.8 (SE) ml/ml VCO2; normal subjects, 22.3 +/- 1.4 ml/ml VCO2; p less than 0.001]). Following heart-lung transplantation, VE/VCO2 slope fell to 24.7 +/- 1.6 ml/ml VCO2, a value which is not significantly different than the value in normal subjects. Patients after heart transplantation show a mean slope value of 25.3 +/- 1.3 ml/ml VCO2, which is not significantly different than the normal value or the value found after heart-lung transplantation. The augmented ventilatory response to exercise did not correlate with the usual chemical modulators of ventilation (arterial pH, arterial carbon dioxide tension, or arterial oxygen tension). These results suggest the following: the existence of a neural system in patients with pulmonary hypertension which results in an augmentation of ventilatory drive in response to exercise; the augmented ventilatory response reflects excessive neural activity of pulmonary afferents during exercise; narrow regulation of the ventilatory response to exercise in normal subjects which is preserved in the denervated lung, indicating that pulmonary afferents are not critical to ventilatory control during exercise in the normal subject; and the possible use of measurements of the ventilatory response to exercise as a noninvasive screening test for pulmonary hypertension.     

The role of exercise ventilation in clinical evaluation and risk stratification in patients with chronic heart failure

BACKGROUND: Patients with chronic heart failure (CHF) are characterised by an increased ventilatory response to exercise. The role of exercise ventilation in the risk stratification and evaluation of patients with CHF has not yet been established. AIM: To examine the relationship between exercise ventilation indices and clinical parameters of CHF and to assess the prognostic value of the ventilatory response to exercise. METHODS: The study group consisted of 87 patients with CHF (72 males, mean age 58 years) with a mean left ventricular ejection fraction of 32%. Ten patients were in NYHA class I, 38 - in NYHA class II, 34 - in NYHA class III, and 5 - in NYHA class IV. The control group consisted of 20 patients without CHF (13 males, mean age 58 years, mean LVEF - 61%). All studied subjects underwent maximal exercise test with gas-exchange measurement. The following parameters were analysed: peak exercise oxygen consumption [peak VO(2) (ml/kg/min)], VE-VCO(2) index [a coefficient of linear regression analysis depicting an association between ventilation (VE) and carbon dioxide production (VCO(2)) during exercise] and VE/VCO(2) ratio at peak exercise to VE/VCO(2) ratio while at rest (VE/VCO(2 peak/rest)). RESULTS: Ventilatory response indices were significantly higher in patients with CHF compared with controls: VE-VCO(2) - 37.9+/-11.1 vs 27.1+/-4.1; VE-VCO(2 peak/rest) - 0.89+/-0.14 vs 0.75+/-0.10 (p<0.001). In CHF patients a significant positive correlation between ventilatory response parameters and NYHA class (VE-VCO(2) - r=0.52; VE/VCO(2 peak/rest) - r=0.47) and a negative correlation with peak VO(2) (VE-VCO(2) - r=-0.52; VE/VCO(2 peak/rest) - r=-0.49) were noted (p<0.0001 for all correlations). No correlation was found between ventilatory parameters and echocardiographic variables or CHF aetiology. During the follow-up period lasting at least 12 months, 17 (22%) patients died. In the univariate Cox model, NYHA class III-IV, decreased peak VO(2) and increased VE-VCO(2) and VE/VCO(2 peak/rest) values were significantly associated with the risk of death. The multivariate analysis revealed that VE/VCO(2 peak/rest) > or =1.0 was the adverse prognostic factor, independent of peak VO(2) (p=0.02) and NYHA class (p=0.01). The Kaplan-Meier analysis showed that prognosis during the 18-month follow-up period in patients with enhanced exercise ventilation was worse than in the remaining patients (59% survival in patients with VE/VCO(2 peak/rest) > or =1.0 59% vs 91% survival in patients with VE/VCO(2 peak/rest) <1.0, p=0.001). CONCLUSIONS: In patients with stable CHF simple exercise ventilation parameters may provide important clinical and prognostic information.