Cardiorespiratory function

ACCURATE EVALUATION OF THE DEGREE OF IMPAIRMENT OF PULMONARY FUNCTION IN PERSONS WITH FIBROSIS AND EMPHYSEMA REQUIRES: (1) ventilatory measurements from rapid spirogram tracings (vital capacity, maximal breathing capacity and the time required to blow the air from the lungs); (2) determination of the degree of bronchospasm present; (3) determination of the degree of pulmonary emphysema (residual air expressed quantitatively as percent of total lung volume); (4) determination of the arterial blood oxygen saturation at rest and immediately after step-up exercise; (5) measurement of the oxygen extraction from inspired air (per cent of oxygen removed) during rest and exercise; (6) determination of the oxygen up-take during exercise; and (7) observation of the duration of dyspnea after step-up exercise. No single physiologic test is adequate in evaluating impairment of pulmonary function, and roentgenograms of the chest are unreliable as a sole basis for appraisal of disability. In industrial medicine, pulmonary function studies make possible (a) more accurate diagnosis and evaluation of pulmonary disability; and (b) earlier detection and thus prevention of prolonged exposure by susceptible individuals to environmental hazards.     

CIGARETTE SMOKE—Its Effect on Pulmonary Function Measurements

Inhaling cigarette smoke with each breath, with the subject at rest, by use of a smoking device that brought more smoke into the lungs than would be the case in ordinary smoking, produced consistent significant decreases in arterial blood oxygen saturation and in arterial pO₂ in most subjects who had severe or very severe pulmonary emphysema. In normal subjects and in those with a moderate degree of emphysema no significant changes in blood gas exchange resulted.No consistent significant changes in blood gas exchange were noted after the smoking of two cigarettes, either with the subject at rest or after a one-minute step-up exercise.A decrease in oxygen uptake occurred when treadmill exercise was done after smoking two cigarettes, and the ventilation volume was also decreased, probably accounting for part of the oxygen decrease.Pulmonary compliance measurements after smoking one cigarette were consistently and significantly decreased in most subjects—normal as well as those with pulmonary emphysema. The elastic work of breathing was increased in the majority of cases.In two cases in which studies were done after the subjects stopped smoking, one for three months and one for two years, significant reductions in residual air were noted.The results indicated that persons with severe or very severe emphysema would be better off to stop smoking.     

Cigarette smoke; its effect on pulmonary function measurements

Inhaling cigarette smoke with each breath, with the subject at rest, by use of a smoking device that brought more smoke into the lungs than would be the case in ordinary smoking, produced consistent significant decreases in arterial blood oxygen saturation and in arterial pO(2) in most subjects who had severe or very severe pulmonary emphysema. In normal subjects and in those with a moderate degree of emphysema no significant changes in blood gas exchange resulted. No consistent significant changes in blood gas exchange were noted after the smoking of two cigarettes, either with the subject at rest or after a one-minute step-up exercise.A decrease in oxygen uptake occurred when treadmill exercise was done after smoking two cigarettes, and the ventilation volume was also decreased, probably accounting for part of the oxygen decrease. Pulmonary compliance measurements after smoking one cigarette were consistently and significantly decreased in most subjects-normal as well as those with pulmonary emphysema. The elastic work of breathing was increased in the majority of cases. In two cases in which studies were done after the subjects stopped smoking, one for three months and one for two years, significant reductions in residual air were noted. The results indicated that persons with severe or very severe emphysema would be better off to stop smoking.     

Exercise hyperventilation, dyspnea sensation, and ergoreflex activation in lone atrial fibrillation

Lone atrial fibrillation may be associated with daily life disability and exercise limitation. The extracardiac pathophysiology of these effects is poorly explored. In 35 subjects with lone atrial fibrillation (mean age 67 +/- 7 yr), we investigated pulmonary function, symptom-limited cardiopulmonary exercise performance, muscle ergoreflex (handgrip exercise) contribution to ventilation, and brachial artery flow-mediated dilation (as a measure of endothelial function) before and after (average interval 20 +/- 5 days) restoring sinus rhythm with external cardioversion. Respiratory volumes and lung diffusing capacity at rest were within normal limits during both atrial fibrillation and after restoring sinus rhythm. Cardioversion was associated with the following changes: a decrease of the slope of exercise ventilation vs. CO2 production (from 35 +/- 5 to 29 +/- 3; P <0.01) and of dyspnea sensation (Borg score from 4 to 2) and an increase of peak oxygen uptake (Vo2; from 16 +/- 4 to 20 +/- 5 ml.min(-1).kg(-1); P <0.01), Vo2 at anaerobic threshold (from 11 +/- 2 to 13 +/- 2 ml.min(-1).kg(-1); P <0.05), and O2 pulse (from 8 +/- 3 to 11 +/- 3 ml/beat; P <0.01). After cardioversion, the observed improvement in ventilatory efficiency was accompanied by a significant peak end-tidal CO2 increase (from 33 +/- 2 to 37 +/- 2 mmHg; P <0.01) and no changes in dead space-to-tidal volume ratio (from 0.23 +/- 0.03 to 0.23 +/- 0.02; P=not significant). In addition, the ergoreflex contribution to ventilation was remarkably attenuated, and the brachial artery flow-mediated dilatation was significantly augmented (from 0.32 +/- 0.07 to 0.42 +/- 0.08 mm; P <0.01). Ten patients had atrial fibrillation relapse and, compared with values after restoration of regular sinus rhythm, invariably showed worsening of endothelial function, exercise ventilatory efficiency, and muscle ergoreflex contribution to ventilation. In subjects with lone atrial fibrillation, an impairment in ventilatory efficiency appears to be involved in the pathophysiology of exercise limitation, and to be primarily related with a demodulated peripheral control of ventilation.     

Effect of a patent foramen ovale on pulmonary gas exchange efficiency at rest and during exercise

The prevalence of a patent foramen ovale (PFO) is ~30%, and this source of right-to-left shunt could result in greater pulmonary gas exchange impairment at rest and during exercise. The aim of this work was to determine if individuals with an asymptomatic PFO (PFO+) have greater pulmonary gas exchange inefficiency at rest and during exercise than subjects without a PFO (PFO-). Separated by 1 h of rest, 8 PFO+ and 8 PFO- subjects performed two incremental cycle ergometer exercise tests to voluntary exhaustion while breathing either room air or hypoxic gas [fraction of inspired O(2) (FI(O(2))) = 0.12]. Using echocardiography, we detected small, intermittent boluses of saline contrast bubbles entering directly into the left atrium within 3 heart beats at rest and during both exercise conditions in PFO+. These findings suggest a qualitatively small intracardiac shunt at rest and during exercise in PFO+. The alveolar-to-arterial oxygen difference (AaDo(2)) was significantly (P < 0.05) different between PFO+ and PFO- in normoxia (5.9 ± 5.1 vs. 0.5 ± 3.5 mmHg) and hypoxia (10.1 ± 5.9 vs. 4.1 ± 3.1 mmHg) at rest, but not during exercise. However, arterial oxygen saturation was significantly different between PFO+ and PFO- at peak exercise in normoxia (94.3 ± 0.9 vs. 95.8 ± 1.0%) as a result of a significant difference in esophageal temperature (38.4 ± 0.3 vs. 38.0 ± 0.3°C). An asymptomatic PFO contributes to pulmonary gas exchange inefficiency at rest but not during exercise in healthy humans and therefore does not explain intersubject variability in the AaDO(2) at maximal exercise.     

Effects of inhaled nitric oxide at rest and during exercise in idiopathic pulmonary fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) usually develop hypoxemia and pulmonary hypertension when exercising. To what extent endothelium-derived vasodilating agents modify these changes is unknown. The study was aimed to investigate in patients with IPF whether exercise induces changes in plasma levels of endothelium-derived signaling mediators, and to assess the acute effects of inhaled nitric oxide (NO) on pulmonary hemodynamics and gas exchange, at rest and during exercise. We evaluated seven patients with IPF (6 men/1 woman; 57 ± 11 yr; forced vital capacity, 60 ± 13% predicted; carbon monoxide diffusing capacity, 52 ± 10% predicted). Levels of endothelin, 6-keto-prostaglandin-F(1α), thromboxane B(2), and nitrates were measured at rest and during submaximal exercise. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion relationships, were assessed breathing ambient air and 40 ppm NO, both at rest and during submaximal exercise. The concentration of thromboxane B(2) increased during exercise (P = 0.046), whereas levels of other mediators did not change. The change in 6-keto-prostaglandin-F(1α) correlated with that of mean pulmonary arterial pressure (r = 0.94; P < 0.005). Inhaled NO reduced mean pulmonary arterial pressure at rest (-4.6 ± 2.1 mmHg) and during exercise (-11.7 ± 7.1 mmHg) (P = 0.001 and P = 0.004, respectively), without altering arterial oxygenation or ventilation-perfusion distributions in any of the study conditions. Alveolar-to-capillary oxygen diffusion limitation, which accounted for the decrease of arterial Po(2) during exercise, was not modified by NO administration. We conclude that, in IPF, some endothelium-derived signaling molecules may modulate the development of pulmonary hypertension during exercise, and that the administration of inhaled NO reduces pulmonary vascular resistance without disturbing gas exchange.     

Pulmonary Hypertension in Patients with Idiopathic Pulmonary Fibrosis – The Predictive Value of Exercise Capacity and Gas Exchange Efficiency

Exercise capacity and survival of patients with IPF is potentially impaired by pulmonary hypertension. This study aims to investigate diagnostic and prognostic properties of gas exchange during exercise and lung function in IPF patients with or without pulmonary hypertension.In a multicentre setting, patients with IPF underwent right heart catheterization, cardiopulmonary exercise and lung function testing during their initial evaluation. Mortality follow up was evaluated.Seventy-three of 135 patients [82 males; median age of 64 (56; 72 years)] with IPF had pulmonary hypertension as assessed by right heart catheterization [median mean pulmonary arterial pressure 34 (27; 43) mmHg]. The presence of pulmonary hypertension was best predicted by gas exchange efficiency for carbon dioxide (cut off ≥152% predicted; area under the curve 0.94) and peak oxygen uptake (≤56% predicted; 0.83), followed by diffusing capacity. Resting lung volumes did not predict pulmonary hypertension. Survival was best predicted by the presence of pulmonary hypertension, followed by peak oxygen uptake [HR 0.96 (0.93; 0.98)].Pulmonary hypertension in IPF patients is best predicted by gas exchange efficiency during exercise and peak oxygen uptake. In addition to invasively measured pulmonary arterial pressure, oxygen uptake at peak exercise predicts survival in this patient population.     

代谢、血液碱化和纯氧影响呼吸调控的人体实验研究I:运动试验*

目的: 在整体整合生理学医学理论的指导下,通过分析正常人运动期间心肺代谢等多系统功能整体整合的连续动态变化,探讨正常环境运动状态下呼吸反应模式的调控机理。方法: 选正常志愿者5名,在美国洛杉矶加州大学Harbor-UCLA医学中心分别进行动脉置管,在常温室内空气状态下完成症状限制性最大极限心肺运动试验(CPET)。在运动过程中,连续测定肺通气指标及每分钟动脉取样的血气分析指标的变化,对CPET期间呼吸气体交换和血气指标的动态变化进行统计分析。结果: 在CPET期间,随着运动功率逐步递增,分钟摄氧量(每呼吸摄氧量×呼吸频率=每搏摄氧量×心率）和分钟通气量(潮气量×呼吸频率)均呈现近于线性渐进性递增(与静息状态比较,P<0.05~0.001);在运动超过无氧阈和呼吸代偿点后,分钟通气量的上升反应更加显著。结论: 人体在运动过程中,为了克服自行车功率计的阻力而发生代谢率改变,呼吸随代谢改变而变化,高强度运动时酸性代谢产物堆积更加加剧呼吸反应。     

Adenovirus vector expressing keratinocyte growth factor using CAG promoter impairs pulmonary function of mice with elastase‐induced emphysema

Pulmonary emphysema impairs quality of life and increases mortality. It has previously been shown that administration of adenovirus vector expressing murine keratinocyte growth factor (KGF) before elastase instillation prevents pulmonary emphysema in mice. We therefore hypothesized that therapeutic administration of KGF would restore damage to lungs caused by elastase instillation and thus improve pulmonary function in an animal model. KGF expressing adenovirus vector, which prevented bleomycin‐induced pulmonary fibrosis in a previous study, was constructed. Adenovirus vector (1.0 × 10⁹ plaque‐forming units) was administered intratracheally one week after administration of elastase into mouse lungs. One week after administration of KGF–vector, exercise tolerance testing and blood gas analysis were performed, after which the lungs were removed under deep anesthesia. KGF‐positive pneumocytes were more numerous, surfactant protein secretion in the airspace greater and mean linear intercept of lungs shorter in animals that had received KGF than in control animals. Unexpectedly, however, arterial blood oxygenation was worse in the KGF group and maximum running speed, an indicator of exercise capacity, had not improved after KGF in mice with elastase‐induced emphysema, indicating that KGF‐expressing adenovirus vector impaired pulmonary function in these mice. Notably, vector lacking KGF‐expression unit did not induce such impairment, implying that the KGF expression unit itself may cause the damage to alveolar cells. Possible involvement of the CAG promoter used for KGF expression in impairing pulmonary function is discussed.

     

Mechanisms of exertional dyspnea in patients with cancer.

Exertional dyspnea is an important symptom in cancer patients, and, in many cases, its cause remains unexplained after careful clinical assessment. To determine mechanisms of exertional dyspnea in a variety of cancer types, we evaluated cancer outpatients with clinically important unexplained dyspnea (CD) at rest and during exercise and compared the results with age-, sex-, and cancer stage-matched control cancer (CC) patients and age- and sex-matched healthy control participants (HC). Participants (n = 20/group) were screened to exclude clinical cardiopulmonary disease and then completed dyspnea questionnaires, anthropometric measurements, muscle strength testing, pulmonary function testing, and incremental cardiopulmonary treadmill exercise testing. Dyspnea intensity was greater in the CD group at peak exercise and for a given ventilation and oxygen uptake (P < 0.05). Peak oxygen uptake was reduced in CD compared with HC (P < 0.05), and breathing pattern was more rapid and shallow in CD than in the other groups (P < 0.05). Reduced tidal volume expansion during exercise correlated with reduced inspiratory capacity, which, in turn, correlated with reduced inspiratory muscle strength. Patients with cancer had a relatively reduced diffusing capacity of the lung for carbon monoxide, reduced skeletal muscle strength, and lower ventilatory thresholds during exercise compared with HC (P < 0.05). There were no significant between-group differences in measurements of airway function, pulmonary gas exchange, or cardiovascular function during exercise. In the absence of evidence of airway obstruction or restrictive interstitial lung disease, the shallow breathing pattern suggests ventilatory muscle weakness as one possible explanation for increased dyspnea intensity at a given ventilation in CD patients.     

Relationships of Oxygen Consumption, Hemodynamics, and Heart Rate Variability with the Functional Class of Coronary Artery Disease Patients

The functional classes (FCs) established according to the criteria of the New York Heart Association were tested for association with oxygen consumption, the state of central hemodynamics, and heart rate (HR) variability in coronary artery disease (CAD) patients. Oxygen consumption, central hemodynamics, and HR variability at rest and during exercise were assayed in 146 CAD patients and 30 healthy individuals (the control group). It was established that the peak oxygen consumption (VO_2max), anaerobic threshold, pulmonary ventilation, systolic and minute blood volume at the threshold load (TL), and HR variability in a supine position significantly decrease and the total vascular peripheral resistance at rest and during exercise increases with increasing FC in CAD patients. The closest correlation of FC was revealed with physical working capacity, anaerobic threshold, age, and peak oxygen consumption. Moderate correlations were established with the chronotropic function of the heart at the threshold load, HR variability, the high- and low-frequency components of the cardiac rhythm at TL, pulmonary ventilation, stroke volume at rest and at TL, and the carbon dioxide ventilation equivalent at TL. In healthy individuals, the peak oxygen consumption closely correlated with the HR variability, the very low frequency component at TL, and physical capacity. With an increase in FC in CAD patients, peak oxygen consumption became more tightly associated with the chronotropic function and the hemodynamic components at TL than with the HR variability in a supine position or at TL.     

Pulmonary gas exchange and acid-base state at 5,260 m in high-altitude Bolivians and acclimatized lowlanders.

Pulmonary gas exchange and acid-base state were compared in nine Danish lowlanders (L) acclimatized to 5,260 m for 9 wk and seven native Bolivian residents (N) of La Paz (altitude 3,600-4,100 m) brought acutely to this altitude. We evaluated normalcy of arterial pH and assessed pulmonary gas exchange and acid-base balance at rest and during peak exercise when breathing room air and 55% O2. Despite 9 wk at 5,260 m and considerable renal bicarbonate excretion (arterial plasma HCO3- concentration = 15.1 meq/l), resting arterial pH in L was 7.48 +/- 0.007 (significantly greater than 7.40). On the other hand, arterial pH in N was only 7.43 +/- 0.004 (despite arterial O2 saturation of 77%) after ascent from 3,600-4,100 to 5,260 m in 2 h. Maximal power output was similar in the two groups breathing air, whereas on 55% O2 only L showed a significant increase. During exercise in air, arterial PCO2 was 8 Torr lower in L than in N (P < 0.001), yet PO2 was the same such that, at maximal O2 uptake, alveolar-arterial PO2 difference was lower in N (5.3 +/- 1.3 Torr) than in L (10.5 +/- 0.8 Torr), P = 0.004. Calculated O2 diffusing capacity was 40% higher in N than in L and, if referenced to maximal hyperoxic work, capacity was 73% greater in N. Buffering of lactic acid was greater in N, with 20% less increase in base deficit per millimole per liter rise in lactate. These data show in L persistent alkalosis even after 9 wk at 5,260 m. In N, the data show 1) insignificant reduction in exercise capacity when breathing air at 5,260 m compared with breathing 55% O2; 2) very little ventilatory response to acute hypoxemia (judged by arterial pH and arterial PCO2 responses to hyperoxia); 3) during exercise, greater pulmonary diffusing capacity than in L, allowing maintenance of arterial PO2 despite lower ventilation; and 4) better buffering of lactic acid. These results support and extend similar observations concerning adaptation in lung function in these and other high-altitude native groups previously performed at much lower altitudes.     

Effect of obesity on respiratory mechanics during rest and exercise in COPD

The presence of obesity in COPD appears not to be a disadvantage with respect to dyspnea and weight-supported cycle exercise performance. We hypothesized that one explanation for this might be that the volume-reducing effects of obesity convey mechanical and respiratory muscle function advantages. Twelve obese chronic obstructive pulmonary disease (COPD) (OB) [forced expiratory volume in 1 s (FEV(1)) = 60%predicted; body mass index (BMI) = 32 ± 1 kg/m(2); mean ± SD] and 12 age-matched, normal-weight COPD (NW) (FEV(1) = 59%predicted; BMI = 23 ± 2 kg/m(2)) subjects were compared at rest and during symptom-limited constant-work-rate exercise at 75% of their maximum. Measurements included pulmonary function tests, operating lung volumes, esophageal pressure, and gastric pressure. OB vs. NW had a reduced total lung capacity (109 vs. 124%predicted; P < 0.05) and resting end-expiratory lung volume (130 vs. 158%predicted; P < 0.05). At rest, there was no difference in respiratory muscle strength but OB had greater (P < 0.05) static recoil and intra-abdominal pressures than NW. Peak ventilation, oxygen consumption, and exercise endurance times were similar in OB and NW. Pulmonary resistance fell (P < 0.05) at the onset of exercise in OB but not in NW. Resting inspiratory capacity, dyspnea/ventilation plots, and the ratio of respiratory muscle effort to tidal volume displacement were similar, as was the dynamic performance of the respiratory muscles including the diaphragm. In conclusion, the lack of increase in dyspnea and exercise intolerance in OB vs. NW could not be attributed to improvement in respiratory muscle function. Potential contributory factors included alterations in the elastic properties of the lungs, raised intra-abdominal pressures, reduced lung hyperinflation, and preserved inspiratory capacity.     

Cardiac secretion of atrial natriuretic factor with exercise in chronic congestive heart failure patients.

We have previously reported a fivefold increase of plasma atrial natriuretic factor (ANF) in patients with congestive heart failure (CHF) compared with normal subjects. However, given the marked increase of ANF under basal conditions, the extent to which ANF secretion can further increase under physiological stress is not been clarified in CHF. We therefore evaluated ANF secretion during ergometric exercise in 11 patients with CHF, with peripheral venous ANF samples obtained at rest and peak exercise. In seven patients, simultaneous peripheral venous and right ventricular ANF samples were obtained to estimate myocardial ANF secretion. Hemodynamic characteristics of exercise included a significant increase of heart rate, mean arterial pressure, and cardiac output (all P < 0.01); reduction of systemic vascular resistance (P < 0.001); and increase of right atrial and pulmonary wedge pressures (P < 0.001). ANF was abnormally elevated at baseline (108 +/- 58 fmol/ml) yet increased further to 183 +/- 86 fmol/ml with exercise (P < 0.003). A step-up of right ventricular ANF, particularly during exercise, was consistent with active myocardial secretion, despite elevated baseline ANF levels.     

Alterations in cerebral autoregulation and cerebral blood flow velocity during acute hypoxia: rest and exercise

We examined the relationship between changes in cardiorespiratory and cerebrovascular function in 14 healthy volunteers with and without hypoxia [arterial O(2) saturation (Sa(O(2))) approximately 80%] at rest and during 60-70% maximal oxygen uptake steady-state cycling exercise. During all procedures, ventilation, end-tidal gases, heart rate (HR), arterial blood pressure (BP; Finometer) cardiac output (Modelflow), muscle and cerebral oxygenation (near-infrared spectroscopy), and middle cerebral artery blood flow velocity (MCAV; transcranial Doppler ultrasound) were measured continuously. The effect of hypoxia on dynamic cerebral autoregulation was assessed with transfer function gain and phase shift in mean BP and MCAV. At rest, hypoxia resulted in increases in ventilation, progressive hypocapnia, and general sympathoexcitation (i.e., elevated HR and cardiac output); these responses were more marked during hypoxic exercise (P < 0.05 vs. rest) and were also reflected in elevation of the slopes of the linear regressions of ventilation, HR, and cardiac output with Sa(O(2)) (P < 0.05 vs. rest). MCAV was maintained during hypoxic exercise, despite marked hypocapnia (44.1 +/- 2.9 to 36.3 +/- 4.2 Torr; P < 0.05). Conversely, hypoxia both at rest and during exercise decreased cerebral oxygenation compared with muscle. The low-frequency phase between MCAV and mean BP was lowered during hypoxic exercise, indicating impairment in cerebral autoregulation. These data indicate that increases in cerebral neurogenic activity and/or sympathoexcitation during hypoxic exercise can potentially outbalance the hypocapnia-induced lowering of MCAV. Despite maintaining MCAV, such hypoxic exercise can potentially compromise cerebral autoregulation and oxygenation.     

Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses.

We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.     

Characteristics of pulmonary diffusing capacity for CO at rest and during exercise

Characteristic patterns of changes in pulmonary diffusing capacity (DL) at rest and during exercise were investigated and characteristics of normal DL values concerned on sex, age, and ethnic groups were examined by viewing our studies and other reports. The relation of DL and pulmonary capillary blood volume (Vc) was represented as a logarithmic regression at rest and as a linear regression during exercise. The curve relation at rest is considered to show that the increase in Vc mainly reflects the process of transport from pulmonary capillary recruitment to pulmonary capillary dilation. The increasing rate of DL was not decreased during exercise, which seemed to be due to an increase in pulmonary blood flow accompanying exercise. The linear regression was also found between DL and oxygen intake during exercise and the slope was always constant among individuals and among subject groups. The general results concerned with sex difference in Japanese or ethnic difference between Japanese and Caucasians in both sexes could show that DL per stature was greater in males or Caucasians than in females or Japanese in young adults, however, the sex or ethnic difference disappeared in middle or old aged group. DL per alveolar volume which showed no sex or ethnic difference in young adults, was greater in middle or old aged group of females or Japanese than in that of males or Caucasians.     

Near-maximal fractional oxygen extraction by active skeletal muscle in patients with chronic heart failure.

Systemic oxygen uptake and deep femoral vein oxygen content were determined at peak exercise in 53 patients with chronic heart failure with impaired systolic function (mean left ventricular ejection fraction 0.18; n = 41) or preserved systolic function (mean left ventricular ejection fraction 0.70; n = 12) and in 6 age-matched sedentary normal subjects. At peak exercise, deep femoral vein oxygen content in heart failure patients with impaired systolic function and preserved systolic function were similar, both significantly lower than that of normal subjects (2.5 +/- 0.1, 2.9 +/- 0.2, and 5.0 +/- 0.1 ml/100 ml, respectively; P < 0.05). Deep femoral venous oxygen content was lower in patients with the greater impairment of aerobic capacity, regardless of the underlying systolic function (r = 0.72, P < 0.01). Fractional oxygen extraction in the skeletal muscle at peak exercise is enhanced in patients with chronic heart failure when compared with normal subjects, in proportion to the degree of aerobic impairment.     

Carbon monoxide and exercise tolerance in chronic bronchitis and emphysema.

The effects of carbon monoxide on exercise tolerance as assessed by the distance walked in 12 minutes were studied in 15 patients with severe chronic bronchitis and emphysema (mean forced expiratory volume in one second 0.56 1, mean forced vital capacity 1.54 1). Each subject walked breathing air and oxygen before and after exposure to sufficient carbon monoxide to raise their venous carboxyhaemoglobin concentration by 9%. There was a significant reduction in the walking distance when the patients breathed air after exposure to carbon monoxide (p less than 0.01), and the significant increase in walking distance seen after exercise when breathing oxygen at 2 1/minute via nasal cannulae was abolished if carbon monoxide has previously been administered. Thus concentrations of carboxyhaemoglobin frequently found in bronchitic patients who smoke may reduce their tolerance of everyday exercise, possibly by interfering with the transport of oxygen to exercising muscles.     

Ozone and high ventilation effects on pulmonary function and endurance performance

Ozone (O3) toxicity is potentiated by exercise-induced expired minute ventilation (VE) for a given exposure, which may also impair endurance performance. Ten healthy, well-trained long-distance runners were exposed on six occasions for 1 h to O3 concentrations of 0, 0.20, or 0.35 parts per million (ppm), during exercise simulating either training or competition, with mean VE = 77.5 1 X min -1. Standard pulmonary function tests, subjective symptoms, and periodic observations of exercise ventilatory response and respiratory metabolism were obtained. Statistical analyses revealed no significant exercise mode effect for pulmonary function, but a significant O3 effect for forced vital capacity and expiratory volume at 1 s was observed. Altered exercise ventilatory pattern response was noted, but there was no significant O3 effect on exercise oxygen uptake, heart rate, VE, or alveolar ventilation. Subjective symptoms increased with O3 concentration. Statistically significant pulmonary function impairment observed at 0.20 ppm O3 suggests that endurance athletes may be more susceptible to the effects of a given O3 concentration than normal young adult males as a result of sustained high mean VE incurred during training and competition. Three subjects were unable to complete both the training and competitive simulations at 0.35 ppm O3. Performance decrements appeared to be the result of physiologically induced respiratory discomfort rather than decrements in pulmonary gas exchange and/or oxygen transport and delivery.