Pulmonary gas exchange in humans during normobaric hypoxic exercise.

Previous studies (J. Appl. Physiol. 58: 978-988 and 989-995, 1985) have shown both worsening ventilation-perfusion (VA/Q) relationships and the development of diffusion limitation during heavy exercise at sea level and during hypobaric hypoxia in a chamber [fractional inspired O2 concentration (FIO2) = 0.21, minimum barometric pressure (PB) = 429 Torr, inspired O2 partial pressure (PIO2) = 80 Torr]. We used the multiple inert gas elimination technique to compare gas exchange during exercise under normobaric hypoxia (FIO2 = 0.11, PB = 760 Torr, PIO2 = 80 Torr) with earlier hypobaric measurements. Mixed expired and arterial respiratory and inert gas tensions, cardiac output, heart rate (HR), minute ventilation, respiratory rate (RR), and blood temperature were recorded at rest and during steady-state exercise in 10 normal subjects in the following order: rest, air; rest, 11% O2; light exercise (75 W), 11% O2; intermediate exercise (150 W), 11% O2; heavy exercise (greater than 200 W), 11% O2; heavy exercise, 100% O2 and then air; and rest 20 minutes postexercise, air. VA/Q inequality increased significantly during hypoxic exercise [mean log standard deviation of perfusion (logSDQ) = 0.42 +/- 0.03 (rest) and 0.67 +/- 0.09 (at 2.3 l/min O2 consumption), P less than 0.01]. VA/Q inequality was improved by relief of hypoxia (logSDQ = 0.51 +/- 0.04 and 0.48 +/- 0.02 for 100% O2 and air breathing, respectively). Diffusion limitation for O2 was evident at all exercise levels while breathing 11% O2.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary gas exchange in humans exercising at sea level and simulated altitude.

In a previous study of normal subjects exercising at sea level and simulated altitude, ventilation-perfusion (VA/Q) inequality and alveolar-end-capillary O2 diffusion limitation (DIFF) were found to increase on exercise at altitude, but at sea level the changes did not reach statistical significance. This paper reports additional measurements of VA/Q inequality and DIFF (at sea level and altitude) and also of pulmonary arterial pressure. This was to examine the hypothesis that VA/Q inequality is related to increased pulmonary arterial pressure. In a hypobaric chamber, eight normal subjects were exposed to barometric pressures of 752, 523, and 429 Torr (sea level, 10,000 ft, and 15,000 ft) in random order. At each altitude, inert and respiratory gas exchange and hemodynamic variables were studied at rest and during several levels of steady-state bicycle exercise. Multiple inert gas data from the previous and current studies were combined (after demonstrating no statistical difference between them) and showed increasing VA/Q inequality with sea level exercise (P = 0.02). Breathing 100% O2 did not reverse this increase. When O2 consumption exceeded about 2.7 1/min, evidence for DIFF at sea level was present (P = 0.01). VA/Q inequality and DIFF increased with exercise at altitude as found previously and was reversed by 100% O2 breathing. Indexes of VA/Q dispersion correlated well with mean pulmonary arterial pressure and also with minute ventilation. This study confirms the development of both VA/Q mismatch and DIFF in normal subjects during heavy exercise at sea level. However, the mechanism of increased VA/Q mismatch on exercise remains unclear due to the correlation with both ventilatory and circulatory variables and will require further study.

Pulmonary gas exchange in humans during exercise at sea level.

Previous studies have shown both worsening ventilation-perfusion (VA/Q) relationships and the development of diffusion limitation during exercise at simulated altitude and suggested that similar changes could occur even at sea level. We used the multiple-inert gas-elimination technique to further study gas exchange during exercise in healthy subjects at sea level. Mixed expired and arterial respiratory and inert gas tensions, cardiac output, heart rate, minute ventilation, respiratory rate, and blood temperature were recorded at rest and during steady-state exercise in the following order: rest, minimal exercise (75 W), heavy exercise (300 W), heavy exercise breathing 100% O2, repeat rest, moderate exercise (225 W), and light exercise (150 W). Alveolar-to-arterial O2 tension difference increased linearly with O2 uptake (VO2) (6.1 Torr X min-1 X 1(-1) VO2). This could be fully explained by measured VA/Q inequality at mean VO2 less than 2.5 l X min-1. At higher VO2, the increase in alveolar-to-arterial O2 tension difference could not be explained by VA/Q inequality alone, suggesting the development of diffusion limitation. VA/Q inequality increased significantly during exercise (mean log SD of perfusion increased from 0.28 +/- 0.13 at rest to 0.58 +/- 0.30 at VO2 = 4.0 l X min-1, P less than 0.01). This increase was not reversed by 100% O2 breathing and appeared to persist at least transiently following exercise. These results confirm and extend the earlier suggestions (8, 21) of increasing VA/Q inequality and O2 diffusion limitation during heavy exercise at sea level in normal subjects and demonstrate that these changes are independent of the order of performance of exercise.

Estimation of ventilation-perfusion inequality by inert gas elimination without arterial sampling.

Estimation of ventilation-perfusion (VA/Q) inequality by the multiple inert gas elimination technique requires knowledge of arterial, mixed venous, and mixed expired concentrations of six gases. Until now, arterial concentrations have been directly measured and mixed venous levels either measured or calculated by mass balance if cardiac output was known. Because potential applications of the method involve measurements over several days, we wished to determine whether inert gas levels in peripheral venous blood ever reached those in arterial blood, thus providing an essentially noninvasive approach to measuring VA/Q mismatch that could be frequently repeated. In 10 outpatients with chronic obstructive pulmonary disease, we compared radial artery (Pa) and peripheral vein (Pven) levels of the six gases over a 90-min period of infusion of the gases into a contralateral forearm vein. We found Pven reached 90% of Pa by approximately 50 min and 95% of Pa by 90 min. More importantly, the coefficient of variation at 50 min was approximately 10% and at 90 min 5%, demonstrating acceptable intersubject agreement by 90 min. Since cardiac output is not available without arterial access, we also examined the consequences of assuming values for this variable in calculating mixed venous levels. We conclude that VA/Q features of considerable clinical interest can be reliably identified by this essentially noninvasive approach under resting conditions stable over a period of 1.5 h.

Ventilation-perfusion inequality in normal humans during exercise at sea level and simulated altitude.

To investigate the effects of both exercise and acute exposure to high altitude on ventilation-perfusion (VA/Q) relationships in the lungs, nine young men were studied at rest and at up to three different levels of exercise on a bicycle ergometer. Altitude was simulated in a hypobaric chamber with measurements made at sea level (mean barometric pressure = 755 Torr) and at simulated altitudes of 5,000 (632 Torr), 10,000 (523 Torr), and 15,000 ft (429 Torr). VA/Q distributions were estimated using the multiple inert gas elimination technique. Dispersion of the distributions of blood flow and ventilation were evaluated by both loge standard deviations (derived from the VA/Q 50-compartment lung model) and three new indices of dispersion that are derived directly from inert gas data. Both methods indicated a broadening of the distributions of blood flow and ventilation with increasing exercise at sea level, but the trend was of borderline statistical significance. There was no change in the resting distributions with altitude. However, with exercise at high altitude (10,000 and 15,000 ft) there was a significant increase in dispersion of blood flow (P less than 0.05) which implies an increase in intraregional inhomogeneity that more than counteracts the more uniform topographical distribution that occurs. Since breathing 100% O2 at 15,000 ft abolished the increased dispersion, the greater VA/Q mismatching seen during exercise at altitude may be related to pulmonary hypertension.

Diffusion limitation in normal humans during exercise at sea level and simulated altitude.

The relative roles of ventilation-perfusion (VA/Q) inequality, alveolar-capillary diffusion resistance, postpulmonary shunt, and gas phase diffusion limitation in determining arterial PO2 (PaO2) were assessed in nine normal unacclimatized men at rest and during bicycle exercise at sea level and three simulated altitudes (5,000, 10,000, and 15,000 ft; barometric pressures = 632, 523, and 429 Torr). We measured mixed expired and arterial inert and respiratory gases, minute ventilation, and cardiac output. Using the multiple inert gas elimination technique, PaO2 and the arterial O2 concentration expected from VA/Q inequality alone were compared with actual values, lower measured PaO2 indicating alveolar-capillary diffusion disequilibrium for O2. At sea level, alveolar-arterial PO2 differences were approximately 10 Torr at rest, increasing to approximately 20 Torr at a metabolic consumption of O2 (VO2) of 3 l/min. There was no evidence for diffusion disequilibrium, similar results being obtained at 5,000 ft. At 10 and 15,000 ft, resting alveolar-arterial PO2 difference was less than at sea level with no diffusion disequilibrium. During exercise, alveolar-arterial PO2 difference increased considerably more than expected from VA/Q mismatch alone. For example, at VO2 of 2.5 l/min at 10,000 ft, total alveolar-arterial PO2 difference was 30 Torr and that due to VA/Q mismatch alone was 15 Torr. At 15,000 ft and VO2 of 1.5 l/min, these values were 25 and 10 Torr, respectively. Expected and actual PaO2 agreed during 100% O2 breathing at 15,000 ft, excluding postpulmonary shunt as a cause of the larger alveolar-arterial O2 difference than accountable by inert gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology of rheumatic heart disease in black shcoolchildren of Soweto, Johannesburg.

A survey to determine the prevalence of rheumatic heart disease (R.H.D.) in Black children was conducted in the creeches and primary schools of the South Western Townships of Johannesburg (Soweto). A total of 12 050 Black children were examined by 10 cardiologists in May to October 1972. The overal prevalence rate of R.H.D. was 6.9 per 1000, with a peak rate of 19.2 per 1000 in children of the seventh school grade. The maximal age incidence was 15-18 years and there was a female preponderance of 1 6:1. A rise in prevalence occurred with increasing family size. Most children (92%) were asymptomatic, and in 82.5% R.H.D. was diagnosed for the first time during the school survey. The commonest valve lesion was mitral regurgitation, which was present in 93% and occurred as an isolated lesion in 47.5%. Lancefield's group A beta-haemolytic streptococcus was isolated from the throats of 52 per 1000 Soweto children. The auscultatory features of a non-ejection systolic click and late systolic murmur were prevalent (13.9 per 1000) and had several epidemiological factors in common with R.H.D. A comprehensive preventative campaign is urgently needed in South Africa, directed at both primary and secondary prophylaxis of R.H.D. The socioeconomic status of the community must be improved if optimal prevention is to be achieved.

Hereditary prolongation of QT interval . Study of two families.

A syndrome has previously been recognized, which is characterized by recurrent episodes of loss of consciousness, some of which end fatally. The electrocardiogram in affected subjects shows prolongation of the QT interval. In the present study, 2 unrelated families with a total membership of 82 were investigated; 30 living subjects were examined and 20 were found to be affected. A further 14 members, 11 of whom died suddenly, were presumed from their histories to have been affected. The condition seems to be much more common, at least in South Africa, than the small number of previously reported cases would suggest. In contrast to the similar syndrome in which congenital deafness is also a feature and in which the disorder is transmitted in an autosomal recessive manner, analysis of the present data reveals an autosomal dominant inheritance with variable penetrance. The fundamental nature of the disorder remains unknown. Though treatment is generally unsatisfactory, beta-adrenergic blocking agents may be of value.