Effect of ruminal CO2 on gas exchange and ventilation in the Hereford calf

The contribution of ruminal CO2 to gas exchange measurements and ventilation was determined in four rumen-fistulated Hereford steers at rest and during exercise. The calves were exercised at 1.4 and 2.2m X s-1 under three treatments: 1)full rumen with fistula sealed, 2) full rumen with fistula open, and 3) empty rumen. Measurements also were made at rest while flushing the empty rumen with either 100% N2 or a mixture of 50% CO2-50% N2. O2 consumption, CO2 production (Mco2), and ventilation were measured by collecting the expired gas. Absorption across the ruminal epithelium during rest increased Mco2 by 3%, whereas absorption and eructation together increased Mco2 by 15%. The respiratory exchange ratio (R) was significantly different among the three treatments at rest, but no differences were observed in R among the treatments during exercise. No changes were observed in minute ventilation among the three conditions, but a decrease in respiratory frequency and an increase in tidal volume occurred when the rumen was empty. These changes in ventilatory pattern may have been due to a decrease in body temperature when the rumen was empty. When the empty rumen was flushed with 50% CO2, Mco2 was increased 21% over the value observed when flushing with 100% N2. CO2 of fermentation origin is added to the expired gas by both eructation and absorption and has a significant effect on R in the resting animal, but no effect on R during exercise.     

Validity of inspiratory and expiratory methods of measuring gas exchange with a computerized system.

The accuracy of a computerized metabolic system, using inspiratory and expiratory methods of measuring ventilation, was assessed in eight male subjects. Gas exchange was measured at rest and during five stages on a cycle ergometer. Pneumotachometers were placed on the inspired and expired side to measure inspired (VI) and expired ventilation (VE). The devices were connected to two systems sampling expired O(2) and CO(2) from a single mixing chamber. Simultaneously, the criterion (Douglas bag, or DB) method assessed VE and fractions of O(2) and CO(2) in expired gas (FE(O(2)) and FE(CO(2))) for subsequent calculation of O(2) uptake (VO(2)), CO(2) production (VCO(2)), and respiratory exchange ratio. Both systems accurately measured metabolic variables over a wide range of intensities. Though differences were found between the DB and computerized systems for FE(O(2)) (both inspired and expired systems), FE(CO(2)) (expired system only), and VO(2) (inspired system only), the differences were extremely small (FE(O(2)) = 0.0004, FE(CO(2)) = -0.0003, VO(2) = -0.018 l/min). Thus a computerized system, using inspiratory or expiratory configurations, permits extremely precise measurements to be made in a less time-consuming manner than the DB technique.     

Effect of aging on ventilatory response to exercise and CO2

Studies were performed to determine the effects of aging on the ventilatory responsiveness to two known respiratory stimulants, inhaled CO2 and exercise. Although explanation of the physiological mechanisms underlying development of exercise hyperpnea remains elusive, there is much circumstantial evidence that during exercise, however mediated, ventilation is coupled to CO2 production. Thus matched groups of young and elderly subjects were studied to determine the relationship between increasing ventilation and increasing CO2 production (VCO2) during steady-state exercise and the change in their minute ventilation in response to progressive hypercapnia during CO2 rebreathing. We found that the slope of the ventilatory response to hypercapnia was depressed in elderly subjects when compared with the younger control group (delta VE/delta PCO2 = 1.64 +/- 0.21 vs. 2.44 +/- 0.40 l X min-1 X mmHg-1, means +/- SE, respectively). In contrast, the slope of the relationship between ventilation and CO2 production during exercise in the elderly was greater than that of younger subjects (delta VE/delta VCO2 = 29.7 +/- 1.19 vs. 25.3 +/- 1.54, means +/- SE, respectively), as was minute ventilation at a single work load (50 W) (32.4 +/- 2.3 vs. 25.7 +/- 1.54 l/min, means +/- SE, respectively). This increased ventilation during exercise in the elderly was not produced by arterial O2 desaturation, and increased anaerobiasis did not play a role. Instead, the increased ventilation during exercise seems to compensate for increased inefficiency of gas exchange such that exercise remains essentially isocapnic. In conclusion, in the elderly the ventilatory response to hypercapnia is less than in young subjects, whereas the ventilatory response to exercise is greater.     

Gas exchange abnormalities after pneumonectomy in conditioned foxhounds

Loss of a major portion of lung tissue has been associated with impaired exercise capacity, but the underlying mechanisms are not well defined. We studied the alterations in gas exchange during exercise before and after left pneumonectomy in three conditioned foxhounds. After pneumonectomy, minute ventilation and O2 consumption at comparable submaximal work loads were unchanged but arterial PCO2 at any work load was higher, implying that ventilatory response to CO2 was impaired. Arterial hypoxemia and an elevated alveolar-arterial O2 tension difference (AaDO2) developed during heavy exercise. Using the multiple inert gas elimination technique, we determined the distributions of ventilation-perfusion (VA/Q) ratios postpneumonectomy. Significant increase in VA/Q inequality developed during exercise while the foxhounds were breathing room air, accounting for an average of 42% of the total increase in AaDO2 while diffusion limitation accounted for 58%. While the animals were breathing hypoxic gas mixture, diffusion limitation accounted for an average of 88% of the total increase AaDO2. Cardiac output and O2 delivery were reduced at a given O2 consumption after pneumonectomy. After pneumonectomy, the animals reached O2 consumptions close to the maximum expected for normal dogs. Compensation for the impairment in O2 delivery post-pneumonectomy occurred mainly by an increase in hemoglobin concentration. Training probably played an important role in returning exercise capacity toward prepneumonectomy levels. We conclude that significant abnormalities in gas exchange develop during exercise after loss of 42% of lung tissue, but the animals demonstrate a remarkable ability to compensate for these changes.     

Inspired CO(2) and O(2) in sleeping infants rebreathing from bedding: relevance for sudden infant death syndrome.

Some infants sleep facedown for long periods with no ill effects, whereas others become hypoxemic. Rebreathing of expired air has been determined by CO(2) measurement; however, O(2) levels under such conditions have not been determined. To evaluate this and other factors influencing inspired gas concentrations, we studied 21 healthy infants during natural sleep while facedown on soft bedding. We measured gas exchange with the environment and bedding, ventilatory response to rebreathing, and concentrations of inspired CO(2) and O(2). Two important factors influencing inspired gas concentrations were 1) a variable seal between bedding and infants' faces and 2) gas gradients in the bedding beneath the infants, with O(2)-poor and CO(2)-rich air nearest to the face, fresher air distal to the face, and larger tidal volumes being associated with fresher inspired air. Minute ventilation increased significantly while rebreathing because of an increase in tidal volume, not frequency. The measured drop in inspired O(2) was significantly greater than the accompanying rise in inspired CO(2). This appears to be due to effects of the respiratory exchange ratio and differential tissue solubilities of CO(2) and O(2) during unsteady conditions.     

Effect of beta-adrenergic blockade on hyperventilation and exercise tolerance in emphysema

Ventilation, heart rate, and arterial blood gas tensions were measured at rest and during incremental exercise in 10 patients with emphysema after intravenous placebo or 7 mg metoprolol. Metoprolol reduced heart rate by 14% (P less than 0.001) and ventilation by 11% (P less than 0.01), but there was no significant difference in arterial O2 or CO2 tension (Pao2 and PaCO2, respectively). Metoprolol increased the time to exhaustion on a cycle ergometer (P less than 0.05) but did not improve the 12-min walking distance. A double-blind randomized crossover comparison of 4 wk treatment with atenolol (100 mg/day), metoprolol (100 mg/day), or matched placebo was performed in 12 patients with emphysema. Both beta-adrenoceptor antagonists reduced resting heart rate by 33% (P less than 0.001) and resting minute ventilation by 11% (P less than 0.025). There was no change in resting or exercise Pao2 or Paco2. During steady-state exercise on a cycle ergometer, atenolol and metoprolol reduced ventilation by 14 and 4%, respectively. This was accompanied by 11 and 5% reductions in O2 consumption (P less than 0.05) and 13 and 6% falls in CO2 production (P less than 0.05). There were no significant changes in tests of exercise tolerance, but forced expiratory volume in 1 s and forced vital capacity were reduced during beta 1-adrenergic blockade. beta 1-Blocking drugs reduce hyperventilation in emphysema by reducing pulmonary gas exchange without a change in arterial blood gas tensions. Increased airflow obstruction prevents this reduction being of therapeutic value.     

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)     

Immediate effects of cigarette smoking on cardiorespiratory responses to exercise

To determine the acute action of cigarette smoking on cardiorespiratory function under stress, the immediate effects of cigarette smoking on the ventilatory, gas exchange, and cardiovascular responses to exercise were studied in nine healthy male subjects. Each subject performed an incremental exercise test to exhaustion on two separate days, one without smoking (control) and one after smoking 3 cigarettes/h for 5 h. The order of the two tests was randomized. Arterial blood gases and pH were measured during rest and all levels of exercise; CO blood levels confirmed the absorption of cigarette smoke. In addition, minute ventilation (VE), end-tidal PCO2 and PO2, O2 uptake (VO2), CO2 production, directly measured blood pressure, electrocardiogram, and heart rate (HR) were recorded every 30 s. The dead space-to-tidal volume ratio (VD/VT), maximal aerobic capacity (VO2max), and anaerobic threshold (AT) were determined from the gas exchange data. Cigarette smoking resulted in a significantly lower VO2max, AT, and VO2/HR (O2 pulse) and a significantly higher HR, pulse-pressure product, and pulse pressure (P less than 0.05) compared with the control. Additionally, a trend toward a higher VD/VT and arterial-end-tidal PCO2 difference was found during exercise after smoking. We conclude that cigarette smoking causes immediate detrimental effects on cardiovascular function during exercise, including tachycardia, increased pulse-pressure product, and impaired O2 delivery. The acute effects on respiratory function were less striking and primarily limited to abnormalities reflecting ventilation-perfusion mismatching.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Measurement of respiratory gas exchange during artificial respiration

This paper reports a new system for the continuous measurements of respiratory gas exchange in ventilated subjects. It involves mixing some of the inspired gas with all of the expired gas and withdrawing the mixture at a constant rate through a dry gas meter that measures the flow. The inspired gas and expired gas mixtures are sampled and O2 and CO2 concentrations measured with a paramagnetic gas analyzer and a capnograph, respectively, to an accuracy of 0.01%. Evidence is presented to confirm the necessary stability and sensitivity of these instruments. It is possible to use the system with high inspired O2 concentrations, with ventilators where there is incomplete separation of inspired and expired gas, and in the presence of intermittent mandatory ventilation, positive end-expiratory pressure, and continuous airway pressure. The system was compared with the N2-dilution method and with the collection of expired gas in a Douglas bag in dog experiments and with patients in the intensive therapy unit. Excellent correlation between these methods was found in all circumstances.     

Effects of previous exercise on the ventilatory determination of the aerobic threshold

To study the effects of previous submaximal exercise on the ventilatory determination of the Aerobic Threshold (AeT), 16 men were subjected to three maximal exercise tests (standard test = ST, retest = RT, and test with previous exercise = TPE ) on a cycle ergometer. The protocol for the three tests consisted of 3 min pedalling against 25 W, followed by increments of 25 W every minute until volitional fatigue. TPE was preceded by 10 min cycling at a power output corresponding to the AeT as determined in ST, followed by a recovery period pedalling against 25 W until VO2 returned to values consistent with the initial VO2 response to 25 W. AeT was determined from the gas exchange curves (ventilatory equivalent for O2, fraction of expired O2, excess of VCO2, ventilation, and respiratory gas exchange ratio) printed every 30 s. The results showed good ST X RT reliability (r = 0.89). TPE showed significantly higher AeT values (2.548 +/- 0.44 1 X min-1) when compared with ST (2.049 +/- 0.331 X min-1) and RT (2.083 +/- 0.30 1 X min-1). There were no significant differences for the sub-threshold respiratory gas exchange ratios among the trials. The sub-threshold VO2 response showed significantly higher values for TPE at power outputs above 50 W. It was concluded that the performance of previous exercise can increase the value for the ventilatory determination of the AeT due to a faster sub-threshold VO2 response.     

Reduction of the Pa(CO2) set point during hyperthermic exercise in the sheep

In animals that rely on the respiratory system for both gas exchange and heat loss, exercise can generate conflict between chemoregulation and thermoregulation. We hypothesized that in panting animals, hypocapnia during hyperthermic exercise reflects a reduction in the arterial CO2 tension (Pa(CO2)) set point. To test this hypothesis, five sheep were subjected to tracheal insufflations of CO2 or air (control) at 3-4 L min(-1) in 3 min bouts at 5 min intervals over 31 min of exercise. During exercise, rectal temperature and minute ventilation (V(E)) rose continuously while Pa(CO2) fell from 35.4+/-3.1 to 18.6+/-2.9 Torr and 34.3+/-2.4 to 18.7+/-1.5 Torr in air and CO2 trials, respectively. Air insufflations did not affect V(E) or Pa(CO2). V(E) increased during CO2 insufflations via a shift to higher tidal volume and lower frequency. CO2 insufflations also increased Pa(CO2), although not above the pre-exercise level. Within 5 min after each CO2 insufflation, Pa(CO2) had decreased to match that following the equivalent air insufflation. These results are consistent with a reduced Pa(CO2) set point or an increased gain of the Pa(CO2) regulatory system during hyperthermic exercise. Either change in the control of Pa(CO2) could facilitate respiratory evaporative heat loss by mitigating homeostatic conflict.     

Effect of beta-adrenergic blockade on response to exercise in sedentary and active subjects

The response to incremental work after placebo and propranolol (80 mg, orally) was studied in 11 sedentary (S) and 11 physically active (PA) healthy subjects. O2 uptake, CO2 output, and minute ventilation were significantly reduced at all or most work rates after propranolol in S subjects, whereas in PA subjects only O2 uptake was occasionally significantly reduced. Maximum work capacity during the propranolol trial was significantly increased by 17% in the S group but was unaltered in the PA group. A subanaerobic threshold constant work test in five sedentary subjects demonstrated that propranolol had no effect on the respiratory response both early and late in exercise. In addition, propranolol did not impair the ability of the respiratory control system to maintain alveolar PCO2 at new set points when external dead space was added during constant load work. We conclude that alterations of gas exchange during incremental work after propranolol administration are related to both physical fitness and type of exercise.     

Effects of hypercarbia on arterial and alveolar oxygen tensions in a model of gram-negative pneumonia

Inspired CO2 causing changes from hypo- to normocapnia has previously been shown to improve arterial O2 tension (PaO2) and to reduce alveolar-arterial O2 difference. The effect of further increases in inspired CO2 to hypercarbic levels has not been studied in inflammatory lung disease. Three days after induction of sublobar Pseudomonas pneumonia, Suffolk sheep were anesthetized and ventilated with a fixed-volume ventilator. After 2.5 h, CO2 was added to the inspired gas to raise arterial CO2 tension (PaCO2) to 60-65 Torr. Four hours later the CO2 was withdrawn and ventilation continued for an additional 2 h. Constant minute ventilation and inspired O2 fraction were maintained. Regional lung perfusion was measured by injection of radioactive microspheres. With the administration of CO2, PaO2 increased significantly from 65.5 to 77.5 Torr as did alveolar O2 tension (from 109.7 to 120.0 Torr) with no significant change in alveolar-arterial O2 difference. There were no significant changes in cardiac output, shunt fraction, O2 uptake, O2 delivery, respiratory quotient, or distribution of regional lung perfusion. We conclude that the increases in alveolar O2 tension and PaO2 with the added CO2 resulted from improved alveolar ventilation.     

Standardized estimation of external respiration function

External respiration in healthy males has, in addition to eupnea, six functionally active variants with one or several indices deviating from the normal values. Hyperpnea and hypopnea are determined by deviations in general oxygen consumption accompanied by adequate changes in pulmonary ventilation and gas exchange. Inhibition of gas exchange in the respiratory parts of the lungs is a typical primary event of hyperventilation, a fact indicated by a decrease in the coefficient of oxygen consumption and a compensatory increase in the minute respiratory volume during hyperventilation. Tension of the respiratory system is especially pronounced during enhanced oxygen consumption (O₂C). Highly effective bradypnea is characterized by infrequent and deep breathing. No tension of the respiratory system is observed even for increased O₂C. This state may be considered a genotypic and phenotypic variant of normal respiration. The data obtained may be used to automate the assessment of gas exchange in the respiratory parts of the lungs.     

New method of respiratory gas analysis: light spectrometer

A multigas concentration analyzer particularly suited for respiratory gas analysis has been developed using a new principle based on the measurement of the intensity of light emitted by excited atoms or ions in a direct current glow discharge. This glow discharge spectral emission gas analyzer (GDSEA), or light spectrometer, simultaneously measures O2, N2, CO2, He, and N2O gas concentrations with a 0-90% response time of 100 ms and a sample rate of less than 20 ml/min in a short gas sample line configuration. Mole accuracy and resolution of the GDSEA using a short sample line were determined in the laboratory to be +/- 0.15 to +/- 0.7% and 0.02-0.05%, respectively. In the clinical setting a comparative evaluation was made with a mass spectrometer in a long sample line, computerized, multibed, respiratory monitoring system. Results indicate a close agreement between the two instruments with differences in mixed inspiratory or expiratory O2 and CO2 concentrations of less than 2% and of derived variables, such as O2 consumption, CO2 production, and respiratory exchange ratio, of less than 5%.     

Respiratory sinus arrhythmia is associated with efficiency of pulmonary gas exchange in healthy humans

Respiratory sinus arrhythmia (RSA) may be associated with improved efficiency of pulmonary gas exchange by matching ventilation to perfusion within each respiratory cycle. Respiration rate, tidal volume, minute ventilation (.VE), exhaled carbon dioxide (.VCO(2)), oxygen consumption (.VO(2)), and heart rate were measured in 10 healthy human volunteers during paced breathing to test the hypothesis that RSA contributes to pulmonary gas exchange efficiency. Cross-spectral analysis of heart rate and respiration was computed to calculate RSA and the coherence and phase between these variables. Pulmonary gas exchange efficiency was measured as the average ventilatory equivalent of CO(2) (.VE/.VCO(2)) and O(2) (.VE/.VO(2)). Across subjects and paced breathing periods, RSA was significantly associated with CO(2) (partial r = -0.53, P = 0.002) and O(2) (partial r = -0.49, P = 0.005) exchange efficiency after controlling for the effects of age, respiration rate, tidal volume, and average heart rate. Phase between heart rate and respiration was significantly associated with CO(2) exchange efficiency (partial r = 0.40, P = 0.03). These results are consistent with previous studies and further support the theory that RSA may improve the efficiency of pulmonary gas exchange.     

Augmentation of CO2 drives by chlormadinone acetate, a synthetic progesterone

We studied 10 male subjects who were administered chlormadinone acetate (CMA), a potent synthetic progesterone, to clarify the physiological basis of its respiratory effects. Arterial blood gas tension, resting ventilation, and respiratory drive assessed by ventilatory and occlusion pressure response to CO2 with and without inspiratory flow-resistive loading were measured before and 4 wk after CMA administration. In all subjects, arterial PCO2 decreased significantly by 5.7 +/- 0.6 (SE) Torr with an increase in minute ventilation by 1.8 +/- 0.6 l X min-1, whereas no significant changes were seen in O2 uptake. During unloaded conditions, both slopes of occlusion pressure and ventilatory response to CO2 increased, being statistically significant in the former but showing nonsignificant trends in the latter. Furthermore, inspiratory flow-resistive loading (16 cmH2O X l(-1) X s) increased both slopes more markedly after CMA. The magnitudes of load compensation, assessed by the ratio of loaded to unloaded slope of the occlusion pressure response curve, were increased significantly. We concluded CMA is a potent respiratory stimulant that increases the CO2 chemosensitivity and neuromechanical drives in the load-compensation mechanism.     

Supramaximal exercise after training-induced hypervolemia. I. Gas exchange and acid-base balance

The effect of an exercise-induced reduction in blood O2-carrying capacity on ventilatory gas exchange and acid-base balance during supramaximal exercise was studied in six males [peak O2 consumption (VO2peak), 3.98 +/- 0.49 l/min]. Three consecutive days of supramaximal exercise resulted in a preexercise reduction of hemoglobin concentration from 15.8 to 14.0 g/dl (P less than 0.05). During exercise (120% VO2peak) performed intermittently (1 min work to 4 min rest); a small but significant (P less than 0.05) increase was found for both O2 consumption (VO2) (l X min) and heart rate (beats/min) on day 2 of the training. On day 3, VO2 (l/min) was reduced 3.2% (P less than 0.05) over day 1 values. No changes were found in CO2 output and minute ventilation during exercise between training days. Similarly, short-term training failed to significantly alter the changes in arterialized blood PCO2, pH, and [HCO-3] observed during exercise. It is concluded that hypervolemia-induced reductions in O2-carrying capacity in the order of 10-11% cause minimal impairment to gas exchange and acid-base balance during supramaximal non-steady-state exercise.     

Effect of increased gas density on pulmonary gas exchange in man.

Pulmonary gas exchange was measured in seven resting supine subjects breathing air or a dense gas mixture containing 21% O2 in sulfur hexafluoride (SF6). The mean value of the alveolar-arterial oxygen difference (AaDO2) decreased from 12.4 on air to 7.0 on SF6 (P less than 0.01), and increased again to 13.4 when air breathing resumed (P less than 0.01). No differences occurred between gas mixtures for O2 consumption, respiratory quotient, minute ventilation, breathing frequency, heart rate, or blood pressure, and the improved oxygen transfer could not be attributed to changes in cardiac output or mixed venous oxygen content in the one subject in which they were measured. These results are best explained by an altered distribution of ventilation during dense gas breathing, so that the ventilation-perfusion ratio (VA/Q) variance was reduced. Of several considered mechanisms, we favor one in which SF6 promotes cardiogenic gas mixing between peripheral parallel units having different alveolar gas concentrations. This mechanism allows for observed increases in arterial carbon dioxide tension and dead space-to-tidal volume ratio during dense gas breathing, and suggests that intraregional VA/Q variance accounts for at least one-half of the resting AaDO2 in healthy supine young men.