Lung gas mixing during expiration following an inspiration of air

The airway system of the lung from the mouth to the pulmonary membrane is modelled by matching a cylindrical model of a pathway through the respiratory region of the lung onto a one-dimensional trumpet model for the conducting airways. The concentration of O₂ in gas expired from this model airway system is investigated following an inspiration of air at two different flow rates (10 litres/min and 85 litres/min). In each case, expiration occurs at the same constant flow rate as that during the previous inspiration. The inspirations, which are studied in an earlier paper, are each of 2 sec duration and begin at a lung volume of 2300 ml and a lung oxygen tension of 98 mm Hg. The equations are solved numerically and plots of expired O₂ concentration against time and against expired volume are shown. It is found that at 85 litres/min, gas mixing in the lung is complete after about 0.7 sec of expiration whereas at 10 litres/min, about 2.6 sec of expiration is required for complete equilibration. It is suggested that the experimental alveolar plateau slope is not in general caused by a slow approach to equilibrium of gas concentrations; except at very low flow rates in the early part of the concentration/time plateau.     

Respiratory gas exchange in the airbreathing fish,Synbranchus marmoratus

Synopsis The partitioning of O₂ uptake between aquatic and aerial gas exchange and its dependence on ambient water PO₂ was studied in the facultative air breathing teleost Synbranchus marmoratus, after acclimation to well aerated water and after acute and chronic exposure to hypoxic water. O₂ uptake was also studied following acute air exposure and after prolonged entrapment in soil. Breathing rates during water and air breathing in response to reduced water PO₂ and tidal volume during air breathing were also studied. S. marmoratus satisfies its O₂ requirement by water breathing alone until water PO₂ falls below 30–50 mm Hg (switching PO₂) depending on the acclimation history. Below the switching PO₂, air breathing is adopted while active water breathing stops. The O₂ uptake varied little for all groups when the principal mode of gas exchange changed at the switching PO₂. The highest O₂ uptake prevailed when the fish employed the mode of gas exchange in operation during the acclimation period (i.e. water breathing for normoxia-acclimated, air breathing for hypoxic-acclimated).Acclimation to chronic hypoxia gave a much higher switching PO₂ 55 mm Hg) than for the other groups (about 30 mm Hg). S. marmoratus maintained its O₂ uptake when acutely exposed to air. When entrapped in soil in an aestivating state, the O₂ uptake was reduced to 25% of that in water or during acute air exposure. The overall gas exchange ratio for air breathing was very low (R_E 0.1).Branchial water pumping increased with lowering of water PO₂. The rate of air breathing was independent of water PO₂.The findings are discussed in the light of the ecophysiological conditions confronting S. marmoratus.     

Effects of acute temperature changes on aerial and aquatic gas exchange, pulmonary ventilation and blood gas status in the South American lungfish, Lepidosiren paradoxa

Lungfish (Dipnoi) are probably sister group relative to all land vertebrates (Tetrapoda). The South American lungfish, Lepidosiren paradoxa, depends markedly on pulmonary gas exchange. In this context, we report on temperature effects on aquatic and pulmonary respiration, ventilation and blood gases at 15, 25 and 35 degrees C. Lung ventilation increased from 0.5 (15 degrees C) to 8.1 ml BTPS kg(-1) min(-1) (35 degrees C), while pulmonary O(2)-uptake increased from 0.06 (15 degrees C) to 0.73 ml STPD kg(-1) min(-1) (35 degrees C). Meanwhile aquatic O(2)-uptake remained about the same ( approximately 0.01 ml STPD kg(-1) min(-1)) at all temperatures. Concomitantly, the pulmonary gas exchange ratio (R(E)) rose from 0.11 (15 degrees C) to 0.62 (35 degrees C), because a larger fraction of total CO(2) output became eliminated by the lung. Accordingly, PaCO(2) rose from 13 (15 degrees C) to 37 mm Hg (35 degrees C), leading to a significant decrease of pHa at higher temperature (pHa=7.58-15 degrees C; 7.33-35 degrees C). The acid-base status of L. paradoxa was characterized by a generally low pH (7.4-7.5), high bicarbonate level (20-25 mM) and PaO(2) ( approximately 80 mm Hg). The increased dependence on the lung at higher temperature parallels data for amphibians. Further, the effects of bimodal gas exchange on temperature-dependent acid-base regulation closely resemble those of anuran amphibians.     

Theoretical basis of single breath gas absorption tests

Absorption of gas from alveoli is examined in a simplified model of the respiratory system during a stylized single breath consisting of constant inspiratory flow, constant expiratory flow, and breathholding. The equations describing gas behavior are general since they are based upon conservation of mass. The equations simplify considerably when gases that are not soluble in pulmonary tissue and/or blood are utilized. In a three-compartment model, diffusing capacity of the lung for carbon monoxide (D _CO ) will be underestimated except when both uneven distribution of lung volume andD _CO are present; under most circumstances, the standard clinical 10-s method [9] is at least as accurate as any other. When pulmonary capillary blood flow is calculated by the one point method [2] in a one-compartment lung, it is underestimated; in the three-compartment model, it is underestimated except when both uneven distribution of . and lung volume are present. The multiple single breath method [2] accurately measuresD _CO and . Measurement of pulmonary tissue volume is improved by correcting the value of the intercept of acetylene absorption to the time when carbon monoxide apparently began rather than utilizing the beginning of inspiration.Nomenclature D _CO diffusing capacity of the lung for CO (ml CO, STPD/min/mm Hg) - pulmonary capillary blood flow rate (L/min) - V _t pulmonary tissue volume (L) - V _A alveolar compartment volume (L) - V _Ao alveolar compartment volume at conclusion of inspiratory flow (L) - inspiratory flow rate (L/sec) - expiratory flow rate (L/sec) - Bunsen coefficient of pulmonary tissue for test gas (ml test gas/ml tissue/atm) - Bunsen coefficient of pulmonary tissue for test gas (ml test gas/ml blood/atm) - F _A fractional pressure of test gas in the alveolar compartment (atm)     

Cutaneous gas exchange in snakes

Summary Cutaneous aquatic gas exchange and pulmonary gas exchange have been compared in an aquatic snakeAchrochordus javanicus and the terrestrial snakeConstrictor constrictor.Gas exchange was measured by closed respirometry with the snakes in air and in water with access to air. Frequency of air breathing, tidal volumes and total lung volumes were also compared in the two species. All measurements were done at 20–22 ° C.The aquaticAchrochordus showed long periods of apnea in submerged condition interrupted by short periods of breathing activity at the surface. Average frequency of air breathing activity was 2.6 times per hour. Breathing in constrictor was more frequent but irregular with an average frequency of 143 breaths per hour.Total lung volume was 66±31 ml/kg body weight and 72.5±59 ml/kg body weight inAchrochordus andConstrictor, respectively. Tidal volumes were 41.5±4.4 ml/kg body weight and 29.5±14.8 ml/kg body weight, largest inAchrochordus. Constrictor had the highest total O₂ uptake ( ) correlating with a higher activity. Total gas exchange ratio (R _E ) was 0.69 forConstrictor and 0.77 forAchrochordus. InConstrictor air breathing accounted for 97% of the total whereas 21% of the CO₂ exchange was aquatic. Corresponding figures forAchrochordus were 92% of total by air breathing with as much as 33% of the CO₂ elimination as aquatic gas exchange.The results demonstrate that the trend among early air breathing vertebrates (fishes and amphibians) of a conservative evolution of CO₂ elimination by air breathing also extends to snakes.Significantly the cutaneous exchange component was highest in the more aquatic species.The results are discussed in relation to recent reports of a higher than alleged role of the skin of reptiles in evaporative water loss.This study was supported by grant HE 12071 from the National Institutes of Health in the U. S. A.     

Transport of O2 along a model pathway through the respiratory region of the lung

A pathway through the system of branching in the respiratory region of the lung is modelled by a circular cylinder, closed at one end, with partitions which define the component respiratory units. In this model the transport of O₂ during inspiration, generated by diffusion is compared with that produced by diffusion together with convection and the importance of convection in the respiratory region in promoting oxygen uptake at the alveolar wall is discussed. For this discussion it is only necessary to consider inspiration. The equations are solved numerically for flow rates of 10, 85 and 200 liters/min. O₂ uptake at the wall and curves of constant O₂ concentration are shown to illustrate the influence of convection. It is found that after a 2 sec inspiration from an O₂ tension of 98 mm Hg and a lung volume of 2300 ml, convection is about 12 per cent as important as diffusion at a flow rate of 85 liters/min, whereas at 10 liters/min convection is only about 0.4 per cent as important as diffusion.     

A Closed-Loop Model of the Respiratory System: Focus on Hypercapnia and Active Expiration

Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. During quiet breathing, pumping air from the lungs is mostly performed by contraction of the diaphragm during inspiration, and muscle contraction during expiration does not play a significant role in ventilation. In contrast, during intense exercise or severe hypercapnia forced or active expiration occurs in which the abdominal “expiratory” muscles become actively involved in breathing. The mechanisms of this transition remain unknown. To study these mechanisms, we developed a computational model of the closed-loop respiratory system that describes the brainstem respiratory network controlling the pulmonary subsystem representing lung biomechanics and gas (O₂ and CO₂) exchange and transport. The lung subsystem provides two types of feedback to the neural subsystem: a mechanical one from pulmonary stretch receptors and a chemical one from central chemoreceptors. The neural component of the model simulates the respiratory network that includes several interacting respiratory neuron types within the Bötzinger and pre-Bötzinger complexes, as well as the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) representing the central chemoreception module targeted by chemical feedback. The RTN/pFRG compartment contains an independent neural generator that is activated at an increased CO₂ level and controls the abdominal motor output. The lung volume is controlled by two pumps, a major one driven by the diaphragm and an additional one activated by abdominal muscles and involved in active expiration. The model represents the first attempt to model the transition from quiet breathing to breathing with active expiration. The model suggests that the closed-loop respiratory control system switches to active expiration via a quantal acceleration of expiratory activity, when increases in breathing rate and phrenic amplitude no longer provide sufficient ventilation. The model can be used for simulation of closed-loop control of breathing under different conditions including respiratory disorders.     

Very low tidal volume ventilation with associated hypercapnia--effects on lung injury in a model for acute respiratory distress syndrome

Background

Ventilation using low tidal volumes with permission of hypercapnia is recommended to protect the lung in acute respiratory distress syndrome. However, the most lung protective tidal volume in association with hypercapnia is unknown. The aim of this study was to assess the effects of different tidal volumes with associated hypercapnia on lung injury and gas exchange in a model for acute respiratory distress syndrome.

Methodology/Principal Findings

In this randomized controlled experiment sixty-four surfactant-depleted rabbits were exposed to 6 hours of mechanical ventilation with the following targets: Group 1: tidal volume = 8–10 ml/kg/PaCO₂ = 40 mm Hg; Group 2: tidal volume = 4–5 ml/kg/PaCO₂ = 80 mm Hg; Group 3: tidal volume = 3–4 ml/kg/PaCO₂ = 120 mm Hg; Group 4: tidal volume = 2–3 ml/kg/PaCO₂ = 160 mm Hg. Decreased wet-dry weight ratios of the lungs, lower histological lung injury scores and higher PaO₂ were found in all low tidal volume/hypercapnia groups (group 2, 3, 4) as compared to the group with conventional tidal volume/normocapnia (group 1). The reduction of the tidal volume below 4–5 ml/kg did not enhance lung protection. However, oxygenation and lung protection were maintained at extremely low tidal volumes in association with very severe hypercapnia and no adverse hemodynamic effects were observed with this strategy.

Conclusion

Ventilation with low tidal volumes and associated hypercapnia was lung protective. A tidal volume below 4–5 ml/kg/PaCO₂ 80 mm Hg with concomitant more severe hypercapnic acidosis did not increase lung protection in this surfactant deficiency model. However, even at extremely low tidal volumes in association with severe hypercapnia lung protection and oxygenation were maintained.     

A system to simulate gas exchange in humans to control quality of metabolic measurements

We have developed a gas exchange simulation system (GESS) to assess the quality control in measurements of metabolic gas exchange. The GESS simulates human breathing from rest to maximal exercise. It approximates breath-by-breath waveforms, ventilatory output, gas concentrations, temperature and humidity during inspiration and expiration. A programmable motion control driving two syringes allows the ventilation to be set at any tidal volume (V _T), respiratory frequency (f), flow waveform and period of inspiration and expiration. The GESS was tested at various combinations of V _T (0.5–2.5 l) and f (10–60 stroke · min⁻¹) and at various fractional concentrations of expired oxygen (0.1294–0.1795); and carbon dioxide (0.0210–0.0690) for a pre-set flow waveform and for expired gases at the same temperature and humidity as room air. Expired gases were collected in a polyethylene bag for measurement of volume and gas concentrations. Accuracy was assessed by calculating the absolute and relative errors on parameters (error = measured−predicted). The overall error in the gas exchange values averaged less than 2% for oxygen uptake and carbon dioxide output, which is within the accuracy of the Douglas bag method. Accepted: 4 June 1998     

Ventilation and gas exchange in the Carpet Python,Morelia spilotes variegata

Summary The structure, dimensions and gas exchanging properties of the lungs of the Australian Carpet PythonMorelia spilotes variegata have been studied by dissection, by sampling lung gas and pulmonary venous blood and by using radioactive techniques to monitor distribution of ventilation ( ) and blood flow ( ). The lungs have alveolar and saccular parts (mean capacities 10.2 and 129.3 ml/kg body weight, respectively). The sacs store inspired air creating a flow through situation which abolishes the dead space effect, prevents large expansions of the alveolar lung and allows gas exchange during both inspiration and expiration. Gas exchange was measured in intubated snakes in the resting and active states at 20–26 °C. In the resting state, respiratory frequency, tidal volume and ventilation were 1.72±0.56/min, 14.8±10.8 ml/kg, 22.04±7.75 ml/kg · min and pulmonary venousP _{O 2},P _{CO 2} and pH were 58.9±14.5 Torr, 21.5±4.2 Torr, and 7.55±0.07 Torr, respectively. R. Q. was low, 0.65±0.11. In the active state both ventilation ( ) and cardiac output increase and blood flow is redistributed more evenly along the alveolar lung, enabling increased O₂ uptake. Since blood flow ( ) in the alveolar lung is stratified (Read and Donnelly, 1972) redistribution of during activity is proposed as a possible reserve capacity for O₂ extraction by reptilian lungs.     

Effect of experimental ventilation of the skin on cutaneous oxygen uptake in the carp,Cyprinus carpio

• 1.1. Cutaneous O₂ uptake in the carp, Cyprinus carpio, was determined at various water flow rates across the skin (.V) ranging from 2.5 to 40 ml/min, using flow-through respirometers.
• 2.2. When thickness of water flow was 2mm, cutaneous O₂ uptake remained stable (about 3.8 nmol/cm²/min) at a .V of 20–40 ml/min and decreased with .V below 20 ml/min.
• 3.3. When thickness of water flow was 4 mm, cutaneous O₂ uptake decreased with .V below 40 ml/min.
• 4.4. Apparent water velocity (U') was calculated dividing .V by an area of a cross section of the water flow (0.5 and 1.0 cm² respectively). In both experiments, cutaneous O₂ uptake decreased with U' below 0.7 cm/sec.
• 5.5. This suggests that cutaneous O₂ uptake in the carp is limited at a low water velocity by a resistance of the hypoxic boundary layer.

     

Modulation of epithelial cell proliferation in culture by dissolved oxygen

Modulation of epithelial cell proliferation by the dissolved oxygen concentration (P_O2) of the growth medium was assessed with primary human foreskin epithelium and a continuous monkey kidney epithelial cell line (LLC-MK₂). Direct measurement of the growth medium P_O2 provides the first quantitative evaluation of epithelial cell proliferation as a function of P_O2 provides the first quantitative evaluation of epithelial cell proliferation as a function of P_O2. Sustained proliferation of LLC-MK₂ cells occurs in serum-free medium equilibrated with a gas phase containing 18% or 30% O₂ v/v. Mid-logarithmic phase cultures rapidly consume dissolved oxygen; this results in a 60–70 mm Hg decline in P_O2 and leads to a stable growth medium P_O2 between 70 and 100 mm Hg, well above anoxic values. In contrast, if culture medium is equilibrated with a gas phase containing 0% or 1% O₂ v/v to yield a growth medium P_O2 ～ 20–40 mm Hg, proliferation of LLC-MK₂ and primary foreskin epithelial cells is retarded, and LLC-MK₂ cells use little dissolved oxygen. Gentle, continuous rocking to prevent diffusion gradient formation enhances proliferation slightly at the higher P_O2, but neither periodic fluid renewals nor continued rocking stimulates cells retarded by a lowered oxygen concentration to resume proliferation. The data collectively demonstrate that epithelial cell proliferation requires a P_O2 > 40 mm Hg, and threshold requirements are probably closer to 70 mm Hg. Glycolysis continues at a P_O2 insufficient for proliferation, but more lactic acid accumulates in actively proliferating cultures than in cultures equilibrated with 0% oxygen. We conclude that epithelial cells in vitro both consume more oxygen and require a higher P_O2 for continued proliferation, and that the oxygen requirement for epithelial cell proliferation exceeds that of a comparable population of fibroblasts for which low oxygen may enhance survival and proliferation.     

Impaired Synthesis of Acetylcholine by Mild Hypoxic Hypoxia or Nitrous Oxide

The effect of mild hypoxic hypoxia on brain metabolism and acetylcholine synthesis was studied in awake, restrained rats. Since many studies of hypoxia are done with animals anesthetized with nitrous oxide (N₂O), the effects of N²O were evaluated. N²O (70%) increased the cerebral cortical blood flow by 33% and the cortical metabolic rate of oxygen by 26%. In addition, the synthesis of acetylcholine in N²O-anesthetized animals, measured with [U-¹⁴C]glucose and [1-²H₂,2-²H₂]choline, decreased by 45 and 53%, respectively. Consequently, mild hypoxia was studied in unanesthetized rats. Control rats breathing 30% O₂ (partial pressure of oxygen, Pao₂= 120 mm Hg) were compared with rats exposed to 15% O₂ (Pao₂= 57 mm Hg) or 10% O₂ (Pao₂= 42 mm Hg). The synthesis of acetylcholine, measured with [U-¹⁴C]glucose, was decreased by 35 and 54% with 15% O₂ and 10% O₂ respectively; acetylcholine synthesis, measured with [1-²H₂,2-²H₂]choline, was decreased by 50 and 68% with 15% O₂ and 10% O₂ respectively. Animals breathing either 15% or 10% O₂ had normal cerebral metabolic rates of oxygen but had increased brain lactates and increased cortical blood flows compared with animals breathing 30% O₂. These results show that even mild hypoxic hypoxia impairs acetylcholine synthesis, which in turn may account for the early symptoms of brain dysfunction associated with hypoxia.     

Respiration of the air breathing fishPiabucina festae

Summary Piabucina festae, a Central American stream fish, breathes air frequently, even in air saturated water, however, is not an obligate air breather. Without access to air, it can maintain routine by aquatic respiration down to aP _wO₂ of about 70 Torr which is its critical O₂ tension (P _cO₂, Fig. 5). Aerial respiration averages 10% of total in air saturated water and 70% in hypoxic water (Fig. 4). At lowP _wO₂ air breathing is more frequent (Fig. 1), and more O₂ is utilized from each air breath (Table 3), and tidal volume may increase (Fig. 7). Vascularized respiratory compartments or cells (Fig. 6), located in the second chamber of the physostomus gas bladder, function for aerial respiration. In ventilation air is gulped and forced through a large pneumatic duct into the gas bladder, excess gas is then released through opercula. Inspiration always precedes expiration and tidal volume is small, keeping gas bladderP _{O 2} low (Table 4). Major differences in the air breathing physiology ofP. festae and other species are its higherP _cO₂, a low aerial in normoxic water, even though air gulps are frequent, and its pattern of inhalation prior to expiration. The interrelationship and optimization of the three gas bladder functions (buoyancy, sound reception, and air breathing) inP. festae is discussed. Aerial respiration may have evolved secondarily to the gas bladder's function in buoyancy control.     

Measurement of breath-by-breath gas exchange during general anaesthesia using a single pneumotachograph

A breath-by-breath gas exchange measurement system using a single pneumotachograph suitable for use during general anaesthesia is described. The system's accuracy has been assessed by a combination of error sensitivity analysis, laboratory testing of the component measurements used to calculate gas exchange and measurements on volunteers and patients. The system is shown to have a mean accuracy of ± 2.6 ml breath⁻¹ for V_CO2 measurements, ± 7.12 ml breath⁻¹ for V_O2 and ± 5.55 ml breath⁻¹ for V_N2O measurement. The application of a lung gas stores correction using argon improved between breath variability by 50%.     

Respiratory gas exchange during thermogenesis inPhilodendron selloum Koch

During peak thermogenesis of anthesis, high rates of respiration by the sterile male florets on the spadix ofPhilodendron selloum significantly reduce the oxygen tension (P_{O 2}) and raise CO₂ tension between the florets. Nevertheless, respiration is not limited by the availability of O₂ under natural conditions. At experimental P_{O 2} below about 17 kPa, however, florets begin to show decreased O₂ consumption. A respiratory exchange ratio of 0.83 indicates that the major energy source is not starch, but is probably lipid.Abbreviations and symbols capacitance of the gas phase for O₂ (ml O₂ cm^-3 kPa^-1) - D_{O 2} binary diffusion coefficient of O₂ in air (cm² min^-1) - K_{O 2} Krogh's diffusion coefficient (ml O₂ cm^-2 min^-1 kPa^-1 cm) - P_{O 2} P_{CO 2} partial pressures of O₂ and CO₂ (kPa) - rate of O₂ consumption (ml O₂ g^-1 h^-1) - F_gas fractional gas volume - P₈₀ O₂ partial pressure at which falls below 80% of maximum - RE respiratory exchange ratio      

Resting metabolic rate and lung function in fasted and fed rough-toothed dolphins,Steno bredanensis

We measured resting metabolic rate (RMR), tidal volume (V_T), breathing frequency (f_R), respiratory flow, and end-expired gases in rough-toothed dolphins (Steno bredanensis) housed in managed care after an overnight fast and 1–2 hr following a meal. The measured average (± standard deviation) V_T (4.0 ± 1.3 L) and f_R (1.9 ± 1.0 breaths/min) were higher and lower, respectively, as compared with estimated values from both terrestrial and aquatic mammals, and the average V_T was 43% of the estimated total lung capacity. The end-expired gas levels suggested that this species keep alveolar O₂ (10.6% or 80 mmHg) and CO₂ (7.6% or 57 mmHg), and likely arterial gas tensions, low and high, respectively, to maximize efficiency of gas exchange. We show that following an overnight fast, the RMR (566 ± 158 ml O₂/min) was 1.8 times the estimated value predicted by Kleiber for terrestrial mammals of the same size. We also show that between 1 and 2 hr after ingestion of a meal, the metabolic rate increases an average of 29% (709 ± 126 ml O₂/min). Both body mass (M_b) and f_R significantly altered the measured RMR and we propose that both these variables should be measured when estimating energy use in cetaceans.     

A sensitive continuous and discontinuous photometric determination of oxygen, carbon dioxide, and carbon monoxide in gases and fluids.

The paper describes a sensitive, rapid, and precise photometric method for the continuous and discontinuous determination of O₂, CO₂, and CO. The method is based on highly specific color reactions: O₂ is determined by its reaction with alkaline catechol + Fe²⁺ yielding intensively colored products, CO₂ is determined by its color reaction with a solution of fuchsin + hydrazine; and CO is determined by its reaction with hemoglobin. The basic experimental equipment is that of the AutoAnalyzer (cf.Wolf, Zander, and Lang, 1976, Anal. Biochem.74, 585), with an additional chamber for the injection of small gas samples in the case of the discontinuous analysis. Continuously analyzing in a standardized gas flow of 1 ml · min^?1 (STPD), the lower limits of the sensitivities are 50 ppm for O₂, 100 ppm for CO₂, and 50 ppm for CO. The discontinuous analysis of the three gases requires the basic experimental equipment plus an airtight chamber. The lower limits of the amounts are 0.1 μl (STPD) for O₂, 0.2 μl for CO₂, and 0.1 μl for CO.     

Effect of high-frequency ventilation on gas exchange and pulmonary vascular resistance in lambs

We studied the effects of conventional mechanical ventilation (CMV) (15 ml/kg tidal volume delivered at 18-25 breaths/min) and high-frequency oscillatory ventilation (HFOV) (less than or equal to 2 ml/kg delivered at 10 Hz) on pulmonary hemodynamics and gas exchange during ambient air breathing and hypoxic gas breathing in 10 4-day-old lambs. After instrumentation and randomization to either HFOV or CMV the animals breathed first ambient air and then hypoxic gas (inspired O2 fraction = 0.13) for 20 min. The mode of ventilation was then changed, and the normoxic and hypoxic gas challenges were repeated. The multiple inert gas elimination technique was utilized to assess gas exchange. There was a significant increase with HFOV in mean pulmonary arterial pressure (Ppa) (20.1 +/- 4.2 vs. 22 +/- 3.8 Torr, CMV vs. HFOV, P less than 0.05) during ambient air breathing. During hypoxic gas breathing Ppa was also greater with HFOV than with CMV (29.5 +/- 5.7 vs. 34 +/- 3.1 Torr, CMV vs. HFOV, P less than 0.05). HFOV reduced pulmonary blood flow (Qp) during ambient air breathing (0.33 +/- 0.11 vs. 0.28 +/- 0.09 l . kg-1 . min-1, CMV vs. HFOV, P less than 0.05) and during hypoxic gas breathing (0.38 +/- 0.11 vs. 0.29 +/- 0.09 l . kg-1 . min-1, P less than 0.05). There was no significant difference in calculated venous admixture for sulfur hexafluoride or in the index of low ventilation-perfusion lung regions with HFOV compared with CMV.(ABSTRACT TRUNCATED AT 250 WORDS)