Biomedical subjects

S C Hempleman

Publications and source records attributed to S C Hempleman.

At least 19 recordsLinked to original sources

PubMed2006

Calcium and avian intrapulmonary chemoreceptor response to CO2.

Intrapulmonary chemoreceptors (IPC) are highly responsive respiratory chemoreceptors that innervate the lungs of birds and diapsid reptiles. IPC are stimulated by low levels of lung Pco(2), inhibited by high levels of lung Pco(2), and their vagal afferents serve as a sensory limb for reflex adjustments of breathing depth and rate. Most IPC exhibit both phasic and tonic sensitivity to CO(2), and spike frequency adaptation (SFA) contributes to their phasic CO(2) responsiveness. To test whether CO(2) responsiveness and SFA in IPC is modulated by a Ca(2+)-linked mechanism, we quantified the role of transmembrane Ca(2+) fluxes and Ca(2+)-related channels on single-unit IPC function in response to phasic changes in inspired Pco(2). We found that 1) broad-spectrum blockade of Ca(2+) channels using cadmium or cobalt and blockade of L-type Ca(2+) channels using nifedipine increased IPC discharge; 2) activation of L-type Ca(2+) channels using BAY K 8644 reduced IPC discharge; 3) blockade of Ca(2+)-activated potassium channels using charybdotoxin (antagonist of large-conductance Ca(2+)-dependent K(+) channel) increased IPC discharge, but neither charybdotoxin nor apamin affected SFA; and 4) blockade of chloride channels, including Ca(2+)-activated chloride channels, with niflumic acid decreased IPC discharge at low Pco(2) and increased IPC discharge at high Pco(2), resulting in a net attenuation of the IPC CO(2) response. We conclude that Ca(2+) influx through L-type Ca(2+) channels has an inhibitory effect on IPC afferent discharge and CO(2) sensitivity, that spike frequency adaptation is not due to apamin- or charybdotoxin-sensitive Ca(2+)-activated K(+) channels in IPC, and that chloride channels blocked by niflumic acid help modulate IPC CO(2) responses.

Action Potentials↗

PubMed2005

Spike firing allometry in avian intrapulmonary chemoreceptors: matching neural code to body size.

Biological rates in small animals are usually higher than those in large animals, yet the maximal rate of action potential (spike) generation in sensory neurons encoding rate functions is similar in all animals, due to the conserved genetics of voltage-gated ion channels. Therefore, sensory signals that vary at rates approaching maximal spike generation rate, as might occur in animals of diminished body size, may require specialized spike coding to convey this information. To test whether spike coding scales allometrically in sensory neurons monitoring signals that change frequency with body size, we recorded action potentials from 70 avian intrapulmonary chemoreceptors (IPC), respiratory neurons that detect lung CO2 changes during breathing, in five different avian species ranging in size from body mass Mb=0.045 kg (lovebirds) to 5.23 kg (geese). Since breathing frequency scales approximately to Mb-1/4 (higher in small birds, lower in large birds), we reasoned that IPC discharge frequencies may also scale to maintain spike information transmission within each breath. We found that phasic action potential discharge pattern, as quantified by the peak discharge rate and the magnitude of spike frequency adaptation, scaled between Mb-0.22 and Mb-0.26, like breathing rate (P<0.05). Previously published values of peak discharge rate in IPC also fit this allometric relationship. We suggest that mass-dependent scaling of neural coding may be necessary for preserving information transmission with decreasing body size.

Action Potentials↗

PubMed2001

Avian intrapulmonary chemoreceptor discharge rate is increased by anion exchange blocker 'DIDS'.

Avian intrapulmonary chemoreceptors (IPC) are neurons that sense lung P(CO(2)) and provide phasic feedback for the control of breathing in birds. To try to understand mechanisms of CO(2) transduction and intracellular pH regulation in IPC, the anion exchange inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) was used to block transmembrane Cl(-)/HCO(3)(-) transport. Single-unit IPC discharge rates were measured at steady intrapulmonary CO(2) levels and during step changes in CO(2) in 15 anesthetized, unidirectionally ventilated adult mallard ducks (Anas platyrhynchos). Measurements were repeated after giving 50, 100 and 200 micromol/kg cumulative i.v. dosages of DIDS. Mean IPC discharge rates at steady (tonic) P(CO(2)) levels were significantly increased by 100 and 200 micromol/kg DIDS, but not by 50 micromol/kg DIDS. Mean dynamic (phasic) IPC responses to CO(2) steps were not significantly affected by DIDS. Results indicate that the DIDS-sensitive Cl(-)/HCO(3)(-) membrane exchanger is involved with tonic CO(2) signal transduction in IPC. However, because some individual IPC were unaffected by DIDS, yet still altered their discharge rate with CO(2), additional mechanisms besides the Cl(-)/HCO(3)(-) exchange are probably required for CO(2) chemotransduction in IPC.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2001

Endosulfan exposure disrupts pheromonal systems in the red-spotted newt: a mechanism for subtle effects of environmental chemicals.

Because chemicals introduced into the environment by humans can affect both long-term survivorship and reproduction of amphibians, discovering the specific mechanisms through which these chemicals act may facilitate the development of plans for amphibian conservation. We investigated the amphibian pheromonal system as a potential target of common environmental chemicals. By treating female red-spotted newts, Notophthalmus viridescens, to a commonly used insecticide, endosulfan, we found that the pheromonal system is highly susceptible to low-concentration exposure. The impairment of the pheromonal system directly led to disrupted mate choice and lowered mating success. There were no other notable physiologic or behavioral changes demonstrated by the animals at the insecticide concentrations administered. Our findings suggest that the amphibian pheromonal system is one of the systems subject to subtle negative effects of environmental chemicals.

Animals↗

PubMed2000

Benzolamide, acetazolamide, and signal transduction in avian intrapulmonary chemoreceptors.

Intrapulmonary chemoreceptors (IPC) are CO(2)-sensitive sensory neurons that innervate the lungs of birds, help control the rate and depth of breathing, and require carbonic anhydrase (CA) for normal function. We tested whether the CA enzyme is located intracellularly or extracellularly in IPC by comparing the effect of a CA inhibitor that is membrane permeable (iv acetazolamide) with one that is relatively membrane impermeable (iv benzolamide). Single cell extracellular recordings were made from vagal filaments in 16 anesthetized, unidirectionally ventilated mallards (Anas platyrhynchos). Without CA inhibition, action potential discharge rate was inversely proportional to inspired PCO(2) (-9.0 +/- 0.8 s(-1). lnTorr(-1); means +/- SE, n = 16) and exhibited phasic responses to rapid PCO(2) changes. Benzolamide (25 mg/kg iv) raised the discharge rate but did not alter tonic IPC PCO(2) response (-9.8 +/- 1.6 s(-1). lnTorr(-1), n = 8), and it modestly attenuated phasic responses. Acetazolamide (10 mg/kg iv) raised IPC discharge, significantly reduced tonic IPC PCO(2) response to -3.5 +/- 3.6 s(-1). lnTorr(-1) (n = 6), and severely attenuated phasic responses. Results were consistent with an intracellular site for CA that is less accessible to benzolamide. A model of IPC CO(2) transduction is proposed.

Acetazolamide↗

PubMed1999

Chronic hypercapnia resets CO2 sensitivity of avian intrapulmonary chemoreceptors.

Avian intrapulmonary chemoreceptors (IPC) are vagal sensory neurons that participate in the control of breathing. IPC action potential frequency is inversely proportional to PCO2, but it is unclear whether low PCO2 or high pH is the immediate stimulus for signal transduction in IPC. To address this question, comparisons were made between single cell neural responses of 34 IPC recorded in 6 anesthetized ducks (Anas platyrhynchos) acclimatized 12 days to 7.5% inspired CO2 and 22 IPC recorded in 9 normal anesthetized ducks. We hypothesized that if respiratory-linked pH changes determine IPC activity, action potential frequency as a function of inspiratory PCO2 (PICO2) should be greater after acclimatization due to metabolic acid-base compensation and higher pH. Conversely, if PCO2 alone determines IPC discharge, action potential frequency vs. PCO2 should be unchanged by acclimatization. Results indicate that after acclimatization ventilation was depressed at 28 and 42 Torr PICO2 (P < 0.05) and mean plasma pH at 40 Torr PCO2 increased from 7.38 +/- 0. 03 to 7.56 +/- 0.02 (P < 0.05), indicating significant metabolic acid-base compensation and HCO-3 retention. Mean IPC discharge rate was elevated by CO2 acclimatization at all PCO2 studied. In acclimatized vs. normal animals, regression analysis of IPC discharge as a function of lnPCO2 showed increased mean intercepts of 81.1 +/- 4.0 vs. 48.4 +/- 3.6 impulses/s (P < 0.05) and increased mean slopes of -19.0 +/- 1.0 vs. -12.0 +/- 1.1 impulses. s-1. lnPCO2-1 (P < 0.05). Results indicate that IPC response to CO2 is mediated by H+ from CO2 hydration and not by CO2 directly.

Adaptation, Physiological↗

PubMed1996

Increased calcium current in carotid body glomus cells following in vivo acclimatization to chronic hypoxia.

1. Rat pups were gestated and born in normoxia (inspired O2 pressure 149 mmHg) or chronic hypoxia (insured O2 pressure 80 mmHg) to test whether chronic hypoxia alters carotid body glomus cell calcium currents. Carotid bodies were removed from 5- to 8-day-old-pups under halothane anesthesia, at which time blood hematocrits averaged 52 +/- 1% (mean +/- SE) in the chronically hypoxic pups and 36 +/- 1% in the normoxic pups (P < 0.05). Glomus cells were then enzymatically isolated from the carotid bodies, and calcium currents were recorded with whole cell patch clamp. 2. Compared with normoxic glomus cells (n = 29), chronically hypoxic glomus cells (n = 32) superfused with 10 mM CaCl2 had larger peak calcium current (146 +/- 16 pA vs. 49 +/- 7 pA, P < 0.05), larger peak calcium current density (12.0 +/- 1.1 pA/pF vs. 7.3 +/- 1.0 pA/pF, P < 0.05), and larger membrane capacitance (12.1 +/- 0.9 pF vs. 7.5 +/- 0.6 pF, P < 0.05). 3. Threshold for calcium current activation was approximately -40 mV. Currents showed little inactivation during 45-ms test pulses and were half-inactivated by a steady holding voltage of -11 +/- 2 mV (n = 15). Currents were reduced 43 +/- 13% by 50 microM nifedipine (n = 6, P < 0.05), and were augmented with barium as the charge carrier. These properties suggest that glomus cell calcium current is carried in part through L-type channels, and that is is relatively resistant to steady-state inactivation. 4. Augmented calcium influx through voltage-gated channels in glomus cells from chronically hypoxic neonatal rats may increase carotid body excitability through increased stimulus-secretion coupling. Overall, acclimatization to chronic hypoxia is known to depress acute hypoxic ventilatory reflex responses in neonates. The observations reported here suggest that inhibition of ventilatory reflexes by chronic hypoxia in neonates occurs centrally rather than peripherally.

Acclimatization↗

PubMed1995

Sodium and potassium current in neonatal rat carotid body cells following chronic in vivo hypoxia.

Chronic hypoxic acclimatization modifies ventilatory reflexes arising from carotid body stimulation. To explore this, the effects of in vivo chronic hypoxia on membrane currents were quantified in chemoreceptive carotid body glomus cells. Pregnant rats were maintained in either normoxia (NORM: inspired oxygen tension 141 mmHg), or hypoxia (CHX: inspired oxygen tension 80 mmHg) from day 3 of gestation, to day 5-10 postpartum. Whole cell patch clamp recordings were then made from the mechanically and enzymatically dissociated carotid body glomus cells of the rat pups (NORM: 41 cells, CHX: 36 cells) and comparisons of means +/- S.E.M. were made with unpaired t-tests. Glomus cells were bright under phase contrast illumination, formed clusters, were histochemically positive for catecholamines and possessed voltage-gated potassium currents that were depressed by acute hypoxia. Acclimatization to chronic hypoxia did not affect rat pup whole body mass (CHX: 12.0 +/- 0.7 g vs. NORM: 11.0 +/- 0.2 g), but it significantly increased blood hematocrit (CHX: 48.7 +/- 0.9% vs. NORM: 37.8 +/- 0.5%, P < 0.05). Sodium current was not uniformly present in glomus cells from either group, but sodium current was observed in a greater proportion of glomus cells isolated from the chronically hypoxic pups (CHX: 72% vs. NORM: 46%, P < 0.05). The mean peak tetrodotoxin-sensitive sodium current evoked by -70 mV to +10 mV depolarizations was greater after hypoxic acclimatization (CHX: -100 +/- 25 pA vs. NORM: -38 +/- 15 pA, P < 0.05), but the sodium current density (pA/pF) was unchanged. In contrast, the mean peak voltage-gated potassium current (pA) evoked by -70 mV to 0 mV depolarizations was unchanged by acclimatization, but the potassium current density (pA/pF) was reduced (P < 0.05). Unchanged sodium current density coupled with decreased potassium current density may make glomus cells more excitable during exposure to chronic in vivo hypoxia.

Animals↗

PubMed1994

Calcium deficient diet, acetazolamide and gas exchange characteristics of avian eggshells.

The effects of calcium deficient diet and acetazolamide on the gas exchange characteristics of avian eggshells were independently investigated in two groups of unmated hens (Gallus domesticus). In one group, eggs were collected during both a normal diet (3.00% Ca) and a calcium deficient diet (0.34% Ca). In another group, eggs were collected both before and after acetazolamide administration (200 mg/kg) per os. Eggshell water vapor conductance (GH2O) increased 30% during the calcium deficient diet and was accompanied by a 21% decrease in eggshell thickness (L). Eggshell GH2O increased 200% one day after acetazolamide administration and was not only accompanied by a 36% decrease in L, but also by an 89% increase in total functional pore area (Ap). We conclude that a calcium deficient diet increases GH2O by eggshell thinning with little effect on Ap. On the other hand, acetazolamide profoundly increases GH2O, not only by eggshell thinning but also by a remarkable increase in Ap.

Acetazolamide↗

PubMed1994

Increased venous PCO2 enhances dynamic responses of avian intrapulmonary chemoreceptors.

We quantified the neural discharge of intrapulmonary chemoreceptors (IPC) innervating the left lungs of anesthetized Pekin ducks. Right and left lungs were separately unidirectionally ventilated. Alternating steps in CO2 concentration (0-6%, 11-s period) were delivered to the left lung under control conditions [mixed venous PCO2, (PVCO2) 43 +/- 4 Torr] and under venous CO2 load conditions (PVCO2 79 +/- 6 Torr). During venous CO2 loading the right lung was ventilated with 10-20% CO2, while the left lung was ventilated with a sufficient flow of gas containing 0% CO2 to maintain normal expired PCO2 (indicated by constant IPC discharge rate). Venous loading increased the peak-to-peak amplitude of the oscillation in IPC discharge by 4.3 +/- 1.8 s-1 (n = 11, P < 0.05), left lung ventilation was increased 2.6-fold, and the IPC step response became more prompt. The mean IPC discharge rate during the CO2 stepping cycle was not significantly affected (11.8 +/- 1.4 during control vs. 10.3 +/- 1.3 s-1 during venous loading). Increased IPC discharge oscillations were due to enhancement of the dynamic overshoot in receptor discharge after the 6-0% downstep in inspired CO2 and to a depression of discharge during 6% inspired CO2. We propose that the phasic enhancement of IPC discharge oscillations during venous CO2 loading may cause feedback inhibition of ventilatory drive.

Administration, Inhalation↗

PubMed1993

Diffusion limitation in comparative models of gas exchange.

Piiper and Scheid (Resp. Physiol. 23: 209-221, 1975) compared different models of external gas exchange with performance indices defined as functions of ventilatory/perfusive and diffusive/perfusive conductance ratios (Gvent/Gperf and Gdiff/Gperf, where Gdiff is diffusing capacity). We expanded their analysis to include: (1) delta pD, the average partial pressure gradient driving diffusion across the exchange barrier, normalized to the maximum gradient available (Pi-Pv), and (2) Jdiff, the sensitivity of total conductance to changes in Gdiff, where total conductance is the ratio of gas flux to the maximum gradient [GTOT = M/(Pi-Pv)]. Although the counter-current model is most efficient, it is more sensitive than cross-current or ventilated pool models to changes in Gdiff. For given Gvent, Gperf and Pi-Pv, maximum GTOT may not be achieved in the counter-current model until Gdiff is over ten-fold greater than that necessary for maximum GTOT in the other models. Experimental data also shows greater Jdiff and diffusion limitation in fish than in birds or mammals. We conclude that counter-current O2 exchange cannot approach ideal levels as closely as the ventilated pool or cross-current models in nature.

Animals↗

PubMed1993

Oxygen and avian eggshell formation at high altitude.

Many birds at high altitude lay eggs with reduced eggshell diffusive conductance to water vapor. Disagreement exists about the cause, but hypotheses include physiological acclimatization and genetic adaptation. To investigate this, we tested for the occurrence of physiological acclimatization and quantified the effect of relieving hypoxia at high altitude. Ten laying hens (Gallus domesticus) were exposed to elevations of 3800 m (PIO2 90 Torr), 3800 m with supplementary oxygen (PIO2 140 Torr), and 1200 m (PIO2 125 Torr). 573 eggs were collected and analyzed during the 17-week experiment. Shell conductance, aggregate pore area, and shell thickness were reduced at 3800 m compared to 1200 m or 3800 m with supplementary oxygen. There was a lag in the response to changes in altitude or PIO2 that corresponded to a time constant of approximately 2.5 weeks. We conclude that physiological acclimatization of eggshell conductance occurs in some chickens, and that it is probably stimulated by hypoxia.

Acclimatization↗

PubMed1993

Effects of training and immobilization on VO2 and DO2 in dog gastrocnemius muscle in situ.

To investigate the effects of exercise training and immobilization on peak O2 uptake (VO2) and effective O2 diffusive conductance (DO2) in skeletal muscle, three groups of purpose-bred hounds [control (C), exercise trained (E), and immobilized (I)] were studied. Group E exercised on a treadmill 1 h/day, 5 days/wk for 8 wk, while groups C and I were cage confined for 8 wk, with group I undergoing left hindlimb immobilization for the last 3 wk. Thereafter, each dog's left gastrocnemius was surgically isolated, pump perfused, and electrically stimulated to elicit peak VO2 in situ at three levels of arterial oxygenation. O2 delivery [(arterial O2 concentration x muscle blood flow)/100 g muscle] was kept constant among the three groups at each level of arterial oxygenation. Compared with group C, peak VO2/100 g muscle was 38, 33, and 19% greater and DO2/100 g muscle was 71, 75, and 68% greater during normoxia, moderate hypoxia, and severe hypoxia, respectively, in group E (P < 0.02), whereas no differences from control were found in group I. We conclude that O2 delivery is not the unique determinant of peak VO2 and that exercise training improves the functional blood-tissue gas exchange properties of the muscle itself. Immobilization sufficient to reduce muscle weight by 31% and citrate synthase activity by 68% has no effect on peak VO2/100 g muscle or DO2/100 g muscle.

Acid-Base Equilibrium↗

PubMed1993

Cardiopulmonary response to exercise in patients with intrapulmonary vascular shunts.

The majority of patients with intrapulmonary right-to-left shunting due to pulmonary arteriovenous malformations-exhibit good maximum exercise capacity (> 70% predicted) despite profound arterial oxygen desaturation. We studied seven such patients to assess tissue oxygen delivery during steady-state exercise. From rest to exercise [50 +/- 7 (SE) W] arterial saturation fell from 80 +/- 3 to 74 +/- 3%, and mean right-to-left shunt increased slightly from 31 +/- 4 to 34 +/- 5% (P = NS). Minute ventilation was high for oxygen uptake, and the ventilatory equivalent was raised (174 +/- 19% predicted) and was correlated with shunt size (r = 0.93). The majority of the patients maintained pulmonary alveolar blood flow within the predicted range for their power output, but total cardiac output was increased to 142 +/- 11% predicted due to flow through the shunt. Consequently, on exercise, oxygen delivery per unit oxygen consumption [2.3-3.3 (normal range 1.6-2.4)] and calculated mixed venous oxygen tension (27.0 +/- 0.8 Torr) were preserved. Arterial PCO2 rose on exercise by 2.8 +/- 1.2 Torr, in proportion to the ratio of flow through the shunt to total cardiac output (r = 0.73), but remained low (33.1 +/- 1.4 Torr) in absolute terms. The high cardiac output on exercise may be facilitated by a low pulmonary vascular resistance (0.33 +/- 0.08 mmHg.1-1.min, measured at rest), which may explain why exercise performance is better in these patients than in patients with equivalent hypoxemia from other causes.

Adolescent↗

PubMed1992

CO2 and avian eggshell formation at high altitude.

We tested the hypothesis that altitude-induced hypocapnia in hens reduces eggshell conductance to water vapor (GH2O). Seven laying hens (Gallus domesticus) native to 1200 m were chronically exposed to high altitude (3800 m), and then to high altitude with sufficient inspired CO2 to relieve hypocapnia (3800 m + CO2). Egg GH2O was measured gravimetrically, shell thickness was measured with a micrometer, and aggregate pore area was calculated from measured values using Fick's law. Comparing results at 1200 m (n = 118) and 3800 m (n = 102), GH2O was reduced from 13.9 +/- 0.2 to 12.6 +/- 0.2 mg/(d.Torr)(mean +/- SE), shell thickness was reduced from 0.297 +/- 0.003 mm to 0.287 +/- 0.003 mm, and calculated aggregate pore area per egg was reduced from 1.97 +/- 0.03 mm2 to 1.72 +/- 0.03 mm2. When hypocapnia was relieved at 3800 m + CO2 (n = 82), GH2O was reduced even further to 11.1 +/- 0.2 mg/(d.Torr), shell thickness increased to 0.305 +/- 0.003 mm, and aggregate pore area was reduced to 1.61 +/- 0.03 mm2. Based on these results we reject our hypothesis. We conclude that hypocapnia is responsible for thin eggshells at altitude. Other physiological stimuli must cause the reductions in eggshell GH2O and pore area.

Altitude↗

PubMed1992

Avian arterial chemoreceptor responses to steps of CO2 and O2.

The responses of avian arterial chemoreceptor preparations to 44-sec steps of inspired CO2 and O2 were quantified. Anesthetized ducks were unidirectionally ventilated, arterial pH was recorded with a fast responding indwelling electrode, and neural activity was recorded from 28 preparations consisting of dissected filaments of the vagus nerve (23 single-fibered, 5 few-fibered). We analyzed responses using cycle-triggered stimulus histograms of neural discharge, cross correlation analysis, and analysis of variance. Average responses of the chemoreceptor preparations to PaCO2 steps from 24 +/- 1 to 38 +/- 1 Torr were larger (per Torr), occurred faster, and appeared more rate sensitive than the responses to PaO2 steps from 101 +/- 3 to 56 +/- 2 Torr. Average responses to CO2 steps usually appeared more rate sensitive when measured during arterial hypoxia than during arterial normoxia. These characteristics are very much like those reported for mammalian arterial chemoreceptors, except that responses of avian chemoreceptor preparations to repetitive CO2 steps were highly variable according to statistical analysis.

Animals↗

PubMed1992

Digital image analysis of shark gills: modeling of oxygen transfer in the domain of time.

Digital radiographic imaging of blood circulation through leopard shark gills establishes a secondary lamellar transit time of 6.5 s. This duration, combined with estimates of cardiac output and hemoglobin-oxygen affinity, permits novel modeling of gill oxygen transfer in the time domain. The temporal model allows assessment of factors contributing to previously noted discrepancies between physiological and morphometric branchial oxygen conductance estimates. Lamellar transit time for shark blood is 20 times greater than human alveolar transit time, and thus correlates with a slower rate of hemoglobin-oxygen binding and a greater diffusion distance.

Animals↗

PubMed1991

Estimating exercise DLO2 and diffusion limitation in patients with interstitial fibrosis.

Inert gas elimination studies in interstitial fibrosis ascribe all of the resting and most (58-83%) of the exercise (A-a)PO2 difference to ventilation-perfusion inequality. The previous paper (Hughes, J.M.B., D.N.A. Lockwood, H.A. Jones and R.J. Clark, (1991) Respir. Physiol. 83:155-166) [corrected] suggests from estimates of global DLO2/Q beta ratios a larger role for diffusion limitation on exercise. Gas exchange data from that paper was analyzed at rest and on exercise for five patients with interstitial fibrosis. Hypoxemia at rest was attributed to VA/Q inequality which was quantified using a log-normal lung model. DLO2 was calculated by Bohr integration. The base 10 LogSDQ at rest averaged 0.5 +/- 0.1 (SEM). On the assumption that VA/Q inequality remained unchanged on exercise, DLO2 (exercise) was estimated to be 14.3 +/- 1.9 ml.min-1.Torr-1. At that level of DLO2, diffusion limitation accounted for 36% +/- 8(SEM)% of the total (A-a)PO2 difference using the log-normal VA/Q model. But estimates of DLO2/Q beta assuming a homogenous lung, ascribed 96% of the (A-a)PO2 gradient on exercise to diffusion limitation. This discrepancy was shown to be related to the shape of the oxygen equilibrium curve and high alveolar PO2 values. On the other hand, analysis in terms of oxygen contents showed that 68 +/- 5% of the (A-a) content difference was accounted for by diffusion limitation. This differs substantially from estimates based on partial pressure alone.

Aged↗