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Ventilatory acclimatization to hypoxia is the time-dependent increase in ventilation that occurs with chronic exposure to hypoxia. Despite decades of research, the physiological mechanisms that increase the hypoxic ventilatory response during chronic hypoxia are not well understood. This review focuses on adaptations within the central nervous system (CNS) that increase the hypoxic ventilatory response. Although an increase in CNS responsiveness had been proposed many years ago, only recently has strong experimental evidence been provided for an increase in the CNS gain in the rat, which has proved to be a good model of VAH in humans. Within the CNS, several neuroanatomical sites could be involved as well as changes in various neurotransmitters, neuromodulators or signalling mechanisms within any of those sites. Lastly, adaptations within the CNS could involve both direct effects of decreased P(O(2)) and indirect effects of increased afferent nerve activity due to chronic stimulation of the peripheral arterial chemoreceptors.

Intermittent hypoxia (IH), or periodic exposure to hypoxia interrupted by return to normoxia or less hypoxic conditions, occurs in many circumstances. In high altitude mountaineering, IH is used to optimize acclimatization although laboratory studies have not generally revealed physiologically significant benefits. IH enhances athletic performance at sea level if blood oxygen capacity increases and the usual level of training is not decreased significantly. IH for high altitude workers who commute from low altitude homes is of considerable practical interest and the ideal commuting schedule for physical and mental performance is being studied. The effect of oxygen enrichment at altitude (i.e., intermittent normoxia on a background of chronic hypoxia) on human performance is under study also. Physiological mechanisms of IH, and specifically the differences between effects of IH and acute or chronic continuous hypoxia remains to be determined. Biomedical researchers are defining the molecular and cellular mechanisms for effects of hypoxia on the body in health and disease. A comparative approach may provide additional insight about the biological significance of these effects.

Cognitive and motor function are known to deteriorate with the hypoxia accompanying high altitude, posing a substantial challenge to the efficient operation of high altitude industrial and scientific projects. To evaluate the effectiveness of enriching room air oxygen by 6% at 5,000 m altitude in ameliorating such deficits, 24 unacclimatized subjects (16 males, 8 females; mean age 37.8, range 20 to 47) underwent neuropsychological testing in a specially designed facility at 3,800 m that can simulate an ambient 5,000 m atmosphere and 6% enrichment at 5,000 m. Each subject was tested in both conditions in a randomized, double-blinded fashion. The 2-h test battery of 16 tasks assessed various aspects of motor and cognitive performance. Compared with simulated breathing air at 5,000 m, oxygen enrichment resulted in higher arterial oxygen saturations (93.0 vs. 81.6%), quicker reaction times, improved hand-eye coordination, and more positive sense of well-being (on 6 of 16 scales), each significant at the p < 0.05 level. Other aspects of neuropsychological function were not significantly improved by 6% additional oxygen.

The hypoxic ventilatory response (HVR) can be modulated by dopamine D(2)-receptors (D(2)-R) in both the carotid body arterial chemoreceptors and the nucleus tractus solitarius (NTS), the primary synapse site of carotid body afferents. We hypothesized that chronic hypoxia alters D(2)-R gene expression to initiate changes in D(2)-R modulation of the HVR and enhance ventilatory acclimatization to hypoxia. Thus, we used a competitive reverse transcription-polymerase chain reaction (RT-PCR) method to quantify changes in D(2)-R mRNA levels in the rat carotid body and NTS after 0, 6, 12, 24, 48, or 168 h of hypobaric hypoxia (P(IO(2))=80 Torr). In the rostral NTS, hypoxia significantly increased D(2)-R mRNA at all time points. In the caudal NTS, D(2)-R mRNA levels initially increased in response to hypoxia and then significantly decreased to 71+/-5% and 71+/-6% of control after 48 and 168 h of hypoxia, respectively. In the carotid body, D(2)-R mRNA levels significantly decreased to 59+/-2% of control after 48 h of hypoxia; however, they significantly increased to 274+/-22% of control after 168 h. These results suggest that changes in D(2)-R mRNA in the arterial chemoreflex pathway and corresponding changes at the protein and signaling levels may contribute to the time-dependent changes in ventilation observed with chronic hypoxia. Specifically, decreased carotid body inhibition by D(2)-R could increase the HVR after 2 days of hypoxia.

Chronic hypoxia increases the hypoxic ventilatory response (HVR) in awake rats and the phrenic nerve response to carotid sinus nerve stimulation in anesthetized rats. An increased O2 sensitivity of the arterial chemoreceptors contributes to the increase in the HVR, but changes in the CNS processing of afferent information from arterial chemoreceptors are also involved. Adult male Sprague-Dawley rats were exposed to 0-7 days of hypobaric hypoxia (PIO2 = 80 Torr). Ventilation was measured in rats exposed to 0, 2 and 7 days of hypoxia using whole-body plethysmography. Ventilation increased after 2 days and remained elevated after 7 days of hypoxia. Following dopamine D2 receptor (D2-R) blockade in the CNS, frequency significantly decreased after 0 and 7 days of hypoxia, but did not change significantly after 2 days of hypoxia. In anesthetized rats, the phrenic nerve response to carotid sinus nerve stimulation was reduced following systemic D2-R blockade in control rats and those exposed to 7 days of hypoxia. After 2 days of hypoxia, there was no effect of blocking systemic D2-R. To determine whether changes in D2-R mRNA precede physiological changes, competitive RT-PCR was used to quantify D2-R mRNA in micropunches from the nucleus tractus solitarius (NTS) in normoxic and chronically hypoxic rats. In hypoxia, D2-R mRNA in the caudal NTS initially increased (6-12 hours) and then decreased below control levels (24 hours-7 days). These results show that chronic hypoxia causes time-dependent changes in D2-R that could result in changes in the ventilatory response to hypoxia.

Chronic exposure to hypoxia results in a time-dependent increase in ventilation called ventilatory acclimatization to hypoxia. Increased O(2) sensitivity of arterial chemoreceptors contributes to ventilatory acclimatization to hypoxia, but other mechanisms have also been hypothesized. We designed this experiment to determine whether central nervous system processing of peripheral chemoreceptor input is affected by chronic hypoxic exposure. The carotid sinus nerve was stimulated supramaximally at different frequencies (0.5-20 Hz, 0.2-ms duration) during recording of phrenic nerve activity in two groups of anesthetized, ventilated, vagotomized rats. In the chronically hypoxic group (7 days at 80 Torr inspired PO(2)), phrenic burst frequency (f(R), bursts/min) was significantly higher than in the normoxic control group with carotid sinus nerve stimulation frequencies >5 Hz. In the chronically hypoxic group, peak amplitude of integrated phrenic nerve activity ( integral Phr, percent baseline) or change in integral Phr was significantly greater at stimulation frequencies between 5 and 17 Hz, and minute phrenic activity ( integral Phr x f(R)) was significantly greater at stimulation frequencies >5 Hz. These experiments show that chronic hypoxia facilitates the translation of arterial chemoreceptor afferent input to ventilatory efferent output through a mechanism in the central nervous system.

The abundance of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, and neuropeptide Y (NPY)-immunoreactive nerve fibers in the carotid body was compared between normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). The immunoreactive fibers appeared as thin processes with many varicosities, and were distributed mainly around the vasculatures. In the normoxic control carotid body, NPY fibers were more numerous than VIP, CGRP, and SP fibers. In the chronically hypoxic rats, the carotid body was enlarged several fold, and the mean absolute number of VIP and NPY fibers was 3.88 and 2.22 times higher than in the normoxic carotid body, respectively, although that of SP and CGRP fibers was not changed. When expressed as density per unit area of the parenchyma, the density of SP and CGRP fibers in the chronically hypoxic carotid body decreased significantly to under 50%, the density of VIP fibers increased significantly 1.80 times, and the density of NPY fibers were unchanged. Immunoreactivity for four neuropeptides was not found in the glomus cells of normoxic or chronically hypoxic carotid bodies. These results suggest that altered peptidergic innervation of the chronically hypoxic carotid body is one feature of hypoxic adaptation. Because these neuropeptides are vasoactive in nature, altered carotid body circulation may contribute to modulation of the chemosensory mechanisms by chronic hypoxia., (Copyright 1998 Elsevier Science B.V.)

We carried out a randomized, double-blind trial at 3800 m altitude to test whether a small degree of room oxygen enrichment at night improves sleep quality, and performance and well-being the following day. Eighteen sea-level residents drove from sea level to 3800 m in one day, and then slept one night in ambient air, and another night in 24% oxygen, the order being randomized. With oxygen enrichment the subjects had fewer apneas (P < 0.01) and spent less time in periodic breathing with apneas (P < 0.01) than when they slept in ambient air. Subjective assessments of sleep quality were also significantly improved. There was a lower acute mountain sickness score during the morning after oxygen-enriched sleep (P < 0.01) and a greater increase in arterial oxygen saturation from evening to morning (P < 0.05). The larger increases in arterial oxygen saturation from evening to morning suggest that the control of breathing may have been altered. Installing an oxygen-enriched room at high altitude is relatively simple and inexpensive, and shows promise for improving well-being of both commuters and residents.

The ventilatory response to hypoxia depends on the pattern and intensity of hypoxic exposure and involves several physiological mechanisms. These mechanisms differ in their effect (facilitation or depression) on different components of ventilation (tidal volume and frequency) and in their time course (seconds to years). Some mechanisms last long enough to affect future ventilatory responses to hypoxia, indicating 'memory' or functional plasticity in the ventilatory control system. A standard terminology is proposed to describe the different time domains of the hypoxic ventilatory response (HVR) and to promote integration of results from different experimental preparations and laboratories. In general, the neurophysiological and neurochemical basis for short time domains of the HVR (seconds and minutes) are understood better than longer time domains (days to years), primarily because short time domains are studied in the laboratory more easily. Understanding the mechanisms for different time domains of the HVR has important implications for both basic and clinical science.

HP 228 is a synthetic heptapeptide analog of alpha-MSH that attenuates the production and release of inflammatory cytokines. The purpose of this study was to define HP 228's effects, alone and in combination with morphine, on resting ventilation and the ventilatory response to hypoxia and hypercarbia. Six healthy nonsmoking young adult males completed the four-session experiment. Subjects first underwent an initial training session. During subsequent sessions, each subject was tested for the respiratory effects of intravenous HP 228 (30 microg/kg), morphine (0.15 mg/kg), or HP 228 (30 microg/kg) plus morphine (0.15 mg/kg) in a double-blind placebo-controlled randomized balanced within-subjects experimental design. Sessions began with baseline measurement of resting ventilation, oxygen consumption, the isocapnic hypoxic ventilatory response (HVR), and normoxic hypercapnic ventilatory response (HCVR). A second set of respiratory measurements were obtained 10 min after completion of HP 228 or placebo infusion. Morphine or placebo was then administered and ventilatory responses were determined 15 and 40 min postinfusion. HP 228 produced cutaneous flushing, but had no significant effect on respiration or hemodynamics. Morphine significantly decreased metabolism, resting ventilation, and hypoxic and hypercarbic ventilatory responsiveness, independent of prior HP 228 administration. A seventh subject experienced a significant cardiac arrhythmia upon exposure to hypoxia after receiving both HP 228 and morphine and was withdrawn from further study. In conclusion, in this early Phase I clinical trial, HP 228 was found to neither depress ventilation nor augment morphine-induced respiratory depression in healthy young males.

The terminal differentiation of myelinating glia involves complex interactions that culminate in the formation of myelin. The POU domain transcription factor Tst-1/Oct-6/SCIP is expressed transiently during myelination, and we report here that it has a critical role in this developmental process. Deletion of the Tst-1/Oct-6/SCIP gene produces a severe defect in peripheral myelination by arresting Schwann cell maturation before axonal wrapping. Unexpectedly, the activation of major myelin-specific genes appears to be unaffected by the Tst-1/Oct-6/SCIP mutation, demonstrating that multiple, independently regulated events are required for terminal differentiation of Schwann cells. In addition, aberrant differentiation and migration of specific neurons in Tst-1/Oct-6/SCIP mutant homozygotes is associated with a fatal breathing defect, providing a model for investigating the regulation of pulmonary homeostasis.

The distribution of substance P and calcitonin gene-related peptide immunoreactive nerve fibers in the trachea was compared between normoxic and chronically hypoxic rats (at 380 mm Hg for 10 weeks). In the normoxic trachea, the immunoreactivity to either peptide was seen in the nerve fibers in four principal locations: a) within and b) under the ciliated epithelium, c) within the smooth muscle bundles in the posterior wall, and d) in the connective tissue and around blood vessels in the lamina propria and submucosa. These immunoreactive fibers within the epithelium and smooth muscle bundles, in the connective tissue, and around blood vessels were thin and displayed some varicosities, and those under the epithelium appeared as thick nerve bundles. When the distribution and density of immunoreactive fibers were compared between normoxic and chronically hypoxic tracheas, there was a difference in number of substance P and calcitonin gene-related peptide immunoreactive fibers penetrating into the epithelium, although there was no difference in the other three locations. The mean number of substance P and calcitonin gene-related peptide immunoreactive intraepithelial fibers per section of the chronically hypoxic trachea was significantly increased. Because substance P and calcitonin gene-related peptide are predominant signal peptides of primary sensory neurons, the increase of substance P and calcitonin gene-related peptide immunoreactive fibers suggests that altered airway reflexes may be a feature of hypoxic adaptation.

During exercise, pulmonary gas exchange in reptiles was predicted to differ from that in mammals because of their less complex lung structure, which might reduce ventilation-perfusion heterogeneity (V/QL) at the expense of pulmonary diffusion limitation. To investigate this, the multiple inert gas elimination technique was used in six Varanus exanthematicus at rest and during maximal exercise. Trace amounts of six inert gases were infused into the external jugular vein and blood samples were collected from the pulmonary artery and the left atrium. Mixed expired gas samples and ventilatory and metabolic data were acquired. Indices of V/QL heterogeneity, calculated using a 50-compartment model, were low at rest (log standard deviation of perfusion distribution, logSDQ = 0.39) and increased significantly with exercise (logSDQ = 0.78). Oxygen diffusion limitation was apparent during exercise and was comparable to reported mammalian values. A molecular-mass-dependent limitation, suggesting limited intrapulmonary gas mixing, was evident only at rest. An increase in left atrial PO2 from 82mmHg at rest to 96 mmHg during exercise was associated with a corresponding decrease in PCO2. These data indicate adequacy of pulmonary ventilation and gas exchange for metabolic demands in exercising varanid lizards and suggest that less complex lung structures are not necessarily linked to increased pulmonary diffusion limitation.

Epidemiological studies suggest that beta-carotene supplementation may decrease atherosclerotic events. Because beta-carotene is transported in low-density lipoprotein (LDL), one mechanism by which this protective effect may occur is through direct inhibition of LDL oxidation. Addition of beta-carotene to LDL in vitro inhibits the susceptibility of LDL to oxidation. In contrast, we have shown that feeding large doses of beta-carotene results in beta-carotene-enriched plasma LDL (16- to 35-fold), but such LDL does not show increased resistance to oxidation. Potential criticisms of our initial study relate to the unique antioxidant properties of beta-carotene. Beta-Carotene provides better quenching of some free radicals, such as singlet oxygen, than others. Additionally, since beta-carotene can easily autooxidize, forming metabolites that can also generate free radicals, it has been argued that at sufficient concentrations in vivo the antioxidant effect of beta-carotene may be diminished. It has thus been suggested that in our initial study we may have failed to properly assess the unique antioxidant effects of beta-carotene by our selection of oxidizing conditions and/or failed to achieve antioxidant activity because of excessive enrichment of LDL with beta-carotene. We now report the effects of feeding lower doses of beta-carotene on the susceptibility of LDL to oxidation and test whether any antioxidant activity of beta-carotene can be detected when different modes of initiating oxidation are used. Because the antioxidant activity of beta-carotene is reputedly most pronounced in low-oxygen environments, we also investigated its effect on LDL oxidation under conditions of reduced oxygen tension.(ABSTRACT TRUNCATED AT 250 WORDS)

The ultrastructural characteristics of the glomus cells in the rat carotid body exposed to extremely long-term hypoxia (10-12 weeks) were investigated. The glomus cells could be classified into four distinct types according to the shape of dense-cored vesicles in the glomus cell cytoplasm: 1) small vesicle cells (SVCs, 50 nm in mean diameter), 2) large vesicle cells (LVCs, 80 nm in mean diameter), 3) dilated eccentric vesicle cells (EVCs, 400-800 nm in diameter), and 4) mixed vesicle cells (MVCs, large and eccentric vesicles). Many clusters of glomus cells were found to contain all four categories of cell types. The appearance of EVCs was a unique and common characteristic of glomus cells in this long-term hypoxia model. We also noted other ultrastructural features with chronic hypoxia which are characteristic of the amphibian carotid labyrinth glomus cells: 1) incomplete covering of glomus cells with the supporting cell missing over a wide area, 2) long thin cytoplasmic projections in the intervascular stroma, and 3) intimate apposition of the glomus cells and pericytes (g-p connection), endothelial cells (g-e connection), plasma cells, and fibrocytes. Because arterial PO2 is generally low in amphibia, these may be general features of hypoxic adaptation and facilitate both uptake of oxygen from blood and release of catecholamine into the blood. The g-p and g-e connections may take part in the regulation of the microcirculation in the enlarged carotid body.

We compared the hypoxic ventilatory response (HVR) of two groups of unrestrained awake male rats (300-550 g): those acclimatized to hypoxia > 7 wk at simulated altitude (380 Torr, n = 12) and sea level controls (n = 8). Chronic catheters were placed in the iliac artery and vein 3-7 days before study. An "on-line" system was used to measure arterial PO2 and PCO2. Arterial blood was drawn via a roller pump past O2 and CO2 electrodes and returned to the vein. Batch samples were taken before and after HVR measurements for calibrating and determining arterial pH and hematocrit. Inspired ventilation, tidal volume, and respiratory frequency were measured with barometric pressure plethysmography at several levels of inspired O2 fraction (0.08-0.30) maintained for 15 min. For isocapnic HVR, inspired CO2 fraction was increased as necessary to maintain arterial PCO2 at the hyperoxic level. In both groups, poikilocapnic HVRs (inspired CO2 fraction = 0) were significantly less than isocapnic HVRs. Isocapnic HVRs were significantly greater in hypoxia-acclimatized (2,783 +/- 233 ml.min-1.kg-1) than in sea level control rats (1,826 +/- 106 ml.min-1.kg-1), mainly due to a significant increase in tidal volume (P < 0.05). In conclusion, relieving hypocapnia in hypoxia, by maintaining isocapnia, reveals a significant increase in the ventilatory response to arterial PO2 in awake rats with chronic hypoxia.

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.

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.

To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1-5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P'CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min-1. Mean P'CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4-7). HVR was independent of test SaO2 (range 60-90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the effects of hypercapnia (FICO2 = 0.07) and hypoxia (FIO2 = 0.13) on the cricothyroid muscle response (peak integrated CT EMG) to graded inspiratory resistance (RI). Five anesthetized dogs spontaneously breathed through the upper airway (UAB) or a side arm of a tracheotomy cannula bypassing the larynx (TB). With room air UAB, graded increases in RI increased CT EMG, upper airway pressure change (Paw) and esophageal pressure change (Pes, indicating increased inspiratory drive), but decreased VT. For room air TB, the effects of RI were much less but still significant. Hypercapnia increased VT, fR, Pes, Paw and CT EMG for any given RI during UAB more than during TB. Hypoxia increased fR but did not increase VT, Pes, Paw, or CT EMG. The results are consistent with a model predicting CT activity as additive functions of inspiratory drive and laryngeal receptor stimulation by Paw and no direct effects of chemoreceptor stimulation on the CT, independent of those resulting from changes in inspiratory drive and upper airway pressure.

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.

We measured ventilation (V1) and arterial blood gases in awake Pekin ducks exposed to normoxia at sea level, normobaric hypoxia achieved by lowering FIO2 at normal barometric pressure (NORMO), and hypobaric hypoxia achieved with a low pressure chamber and 21% O2 (HYPO). Average normoxic values were: V1 = 0.46 L . (kg.min)-1, PaO2 = 99.7 Torr, PaCO2 = 30.1 Torr. At PIO2 = 90 Torr, NORMO and HYPO measurements were not significantly different (P greater than 0.05). At PO2 = 46 Torr, NORMO V1 was less than HYPO V1 but blood gases were not significantly different: VI = 1.00 vs 1.45 L . (kg.min)-1; PaO2 = 31.3 vs 33.0 Torr; PaCO2 = 11.5 vs 10.6 Torr. Although both tidal volume (VT) and respiratory frequency (fR) were greater in HYPO, similar blood gases with NORMO and HYPO suggest similar parabronchial ventilation. The results suggest increased physiologic dead space, caused by reduced efficacy of aerodynamic valving, with reduced gas density in hypobaria.

To understand the structural basis of avian gas exchange better, we made a morphometric study of domestic and Canada goose lungs. The volume of glutaraldehyde-fixed domestic goose lungs (30 cm3/kg body weight) was similar to that determined from silicone casts of Canada goose lungs by Duncker (33 cm3/kg). To examine finer structures, we rapidly froze goose lungs under physiologic conditions, fixed tissue samples by a freeze substitution procedure and analyzed samples with stereological methods. From light micrographs we determined that about 55% of the lung is parabronchi in both species. Volume densities of air capillaries, blood capillaries and tissue and surface:volume ratios of these same structures were determined from electron micrographs. Our measurements agree with those from glutaraldehyde-fixed Canada goose lungs from other laboratories. Gas exchange surface area was largest in the good flier (Canada goose) but both birds had larger surface areas than comparably sized mammals. The harmonic mean blood-gas barrier thickness is smaller in both species of birds (0.3 microns) than in mammals. Thus, membrane diffusing capacities for gases should be larger in birds than in mammals. Pulmonary blood capillary transit time, as calculated from blood capillary volume and normal levels of cardiac output, are longer in birds than in mammals and should allow more time for blood-gas equilibrium. Pleats and folds were frequently observed in air and blood capillaries, suggesting that the avian lung may not be as rigid as was previously thought and that capillary volumes and surface areas may change under physiologic conditions.

The effects of body temperature (Tb) on pulmonary stretch receptor (PSR) and CO2-sensitive intrapulmonary chemoreceptor (IPC) response characteristics may have important effects on ventilatory control in reptiles. In this study, three questions were addressed: (1) what are the effects of Tb on PSR and IPC responses to airway pressure (Paw) and lung CO2 (PCO2); (2) what are the effects of acute (less than 12 h) vs chronic (greater than 1 week) changes in Tb on both receptor groups; and (3) can predicted changes in the fractional dissociation of imidazole (alpha im), calculated via independent changes in Tb and PCO2, explain the CO2-sensitivity of either IPC or PSR? Single fiber PSR and IPC responses to Paw, PCO2 and Tb were determined in 11 anesthetized Alligator mississippiensis (pentobarbital; 30 mg/kg), acclimated at 20 degrees C (N = 5) or at 30 degrees C (N = 6). PSR activity increased as Paw increased at both Tb, but PSR activity and sensitivity to Paw were lower at 20 degrees C. The average Q10 was 2.1. Increasing inhaled CO2 from 1 to 7% decreased PSR activity by 27 +/- 6% at 20 degrees C and 18 +/- 5% at 30 degrees C. IPC activity decreased as PCO2 increased at both Tb, but IPC activity and sensitivity were reduced at 20 degrees C. The average Q10 was 3.2. Increasing Paw from 2 to 10 cm H2O had inconsistent effects on IPC activity. There were no differences between the effects of acute or chronic changes in Tb on either PSR or IPC responses. Predicted changes in alpha im could not explain the CO2-sensitivity of either IPC or PSR. We conclude that PSR and IPC adapt rapidly to Tb changes. The larger Q10 of IPC suggests that the relative role of IPC vs PSR in ventilatory control may be greater at elevated body temperatures.

Variations of CO2 and O2 concentrations within a respiratory cycle were recorded at various sites in the bronchial system of anesthetized, spontaneously ventilating ducks, using small metal cannulae introduced into the main bronchus (MB), a medioventral (MV) or mediodorsal (MD) secondary bronchus and connected to a mass spectrometer for continuous gas analysis. The following results were obtained and conclusions drawn. (1) Since during inspiration, CO2 concentration (FCO2) was close to zero all along MB and since FCO2 was nearly constant throughout the respiratory cycle in MV, it must be inferred that on inspiration, no significant amount of air passes directly either from MV to MB or in the opposite direction, there being thus a complete functional valving of the MV orifices. In particular the Hazelhoff loop mechanism (inspiratory reflux of lung gas into the MB) is not operative. (2) During expiration, FCO2 in MV was only slightly higher than that in the trachea, but substantially above FCO2 deep in MB. This suggests that most of the expiratory flow from caudal air sacs is diverted through the paleopulmo and only little exits directly through MB. It is shown that the functional valving of bronchial air flow is advantageous for gas exchange as it reduces air shunts and provides a nearly steady lung ventilation.

We measured V/Q distributions with the multiple inert gas elimination technique in five anesthetized artificially ventilated American alligators at 24 degrees C. The overall V/Q was relatively high (2.0 to 7.2) because of continuous artificial ventilation. The V/Q distributions were usually unimodal (log standard deviation of Q distribution averaged 0.47 +/- 0.09 [SD] and there was considerable shunt (28.5 +/- 10.3% of cardiac output). The data are consistent with a pulmonary, rather than central cardiovascular shunt. We also detected a molecular weight dependent limitation to inert gas elimination. The difference in error of fit to enflurane and cyclopropane retentions was significantly greater than predicted from experimental error. The estimated stratification diffusing capacity, a measure of this limitation, was 10% of the value estimated for mammals and similar to morphometric estimates of membrane diffusing capacity in alligators, which is comparatively low. Hence, even though the multicameral lungs of alligators are unevenly partitioned and have large gas phase diffusion spaces, V/Q matching and molecular weight dependent limitations are relatively small. Shunt, dead space and membrane diffusion resistances can be more important limitations of gas exchange.

We have detected acetone in several brands of heparin. If uncorrected, this leads to errors in measuring acetone in blood collected in heparinized syringes, as in the multiple inert gas elimination technique for measuring ventilation-perfusion ratio (VA/Q) distributions. Error for acetone retention [R = arterial partial pressure-to-mixed venous partial pressure (P-V) ratio] is usually small, because R is normally near 1.0, and the error is similar in arterial and mixed venous samples. However, acetone excretion [E = mixed expired partial pressure (P-E)-to-P-V ratio] will appear erroneously low, because P-E is accurately measured in dry syringes, but P-V is overestimated. A physical model of a homogeneous alveolar lung at room temperature and without dead space shows: the magnitude of acetone E error depends upon the ratio of blood sample to heparinized saline volumes and acetone partial pressures, without correction, acetone E can be less than that of less soluble gases like ether, a situation incompatible with conventional gas exchange theory, and acetone R and E can be correctly calculated using the principle of mass balance if the acetone partial pressure in heparinized saline is known. Published data from multiple inert gas elimination experiments with acetone-free heparin, in our labs and others, are within the limits of experimental error. Thus the hypothesis that acetone E is anomalously low because of physiological mechanisms involving dead space tissue capacitance for acetone remains to be tested.

We measured shunt in seven anesthetized, mechanically ventilated Pekin ducks by the multiple inert gas elimination technique (MIGET) and by the oxygen method during 100% O2 breathing (O2 shunt). MIGET shunt measures only intrapulmonary shunt but O2 shunt measures intra- and extrapulmonary shunt (e.g. bronchial drainage). O2 shunt was calculated from oxygen contents of blood estimated from measured PO2 and standard O2 equilibrium curves at appropriate pH and hematocrit measured in 4 other ducks. In normal lungs MIGET shunt was 1.3 +/- 0.4 (mean +/- SEM) percent of cardiac output and O2 shunt was 6.3 +/- 1.3%. O2 shunt exceeded MIGET shunt by 5.4 +/- 1.4% which we attribute to extrapulmonary shunts. These include part of the bronchial circulation, thebesian veins and vertebral venous-pulmonary circulation connections. Both MIGET and O2 shunts increased when water was introduced into lungs. Overall, the relationship between % MIGET shunt and % O2 shunt was described by the equation: O2 shunt = 0.86 X MIGET + 5.67 (r = 0.96, n = 24).

We measured mean pulmonary arterial pressure (Ppa) during temporary unilateral pulmonary arterial occlusion (TUPAO) in 10 ducks. Ppa increased from 11.4 +/- 0.8 mmHg during control conditions to 18.8 +/- 1.8 during TUPAO. In 5 of the 10 ducks we also measured mean left atrial pressure (Pla) and cardiac output (Q). In these ducks Ppa significantly increased with TUPAO from 13.9 +/- 0.4 to 22.0 +/- 1.2 mmHg, whereas Pla and Q did not change significantly. Pulmonary vascular resistance (PVR) increased from 10.6 +/- 1.3 to 24.1 +/- 5.3 mmHg X min X 1(-1) on TUPAO. By assuming equal vascular resistance in either lung it can be calculated that the vascular resistance in only one lung was 22.5 +/- 3.5 mmHg X min X 1(-1) during control conditions. Thus doubling flow resulted in no significant change in one lung's vascular resistance. A morphometric study of both lungs of a domestic goose that were rapidly frozen during TUPAO indicated very little compliance in pulmonary blood capillaries. The relative volume of exchange tissue occupied by blood capillaries was 0.28 in the occluded lung and 0.36 in the perfused lung. Surface-to-volume ratios of blood capillaries were 12,524 cm-1 in the occluded lung and 11,056 cm-1 in the perfused lung. We conclude that PVR in birds is relatively insensitive to changes in Q, in contrast to mammals.

O2 diffusing capacity (DO2) was measured in anesthetized, unidirectionally ventilated ducks during hypercapnic hypoxia. DO2 averaged 78.2 mumol X (min X Torr)-1. This value increased to 97.3 mumol X (min X Torr)-1 after correction for ventilation-perfusion inequality. DO2 increased when pulmonary O2 exchange (MO2) and pulmonary blood flow (Q) were increased by either 2,4 dinitrophenol (DNP,ca. 5 mg/kg i.v.) or temporary unilateral pulmonary artery occlusion (TUPAO). DO2 increased with MO2 42.4 mumol X (mmol X Torr)-1 (R = 0.664), and with Q 80.3 mumol X (L X Torr)-1 (R = 0.895). Since there is evidence against expansion of membrane diffusing capacity through recruitment and distention of pulmonary capillaries in avian lungs, we suggest that the close coupling of DO2 to Q reflects a reduction of functional lung heterogeneity at higher blood flows, perhaps due to better matching of V to D, or D to Q.

Arterial PO2 in resting, normoxic avian lungs in not at the level of predicted for an ideal crosscurrent lung. In contrast to healthy alveolar lungs, such a reduction in efficiency of O2 exchange from optimal levels cannot be totally explained by ventilation/perfusion inequality, and the discrepancy is most likely related to diffusion resistances. The diffusing capacity of avian lungs (DLO2) will depend on: 1) stratification in the air capillaries, 2) blood-gas barrier morphology, 3) O2-Hb kinetics ( theta ), and 4) diffusive/perfusive conductance (D/ beta bQ) matching. Stratification in air capillaries, the membrane diffusing capacity, and time available in pulmonary capillaries for arterialization do not appear to be limiting at rest. D/ beta bQ inequality is expected in normoxic avian lungs but predictive models show that this should not limit O2 uptake. However, these resistances may interact in crosscurrent lungs or there may be other unknown diffusion limitations (e.g., theta ) to reduce PaO2 in birds. Recent morphologic evidence suggests DLO2 may increase in birds during exercise and V/Q and D/ beta bQ inequality would be expected to have less of an effect during hypoxia. Together, these factors may reconcile the relatively low PaO2 in resting birds at sea level and their ability to exercise at high altitudes.

Ventilation and blood gases were measured in unanesthetized ducks at various levels of inspired CO2 partial pressure (PICO2). Ventilation was markedly augmented with increasing PICO2, whereas arterial and mixed venous PCO2 stayed essentially constant up to a PICO2 of about 20 torr and changed only slightly between that and the highest level tested (34 torr). After carbonic anhydrase had been blocked, blood PCO2 was elevated at all levels of PICO2 but the ventilatory response to increases in PICO2 were attenuated. The response to CO2 in the normal bird (before administration of acetazolamide) shows similarities to that in mammals. Qualitative differences between both classes of vertebrates after blockade of carbonic anhydrase may, however, suggest differences in their systems that control ventilation.

We modified the multiple inert gas elimination technique, which was originally developed for alveolar lungs, to measure continuous distributions of V/Q in the cross-current lungs of birds. In theory, the method is also applicable to counter-current gas exchangers. The algorithms for inferring essentially continuous V/Q distributions from a limited number of measurements and the least-squares approach for dealing with experimental error are independent of the model of gas exchanger being studied. A Monte-Carlo procedure was used to predict the expected frequency of occurrence of given magnitudes of experimental error for each model. If the observed frequency distribution of error exceeds the predicted, then this indicates an incorrect choice of model (analogous to chi-square tests). Thirty-four data sets from 8 geese indicate that: (1) the assumptions of the technique are adequately met; (2) the alveolar model is not appropriate for birds, but the cross-current model is; and therefore; (3) the cross-current modification of the multiple inert gas elimination technique can be used to assess V/Q inequality in avian lungs.

The effects of airway CO2 and pressure on pulmonary vagal afferent fibers were studied in seven anesthetized alligators Alligator mississippiensis, at room temperature (24 degrees C). Of 49 receptors which fired in phase with ventilation, 13 behaved like mammalian rapidly adapting pulmonary stretch receptors, 19 like mammalian slowly adapting pulmonary stretch receptors (PSR), and 17 like avian intrapulmonary CO2-sensitive chemoreceptors (IPC). PSR and IPC were positively localized to the lung by punctate stimulation or response to airway CO2 changes during pulmonary artery occlusion. PSR discharge frequency (fPSR) was measured at airway pressures (Paw) from 0 to 15 cm H2O at FICO2 = 0.01 in 14 receptors. fPSR increased in all receptors throughout the range of Paw studied. In 13 PSR, increasing FICO2 from 0.01 to 0.07 decreased fPSR 23 +/- 13% (+/- SEM) at Paw = 2 cm H2O and 14 +/- 7% at 15 cm H2O. IPC discharge frequency (fIPC) decreased as FICO2 increased and most discharged less than 1 sec-1 at FICO2 = 0.03. In 7 IPC at FICO2 = 0.01, increasing Paw from 2 to 15 cm H2O increased fIPC 17 +/- 5% after pulmonary artery occlusion demonstrating some mechanosensitivity in alligator IPC. Although both IPC and PSR showed mechanosensitivity and CO2-sensitivity, the two receptor types were distinct. PSR were 13 times more sensitive to Paw changes than IPC and IPC were 14 times more sensitive to FICO2 changes than PSR. We did not find any receptors with intermediate CO2- or mechanosensitivities that could represent a transitional form of receptor. These results predict that IPC and PSR may have different roles in reflex ventilatory control.

We assessed ventilation-perfusion inequality in 8 anesthetized, tidally ventilated geese in terms of continuous V/Q distributions using the multiple inert gas elimination technique modified for cross-current avian lungs (Powell and Wagner, 1982). Thirty-four data sets were collected. Allowing for differences in solubility, high molecular weight gases (Enflurane, SF6) were not retained in the blood to any greater extent than the other gases, suggesting that diffusion in the gas phase is functionally complete. Shunt averaged only 0.4 +/- 0.1% (SEM) of cardiac output and areas of low V/Q were seldom seen. Twenty-nine of the 34 data sets had bimodal V/Q distributions with 10.6 +/- 1.4% of expired ventilation and 0.3 +/- 0.1% of cardiac output in a high V/Q mode; the physiological basis of the high mode is unknown. The log-standard deviation of the main Q mode averaged 0.56 or slightly greater than that for healthy men, dogs, or earlier estimates from unidirectionally ventilated birds. It is predicted that CO2 will be more impaired by such V/Q inequality than O2, but that increased ventilation will overcome the CO2 impairment more easily than that of O2 transport.

We investigated the influence of intrapulmonary chemoreceptors (IPC) on ventilatory movements in anesthetized chickens when PCO2 profiles along the parabronchi were changed. In all experiments the right lung was denervated, both lungs unidirectionally ventilated, and PaCO2 kept constant. In series 1 (7 birds), gas flow and the PCO2 profile in the left lung were reversed. PaCO2, PECO2 and ventilatory movements did not change. In Series 2 (4 birds), PCO2 in caudal regions of the innervated lung was elevated by increasing gas flow and P1CO2 from 0 to 21 Torr. Ventilatory movements did not change. In Series 3 (4 birds), either lung was over-ventilated with 7 or 49 Torr P1CO2, alternating the gases between lungs every 100 sec. Ventilatory movements changes with P1CO2 but much less than predicted from P1CO2 effects in the non-perfused, innervated lung. From the longitudinal distribution of IPC and PCO2 profiles in the lung we predicted moderate to large changes in ventilatory movements in all series. The discrepancy between predicted and observed results in Series 1 and 2 indicates that IPC in caudal regions of the lung have little effect on ventilation under the conditions examined. In Series 3, observed ventilatory movements were less sensitive to P1CO2 than predicted, indicating that IPC sense a different PCO2 than the PCO2 profile in the parabronchial lumen and that IPC have a significant sensitivity to pulmonary blood PCO2.

We measured deadspace (VD) in ducks using CO2 expirograms (plots of expired PCO2 vs expired volume) obtained during artificial ventilation at different tidal volumes (VT) and respiratory system volumes (VRS). Conventional analysis of the expirograms for Bohr and Fowler VD indicated both were larger than anatomic VD. Most expirograms at VT less than or equal to 100 ml had terminal slopes greater than predicted for lung gas and violated the usual assumptions of the Fowler calculation. Bohr VD was not affected by VRS but increased with VT. This can be explained by expired PCO2 not reaching lung values at low VT and an expiratory mesobronchial ventilatory shunt. We propose a measure of mesobronchial shunt corresponding to a volume of gas exhaled in one breath from caudal air sacs through the mesobronchus (VM). VM/VT changes with pump vs constant flow ventilation indicating sensitivity of VM to flow pattern. We estimate mesobronchial shunting is greatest at the beginning of expiration and approaches zero only near the end of a 200 ml expiration with constant flow ventilation.

The role of intrapulmonary chemoreceptors in the breath-to-breath control of spontaneous breathing was studied in anesthetized ducks by stimulating these receptors with changes in mixed venous CO2 loads during prolonged circulation time to the carotid bodies and brain by vascular loops placed in both brachiocephalic arteries. Blood equilibrated with gas mixtures of high (85% CO2-15% O2) or low CO2 (air) was infused into the right ventricle at 100 ml . min-1, while simultaneously withdrawing blood from the entrance of the right atrium at the same rate. A variety of cardiopulmonary and blood gas variables were measured. Infusing blood of high PCO2 increased both respiratory frequency and tidal volume long before the altered blood could have reached the carotid bodies or brain. The increase in ventilation was not enough to prevent a rise in PaCO2. Infusing blood of low PCO2 decreased both respiratory frequency and tidal volume. Again, the changes in respiration occurred before the infused blood had reached the carotid bodies or the brain. Infusion of blood similar in PCO2 to mixed venous blood did not significantly alter ventilation or arterial blood gases. The rapidity of the ventilation response to a change in mixed venous CO2 load led us to conclude that the intrapulmonary chemoreceptors can detect changes in mixed venous CO2 loads and that they initiate a ventilatory change appropriate to minimize alterations in PaCO2. These receptors, thus, can control breathing on a breath-to-breath basis in birds.

We have estimated the relative importance of changes in blood PCO2 and pH in determining activity of intrapulmonary chemoreceptors (IPC) in the unidirectionally ventilated duck. The response of single unit vagal afferents from IPC to changing lung gas PCO2 was tested before and after changing blood pH by intravenous infusion of NaHCO3. Using multiple linear regression analysis, we calculated how much of the change in IPC activity for a given change in PCO2 was due to the changing PCO2 at constant pH (CO2 sensitivity) or to the change in pH concomitant with the change in PCO2 (H+ sensitivity). For 10 IPC, the CO2 sensitivity was on the average 2.3 times larger than the H+ sensitivity. Changes in pH as well as PCO2 of lung blood should be considered in assessing the role of IPC in control of breathing.

The CO2 sensitivity of intrapulmonary CO2 receptors (IPC) in the duck was studied, before (Control) and after blockade of carbonic anhydrase by Diamox, by recording single unit afferent activity in the vagus nerve. During Control, IPC activity decreased with increasing airway CO2 concentration. After Diamox administration, the discharge from IPC was higher at all levels of airway PCO2, and the receptors' CO2 sensitivity was markedly attenuated. Comparing these results with measurements on ventilation and blood gases of the duck under similar experimental conditions (Powell et al., 1978b) suggests that IPC play a role in the adjustment of ventilation to altered concentrations of inspired CO2; IPC may thus be a significant component in the control of breathing under physiological conditions.

The steady-state discharge of fourteen arterial chemoreceptor preparations were recorded from the left cervical vagi of unidirectionally ventilated, pentobarbitone anaesthetized ducks. All were excited by both hypoxia and hypercapnia and these stimuli interacted multiplicatively, as they do in mammals. We located the receptive fields of three preparations by observing their responses to i.v. injections of 2,4-dinitrophenol before, during and after occlusion of various arteries. The responses of two preparations were consistent with their location in the ipsilateral carotid body, but the responses of one, containing two active fibres, suggested that its discharge originated in aortic bodies. The discharge of eleven preparations was not random, but came in short high frequency bursts. As stimulus intensity was increased by either hypoxia or hypercapnia the average number of impulses per burst decreased. We have shown that the arterial chemoreceptors of the duck are sensitive to both hypoxia and hypercapnia. Because the steady-state stimulus-response characteristics are essentially the same as those of mammals we suppose that both mammalian and avian chemoreceptors are excited by the same basic mechanism. We also show that ducks have active extra-carotid arterial chemoreceptors.

CO2 tensions in the caudal air sacs of birds cannot be quantitatively predicted by current models of avian respiration, mainly because the contribution of neopulmonic parabronchial gas exchange has not been determined. To overcome this problem we studied penguins that have purely paleopulmonic lungs. Three penguins were anesthetized, intubated, and ventilated at a constant respiratory rate and different tidal volumes (VT). PO2 and PCO2 were measured in arterial blood and end-expired, mixed-expired, interclavicular air sac, and caudal thoracic air sac gas. Interclavicular air sac and end-expired gas had similar compositions. Caudal thoracic air sac gas was intermediate in composition to end-expired and inspired gas, and its PCO2 was 1.5-3.5 times greater than the value predicted from reinhaled dead space. This difference between measured and predicted caudal thoracic air sac PCO2 increased with VT but showed no relationship to changes in dead space-to-VT ratio. The difference is not explained by stratification or diffusive gas exchange across air sac walls. The results can be explained by postulating that inspired gas passes over exchange surfaces on its path to caudal air sacs. This is unexpected in the purely paleopulmonic lungs of penguins and suggests that airflow may not be caudocranial in all paleopulmonic parabronchi.

Gas exchange in avian lungs is described by a cross-current model that has several differences from the alevolar model of mammalian gas exchange [e.g., end-expired PCO2 greater than arterial PCO2 (PaCO2)]. Consequently the methods available for estimating effective ventilation and physiological dead space (VDphys) in alveolar lungs are not suitable for an analysis of gas exchange in birds. We tested a method for measuring VDphys in birds that is functionally equivalent to the conventional alveolar VDphys. A cross-current O2-CO2 diagram was used to define the ideal expired point (PEi) and VDphys was calculated as from the equation, VDphys = [(PEiCO2--PECO2)/PEiCO2]. VT, where VT is tidal volume. In seven Pekin ducks VDphys was 13.8 ml greater than anatomic dead space and measured changes in the instrument dead space volume. VDphys also reflected changes in ventilation-perfusion inequality induced by temporary unilateral pulmonary arterial occlusion. Bohr dead space, calculated by substituting end-expired PCO2 for PEiCO2, was insensitive to such inhomogeneity. Enghoff dead space, calculated by substituting PaCO2 for PEiCO2, is theoretically incorrect for cross-current gas exchange and was often less than anatomic dead space. We conclude that VDphys is a useful index of avian gas exchange and propose a standard definition for effective parabronchial ventilation (VP) analogous to alveolar ventilation (i.e., VP = VE--VDphys, where VE is total ventilation).

We studied gas exchange in anesthetized ducks and geese artificially ventilated at normal tidal volumes (VT) and respiratory frequencies (fR) with a Harvard respirator (control ventilation, CV) or at low VT-high fR using an oscillating pump across a bias flow with mean airway opening pressure regulated at 0 cmH2O (high-frequency ventilation, HFV). VT was normalized to anatomic plus instrument dead space (VT/VD) for analysis. Arterial PCO2 was maintained at or below CV levels by HFV with VT/VD less than 0.5 and fR = 9 and 12 s-1 but not at fR = 6 s-1. For 0.4 less than or equal to VT/VD less than or equal to 0.85 and 3 s-1. less than or equal to fR less than or equal to 12 s-1, increased VT/VD was twice as effective as increased fR at decreasing arterial PCO2, consistent with oscillatory dispersion in a branching network being an important gas transport mechanism in birds on HFV. Ventilation of proximal exchange units with fresh gas due to laminar flow is not the necessary mechanism supporting gas exchange in HFV, since exchange could be maintained with VT/VD less than 0.5. Interclavicular and posterior thoracic air sac ventilation measured by helium washout did not change as much as expired minute ventilation during HFV. PCO2 was equal in both air sacs during HFV. These results could be explained by alterations in aerodynamic valving and flow patterns with HFV. Ventilation-perfusion distributions measured by the multiple inert gas elimination technique show increased inhomogeneity with HFV. Elimination of soluble gases was also enhanced in HFV as reported for mammals.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied discharge frequencies of 12 intrapulmonary chemoreceptors in the paleopulmonic lung of an emu (Dromiceius novaechollandiae) during unidirectional, artificial ventilation when step changes and static CO2 concentrations were given. Discharge frequency in afferent neurons from the receptors increased as intrapulmonary CO2 decreased. The response of the receptors to various static intrapulmonary CO2 concentrations was similar to that previously demonstrated for the duck and chicken. The median sensitivity of the emu receptors at one-half maximal discharge was 4.6 imp-(sec-0.01 F1CO2)-1. Discharge frequencies altered phasically in nine of 12 receptors when step changes in CO2 of 3.3% at 1.6 Hz were given in the unidirectional gas stream while four of 12 modulated their discharge when the CO2 changes were as rapid as 3.2 Hz. Hence, some receptors can respond to rapid fluctuations in CO2 in their microencironment. We conclude that intrapulmonary chemoreceptors in the paleopulmonic lung of the emu exhibit similar characteristics to those in birds that possess varying amounts of neopulmonic parabronchi, such as the duck and chicken.