Alveostat, an alveolar PACO2 and PAO2 control system.

In the study of the physiological regulation of respiration through a control system model it is necessary to test the ventilatory response to various forcing functions of either the parrtial pressure of alveolar carbon dioxide (PACO2) or oxygen (PAO2). Since PACO2 and PAO2 are both functions of alveolar ventilation and metabolic rate, such a result cannot be obtained by merely changing the composition of the inspired gases without a feedback control. Thus a servomechanism is necessary. The input to the servomechanism is an instantaneous determination of PACO2 and PAO2. This is accomplished by using the criterion of equality of the exchange ratio in mean alveolar gas and mean expired gas. The servomechanism described has three essential characteristics: rapidity, accuracy, and stability. In experiments of step, ramp, and sinusoidal forcing functions, variations of PACO2 have been obtained without change in PAO2, and step variations of PAO2 have been obtained without change in PACO2.     

Phylogenetic relationships within the Laridae (Charadriiformes: Aves) inferred from mitochondrial markers

Gulls (Aves: Laridae) constitute a recent and cosmopolite family of well-studied seabirds for which a robust phylogeny is needed to perform comparative and biogeographical analyses. The present study, the first molecular phylogeny of all Larids species (N=53), is based on a combined segment of mtDNA (partial cytochrome b and control region). We discuss our phylogenetic tree in the light of previous suggestions based on morphological, behavioral, and plumage characters. Although the phylogeny is not fully resolved, it highlights several robust species groups and confirms or identifies for the first time some sister relationships that had never been suggested before. The Dolphin Gull (Leucophaeus scoresbii) for instance, is identified as the sister species of the Grey Gull (Larus modestus) and the Ross's Gull (Rhodostethia rosea) forms a monophyletic group with the Little Gull (Larus minutus). Our results clearly demonstrate that the genus Larus as currently defined is not monophyletic, since current taxonomy of gulls is based on the use of convergent phenotypic characters. We propose a new systematic arrangement that better reflects their evolutionary history.     

Roles of environmental cues for embryonic incubation and hatching in mudskippers

Reproduction on mudflats requires that eggs are protected from different environmental challenges during development and hatch when environmental conditions are favorable for survival of juveniles. Mudskippers are air-breathing, amphibious gobies of the subfamily Oxudercinae, and one of a few vertebrates that reside on mudflats. They excavate burrows in mudflats and deposit eggs in them. However, these burrows are filled with extremely hypoxic water, in which eggs could not survive. To secure embryonic development within their burrows, the burrow-guarding parental fish (a male or mating pair) store fresh air in an egg chamber, located near the bottom or at mid-depth in a burrow, by transporting mouthfuls of air during each low tide. The Japanese mudskipper, Periophthalmus modestus, is the best-studied species regarding reproductive strategies. The air-supplying behavior appears to be predominantly governed by the oxygen levels within egg chambers, but also by some other factor that is possibly related to the tidal cycle. When embryonic development is complete, the burrow-guarding male P. modestus removes the air from the egg chamber and releases the air outside the burrow on a nocturnal rising tide. Consequently, the tide floods the egg chamber and induces hatching. Because P. modestus eggs only have a 5-6 day window for hatching competence, the male's initial selection of the position for the burrow in the intertidal zone and the timing of spawning relative to the tidal cycle are both important factors in hatching success. This is particularly crucial for those burrows in higher intertidal zones, which may be reached only by spring high tides. Not much is known for other mudskippers, but it is likely that they also employ similar reproductive strategies. The objective of this review is to summarize available information on reproductive strategies of mudskippers, and to discuss future directions to better elucidate mechanisms and adaptive significance for the reproduction of mudskippers. Further comparative studies with both mudskippers and other oxudercine gobies dwelling mudflats could shed new light on how vertebrates solved problems of reproduction when they expanded habitats to environments in an air-water interface.     

A comparison of indirect methods for continuous estimation of arterial PCO2 in men

Four different measures (PETCO2, PACO2, PADCO2, and PJCO2) for indirectly estimating arterial PCO2 (PaCO2) from respired gas at the mouth have been investigated. PETCO2 was the end-tidal PCO2. PACO2 was calculated using a reconstruction of the alveolar oscillation of PCO2 obtained from the end-tidal "plateau" in PCO2. PADCO2 was calculated as for PACO2 except that the effects of dead space were incorporated. PJCO2 was calculated from an empirical relationship involving PETCO2 and tidal volume. Six subjects were studied at rest and during cycle ergometry at 50 and 100 W while breathing a variety of gas mixtures. Arterial samples were drawn for determination of true PaCO2. The differences for each method between estimated and true PaCO2 at rest and at 50 and 100 W were as follows: PETCO2, -1.35 +/- 2.64, 1.67 +/- 2.31, and 2.67 +/- 2.02 (SD) Torr; PaCO2, -2.15 +/- 2.73, -0.80 +/- 2.18, and -0.35 +/- 2.31 (SD) Torr; PADCO2, -1.55 +/- 2.54, 0.25 +/- 2.16, and 0.63 +/- 2.26 (SD) Torr; and PJCO2, -1.41 +/- 2.30, 0.12 +/- 1.79, and 0.08 +/- 1.96 (SD) Torr. It is concluded that, at rest, all methods significantly underestimate true PaCO2 and during exercise PETCO2 significantly overestimates PaCO2, but no bias was detected for any of the other methods.     

Validation of a maskless CO2-response test for sleep and infant studies

The Hazinski method is an indirect, noninvasive, and maskless CO2-response test useful in infants or during sleep. It measures the classic CO2-response slope (i.e., delta VI/delta PCO2) divided by resting ventilation Sr = (VI'--VI')/(VI'.delta PCO2) between low (')- and high (')-inspired CO2 as the fractional increase of alveolar ventilation per Torr rise of PCO2. In steady states when CO2 excretion (VCO2') = VCO2', Hazinski CO2-response slope (Sr) may be computed from the alveolar exchange equation as Sr = (PACO2'--PICO2')/(PACO2'--PICO2') where PICO2 is inspired PCO2. To avoid use of a mask or mouthpiece, the subject breathes from a hood in which CO2 is mixed with inspired air and a transcutaneous CO2 electrode is used to estimate alveolar PCO2 (PACO2). To test the validity of this method, we compared the slopes measured simultaneously by the Hazinski and standard steady-state methods using a pneumotachograph, mask, and end-tidal, arterial, and four transcutaneous PCO2 samples in 15-min steady-state challenges at PICO2 23.5 +/- 4.5 and 37 +/- 4.1 Torr. Sr was computed using PACO2 and arterial PCO2 (PaCO2) as well as with the four skin PCO2 (PSCO2) values. After correction for apparatus dead space, the standard method was normalized to resting VI = 1, and its CO2 slope was designated directly measured normalized CO2 slope (Sx), permitting error to be calculated as Sr/Sx.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood oxygen transport and metabolism of the confined lugworm Arenicola marina (L.).

Oxygen consumption (MO2), haemoglobin oxygen saturation level (SVO2) and pH (pHv) in prebranchial blood were measured in lugworms experimentally confined in sea water at 15 degrees C. Total blood flow through the gills (Vb) was estimated. For sea water oxygen partial pressure (PwO2) between 120 and 150 Torr MO2, SVO2 and Vb were high and nearly constant. For PwO2 less than 120 Torr, Vb fell quickly, MO2 progressively dropped, and metabolism remained aerobic at the expense of the prebrancial blood oxygen store. For PwO2 less than 50 Torr, Vb and SvO2 values were extremely low, and the low pHv and the modified buffer power of the surrounding sea water showed that anaerobic metabolism was occurring. Changes in respiratory gas exchanges and metabolism during the tidal cycle are deduced from the comparison of these results with data obtained in the field.     

A visual aid for teaching ventilation-perfusion relationships

To help students understand the concept of the ventilation-perfusion ratio (VA/Q) and the effects that VA/Q mismatching has on pulmonary gas exchange, a "sliding rectangles" visual aid was developed to teach VA/Q relationships. Adjacent rectangles representing "ventilation" and "perfusion" are slid past one another so that portions of the ventilation and perfusion rectangles are not touching, illustrating the concepts of dead-space ventilation (VD) and shunt flow (QS). The portion of the ventilation bar representing VD is further subdivided into anatomical and alveolar VD and used to show the effects of alveolar dead space on the PO2 (PAO2) and PCO2 of alveolar air (PACO2); movement away from the "ideal" point). Similarly, the portion of the perfusion bar representing QS is used to define anatomical and physiological shunts and the effect of shunts on the PO2 (PaO2) and PCO2 of arterial blood (PaCO2). The genesis of the PAO2-PaO2 (A-a) PO2 difference as well as the effects of VA/Q mismatching and diffusion abnormalities can all be discussed with this visual aid. This approach has greatly assisted some students in mastering this traditionally difficult area of respiratory physiology.     

Slow respiratory stimulant effect of hyperoxia in chemodenervated decerebrate cats.

A direct stimulating action of oxygen on the CO2 respiratory control system was determined from steady-state and dynamic observations in unanesthetized decerebrate cats. In peripheral nerve-intact animals, inhalation of oxygen (1 atm) produced a small but significant shift to the left as well as a decrease in slope in the steady-state VT vs. log PACO2 relationship. Carotid sinus neurotomy more than doubled the shift, to the extent that the mean PACO2 apneic point was lowered by 6.5 mmHg. Neither vagotomy nor chronic ablation of the area postrema had any detectable influence on the stimulating effect of oxygen on CO2 responsiveness. The arterial-alveolar PCO2 difference, prior to and following carotid chemo-denervation, remained unchanged or was increased by a negligible amount during oxygen inhalation. The oxygen threshold for respiratory stimulation, obtained isocapnically, occurred between 115 and 200 mmHg; VT then increased exponentially tending to level off as PAO2 approached 1 atm. The dynamic response to sudden presentation of oxygen after carotid chemodenervation consisted of a monotonic rise in VT, starting after 20-30 s with a t 1/2 of about 75 s.     

Pulmonary gas exchange in humans during normobaric hypoxic exercise

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

Relationship between hypercapnic and hypoxic stimuli of respiration during muscular activity]

Pulmonary ventilation (V) and alveolar gas composition (PACO2, PAO2) were studied in 12 healthy men who performed gradual muscular work under conditions of controlled hypercapnia, hypoxia, hyperoxia or their combinations. The respiratory response was estimated by absolute values of ventilation at the given PACO2 value and by its rise by 1 mm Hg of increased PACO2 (delta V/delta PACO2) under rest and under transitional and steady-state exercise. The exercise on-switch was accompanied by displacement to the top and an increased slope of the response curve (delta V/delta PACO2) not related to the work load. These changes suggest multiplicative interaction of the neurogenic and hypercapnic drives in the load switch-on. During steady-state exercise an important role of the hypoxic drive was revealed: hypoxemia induced a shift of the delta V/delta PACO2 response curve to a higher level, especially with the great work load. Thus the positive interaction between the hypercapnic and hypoxic respiratory drive augments with muscular exercise.     

Avian wildlife reservoir of Campylobacter fetus subsp. jejuni, Yersinia spp., and Salmonella spp. in Norway

Cloacal swabs from 540 wild-living birds were cultured for Campylobacter fetus subsp. jejuni, Yersinia spp., and Salmonella spp. The carrier rates detected were as follows: C. fetus subsp. jejuni, 28.4%; Yersinia spp., 1.2%; and Salmonella spp., 0.8%. All birds were apparently healthy when captured. C. fetus subsp. jejuni was isolated from 11 of the 40 bird species examined. Among birds inhabiting the city of Oslo, the highest isolation rate was found in crows (Corvus corone cornix) (89.8%), followed by gulls (Larus spp.) (50.0%) and domestic pigeons (Columba livia domesticus) (4.2%). The gulls and crows scavenge on refuse dumps. High carrier rates were also detected among the following birds from nonurban, coastal areas: puffin (Fratercula arctica) (51.3%), common tern (Sterna hirundo) (5.6%), common gull (Larus canus) (18.9%), black-headed gull (Larus ridibundus) (13.2%), and herring gull (Larus argentatus) (4.2%). The list of species harboring C. fetus subsp. jejuni also includes the Ural owl (Strix uralensis), goldeneye (Bucephala clangula), and reed bunting (Emberiza schoeniclus). The following five Yersinia strains were isolated: Y. kristensenii (two strains), Y. intermedia (two strains), and "Yersinia X2" (one strain). Four strains belonging to the genus Salmonella were isolated from three different species of gulls. These isolates were identified as S. typhimurium, S. indiana, and S. djugu. The results indicate that campylobacters are a normal component of the intestinal flora in several bird species, whereas Salmonella and Yersinia carriers are more sporadic.     

Exchange of oxygen across the epicardial surface distorts estimates of myocardial oxygen consumption

The rate of oxygen consumption of isolated, Langendorff-circulated, saline-perfused hearts of guinea pigs, rats, and rabbits was measured using the classical Fick Principle method. The heart was suspended in a glass chamber the oxygen partial pressure, PO2, of which could be varied. The measured rate of oxygen consumption was found to vary inversely with the ambient (heart chamber) PO2. This result prevailed whether the chamber was filled with air, saline, or oil, and whether the pericardium was present or the heart was wrapped in Saran. The effect varied inversely with heart size both within and across species. It is concluded that the epicardial surface is permeable to oxygen which will diffuse either into or out of the heart as the PO2 gradient dictates. In either case the classically measured rate of oxygen consumption will be in error. The error can be large in studies of cardiac basal metabolism. A simple model is developed to describe the observed rate of oxygen consumption as classically measured. The measured rate is partitioned into two components: the true rate of oxygen consumption of the heart, and the rate of loss of oxygen by diffusive exchange across the epicardial surface. The latter component is proportional to the gradient of oxygen partial pressure from myocardium to environment and to the diffusive oxygen conductance of myocardial tissue. Application of the model allows the true rate of oxygen consumption of the heart to be recovered from measured values which may be considerably in error.     

Avian wildlife reservoir of Campylobacter fetus subsp. jejuni, Yersinia spp., and Salmonella spp. in Norway.

Cloacal swabs from 540 wild-living birds were cultured for Campylobacter fetus subsp. jejuni, Yersinia spp., and Salmonella spp. The carrier rates detected were as follows: C. fetus subsp. jejuni, 28.4%; Yersinia spp., 1.2%; and Salmonella spp., 0.8%. All birds were apparently healthy when captured. C. fetus subsp. jejuni was isolated from 11 of the 40 bird species examined. Among birds inhabiting the city of Oslo, the highest isolation rate was found in crows (Corvus corone cornix) (89.8%), followed by gulls (Larus spp.) (50.0%) and domestic pigeons (Columba livia domesticus) (4.2%). The gulls and crows scavenge on refuse dumps. High carrier rates were also detected among the following birds from nonurban, coastal areas: puffin (Fratercula arctica) (51.3%), common tern (Sterna hirundo) (5.6%), common gull (Larus canus) (18.9%), black-headed gull (Larus ridibundus) (13.2%), and herring gull (Larus argentatus) (4.2%). The list of species harboring C. fetus subsp. jejuni also includes the Ural owl (Strix uralensis), goldeneye (Bucephala clangula), and reed bunting (Emberiza schoeniclus). The following five Yersinia strains were isolated: Y. kristensenii (two strains), Y. intermedia (two strains), and "Yersinia X2" (one strain). Four strains belonging to the genus Salmonella were isolated from three different species of gulls. These isolates were identified as S. typhimurium, S. indiana, and S. djugu. The results indicate that campylobacters are a normal component of the intestinal flora in several bird species, whereas Salmonella and Yersinia carriers are more sporadic.     

Ventilatory interaction between hypoxia and [H+] at chemoreceptors of man.

By measuring ventilation during isocapnic progressive hypoxia, peripheral chemoreceptor sensitivity to acute hypoxia (deltaV40) was measured in five normal young men under four sets of conditions: 1) at sea level at the subject's resting PCO2, 2) at sea level with PCO2 5 Torr above resting PCO2, 3) after 24 h at a simulated altitude of 4,267 m (PB = 447 Torr) at the subject's resting PCO2 measured during acute hyperoxia, and 4) after 24 h at high altitude, with PCO2 elevated to the subject's sea-level resting PCO2. With this experimental design, we were able to systematically vary the PCO2 and [H+] at the peripheral and central chemoreceptors of man. When mean pHa was decreased from 7.424 to 7.377 without significant change in PACO2, the mean deltaV40 increased from 18.0 to 55.9 1/min. Conversely, when mean PACO2 was altered between 33.8 and 41.6 Torr with pHa held relatively constant, the mean deltaV40 did not change. This suggests that it is the H+ and not CO2 which interacts with hypoxia in stimulating the ventilation of man. An additional finding was that the intrinsic sensitivity of the peripheral chemoreceptors to acute hypoxia did not change during 24 h of acclimatization to high altitude.     

Factors in the development of arterial hypoxemia in middle-aged and elderly people

Partial pressure of oxygen and carbon dioxide in alveolar air and arterial blood, lung diffusion capacity and its components, ventilation parameters, ventilation-perfusion ratio were determined in healthy people aged 60-89 (45 subjects) and aged 20-31 (19 subjects, controls). In elderly and old people PO2 in arterial blood was found to decrease with increasing alveolar-arterial PO2 gradient. In other words, arterial hypoxemia was determined by the disturbance in gas exchange between alveolar air and blood of lung capillaries. The diffusion capacity of lung decreased at the expense of membrane factor. Its age-related dynamics was mainly due to a decrease in the pulmonary diffusion surface occurring because of improper coordination of ventilation and perfusion in the lungs. The discrepancy of pulmonary ventilation and perfusion proved to be the leading factor of arterial hypoxemia in late ontogenesis.     

Craniogenesis in the laughing gull (Larus ridibundus L.). The reconstruction of the basic plan of the bird

To contribute to the knowledge of the cranium of older bird embryos, the chondrocranium and osteocranium of the Black-headed Gull (Larus ridibundus) are described. The chondrocranium of the Black-headed Gull is compared with the chondrocranium of other bird species with special consideration of functional and phylogenetic aspects. As a result a "grundplan" of the bird chondrocranium is reconstructed. Most of the chondrocranial autapomorphies of birds are connected with the enlargement of the eyes, the development of a beak and a prokinetic skull, and the reduction of the olfactory system.     

Oxygen uptake, diffusion limitation, and diffusing capacity of the bipectinate gills of the abalone, Haliotis iris (Mollusca: Prosobranchia)

Extant abalone retain an ancestral system of gas exchange consisting of paired bipectinate gills. This paper examines the hypothesis that fundamental inefficiencies of this arrangement led to the extensive radiation observed in prosobranch gas exchange organs. Oxygen uptake at 15 degrees C was examined in the right gill of resting adult blackfoot abalone, Haliotis iris Martyn 1784. Pre- and post-branchial haemolymph and water were sampled and oxygen content, partial pressure (Po2), pH, and haemocyanin content measured; in vivo haemolymph flow rate was determined by an acoustic pulsed-Doppler flowmeter. During a single pass across the gills, mean seawater Po2 fell from 138.7 Torr to 83.4 Torr, while haemolymph Po2 rose from 37.2 Torr to 77.0 Torr raising total O2 content from 0.226 to 0.346 mmol L(-1). Haemolymph flowed through the right gill at a mean rate of 9.6 mL min(-1) and carried 0.151 to 0.355 mmol L(-1) of haemocyanin (mean body mass 421 g). Only 34.7% of the oxygen carried in the arterial haemolymph was taken up by the tissues and less than half of this was contributed by haemocyanin. A diffusion limitation index (Ldiff) of 0.47-0.52, a well-matched ventilation-perfusion ratio (1.2-1.4) and a diffusing capacity (D) of 0.174 micromol O2 kg(-1) Torr(-1) indicate that the gills operate efficiently and are able to meet the oxygen requirements of the resting abalone.     

Evaluation of factors affecting relationship between transcutaneous PO2 and probe temperature

Several studies on transcutaneous O2 probes have shown that the transcutaneous PO2 increases to approximately 80% of the arterial PO2 when the probe is heated to 44 degrees C. It is not known whether this result reflects near-complete thermic arterialization or rather other factors such as the temperature-linked right shift of the hemoglobin O2-binding curve. In many clinical applications of transcutaneous probes the use of 44 degrees C is a major disadvantage because of the risk of skin burns. The development of new probes operating at lower temperatures is hampered by the lack of data on the temperature dependence of the factors influencing the relationship between the transcutaneous PO2 and the probe temperature. The present study attempts to estimate the temperature dependence of 1) the degree of arterialization of the blood in the skin capillaries, 2) the PO2 difference across the epidermis caused by the diffusion gradient and the epidermal O2 consumption, and 3) the arteriovenous saturation difference over the skin capillaries. The estimation is based on simultaneously measured transcutaneous PO2, PCO2, and argon partial pressure (PAr) values at seven different probe temperatures. The transcutaneous PCO2 is assumed equal to the mean capillary PCO2, which is used to calculate the mean capillary PO2 by the aid of a skin model. The O2 diffusion gradient is estimated from the transcutaneous PAr, and the PO2 difference caused by the epidermal O2 consumption is set equal to the difference between the mean capillary and transcutaneous PO2 less the partial pressure difference caused by the diffusion gradient. The degree of arterialization was found to be 53% at 38 degrees C and 65% at 44 degrees C. The partial pressure difference caused by the epidermal O2 consumption decreased from 33 Torr at 38 degrees C to 6 Torr at 44 degrees C. The PO2 difference across the epidermis caused by the diffusion gradient was 7 Torr at 38 degrees C and 5 Torr at 44 degrees C. The arteriovenous saturation difference fell from 31% at 38 degrees C to 12% at 44 degrees C.     

Oxygen binding properties,capillary densities and heart weights in high altitude camelids

Summary The oxygen binding properties of the blood of the camelid species vicuna, llama, alpaca and dromedary camel were measured and evaluated with respect to interspecific differences. The highest blood oxygen affinity, not only among camelids but of all mammals investigated so far, was found in the vicuna (P₅₀=17.6 Torr compared to 20.3–21.6 Torr in the other species). Low hematocrits (23–34%) and small red blood cells (21–30 m³) are common features of all camelids, but the lowest values are found in theLama species. Capillary densities were determined in heart and soleus muscle of vicuna and llama. Again, the vicuna shows exceptional values (3720 cap/mm² on average in the heart) for a mammal of this body size. Finally, heart weight as percent of body weight is higher in the vicuna (0.7–0.9%) than in the other camelids studied (0.5–0.7%). The possibility that these parameters, measured in New World tylopodes at sea level, are not likely to change considerably with transfer to high altitude, is discussed.In the vicuna, a unique combination of the following features seems to be responsible for an out-standing physical capability at high altitude: saturation of blood with oxygen in the lung is favored by a high blood oxygen affinity, oxygen supply being facilitated by low diffusion distances in the muscle tissue. Loading, as well as unloading, of oxygen is improved by a relatively high oxygen transfer conductance of the red blood cells, which is due to their small size and which compensates the negative effect of a low hematocrit on the oxygen conductance of blood. Blood oxygen transport is presumably favored by two factors: a relatively large heart mass and, as a result of low hematocrit, a low blood viscosity. Both are advantageous for achieving a high maximal cardiac output.     

Step changes in end-tidal CO2: methods and implications.

A dynamic end-tidal forcing technique for producing step changes in end-tidal CO2 with end-tidal O2 held constant independent of the ventilation response or the mixed venous return is introduced for characterizing the human ventilation response to end-tidal CO2 step changes for both normoxic (PAO2 = 125 Torr) and hypoxic (PAO2 = 60 Torr) conditions. The ventilation response approaches a steady state within 5 min. In normoxia, the on-transient is faster than the off-transient, presumably reflecting the action of cerebral blood flow. The hypoxic step response is faster than the normoxic response presumably reflecting the increased contribution from the carotid body. The delay in the ventilation response after the change in end-tidal CO2 is less in hypoxia than in normoxia and reflects the action of a transport delay and that of a virtual delay. These delays are interpreted with respect to the high-frequency phase shift data for the same subject, generated using sinusoidal end-tidal forcing. The methods of others for experiments utilizing step changes in inspired CO2 are considered with respect to our methods.