Ventilatory responses to intravenous and airway CO2 administration in anesthetized dogs

The ventilatory responses to steady-state venous CO2 loading (iv CO2) and CO2 inhalation have been observed in chloralose-urethan-anesthetized dogs. Intravenous CO2 was administered by increasing the CO2 fraction of gas ventilating a membrane gas exchanger in an arteriovenous bypass; blood flow rate was fixed at 30 ml/min. During the study, we identified a time-dependent hyperventilation in all 14 experimentally treated dogs and in 4 additional sham-treated dogs. When we tested 8 of these animals with a protocol having small progressive increments in iv CO2 loading rate, we observed a response approaching isocapnia during iv CO2 and a large hypocapnia when we returned to control conditions. The use of a randomized protocol in 6 animals demonstrated the necessity of accounting for this systematic base-line shift, because before doing so the response depended more on the passage of time than on the nature of the CO2 load. After this analytical adjustment was made, there was no significant difference between the respiratory controller gains (delta nu E/delta Paco2) for inhaled and iv CO2.     

Respiratory responses to intravenous and intrapulmonary CO2 in awake dogs

Ventilatory responses to CO2 inhalation and CO2 infusion were compared in the awake dog. The CO2 was introduced directly into the systemic venous blood via a membrane gas exchanger in a femoral arteriovenous shunt circuit, and the extracorporeal blood flow, QX, was maintained constant at one of two rates: low, 0.5 l/min; or high, 2.0 l/min. A total of 13 experiments was performed in four dogs comprising 50 control and 25 inhalation and infusion observations at each of the two flow rates. Comparison of CO2-response curve slopes, S = delta V E/delta PaCO2, between CO2 inhalation and infusion showed no significant difference either within or between flow rates. The mean value of S for all conditions was 1.88 l/min per Torr with a 95% confidence interval of 1.66 -2.14. An independent additive ventilatory drive amounting to 28% of low-flow control VE was found at the highflow rate. We conclude that at constant blood flow the responses to both CO2 inhalation and infusion are hypercapnic and not significantly different.     

Ventilatory and metabolic responses of a bat,Phyllostomus discolor,to hypoxia and CO2: implications for the allometry of respiratory control

The ventilatory and metabolic responses of lesser spear-nosed bats to hypoxia and hypercapnia were measured to determine whether these corresponded to preliminary allometries and a positive relationship between hypoxic ventilatory threshold andP ₅₀. Ventilatory responses of lesser spear-nosed bats to 3, 5 and 7% CO₂ differed significantly from ventilation on air and each other. The magnitude of their ventilatory response to CO₂ is consistent with the prediction of a smaller ventilatory response to hypercapnia in small compared to large mammals [ ; Williams et al. (1994)]. Among 12, 10 and 8% O₂ treatments only the ventilatory response to 8% O₂ differed significantly from ventilation on air or the other treatments. Metabolic rate was significantly reduced at both 10 and 8% O₂. The hypoxic ventilatory response of these bats does not support the prediction of a greater response in small compared to large mammals [ ; Boggs and Tenney (1984)]. Their metabolic response is consistent with the hypoxic hypometabolism typical of small mammals, though not of comparable magnitude. The response, expressed as percent change in convection requirement ( ), is also less than that observed in other small mammals. This relative insensitivity to hypoxia may be associated with this bat's unusually high affinity hemoglobin (P₅₀=27.5 torr).     

Effect of Mechanical Loading on Ventilatory Response to CO2 and CO2 Excretion

The ventilatory response to CO₂ (S) and respiratory exchange ratio have been measured in 10 healthy subjects breathing naturally and through added resistive loads. The changes in these values produced by the added loads were shown to be correlated with the unloaded CO₂ responsiveness. The results indicated that poorly responsive individuals had a greater depression of ventilatory response to CO₂ and were more liable to retain CO₂.These observations raise the possibility that the constitutional CO₂ responsiveness of an individual influences the alveolar ventilation achieved in the presence of airways obstruction. The propensity to develop respiratory failure may thus be conditioned by the premorbid CO₂ responsiveness.     

Ventilatory CO2 response in endurance-trained rats

A CO2 rebreathing technique was used to assess possible changes in the ventilatory response to CO2 in rats following a 14-week swim training program. Over the final 9 weeks, the rats swam 1 hr per day with a weight of 2.5% of the body weight attached to the tail. Ventilation was measured by a barometric method in awake, restrained rats in a total body plethysmography at CO2 concentrations of 0, 2, 4, 6, and 8%, with an initial O2 concentration of approximately 100%. Ventilation increased in the trained rats with increasing CO2 from 775ml . min-1 . kg-1 at 0% CO2 to 1,387 ml . min-1 . kg-1 at 8% CO2. This increase was a consequence of a 34% increase in tidal volume and a 32% increase in breathing frequency. In comparison with a group of sedentary control rats, there was a significantly higher ventilation and tidal volume at 0% CO2; however, this difference disappeared with increasing levels of CO2. A significantly lower resting heart rate was observed in the exercised (296 +/- 44 beats . min-1, mean +/- SD) compared to the sedentary control rats 380 +/- 42). It was concluded that, while the normal training response of resting bradycardia was observed following this duration and intensity of training, endurance swimming had no significant effect on the ventilatory response to CO2 in the rat.     

Response time and sensitivity of the ventilatory response to CO2 in unanesthetized intact dogs: central vs. peripheral chemoreceptors.

We assessed the speed of the ventilatory response to square-wave changes in alveolar P(CO2) and the relative gains of the steady-state ventilatory response to CO2 of the central chemoreceptors vs. the carotid body chemoreceptors in intact, unanesthetized dogs. We used extracorporeal perfusion of the reversibly isolated carotid sinus to maintain normal tonic activity of the carotid body chemoreceptor while preventing it from sensing systemic changes in CO2, thereby allowing us to determine the response of the central chemoreceptors alone. We found the following. 1) The ventilatory response of the central chemoreceptors alone is 11.2 (SD = 3.6) s slower than when carotid bodies are allowed to sense CO2 changes. 2) On average, the central chemoreceptors contribute approximately 63% of the gain to steady-state increases in CO2. There was wide dog-to-dog variability in the relative contributions of central vs. carotid body chemoreceptors; the central exceeded the carotid body gain in four of six dogs, but in two dogs carotid body gain exceeded central CO2 gain. If humans respond similarly to dogs, we propose that the slower response of the central chemoreceptors vs. the carotid chemoreceptors prevents the central chemoreceptors from contributing significantly to ventilatory responses to rapid, transient changes in arterial P(CO2) such as those after periods of hypoventilation or hyperventilation ("ventilatory undershoots or overshoots") observed during sleep-disordered breathing. However, the greater average responsiveness of the central chemoreceptors to brain hypercapnia in the steady-state suggests that these receptors may contribute significantly to ventilatory overshoots once unstable/periodic breathing is fully established.     

Crop responses to CO2 enrichment

Carbon dioxide is rising in the global atmosphere, and this increase can be expected to continue into the foreseeable future. This compound is an essential input to plant life. Crop function is affected across all scales from biochemical to agro-ecosystem. An array of methods (leaf cuvettes, field chambers, free-air release systems) are available for experimental studies of CO₂ effects. Carbon dioxide enrichment of the air in which crops grow usually stimulates their growth and yield. Plant structure and physiology are markedly altered. Interactions between CO₂ and environmental factors that influence plants are known to occur. Implications for crop growth and yield are enormous. Strategies designed to assure future global food security must include a consideration of crop responses to elevated atmospheric CO₂. Future research should include these targets: search for new insights, development of new techniques, construction of better simulation models, investigation of belowground processes, study of interactions, and the elimination of major discrepancies in the scientific knowledge base.     

Ventilatory and metabolic responses to hypoxia in the smallest simian primate, the pygmy marmoset.

The pygmy marmoset (Cebuella pygmaea) is the smallest New World Monkey (average body mass of 120-130 g). As such, it faces possible challenges to thermoregulation. Small mammals (e.g., rats) are well known to lower body temperature and metabolism in response to hypoxia; however, small primates have not been studied in this respect nor have, in general, the interactions between metabolism and ventilation. Because little is known about these responses in small primates, it seemed of great interest to assess the hypoxia-induced metabolic depression and drop in body temperature and the associated ventilatory requirements in this species under hypoxic conditions. Exposure to graded hypoxia (30 min at each of 18, 16, 14, 12, and 10% O(2)) caused body temperature to drop from the normoxic value of 39 to 37 degrees C. This was accompanied by a marked metabolic depression (O(2) consumption was approximately 68% of the normoxic value, implying a suppression of metabolism greater than that predicted from a typical value of the effect of 10 degrees C change on metabolism of 2-3 times). Minute ventilation declined in parallel to metabolism, maintaining a constant air-convection requirement during hypoxia; thus this species did not show the typical mammalian hyperventilation. Acute exposure to 10% O(2) led to a similar overall decline in metabolism and body temperature and qualitative differences in the timing of these changes. The pygmy marmoset shares some similarities in its hypoxic metabolic response with other mammals of similar size yet appears to be unique in its much diminished ventilatory response to hypoxia.     

12CO2 emission from different metabolic pathways measured in illuminated and darkened C3 and C4 leaves at low,atmospheric and elevated CO2 concentration

The detection of 12CO2 emission from leaves in air containing 13CO2 allows simple and fast determination of the CO2 emitted by different sources, which are separated on the basis of their labelling velocity. This technique was exploited to investigate the controversial effect of CO2 concentration on mitochondrial respiration. The 12CO2 emission was measured in illuminated and darkened leaves of one C4 plant and three C3 plants maintained at low (30-50 ppm), atmospheric (350-400 ppm) and elevated (700-800 ppm) CO2 concentration. In C3 leaves, the 12CO2 emission in the light (Rd) was low at ambient CO2 and was further quenched in elevated CO2, when it was often only 20-30% of the 12CO2 emission in the dark, interpreted as the mitochondrial respiration in the dark (Rn). Rn was also reduced in elevated CO2. At low CO2, Rd was often 70-80% of Rn, and a burst of 12CO2 was observed on darkening leaves of Mentha sativa and Phragmites australis after exposure for 4 min to 13CO2 in the light. The burst was partially removed at low oxygen and was never observed in C4 leaves, suggesting that it may be caused by incomplete labelling of the photorespiratory pool at low CO2. This pool may be low in sclerophyllous leaves, as in Quercus ilex where no burst was observed. Rd was inversely associated with photosynthesis, suggesting that the Rd/Rn ratio reflects the refixation of respiratory CO2 by photosynthesizing leaves rather than the inhibition of mitochondrial respiration in the light, and that CO2 produced by mitochondrial respiration in the light is mostly emitted at low CO2, and mostly refixed at elevated CO2. In the leaves of the C4 species Zea mays, the 12CO2 emission in the light also remained low at low CO2, suggesting efficient CO2 refixation associated with sustained photosynthesis in non-photorespiratory conditions. However, Rn was inhibited in CO2-free air, and the velocity of 12CO2 emission after darkening was inversely associated with the CO2 concentration. The emission may be modulated by the presence of post-illumination CO2 uptake deriving from temporary imbalance between C3 and C4 metabolism. These experiments suggest that this uptake lasts longer at low CO2 and that the imbalance is persistent once it has been generated by exposure to low CO2.     

Ventilatory response to inspired CO2 in the lizard, Tupinambis nigropunctatus

Elevating inspired levels of CO2 (1-4%) in Tupinambis nigropunctatus leads to an increase in tidal volume, mean expiratory flow, mean inspiratory flow, duration of the non-ventilatory period, inspiratory duration, expiratory duration and end inspiratory lung volume. Minute ventilation is variable and end expiratory volume decreases. An increase or decrease in CO2 concentration surrounding the head affects the duration of the non-ventilatory period before the altered CO2 concentration is inspired into the lungs. The change in duration of the non-ventilatory period before altered CO2 concentration is inspired into the lungs is probably mediated by CO2 sensitive receptors located in the mouth, nose or on the head surface.     

Hormonal and metabolic responses to intracarotid and intrajugular infusion of beta-endorphin in normal dogs

The hormonal and metabolic responses of beta-endorphin infused cephalad into the carotid artery, or via the jugular vein, were examined in 10 normal dogs. The intracarotid administration of beta-endorphin resulted in significant increases in plasma glucagon, adrenocorticotropin, and cortisol levels. Hepatic glucose production increased only transiently and there was no significant change in glucose disappearance or plasma glucose concentrations. Infusion of beta-endorphin in the jugular vein gave rise to significant increases in glucagon and cortisol levels and to a transient increase in plasma epinephrine. Although no significant changes in glucose kinetics could be demonstrated, there was a slight transient decrease in plasma glucose concentrations. In conclusion, both intracarotid and intrajugular infusions of beta-endorphin stimulated glucagon secretion independent of circulating catecholamines, and increased cortisol release, probably through activation of the pituitary-adrenocortical axis.     

Ventilatory response to exercise in aged runners breathing He-O2 or inspired CO2.

The ventilatory response to exercise below ventilatory threshold (VTh) increases with aging, whereas above VTh the ventilatory response declines only slightly. We wondered whether this same ventilatory response would be observed in older runners. We also wondered whether their ventilatory response to exercise while breathing He-O(2) or inspired CO(2) would be different. To investigate, we studied 12 seniors (63 +/- 4 yr; 10 men, 2 women) who exercised regularly (5 +/- 1 days/wk, 29 +/- 11 mi/wk, 16 +/- 6 yr). Each subject performed graded cycle ergometry to exhaustion on 3 separate days, breathing either room air, 3% inspired CO(2), or a heliox mixture (79% He and 21% O(2)). The ventilatory response to exercise below VTh was 0.35 +/- 0.06 l x min(-1) x W(-1) and above VTh was 0.66 +/- 0.10 l x min(-1) x W(-1). He-O(2) breathing increased (P < 0.05) the ventilatory response to exercise both below (0.40 +/- 0.12 l x min(-1) x W(-1)) and above VTh (0.81 +/- 0.10 l x min(-1) x W(-1)). Inspired CO(2) increased (P < 0.001) the ventilatory response to exercise only below VTh (0.44 +/- 0.10 l x min(-1) x W(-1)). The ventilatory responses to exercise with room air, He-O(2), and CO(2) breathing of these fit runners were similar to those observed earlier in older sedentary individuals. These data suggest that the ventilatory response to exercise of these senior runners is adequate to support their greater exercise capacity and that exercise training does not alter the ventilatory response to exercise with He-O(2) or inspired CO(2) breathing.     

Plant responses to past concentrations of CO2

The influence of recent historical changes in atmospheric CO₂ have been investigated by two methods: 1, the responses of leaf development and physiology as indicated by leaves stored in herbaria and 2, by investigating the differential growth responses of populations originating from naturally different CO₂ concentrations. Herbarium leaves indicate that stomatal density and leaf nitrogen have decreased over the last 150 to 200 years, while water use efficiency, estimated from leaf ¹³C and historical measurements of climate, has increased.Natural populations ofBoehmeria cylindrica were found growing at sites, in Florida, with CO₂ mole fractions varying naturally from 350 µmol mol^-1 to 505 µmol mol^-1. Plants were grown in the controlled environment, using seeds originating from populations occurring in the different CO₂ mole fractions. Plants from the different ambient CO₂ mole fractions showed different rates of growth and different non-linear responses of the shoot to root ratio in response to changes in the CO₂ mole fraction from 350 to 675 µmol mol^-1.The proposal that plants originating from high altitude will whow greater stimulations of growth with an increase in CO₂, than plants from low altitude, was rejected in experiments which simulated the atmospheric pressure at altitudes of 0 and 2000m, at CO₂ mole fractions of 350 and 700 µmol mol^-1 and on populations ofPlantago major originating from altitudes of 0 and 3335 m.