CO2 Stores Research Articles

Extracellular and Intracellular Carbon Dioxide Concentration as a Function of Temperature in the Toad Bufo Marinus

Previous studies of reptiles and amphibians have shown that changing the body temperature consistently produces transient changes in the respiratory exchange ratio (RE) and, hence, changes in whole-body CO2 stores, and that the extracellular fluid compartment contributes to the temperature-related changes in CO2 stores. The purpose of this study was to determine whether the intracellular fluid compartment contributes to the changes in CO2 stores in undisturbed resting cane toads. Increasing body temperature from 10 to 30 degrees C temporarily elevated RE, and returning body temperature to 10 degrees C temporarily lowered RE. The estimated average change in whole-body CO2 stores associated with the transient changes in RE was 1.0 +/- 0.8 mmol kg-1 (+/- S.D., N = 6). Plasma [CO2] and, thus, extracellular fluid [CO2], were unaffected by the temperature change. Plasma calcium levels were also unaffected, so that bone CO2 stores did not contribute to changes in whole-body CO2 stores. Intracellular [CO2] was determined for the lung, oesophagus, stomach, small intestine, liver, ventricle, red blood cells, skin and 14 skeletal muscles. [CO2] was significantly lower (P < 0.05) at higher temperature in 10 of these, and seven others, although not statistically significant (P > 0.05), had mean values at least 0.5 mmol kg-1 lower at the higher temperature. The average change in intracellular [CO2] for all tissues examined was -0.165 mmol kg-1 degrees C-1. We conclude that, in cane toads, the temperature-related transients in RE result from intracellular CO2 adjustments, that different tissues have unique intracellular CO2/temperature relationships, and that a combination of respiratory and ion-exchange mechanisms is used to adjust pH as temperature changes.

A method for estimating bicarbonate buffering of lactic acid during constant work rate exercise.

A method to estimate the CO2 derived from buffering lactic acid by HCO3- during constant work rate exercise is described. It utilizes the simultaneous continuous measurement of O2 uptake (VO2) and CO2 output (VCO2), and the muscle respiratory quotient (RQm). The CO2 generated from aerobic metabolism of the contracting skeletal muscles was estimated from the product of the exercise-induced increase in VO2 and RQm calculated from gas exchange. By starting exercise from unloaded cycling, the increase in CO2 stores, not accompanied by a simultaneous decrease in O2 stores, was minimized. The total CO2 and aerobic CO2 outputs and, by difference, the millimoles (mmol) of lactate buffered by HCO3- (corrected for hyperventilation) were estimated. To test this method, ten normal subjects performed cycling exercise at each of two work rates for 6 min, one below the lactic acidosis threshold (LAT) (50 W for all subjects), and the other above the LAT, midway between LAT and peak VO2 [mean (SD), 144 (48) W]. Hyperventilation had a small effect on the calculation of mmol lactate buffered by HCO3- [6.5 (2.3)% at 6 min in four subjects who hyperventilated]. The mmol of buffer CO2 at 6 min of exercise was highly correlated (r = 0.925, P < 0.001) with the increase in venous blood lactate sampled 2 min into recovery (coefficient of variation = +/- 0.9 mmol.l-1). The reproducibility between tests done on different days was good. We conclude that the rate of release of CO2 from HCO3- can be estimated from the continuous analysis of simultaneously measured VCO2, VO2, and an estimate of muscle substrate.

Tissue gas stores of the body and head-out immersion in humans

Breath-by-breath gas exchange was studied in 10 subjects during and after transitions between dry conditions and head-out immersion in thermoneutral conditions. Cardiac index (CI) was estimated by means of impedance cardiography. Previous largely qualitative models of changes in tissue gas stores after blood volume shifts could be confirmed and extended to include a quantitative analysis of O2 and CO2 tissue stores. An increase in CI by 47.0% during immersion was associated with an increase in the tissue O2 stores by 122 ml/m2 and a decrease in the tissue CO2 stores by 148 ml/m2. The time constants for the recovery of O2 uptake (tau O2) and CO2 elimination after initial increases after the dry-to-immersion transition were 32.4 and 79.3 s, respectively. The decrease in CI on return to the dry conditions was associated with a drop in tissue O2 stores and a tau O2 of 144 s. The increase in tissue O2 stores during immersion as well as the difference in tau O2 between the two transitions were larger than could be explained by the change in CI only. This was attributed to changes in the distributions of peripheral blood flow and venous blood volume. Compared with the O2 stores, the decrease in CO2 stores was better predicted by the change in CI. The present results emphasize that the changes in pulmonary and tissue gas exchange imposed by head-out immersion transients mainly reflect movement of gas in and out of body stores.

Oral [13C]bicarbonate measurement of CO2 stores and dynamics in children and adults

During exercise, less additional CO2 is stored per kilogram body weight in children than in adults, suggesting that children have a smaller capacity to store metabolically produced CO2. To examine this, tracer doses of [13C]bicarbonate were administered orally to 10 children (8-12 yr) and 12 adults (25-40 yr) at rest. Washout of 13CO2 in breath was analyzed to estimate recovery of tracer, mean residence time (MRT), and size of CO2 stores. CO2 production (VCO2) was also measured breath by breath using gas exchange techniques. Recovery did not differ significantly between children [73 +/- 13% (SD)] and adults (71 +/- 9%). MRT was shorter in children (42 +/- 7 min) compared with adults (66 +/- 15 min, P less than 0.001). VCO2 per kilogram was higher in the children (5.4 +/- 0.9 ml.min-1.kg-1) compared with adults (3.1 +/- 0.5, P less than 0.0001). Tracer estimate of CO2 production was correlated to VCO2 (r = 0.86, P less than 0.0001) and when corrected for mean recovery accurately predicted the VCO2 to within 3 +/- 14%. There was no difference in the estimate of resting CO2 stores between children (222 +/- 52 ml CO2/kg) and adults (203 +/- 42 ml CO2/kg). We conclude that orally administered [13C]bicarbonate can be used to assess CO2 transport dynamics. The data do not support the hypothesis of lower CO2 stores under resting conditions in children.

Evidence that diffusion limitation determines oxygen uptake kinetics during exercise in humans.

To determine the role of arterial O2 content on the mechanism of muscle O2 utilization, we studied the effect of 2, 11, and 20% carboxyhemoglobin (COHb) on O2 uptake (VO2), and CO2 output (VCO2) kinetics in response to 6 min of constant moderate- and heavy-intensity cycle exercise in 10 subjects. Increased COHb did not affect resting heart rate, VO2 or VCO2. Also, the COHb did not affect the asymptotic VO2 in response to exercise. However, VO2 and VCO2 kinetics were affected differently. The time constant (TC) of VO2 significantly increased with increased COHb for both moderate and heavy work intensities. VO2 TC was positively correlated with blood lactate. In contrast, VCO2 TC was negatively correlated with increased COHb for the moderate but unchanged for the heavy work intensity. The gas exchange ratio reflected a smaller increase in CO2 stores and faster VCO2 kinetics relative to VO2 with increased COHb. These changes can be explained by compensatory cardiac output (heart rate) increase in response to reduced arterial O2 content. The selective slowing of VO2 kinetics, with decreased blood O2 content and increased cardiac output, suggests that O2 is diffusion limited at the levels of exercise studied.

Factors affecting respiratory system stability.

Periodic breathing (recurrent central apneas) occurs frequently during sleep. Periodic breathing can arise as a result of unstable behavior of the respiratory control system. A mathematical model of the respiratory control system was used to investigate, systematically, the effect of severity of disturbances to respiration and certain system parameters on periodic breathing occurring during sleep. The model consisted of multi-compartment representation of O2 and CO2 stores, a peripheral controller sensitive to O2 and CO2, and a central controller sensitive to CO2. The effects of hypoxia and hypercapnia on the upper airway muscles were not considered in the model. Episodes of hyperventilation or asphyxia were used to disturb the control system and explore the boundaries of stable breathing. Circulation time and metabolic rate were also varied. Simulations with the model produced the following findings: The number of central apneas associated with periodic breathing were greater as circulation time increased; controller gain increases also made the number of apneas greater, although periodic breathing occurs with lower controller gains as circulation time increases. At each level of circulation time there was a range of controller gain changes which caused little change in the number of apneas. There were more apneas with hypoxia; also the number of apneas increased with sleep-associated reductions in metabolic rate. The more rapidly resting PCO2 rose at sleep onset, the greater the likelihood of recurrent apneas. Finally, the more intense the disturbance, the more apneas there were.

CO2 control of the respiratory system: Plant dynamics and stability analysis

A stability analysis of respiratory chemical control is developed using a mathematical model of CO2 mass transport dynamics. Starting with a 3-compartment model of CO2 stores that distinguishes alveolar, muscle, and other tissue, model reduction techniques are applied to obtain a first-order representation of the respiratory plant. This model contains an effective tissue volume for CO2, whose derived value is much smaller than previously predicted. To investigate oscillatory instabilities, a controller which incorporates only peripheral chemoreceptor responses was added to the first-order plant model. An explicit stability index (SI) is obtained analytically from a linearized version of this model. SI varies directly with the controller gain and circulation delay time and inversely with the effective tissue volume and inspired CO2 concentration. Numerical simulations using the first-order nonlinear model show that SI is a good predictor of system stability. According to the linearized model, the system is stable for SI less than 1; from the nonlinear model, the system is stable for SI less than 1.1. For typical normal adults, the SI value is well within the stable region.

Arterial Blood Gas Monitoring

A clinically relevant presentation of interpretation of arterial blood gas measurements in the critically ill patient is presented. Oxygenation deficits are discussed in relation to differentiation of pulmonary, cardiovascular, and metabolic causes. Metabolic acid base balance is discussed with special emphasis on the low cardiac output state (CPR). Ventilation deficits are discussed in terms of alveolar ventilation, deadspace ventilation and CO2 stores. The future trends of continuous blood gas monitoring are discussed.

Time-course of blood acid-base state during arousal from hibernation in the European hamster.

1. Arterial blood was sampled at 15 min-intervals in European hamsters Cricetus cricetus fitted with indwelling catheters, from deep hibernation to full arousal. Temperature-corrected pH and PCO2, respectively pH* and P*CO2, were directly measured at 37 degrees C. 2. Deep hibernation corresponded to a respiratory acidosis: pH* = 7.01 +/- 0.01 (mean +/- SE), P*CO2 = 160 +/- 4 Torr (n = 9 animals). 3. Three periods could be distinguished in the arousal: (i) a period of hyperventilation (28 +/- 5 min), in which P*CO2 was reduced to 79 +/- 4 Torr, while cheek pouch temperature increased only by 0.9 +/- 0.2 degrees C; (ii) a period of metabolic acidification by lactate accumulation (84 +/- 6 min), corresponding to the period of peak thermogenesis; (iii) a progressive return to euthermic conditions (104 +/- 10 min), by simultaneous respiratory and metabolic alkalinization. 4. Over 60% of the blood CO2 stores accumulated at the beginning of the hibernation bout were released by hyperventilation during the first period, prior to the full development of thermogenesis. This is in agreement with the hypothesis of an inhibitory role of the respiratory acidosis in hibernation.

The differences in CO2 kinetics during incremental exercise among sprinters, middle, and long distance runners.

The purpose of this study was to investigate the differences in kinetics of CO2 output (VCO2) during incremental exercise in sprinters (S), middle (MD), and long distance runners (LD). In the steady state exercise, the VCO2 was linearly related to the O2 uptake (VO2). In the incremental exercise below anaerobic threshold (AT), the VCO2 was also linearly related to the VO2. The difference between the VCO2 estimates from the regression lines obtained in steady state and incremental exercise was added from the start of exercise up to a given time. The added values were defined as CO2 stores. The CO2 stores per body weight were significantly related to mixed venous CO2 pressure (PVCO2) determined by the CO2 rebreathing method. The slopes of the regression lines between PVCO2 and CO2 stores per body weight were not different among three groups. If VCO2 above AT is estimated from the VO2 using the regression line obtained in incremental exercise below AT, the estimated VCO2 is lower than the measured VCO2. The sum of the differences in VCO2 up to a given time was defined as CO2 excess. The CO2 excess per body weight was significantly related to delta LA (the difference between blood lactates at 5 min after exercise and at rest). The ratios of CO2 excess per body weight to delta LA were 3.30 +/- 1.49, 4.16 +/- 2.33, and 5.55 +/- 2.05 for sprinters, middle, and long distance runners, respectively. This ratio obtained in sprinters was significantly lower than that in long distance runners (p less than 0.01).

Aerobic and anaerobic correlates of mechanical work by gastrocnemius muscles of the aquatic amphibian Xenopus laevis.

Isolated, saline-perfused gastrocnemius muscles of Xenopus laevis were used to assess the relationships between aerobic and anaerobic metabolism during conditions of rest, isotonic contraction and recovery. The major part (85%) of the energy used during 25 min of isotonic contractions in the saline-perfused muscles was from anaerobic rather than aerobic sources. However, the small contribution made by oxidative metabolism during activity can be attributed, in part at least, to limitations imposed by the rate of perfusion and the low O2 capacity of the perfusate. The respiratory exchange ratio (R = VCO2/VO2) of saline-perfused gastrocnemius muscles of Xenopus was 0.82 at rest, increasing to values well above 1.0 during activity. The elevated R value is consistent with liberation of CO2 by metabolic acid titration of the bicarbonate buffer system of the saline perfusate. Recovery from exercise was characterized as a period of net CO2 retention (R values of 0.4) presumably reflecting a replenishment of depleted CO2 stores. Depending on the acid-base status of the venous outflow from the isotonically contracting muscles, hydrogen ions were found to be released at either a greater rate (alkalosis) or slower rate (acidosis) than that of lactate.

Immediate CO2 storage capacity at the onset of exercise.

The purpose of the present study was to obtain the immediate CO2 storage capacity at the onset of exercise. The CO2 stores at the onset of the exercise were calculated from the difference between the respiratory gas exchange ratio (R) and the metabolic gas exchange ratio (RQ: R obtained at 5.5 min of exercise). The CO2 stores per body weight (CO2 stores/w) were linearly related to the CO2 pressure (P'vCO2) determined by the CO2 rebreathing method (r = 0.713, p less than 0.001), the slope being 0.330 ml/(mmHg X kg). The CO2 stores were then corrected for change in O2 stores with exercise, that defined as total CO2 stores. P'vCO2 was also corrected for the effect of lung-bag volume shrinkage and Haldane effect during CO2 rebreathing, that defined as true PvCO2. The total CO2 stores/w were also related linearly to the true PvCO2 (r = 0.725, p less than 0.001), the slope of the regression line defined as the immediate CO2 storage capacity being 0.650 ml/(mmHg X kg).

Coupling of external to internal respiration.

Oxygen is required to generate chemical energy (ATP) to allow muscle contraction. The amount of chemical energy required is directly proportional to the work rate performed. Early in exercise, the muscle creatine phosphate and oxygen stores, primarily in the form of oxymyoglobin and oxyhemoglobin (oxygen content of venous blood decreases), are used for energy. This allows time for cardiac output and ventilation to increase to satisfy the total O2 requirement. Steady-state time depends on the level of work relative to the anaerobic threshold (AT). For work rates below the AT, steady-state for VO2 is achieved by 3 min and by 4 min for VCO2 and VE. For work rates above the AT, steady-states are considerably delayed or not achieved. For purposes of description of the pattern of external respiration (gas exchange at the lungs), three phases are defined. Phase I is the initial increase in VO2 and VCO2 at the start of exercise, lasting approximately 15 s. Because the gas exchange ratio (R) typically doesn't change during Phase I, the initial increase in VO2 and VCO2 must be due primarily to an increase in pulmonary blood flow and proportional increase in ventilation (cardiodynamic phase). Phase II is the exponential-like increase in VO2 and VCO2, which follow Phase I and terminates in a steady-state or asymptotic value (Phase III). At moderate work, VO2 increases more rapidly than VCO2 during Phase II (CO2 stores increase). Therefore, R decreases before it increases to the steady-state. Below the AT, the rate of external respiration equals the rate of internal respiration during Phase III.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of Directly Determined and Calculated Plasma Bicarbonate Concentration in the Turtle Chrysemys Picta Bellii at Different Temperatures

Comparison of Directly Determined and Calculated Plasma Bicarbonate Concentration in the Turtle <i>Chrysemys Picta Bellii</i> at Different Temperatures

Influence of body CO2 stores on ventilatory dynamics during exercise.

Pulmonary CO2 flow (the product of cardiac output and mixed venous CO2 content) is purported to be an important determinant of ventilatory dynamics in moderate exercise. Depletion of body CO2 stores prior to exercise should thus slow these dynamics. We investigated, therefore, the effects of reducing the CO2 stores by controlled volitional hyperventilation on cardiorespiratory and gas exchange response dynamics to 100 W cycling in six healthy adults. The control responses of ventilation (VE), CO2 output (VCO2), O2 uptake (VO2), and heart rate were comprised of an abrupt increase at exercise onset, followed by a slower rise to the new steady state (t1/2 = 48, 43, 31, and 33 s, respectively). Following volitional hyperventilation (9 min, PETCO2 = 25 Torr), the steady-state exercise responses were unchanged. However, VE and VCO2 dynamics were slowed considerably (t1/2 = 76, 71 s) as PETCO2 rose to achieve the control exercise value. VO2 dynamics were slowed only slightly (t1/2 = 39 s), and heart rate dynamics were unaffected. We conclude that pulmonary CO2 flow provides a significant stimulus to the dynamics of the exercise hyperpnea in man.

The effects of hypercapnia on the metabolic response to steady-state exercise.

Studies on isolated muscle and resting man have demonstrated that altering CO2 stores influences intracellular lactate production and/or tissue lactate release. In the present project, subjects (N = 6) performed steady-state exercise for 30 min while inspiring 0, 2, 4, or 6% CO2 and 21% O2. They were tested on eight occasions, four at 50% and four at 65% VO2max. Arterialized venous blood PCO2 increased in proportion to FICO2 (P less than 0.05). Blood pH had a similar but inverse relationship, decreasing from 7.371 to 7.233 (P less than 0.05). The VI increased directly with PCO2 (P less than 0.05), but no differences were found for VO2 or VO2. The R decreased in proportion to PCO2 (P less than 0.05) at both exercise intensities. Blood lactate was reduced (P less than 0.05) with CO2. At 65% VO2max lactate had an inverse linear relationship with blood PCO2 (P less than 0.05). The mean lactate decreased 43% from 3.88 mM . l-1 with 0% CO2 to 2.22 mM . l-1 with 6% CO2. The R shift suggest that carbohydrate metabolism may have been inhibited and lipid metabolism enhanced.

Changes in arterial blood gases during and after a period of oxygen breathing in patients with chronic hypercapnic respiratory failure and in patients with asthma.

1. Ten patients with chronic hypercapnic respiratory failure (group 1) and eight patients with asthma (group 2) breathed pure O2 from an MC mask for 60 min. Blood gases were measured during this period and for the subsequent 45 min. 2. In mine of ten patients in group 1 and in all eight patients in group 2 arterial O2 tension (Pa,O2) fell to values lower than had been obtained before O2 was given. 3. These undershoots in Pa,O2 are unrelated to changing CO2 stores or to hypoventilation, and are more likely due to persistence of altered ventilation-perfusion ratios associated with O2 breathing. 4. Magnitude of the undershoots is usually small, and periods of less than 15 min of O2 are unlikely to be harmful.

Acid-base relationships in the blood of the toad, Bufo marinus. III. The effects of burrowing.

When Bufo marinus burrows, the skin becomes intimately surrounded by substrate but the nares always remain exposed to the surface air. Upon entering into a state of dormancy the animal hypoventilates and this together with the loss of the skin as a respiratory site results in a rise in arterial blood PCO2 despite a probable decline in metabolism. Even though lung ventilation falls, the toad regulates blood pH and the respiratory acidosis is progressively compensated for by a progressive increase in plasma [HCO3-] along the course of an elevated PCO2 isopleth. At steady state, the acidosis is fully compensated for by a new equilibrium ratio of HCO3- to PCO2 at the same pH as the non-burrowed animal. Arousal from the dormant state at this time results in a marked lung hyperventilation and a sharp decline in body CO2 stores.

Mechanism of the ventilatory response to carbon monoxide.

The effects of carbon monoxide on ventilation were studied in unanesthetized goats. Responses to single breaths of 10-25% CO in O2, which rapidly raised carboxyhemoglobin (COHb) from 5 to 60%, were considered to reflect peripheral chemoreceptor-mediated reflexes whereas responses to continuous inhalation of 1% CO in O2, which slowly raised COHb from 0 to 60%, were considered to reflect both peripheral chemoreceptor and nonperipheral chemoreceptor mechanisms. In each of six goats, single breaths of CO failed to elicit any immediate ventilatory response. However, slow buildup of carboxyhemoglobinemia in the same animals always elicited ventilatory stimulation (from a mean of 7.43 to 16.02 liter/min, P less than 0.001) beginning 5-6 min after onset of 1% CO in O2 inhalation when COHb saturation reached 50-60%. In eight studies of six animals HCO3- concentration fell (from 21.3 to 15.8 meq/liter; P less than 0.001) and lactate concentration rose (from 2.5 to 4.2 meq/liter; P less than 0.05) in the cisternal cerebrospinal fluid during the CO-induced hyperpnea. Additional studies ruled out ventilatory stimulation from left heart failure or enhanced chemo-sensitivity to carbon dioxide. Although the delayed hyperpnea was associated with a hyperdynamic cardiovascular response to CO, blockade of these circulatory effects with propranolol (2 mg/kg) failed to abolish the delayed hyperpnea; however, the propranolol did unmask an element of ventilatory depression which preceded the hyperpnea. Conclusions were: (a) hyperventilation in response to CO inhalation is not mediated by the carotid bodies; (b) the delayed hyperpnea in response to CO inhalation is primarily due to brain-cerebrospinal fluid acidosis; (c) mobilization of body CO2 stores due to the circulatory response to CO may obscure an initial depression of ventilation by CO.

Lung carbonate dehydratase (carbonic anhydrase), CO2 stores and CO2 transport.

A study of CO2 storage in excised, exsanguinated lungs revealed that CO2 stores include a compartment which reaches equilibration very rapidly (less than 3s) and a slower compartment which equilibrates with a half-time of approximately 15 s. Inhibition of carbonate dehydratase (carbonic anhydrase, EC 4.2.1.1) does not change the slope of the total CO2 dissociation curve of the lung but does increase the slow compartment at the expense of the fast. CO2 diffusion across the pleura is approximately 20 times faster than that of O2, a relationship that is not affected by inhibition of carbonate dehydratase. The role of tissue CO2 stores in limiting respiratory fluctuations of PCO2 or pH in arterial blood is only minor and may be of significance only in rapid, deep inspiration. CO2 uptake or release by the stores is out of phase with blood CO2 exchange. As a consequence, the time course of CO2 exchange at the mouth during expiration cannot be used to predict alveolar or capillary CO2 exchange.