Influence of increased metabolic rate on [13C]bicarbonate washout kinetics.

The effect of changes in metabolic rate on the dynamics of CO2 exchange among its various compartments in the human body is not well understood. We examined CO2 dynamics in six healthy male subjects using an intravenous bolus of [13C]bicarbonate. Subjects were studied while resting, during light exercise [50% of the lactate threshold (LT), 3-4 times resting O2 uptake (VO2)], and during moderate exercise (95% of the LT, 6 times resting VO2). The sum of three exponential terms well described the washout of 13CO2 in exhaled breath both at rest and during each exercise level despite substantial increases in metabolic rate accompanying the exercise studies. Average recovery of 13C label rose from 67% during rest to 80% during light and moderate exercise (P less than 0.01). The estimate of CO2 elimination (VCO2) calculated from the washout parameters and corrected for recovery was in very good agreement with the VCO2 directly measured simultaneously breath by breath (r = 0.993, SE for VCO2 = 0.079 l/min). By use of a three-compartment mammillary model, the quantity of CO2 in the central pool (Q1) doubled from rest to light exercise (233 +/- 60 to 479 +/- 76 mmol, P less than 0.01) but did not change further with moderate exercise (458 +/- 74 mmol). Rate constants for exchange between pools and for irreversible loss from the system tended to increase with metabolic rate, but there was large variation in the responses. We conclude that the compartmental dynamics of CO2 transport and storage are very sensitive to changes in metabolic rate induced by exercise

Increase in bicarbonate stores with exercise.

We previously described bicarbonate exchange dynamics in humans at rest and during exercise using a three-compartment model. In the present study we tested the effect of certain assumptions of this model on the prediction of the change in exchangeable bicarbonate with the increased metabolic rate of exercise. We compared this prediction with a measurement of CO2 retention after exercise onset determined from gas exchange data. The change in tissue bicarbonate stores was estimated from differences in the kinetics of adjustment of VO2 and VCO2, and this was added to an estimate of the changes in venous blood gas stores to estimate the total change in bicarbonate. When the commonly held assumption that endogenous CO2 production, thought to occur in a rapidly equilibrating peripheral compartment at rest, was also applied to the exercise condition, the three-compartment bicarbonate model predicted an unphysiologically large increase in bicarbonate stores (700 mmol, or over 15 L). In contrast, the 'gas exchange' approach predicted a relatively small increase in bicarbonate (26 mmol), consistent with other reports. The incompatibility of these findings with the assumption about the source of endogenous CO2 production in the bicarbonate model requires that the underlying physiological correlates of the three compartments change from rest to exercise

Increase in bicarbonate stores with exercise.

We previously described bicarbonate exchange dynamics in humans at rest and during exercise using a three-compartment model. In the present study we tested the effect of certain assumptions of this model on the prediction of the change in exchangeable bicarbonate with the increased metabolic rate of exercise. We compared this prediction with a measurement of CO2 retention after exercise onset determined from gas exchange data. The change in tissue bicarbonate stores was estimated from differences in the kinetics of adjustment of VO2 and VCO2, and this was added to an estimate of the changes in venous blood gas stores to estimate the total change in bicarbonate. When the commonly held assumption that endogenous CO2 production, thought to occur in a rapidly equilibrating peripheral compartment at rest, was also applied to the exercise condition, the three-compartment bicarbonate model predicted an unphysiologically large increase in bicarbonate stores (700 mmol, or over 15 L). In contrast, the 'gas exchange' approach predicted a relatively small increase in bicarbonate (26 mmol), consistent with other reports. The incompatibility of these findings with the assumption about the source of endogenous CO2 production in the bicarbonate model requires that the underlying physiological correlates of the three compartments change from rest to exercise

13CO2 washout kinetics in acute hypercapnia.

The redistribution of CO2 and bicarbonate throughout the body following perturbations of normal respiration is not well described. We used tracer techniques to examine CO2-bicarbonate dynamics in an animal model in which acute hypercapnia was induced by hypoventilation. Eleven rabbits were anesthetized, tracheostomized, paralyzed and ventilated. In five animals PaCO2 was kept between 30 and 35 mmHg (control, C) while in six PaCO2 was held between 65 and 70 mmHg (acute hypercapnia, AH). A bolus of [13C]bicarbonate was given intravenously. Breath samples were obtained for 13CO2 by isotope ratio mass spectrometry and CO2 output (VCO2) was measured breath-by-breath for 240 min. There was no difference in the VCO2 between C [5.6 +/- 1.8 (SD) ml/min per kg] and AH (5.3 +/- 0.8). The 13CO2 washout for both C and AH was well fit by the sum of three exponentials. Only the time constant of the third (slowest) exponential was significantly longer in AH (103 +/- 11 min) compared with C (75 +/- 15, P less than 0.01). The mean residence time in AH (82 +/- 9 min) was significantly lower than in C (57 +/- 10, P less than 0.001). The estimated mass of exchangeable CO2 and bicarbonate was significantly greater in AH (443 +/- 37 ml per kg) compared with C (312 +/- 63, P less than 0.005). Compartmental analysis indicated that the increase in CO2-bicarbonate occurred primarily in the slowly exchanging pool. The data suggest that acute hypercapnia may be accompanied by a redistribution of exchangeable CO2 and bicarbonate in the body