Influence of increased metabolic rate on [^(13)C]bicarbonate washout kinetics

The effect of changes in metabolic rate on the dynamics of CO_2 exchange among its various compartments in the human body is not well understood. We examined CO_2 dynamics in six healthy male subjects using an intravenous bolus of [^(13)C]bicarbonate. Subjects were studied while resting, during light exercise [50% of the lactate threshold (LT), 3-4 times resting O_2 uptake (V_(O_2))], and during moderate exercise (95% of the LT, 6 times resting V_(O_2)). The sum of three exponential terms well described the washout of ^(13)CO_2 in exhaled breath both at rest and during each exercise level despite substantial increases in metabolic rate accompanying the exercise studies. Average recovery of ^(13)C label rose from 67% during rest to 80% during light and moderate exercise (P less than 0.01). The estimate of CO_2 elimination (V_(CO_2)) calculated from the washout parameters and corrected for recovery was in very good agreement with the V_(CO_2) directly measured simultaneously breath by breath (r = 0.993, SE for V_(CO_2) = 0.079 l/min). By use of a three-compartment mammillary model, the quantity of CO_2 in the central pool (Q_1) 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 CO_2 transport and storage are very sensitive to changes in metabolic rate induced by exercise