Rebreathing in a closed system can be used to estimate mixed venous
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\begin{document}$$P_{{\rm CO}_{2}}\;(P\bar{v}_{{\text{CO}}_2})$$\end{document} and cardiac output, but these estimates are affected by
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\begin{document}$$\dot{V}_{\rm A}/\dot{Q}$$\end{document} heterogeneity. The purpose of this study was to validate a mathematical model of CO2 exchange during CO2 rebreathing in 29 patients with chronic obstructive pulmonary disease (COPD), with baseline arterial
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\begin{document}$$P_{{\rm CO}_{2}}\;(\hbox{Pa}_{{\rm CO}_{2}})$$\end{document} ranging from 28 to 60 mmHg. Rebreathing increased end-tidal
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\begin{document}$$P_{{\rm CO}_{2}}\;(\hbox{PET}_{{\rm CO}_{2}})$$\end{document} by 20 mmHg over 2.2 min. This model employed baseline values for inspired (bag)
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\begin{document}$$P_{{\rm CO}_{2}},$$\end{document} estimated
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\begin{document}$$P\bar{v}_{{\text{CO}}_2},$$\end{document} distribution of ventilation and blood flow in one high
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\begin{document}$$\dot{V}_{\rm A}/\dot{Q}$$\end{document} and one low
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\begin{document}$$\dot{V}_{\rm A}/\dot{Q}$$\end{document} compartment, the ventilation increase and conservation of mass equations to simulate time courses of
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\begin{document}$$\hbox{PI}_{{\rm CO}_{2}},\hbox{PET}_{{\rm CO}_{2}},\; P\bar{v}_{{\text{CO}}_{2}}$$\end{document} and
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\begin{document}$$\hbox{Pa}_{{\rm CO}_{2}}.$$\end{document} Measured
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\begin{document}$$\hbox{PI}_{{\rm CO}_{2}}$$\end{document} and
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\begin{document}$$\hbox{PET}_{{\rm CO}_{2}}$$\end{document} during rebreathing differed by an average (SEM) of 1.4 (0.4) mmHg from simulated values. By end of rebreathing, predicted
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\begin{document}$$P\bar{v}_{{\text{CO}}_2}$$\end{document} was lower than measured and predicted
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\begin{document}$$\hbox{Pa}_{{\rm CO}_{2}},$$\end{document} indicating gas to blood CO2 flux. Estimates of the ventilatory response to CO2, quantified as the slope (S) of the ventilation increase versus
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\begin{document}$$\hbox{PET}_{{\rm CO}_{2}},$$\end{document} were inversely related to gas-to-blood
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\begin{document}$$P_{{\rm CO}_{2}}$$\end{document} disequilibria due to
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\begin{document}$$\dot{V}_{\rm A}/\dot{Q}$$\end{document} heterogeneity and buffer capacity (BC), but not airflow limitation. S may be corrected for these artifacts to restore S as a more valid noninvasive index of central CO2 responsiveness. We conclude that a rebreathing model incorporating baseline
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\begin{document}$$\dot{V}_{\rm A}/\dot{Q}$$\end{document} heterogeneity and BC can simulate gas and blood
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\begin{document}$$P_{{\rm CO}_{2}}$$\end{document} in patients with COPD, where
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\begin{document}$$\dot{V}_{\rm A}/\dot{Q}$$\end{document} variations are large and variable.
