Abusing the Fick Principle

Dear Editor-in-Chief: We wish to take umbrage with the data, analysis, and conclusions regarding the interrelationships among cardiac output 𝑄̇, V̇O2max, and O2 extraction presented in the recent paper by LePretre and colleagues (7). The authors utilized the eponymous Fick principle, which is based on simple mass balance considerations and states that can be calculated from simultaneous measurement of V̇O2, and the arterial (CaO2) and mixed venous (CV̇vO2) blood O2 contents (i.e., O2 extraction): Following the landmark publication in 1870, Adolf Fick’s principle has formed a fundamental cornerstone of cardiovascular physiology and medicine (2). For example, in the late 1800s it was used to measure 𝑄̇ in dogs (4) and horses (13), and following the first successful heart catheterization by Werner Forssman in 1929, in man (3,6). Today, with multiple invasive and noninvasive techniques to measure 𝑄̇, the Fick principle is often used to determine O2 extraction: and it is using this form that LePretre et al. supposedly derived their O2 extraction data depicted in Figure 5 and Table 3 of their publication. As evident from equations 1 and 2 above, it is impossible for O2 extraction (CaO2 − CV̄O2) to be changing while both 𝑄̇ and V̇O2 are constant. However, their Figure 5 demonstrates an approximately 30% decrease in CaO2 − CV̄2 at constant rates of 𝑄̇ and V̄O2 (see their Fig. 4) during heavy/severe exercise. Moreover, the mean values for O2max and 𝑄̇max presented in their Table 3 are not consistent with the maximal O2 extraction data in that table. Specifically, the values presented are 13.2, 13.1, and 13.3 mL O2·100 mL−1 blood, whereas those calculated from their data are 20–40% higher (i.e., 15.7, 17.9, and 16.9 mL O2·100 mL−1 blood, respectively). In conclusion, the data presented by LePretre et al. (7) appear to be inconsistent with basic principles of mass balance as delineated by the Fick principle. Moreover, investigations that have measured O2 extraction directly either across the body or exercising limbs at heavy/severe exercise intensities (1,5,9–11) do not demonstrate either a temporal or intensity-related reduction in O2 extraction as depicted by LePretre et al. Indeed, from the relationship established between 𝑄̇ and O2 for dynamic exercise, O2 extraction must increase as a hyperbolic function of muscle(s) and pulmonary O2 (8,12). Thus, it may be appropriate to hold in question the fidelity of the data presented by LePretre et al. and their conclusions based upon that data. Danielle J. Padilla Timothy I. Musch David C.