Defining the relationship of oxygen delivery and consumption: use of biologic system models

To determine the most appropriate mathematical description of the relationship between oxygen consumption and oxygen delivery, we compared the statistical validity of a piecewise linear model to two different biologic system models--Michaelis-Menten (MM) kinetics (used for enzyme systems) and the exponential dose-response relationship (used to describe drug administration and induced response). Nine rabbits underwent five incremental steps of normovolemic hemodilution to progressively decrease DO2. VO2 was measured concurrently by a metabolic gas monitor. All three models (piecewise linear, Michaelis-Menten, and exponential) provided a very close population curve fit to the data points (r2 = 0.88, 0.91, and 0.92). However, there were significant differences in maximum predicted VO2 (VO2max)--6.8, 9.9, 7.2 ml O2.kg-1.min-1 (P < 0.0002)--and a wide range in the model-specific parameters for individual rabbits (critical DO2 6.5-11.8 ml O2.kg-1.min-1, Km 4.2-11.4 ml O2.kg-1.min-1, and kappa 0.12-0.23 ml O2-1.kg.min). In the curvilinear models, average and population parameters were not significantly different. However, in the piecewise linear model, population critical DO2 (10.9 ml O2.kg-1.min-1) was 30% more than the average critical DO2 (8.4 ml O2.kg-1.min-1) for the nine rabbits (P < 0.005). VO2max values predicted by the piecewise linear and exponential dose-response model were more consistent with those in previous publications than was the higher VO2max predicted by the MM model. The difference in the average versus population critical DO2 in the piecewise linear model meant that population modeling was inaccurate because it yielded a critical DO2 higher than that demonstrated by eight of nine individual rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)