Defining origin of positive slope in hypercapnic ventilatory response curve

The sensitivity to CO2 as a respiratory stimulant has traditionally been studied by exposing organisms to progressively increasing levels of inspired CO2 while measuring the corresponding increase in minute ventilation (V). Plots of V as a function of end-tidal CO2 concentration reveal a complex function with a "dogleg" shape. Only the positive slope of the V function is taken as an index of chemosensitivity, but the starting points for such analyses are often chosen arbitrarily. This paper examined the hypotheses that the range of CO2 concentrations over which V slopes are compared may be mathematically defined and that arbitrary choices of this analytic range may influence conclusions about the hypercapnic ventilatory response (HCVR). Three mathematical models attempted to define the origin of the positive slope for the HCVR curve using empirically derived data. The results revealed good agreement that the origin of the positive HCVR slope may be reliably defined by a point that joins the horizontal and positive slope of the HCVR curve. In addition to identifying the "joint-point" statistic, the results suggest that arbitrarily defining the range of CO2 values over which V is analyzed can be replaced by quantitative approaches for identifying the origin of the ventilatory response to hypercapnia.