Extent to which pulmonary vascular responses to PCO2 and PO2 play a functional role within the healthy human lung

Abstract

Regional blood flow in the lung is known to be influenced by the alveolar PCO2 and alveolar PO2. For the healthy lung, the extent to which this influence is of functional importance in limiting heterogeneity in alveolar gas composition by matching regional perfusion (q) to regional ventilation (v) remains unclear. To address this issue, the efficiency of regulation (E) was defined as the percent correction to an initial perturbation in regional alveolar gas composition generated by the pulmonary vascular response to the disturbance. This study develops the theory to calculate E from global measurements of vascular reactivity to CO2 and O2 in human volunteers. For O2, these data were available from the literature. For CO2, an experimental component of the present study used Doppler echocardiography to evaluate the magnitude of the global vascular response to hypercapnia and hypocapnia in 12 volunteers over a timescale of approximately 0.5 h. The results suggest a value for E of approximately 60% over a wide range of values for v-to-q ratio (approximately 0.1-10) encompassing those found in normal lung. At low v/q (<0.65), the vascular response to O2 forms the dominant mechanism; however, at higher v/q (>0.65), the response to CO2 dominates. The values for E suggest that the pulmonary vascular responses to both CO2 and O2 play a significant role in ventilation-perfusion matching in the healthy human lung.

Fig. 1.

Depiction of the control system regulating the local alveolar Pco₂ (Pa_CO2) within the lung [for alveolar Po₂ (Pa_O2), the analysis is analogous]. A and B illustrate the derivation of Eq. 15. In A, the lines represent variables [e.g., Δ(v̇/q̇), where v̇/q̇ is ventilation-to-perfusion ratio] within the control system, the rectangular boxes depict the transforms for the change in 1 variable brought about by the change in another, and the circle represents the addition of the changes in 2 incoming variables to generate an outgoing variable. In the absence of any disturbance (i.e., h₀ = 0), ΔPa_CO2 and Δ(v̇/q̇) are both 0, and the control system is at point 1 (see B). A step-function finite disturbance in Pa_CO2 (i.e., h₀ ≠ 0) is illustrated at point 2 in B. If no feedback is present (an open loop), then this disturbance would result in a disturbance of v̇/q̇ illustrated at point 3 in B. However, in the presence of feedback (a closed loop), the control system is at point 4 in B. Here, the final value for ΔPa_CO2 is h₁ [and the final value for Δ(v̇/q̇) is h₁H]. Summation at the junction depicted by the circle in A yields the result that ΔPa_CO2 (= h₁) = h₀ − KHh₁, which is Eq. 15.

Fig. 2.

Top: Pa_CO2 and Pa_O2 as a function of regional v̇/q̇. Middle: feedback loop gains for the regulation of regional v̇/q̇ by hypercapnic and hypoxic pulmonary vasoconstriction. Bottom: efficiencies of regulation of regional v̇/q̇ by hypercapnic and hypoxic pulmonary vasoconstriction. Dashed lines, responses relating to CO₂; dotted lines, responses relating to O₂; solid lines, combined responses to both CO₂ and O₂. Note that the regulatory effect of O₂ is greater than that for CO₂ at low values for v̇/q̇, that the regulatory effect of CO₂ is greater than that for O₂ at higher values of v̇/q̇, and that the total regulatory efficiency remains relatively constant over the range of values displayed for v̇/q̇.

Fig. 3.

Composition of respired gas during each of the 3 main protocols. Top: hypercapnia protocol consisting of a 25-min period of euoxic hypercapnia preceded and followed by a 5-min period of euoxic eucapnia. Ventilation was spontaneous throughout. Middle: hypocapnia protocol consisting of a 25-min period of euoxic hypocapnia preceded and followed by a 5-min period of euoxic eucapnia. The volunteers undertook voluntary hyperventilation throughout. Bottom: control protocol consisting of a 35-min period of euoxic eucapnia. Ventilation was spontaneous throughout. Left: values during the determination of the maximum pressure difference across the tricuspid valve (ΔPmax). Right: values during the determination of cardiac output. Results show inspired Pco₂ (Pi_CO2; triangles), inspired Po₂ (Pi_O2; diamonds), end-tidal Pco₂ (Pet_CO2; circles), and end-tidal Po₂ (Pet_O2; squares). Closed symbols indicate periods of either hypercapnia or hypocapnia; open symbols indicate periods of eucapnia. Data are means for 12 subjects; error bars are ± SE. Note that, in the hypercapnia protocol, Pi_CO2 is close to 40 Torr during euoxic hypercapnia, which coincidentally is very close to Pet_CO2 before and after this period.

Fig. 4.

Tricuspid valve maximum pressure difference (ΔPmax) during the 3 main protocols: hypercapnia (circles), hypocapnia (squares), and control (triangles). Closed symbols indicate measurements made under hypercapnic (hypercapnia protocol) or hypocapnic (hypocapnia protocol) conditions; open symbols indicate measurements made under eucapnic conditions. Data are means for 12 subjects; error bars are ± SE. ΔPmax was significantly affected by both hypercapnia and hypocapnia compared with control (P < 0.001, rmANOVA).

Fig. 5.

Cardiac output (top), stroke volume (middle), and heart rate (bottom) during the 3 main protocols: hypercapnia (circles), hypocapnia (squares), and control (triangles). Closed symbols indicate measurements made under hypercapnic (hypercapnia protocol) or hypocapnic (hypocapnia protocol) conditions; open symbols indicate measurements made under eucapnic conditions. Data are means for 12 subjects; error bars are ± SE.

Fig. 6.

Example for a single volunteer (number 1256) of the fit of the model for the response of ΔPmax in 2 protocols. Top: hypercapnia protocol. Bottom: hypocapnia protocol. Solid lines = model response; symbols = experimental data points.

Fig. 7.

Average of the model outputs for ΔPmax, heart rate, stroke volume, and cardiac output compared with mean data. Left: hypercapnia protocol. Right: hypocapnia protocol. Solid lines = model response; symbols = experimental data points.