Introduction
Increasing spatial resolution of ventilation and blood flow measurements in the lung has revealed an unexpected heterogeneity in their distributions. Despite this variability, efficient gas exchange occurs through the matching of regional ventilation and blood flow. New methods and studies performed in prolonged microgravity now demonstrate that the traditional concepts of ventilation and perfusion matching need to be reformulated.
Methods
Regional perfusion and ventilation distributions are commonly inferred from indirect methods such as inert gas washout studies or the multiple inert gas elimination technique (MIGET). These methods do not provide any spatial information. New fluorescent microsphere methods provide direct measures of regional ventilation and perfusion and their spatial distributions in laboratory animals. Fluorescent markers of ventilation and perfusion can be administered at different timepoints and physiologic conditions. Post mortem fluorescent measurements are determined to lung pieces ~2 cm3 in volume and the spatial location of each piece noted. Using computer algorithms derived by Olska and associates, estimates of ventilation and perfusion to each lung piece can be used to determine regional alveolar gas pressures. Whole lung gas exchange can be predicted by incorporating mixed venous blood gas pressures, gas solubilities, hemoglobin concentrations, and the hemoglobin-oxygen dissociation relationship.
Results
Estimates of regional ventilation and perfusion appear to be accurate because they correctly predict whole lung respiratory and inert gas exchange. The data can also be reduced to a 50-compartment model and represented as flow and ventilation weighted distribution for direct comparison to MIGET. These high-resolution methods also allow ventilation/perfusion ratios and alveolar O2 partial pressures to be explored in the spatial domain. Direct measures of regional ventilation and perfusion provide a new perspective and insights into mechanisms producing efficient gas exchange. One concept emerging from these new perspectives is that the respiratory system is a fractal structure. The advantages of a fractal structure include maximizing gas exchange surface area, minimizing energy requirements, minimizing construction costs, and conserving building instructions (DNA). The disadvantage of a fractal system is the inherent heterogeneity of perfusion and ventilation. Recent studies suggest that perfusion heterogeneity becomes increasingly greater all of the way down to the level of gas exchange. Because active regulation is not apparent in the normal lung, ventilation and perfusion are likely matched on a structural basis in normal lungs during normoxia.
Conclusions
Regional perfusion and ventilation are determined primarily through fractal structures. These fractal systems create heterogeneous distributions that do not appear to be matched by active regulation in the normal lung during normoxia.
References