Analysis of flow resistance in the pulmonary arterial circulation: implications for hypoxic pulmonary vasoconstriction.

Abstract

Hypoxic pulmonary vasoconstriction (HPV) plays an essential role in distributing blood in the lung to enhance ventilation-perfusion matching and blood oxygenation. In this study, a theoretical model of the pulmonary vasculature is used to predict the effects of vasoconstriction over specified ranges of vessel diameters on pulmonary vascular resistance (PVR). The model is used to evaluate the ability of hypothesized mechanisms of HPV to account for observed levels of PVR elevation during hypoxia. The vascular structure from pulmonary arteries to capillaries is represented using scaling laws. Vessel segments are modeled as resistive elements and blood flow rates are computed from physical principles. Direct vascular responses to intravascular oxygen levels have been proposed as a mechanism of HPV. In the lung, significant changes in oxygen level occur only in vessels less than 60 μm in diameter. The model shows that observed levels of hypoxic vasoconstriction in these vessels alone cannot account for the elevation of PVR associated with HPV. However, the elevation in PVR associated with HPV can be accounted for if larger upstream vessels also constrict. These results imply that upstream signaling by conducted responses to engage constriction of arterioles plays an essential role in the elevation of PVR during HPV.NEW & NOTEWORTHY A theoretical model of the pulmonary vasculature is used to predict the effects of vasoconstriction over specified ranges of vessel diameters on pulmonary vascular resistance (PVR). The model shows that observed levels of hypoxic vasoconstriction in terminal vessels cannot account for the elevation of PVR associated with hypoxic pulmonary vasoconstriction (HPV). Upstream signaling by conducted responses to engage constriction of arterioles, therefore, plays an essential role in the elevation of PVR during HPV.