UC San Diego

For a given combination of inspired and mixed venous gases, the local partial pressures of oxygen (pO₂) and carbon dioxide (pCO₂) in capillary blood after gas exchange has occurred is determined by the proportion of delivered fresh gas (alveolar ventilation, VA) to blood flow (perfusion, Q), termed ventilation-perfusion (VA/Q) ratio. Non-uniformity of VA/Q among different lung regions impairs overall gas exchange, and hence decreases pulmonary function. However, pulmonary vascular tone is known to be sensitive to local pO₂ and pCO₂, providing a mechanism whereby blood flow may be actively regulated, and ventilation-perfusion matching maintained. Yet, the temporal dynamics of blood flow in the human lung have been largely unexplored due to the lack of appropriate tools. This dissertation presents three original studies utilizing recently developed techniques in magnetic resonance imaging (MRI) to acquire dynamic measures of regional blood flow in the healthy human lung, in an attempt to characterize spatio-temporal patterns associated with active blood flow regulation and thereby gain insight into its role in normal physiologic function. Using the MRI method of arterial spin labeling (ASL), dynamic series of flow-weighted images were produced in a single sagittal slice of the right lung of several subjects while breathing air, and while exposed to a series of physiologic challenges involving either changes in inspired oxygen, administration of a pulmonary vasodilator (nitric oxide, NO), or elevation of end-tidal CO₂ (hypercapnia). Effects of vascular regulatory activity on the distribution of blood flow were assessed utilizing fluctuation dispersion (FD), a measure of overall spatio- temporal change, regional difference maps, and an ANOVA- like variance-partitioning scheme. Hypoxia increased temporal variability, hypercapnia increased spatial variability, and both led to changes in the pattern of blood flow but over different spatial scale-lengths, with hypoxia driving redistribution over larger regions. Further, the normoxic lung was found to exhibit vasomotor tone at rest that served to mitigate the effects of gravity on blood flow. These studies support the notion of gas exchange as an active as opposed to passive process, with complementary roles for O₂ and CO₂ mediated vascular regulation in ensuring the efficiency of uptake and elimination of gases