Intrapulmonary arteriovenous anastomoses (IPAVA) have been known to exist as part of the normal pulmonary vasculature for over 50 years but have been underappreciated by physiologists and clinicians. Using a technique called saline contrast echocardiography we and others have demonstrated that during exercise or when breathing low oxygen gas mixtures IPAVA open, but breathing 100% oxygen during exercise prevents them from opening. However, the mechanism(s) for this dynamic regulation and the role IPAVA play in affecting pulmonary gas exchange efficiency remain unknown. In Chapter IV the infusion of epinephrine and dopamine into resting subjects opened IPAVA. While it is possible this opening was due to the direct vasoactive action of these catecholamines, the opening may simply be due to increases in cardiac output and pulmonary artery systolic pressure secondary to the cardiac effects of these drugs. In Chapter V I used Technetium-99m labeled macroaggregated albumin (99mTc-MAA) to quantify blood flow through IPAVA in exercising healthy humans. Initial attempts to correct for attenuation of the emitted signal were unsuccessful due to the time necessary for data acquisition and the resulting accumulation of free-99mTc. However, I used a blood sample to calculate freely circulating 99mTc which could be subtracted from the shunt fraction. Using this procedure I demonstrated for the first time using filtered solid particles that breathing 100% oxygen reduces blood flow through IPAVA during exercise. Finally, in Chapter VI I tackled the elephant in the room surrounding IPAVA in healthy humans: do these vessels play a role in pulmonary gas exchange efficiency? Our data suggest that the efficiency of pulmonary gas exchange is dependent on the driving pressure gradient for oxygen and the distance to blood flowing through the core of IPAVA. As such, with increases in exercise intensity the diffusion distance and transit time of blood at the core of IPAVA prevent complete gas exchange, thus blood flow through IPAVA acts as a shunt. This dissertation includes previously unpublished co-authored material.

<p>In birds like the Zebra finch (Taeniopygia guttata) the female, but not the male develop a brood patch upon incubation of eggs. The brood patch functions to increase heat exchange between the bird and the eggs. Development of the brood patch includes de-feathering, increased vascularization and edema formation. The increased vascularization is due to the development of arteriovenous anastomoses, AVA. The AVA are thermoregulatory vessels involved in cold induced vasodilation, CIVD, demonstrated to occur in the brood patch. Nitric oxide, NO, which is a well known vasodilator is a candidate substance for involvement in CIVD. In this study a NO-generating gel was applied to the brood patch of male and female zebra finches. Vasodilation was found to be markedly larger in females than in males. The larger vasodilation in the female brood patch is probably because NO vasodilate AVA selectively more than any other vessels. The study also investigated whether vasodilation would cause an increase in brood patch temperature. No definite changes in brood patch temperature could be observed and no conclusions could be drawn in the matter.</p>

In birds like the Zebra finch (Taeniopygia guttata) the female, but not the male develop a brood patch upon incubation of eggs. The brood patch functions to increase heat exchange between the bird and the eggs. Development of the brood patch includes de-feathering, increased vascularization and edema formation. The increased vascularization is due to the development of arteriovenous anastomoses, AVA. The AVA are thermoregulatory vessels involved in cold induced vasodilation, CIVD, demonstrated to occur in the brood patch. Nitric oxide, NO, which is a well known vasodilator is a candidate substance for involvement in CIVD. In this study a NO-generating gel was applied to the brood patch of male and female zebra finches. Vasodilation was found to be markedly larger in females than in males. The larger vasodilation in the female brood patch is probably because NO vasodilate AVA selectively more than any other vessels. The study also investigated whether vasodilation would cause an increase in brood patch temperature. No definite changes in brood patch temperature could be observed and no conclusions could be drawn in the matter.