Pulmonary gas exchange, diffusion and intra-pulmonary arteriovenous shunting during physiological stress

运动对肺系统造成压力，以维持足够的肺气体交换。随着运动的增加，肺弥散能力必须增加，以满足增加的需氧量，并防止扩散限制。运动时弥散能力（DLCO）的增加是通过肺毛细血管的募集和扩张来实现的，从而导致肺毛细血管血容量（Vc）和弥散膜容量（Dm）的增加。尽管运动增加了DLCO，但大多数健康人群的肺气体交换会出现损伤，这可以通过肺泡与动脉PO2差异（AaDO2）的增加来量化。我们的研究小组先前提供的证据表明，运动增加的AaDO2可能是由于解剖性肺内动静脉分流（IPAVAs）的增加。

Exercise represents a stress to the pulmonary system to maintain adequate pulmonary gas exchange. With incremental exercise, pulmonary diffusing capacity must increase to meet the increased oxygen demand, and prevent a diffusion limitation. The increase in diffusing capacity (DLCO) with exercise is accomplished by pulmonary capillary recruitment and capillary distention which results in an increase in both pulmonary capillary blood volume (Vc) and diffusing membrane capacity (Dm). Despite an increase in DLCO with exercise, most healthy humans develop an impairment in pulmonary gas exchange as quantified by an increase in the alveolar to arterial PO2 difference (AaDO2), and our group has previously provided evidence that the increased AaDO2 with exercise may be due to the recruitment of anatomical intra-pulmonary arteriovenous shunts (IPAVAs). The overall objective of my NSERC-funded research program is to understand factors controlling pulmonary gas exchange, diffusing capacity, and the mechanism and consequences of IPAVAs recruitment at rest and during exercise. Over the next grant cycle we plan to further examine pulmonary vascular regulation, pulmonary diffusion and IPAVAs to better understand pulmonary gas exchange during physiological stress such as exercise. The specific aims of the grant are: Aim 1: To determine the effect of dopamine on pulmonary capillary blood volume, diffusing capacity and intra-pulmonary arteriovenous shunting during exercise. Aim 2: To determine the effect of dopamine blockade on pulmonary capillary blood volume, diffusing capacity and pulmonary arterial systolic pressure. Aim 3: To determine the effect of pulmonary capillary blood volume on arteriovenous shunt recruitment. Aim 4: To determine the relationship between anatomic arteriovenous shunting, ventilation-perfusion matching, diffusion limitation and right-to-left shunt. Aim 5: To evaluate precapillary gas exchange of oxygen and inert gas in the pulmonary circulation. Aims 1-3 will be done in our state-of-the art CFI-funded laboratory, and will use pharmacological agents to influence the pulmonary circulation and determine the effects on DLCO, Vc and IPAVAs. Aims 4&5 will be conducted in a canine model and will help resolve the long-standing controversy around anatomical vs. gas exchange shunt, as well as the potential existence of precapillary gas exchange within the lung.