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。***我的nserc资助的研究项目的总体目标是了解控制肺气体交换、扩散能力的因素，以及在休息和运动期间IPAVAs招募的机制和后果。在下一个拨款周期，我们计划进一步研究肺血管调节、肺弥散和IPAVAs，以更好地了解生理应激（如运动）期间的肺气体交换。******该资助的具体目的是：***目的1：确定多巴胺对运动时肺毛细血管血容量、弥散能力和肺内动静脉分流的影响。***目的2：观察多巴胺阻断对肺毛细血管血容量、弥散能力及肺动脉收缩压的影响。******目的3：探讨肺动脉毛细血管血容量对动静脉分流募集的影响。******目的4：确定解剖动静脉分流、通气灌注匹配、扩散限制与右至左分流的关系。******目的5：评价肺循环中氧气和惰性气体的毛细前气体交换。******目标1-3将在我们最先进的cfi资助的实验室进行，并将使用药理学药物影响肺循环并确定对DLCO， Vc和IPAVAs的影响。目的4和5将在犬模型中进行，并将有助于解决长期以来关于解剖与气体交换分流的争议，以及肺内毛细前气体交换的潜在存在

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.**