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

运动是对肺脏系统维持足够的肺气体交换的一种压力。随着递增运动，肺弥散能力必须增加，以满足增加的氧气需求，并防止扩散限制。运动后弥散能力(DLCO)的增加是通过肺毛细血管再充盈和毛细血管扩张来实现的，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，但大多数健康人都出现了肺泡与动脉血氧分压差(AaDO2)增加来量化的肺气体交换障碍，我们小组先前提供的证据表明，运动后AaDO2增加可能是由于解剖肺内动静脉分流(IPAVA)的招募。*我的NSERC资助的研究计划的总体目标是了解控制肺气体交换的因素、弥散能力，以及在静息和运动中招募IPAVA的机制和后果。在下一个赠款周期，我们计划进一步研究肺血管调节、肺弥散和肺静脉曲张，以更好地了解在运动等生理应激过程中的肺气体交换。*赠款的具体目标是：*目标1：确定多巴胺对运动时肺毛细血管血容量、弥散量和肺动静脉内分流的影响。*目标2：确定多巴胺阻断对肺毛细血管血容量、弥散量和肺动脉收缩压的影响。*目的3：确定肺毛细血管血容量对动静脉分流复张的影响。*目标4：确定解剖动静脉分流、通气-灌流匹配、弥散受限与右向左分流的关系。*目标5：评估肺循环中氧和惰性气体的毛细血管前气体交换。*AIMS 1-3将在我们由CFI资助的最先进的实验室进行，并将使用药物来影响肺循环，并确定对DLCO、VC和IPAVA的影响。AIMS 4和5将在犬模型中进行，将有助于解决长期存在的关于解剖与气体交换分流的争议，以及肺内可能存在的毛细血管前气体交换**。

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.**