Pulmonary gas exchange during physiological stress

运动对肺部系统产生压力，以维持足够的气体交换。随着运动需氧量的增加，肺弥散量（DLCO）必须增加，以防止扩散限制。由于毛细血管募集和肺毛细血管血容量（Vc）增加，DLCO增加。尽管DLCO随着运动而增加，但DLCO与心输出量的比率（DLCO/Q）随着递增运动而下降，并且大多数健康人发展出气体交换受损，如通过肺泡与动脉氧差的增加来量化的。运动引起的气体交换损伤的一个潜在机制是肺内动静脉动脉瘤（IPAVA）的募集，这些血管绕过气体交换单元，关于这些血管的大小和意义仍有很多未知之处。或者，运动引起的气体交换障碍可能是由于继发于红细胞通过时间减少的扩散限制;然而，气体交换、扩散限制和通过时间之间的关系尚未得到很好的研究。我们最近的研究表明，与未经训练的运动员相比，经过训练的耐力运动员具有上级DLCO，这表明长期运动训练可能导致促进更大DLCO的变化。这种DLCO增强的机制尚不清楚，可能与受过训练的运动员的血容量更大和/或毛细血管募集阈值更低有关。此外，运动训练是否/如何导致DLCO、Vc和扩散膜（Dm）的变化仍有待确定。 这项由NSERC资助的研究计划的总体目标是了解在休息和运动时决定弥散能力和肺气体交换的因素。 具体目标：1。确定犬模型中IPAVA的功能大小，以及IPAVA募集是否与缺氧时的扩散限制相关。2.通过多种惰性气体消除技术评估，确定运动期间解剖性动静脉畸形的募集是否与受损的气体交换和扩散限制相关。3.通过多种惰性气体消除技术评估，确定运动期间气体交换受损是否与红细胞通过时间缩短和扩散受限相关。4.确定经过培训与未经培训的受试者是否具有不同的肺毛细血管募集伴灌注压升高。5.确定血容量对经培训和未经培训参与者弥散量和毛细血管灌注的影响。6.确定慢性有氧训练是否：1）增加静息和运动DLCO、Vc和Dm，继发于血容量增加，2）调节运动期间的扩散限制和气体交换。这项工作将使用我们新的世界级方法来确定肺扩散和气体交换是如何调节的，以及它们如何适应慢性运动训练。

Exercise represents a stress to the pulmonary system to maintain adequate gas exchange. As oxygen demand increases with exercise, pulmonary diffusing capacity (DLCO) must increase to prevent a diffusion limitation. DLCO increases due to capillary recruitment and greater pulmonary capillary blood volume (Vc). Despite an increase in DLCO with exercise, the ratio of DLCO to cardiac output (DLCO/Q) drops with incremental exercise, and most healthy humans develop an impairment in gas exchange as quantified by an increase in the alveolar to arterial oxygen difference. A potential mechanism for the gas exchange impairment with exercise is the recruitment of anatomical intra-pulmonary arteriovenous anastomoses (IPAVAs) which bypass the gas exchange units, and much remains unknown about the size and significance of these vessels. Alternatively, the gas exchange impairment with exercise may be due to a diffusion limitation secondary to reduced red blood cell transit time; however, the relationship between gas exchange, diffusion limitation and transit time has not been well examined. Our recent work has shown that trained endurance athletes have superior DLCO as compared to untrained, suggesting that chronic exercise training may lead to changes that facilitate greater DLCO. The mechanism(s) for this enhanced DLCO are unclear, and may be related to greater blood volume and/or a lower capillary recruitment threshold in trained athletes. Further, whether/how exercise training leads to changes in DLCO, Vc and diffusion membrane (Dm) remains to be determined. The overall objective of this NSERC-funded research program is to understand factors determining diffusing capacity and pulmonary gas exchange at rest and during exercise. Specific Aims: 1. To determine the functional size of IPAVAs in a canine model, and whether IPAVA recruitment is associated with a diffusion limitation in hypoxia. 2. To determine whether recruitment of anatomical arteriovenous anastomoses during exercise is associated with impaired gas exchange and diffusion limitation as evaluated by the multiple inert gas elimination technique. 3. To determine whether impaired gas exchange during exercise is associated with reduced red blood cell transit time and diffusion limitation as evaluated by the multiple inert gas elimination technique. 4. To determine whether trained vs. untrained participants have divergent pulmonary capillary recruitment with increased perfusion pressure. 5. To determine the effect of blood volume on diffusing capacity and capillary perfusion in trained and untrained participants. 6. To determine if chronic aerobic training: 1) increases resting and exercise DLCO, Vc and Dm secondary to increased blood volume, 2) modulates diffusion limitation and gas exchange during exercise. This work will use our novel world-class approaches to determine how pulmonary diffusion and gas exchange are regulated, and how they may adapt to chronic exercise training.