Mechanisms and consequences of intra-pulmonary arteriovenous shunting

我们对肺的经典理解是，血液从右心室流出，通过肺动脉，进入小动脉，然后进入毛细血管，在那里氧气和二氧化碳进行交换。然后血液通过小静脉和静脉回流到心脏，最后到达左心房。令人惊讶的是，我们发现，在正常健康人群中，运动可以使绕过肺毛细血管（即直接从动脉/小动脉流向小静脉/静脉）的血管在肺部聚集。这一发现违背了我们对血液流经肺部的基本理解。这些大直径血管（即肺内分流）的招募似乎：1。损害肺内氧气和二氧化碳的交换；降低肺内驱动压（即肺动脉压）。该资助的目的是更仔细地检查导致肺内分流在肺中打开的原因，并进一步确定招募这些分流的后果。

Our classic understanding of the lung is that blood flows from the right ventricle, through the pulmonary arteries, to arterioles, and then to the capillaries where oxygen and carbon dioxide are exchanged. The blood then returns back to the heart through venules, then veins before reaching the left atrium. Surprisingly, we have found that exercise in normal healthy people causes blood vessels to be recruited in the lung that bypass the pulmonary capillaries (i.e. direct blood flow from arteries/arterioles to venules/veins). This finding goes against our basic understanding of blood flow through the lung. The recruitment of these large-diameter by-vessels (i.e. intra-pulmonary shunts) appears to: 1. Impair the exchange of oxygen and carbon dioxide in the lung, 2. Reduce the driving pressure (i.e. the pulmonary artery pressure) in the lung. The purpose of the grant is to more closely examine what is causing these intra-pulmonary shunts to open in the lung, and to further determine the consequences of recruiting these shunts. Specific questions we will examine include: 1. Determining if certain hormones released during exercise recruit these intra-pulmonary shunts at rest. 2. Determining if blocking the effect of these hormones prevents intra-pulmonary shunts during exercise. 3. Determining if increasing lung blood flow (like what occurs with exercise) recruits these intra-pulmonary shunts at rest. 4. Determining if increasing breathing rate (like what occurs with exercise) recruits these intra-pulmonary shunts at rest. 5. Determining if exercise training recruits these intra-pulmonary shunts. 6. Determining if these intra-pulmonary shunts help prevent lung damage with exercise. 7. Determine if there are differences between men and women. To examine these questions we will study young healthy subjects. Arterial blood samples will be obtained to evaluate oxygen exchange, intra-pulmonary shunt will be examined using advanced heart and lung scanning. The proposed studies will be the first significant program designed to examine what is causing these intra-pulmonary shunts to open and what are their consequences.