Mechanisms and consequences of intra-pulmonary arteriovenous shunting

我们对肺的经典理解是，血液从右心室流经肺动脉，流向小动脉，然后流向毛细血管，在那里氧气和二氧化碳进行交换。然后，血液通过小静脉返回心脏，然后是静脉，然后到达左心房。令人惊讶的是，我们发现，正常健康人的运动会导致肺内血管重新聚集，绕过肺毛细血管(即从动脉/小动脉直接流向小静脉/静脉)。这一发现违背了我们对血液流经肺部的基本理解。这些大直径的副血管(即肺内分流)的募集似乎是：1.损害肺内氧气和二氧化碳的交换，2.降低肺内的驱动压(即肺动脉压)。拨款的目的是更仔细地研究是什么原因导致这些肺内分流在肺内开放，并进一步确定招募这些分流的后果。 我们将研究的具体问题包括：1.确定运动中释放的某些荷尔蒙是否在休息时招募这些肺内分流。2.确定阻断这些激素的作用是否可以防止运动时的肺内分流。3.确定增加肺血流量(就像运动时发生的情况)是否会在休息时招募这些肺内分流。4.确定增加的呼吸频率(就像运动时发生的那样)是否会在休息时招募这些肺内分流。5.确定运动训练是否招募了这些肺内分流。6.确定这些肺内分流是否有助于防止运动造成的肺损伤。7.确定男性和女性之间是否存在差异。 为了研究这些问题，我们将研究年轻健康的受试者。将采集动脉血样本以评估氧交换，肺内分流将使用先进的心肺扫描进行检查。这项拟议的研究将是第一个重要的计划，旨在检查是什么导致这些肺内分流打开，以及它们的后果是什么。

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.