Wagner E M, Foster W M
Department of Medicine, The Johns Hopkins University, Baltimore, Maryland 21224, USA.
Environ Health Perspect. 2001 Aug;109 Suppl 4(Suppl 4):563-5. doi: 10.1289/ehp.01109s4563.
Although a role for the airway circulation in the clearance of inhaled particles is generally assumed, there is little information to confirm its importance. We studied the effects of decreased bronchial blood flow on the uptake of the soluble tracer technetium=99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) from subcarinal airways in sheep (n = 7). The bronchial artery was cannulated and perfused with autologous blood at a control flow (0.6 mL/min/kg) or when the perfusion pump was stopped (no flow). (99m)Tc-DTPA (6-10 microL) was delivered by a microspray nozzle inserted through a bronchoscope to a fourth-generation bronchus both during control blood flow conditions and no-flow conditions. Airway retention (by scintigraphy) and blood uptake were monitored for 30 min after the local deposition of (99m(Tc-DTPA. During control flow conditions, 30 min after the delivery of the radiolabel, 21% of the tracer remained at the deposition site. Of the total delivered tracer, maximum blood uptake was 18% (n) = 3). When bronchial perfusion was stopped, airway retention 30 min after deposition increased to 43%, and maximum blood uptake decreased to 7% of the total delivered tracer. Although mucociliary clearance was not directly measured, radiolabel tracer was observed to move progressively from the deposition site up to larger airways and contributed to the overall removal of tracer from the site of deposition during both flow conditions. However, these results demonstrate that decreased bronchial perfusion increases airway retention by limiting vascular uptake of the soluble tracer. These results emphasize the importance of normal perfusion of the airway vasculature for uptake of therapeutic agents delivered specifically to the conducting airways.
虽然一般认为气道循环在清除吸入颗粒中起作用,但几乎没有信息能证实其重要性。我们研究了支气管血流减少对绵羊(n = 7)隆突下气道摄取可溶性示踪剂锝-99m标记的二乙三胺五乙酸(99mTc-DTPA)的影响。将支气管动脉插管,并以对照流量(0.6 mL/分钟/千克)或在灌注泵停止时(无血流)用自体血液进行灌注。在对照血流条件和无血流条件下,通过插入支气管镜的微喷雾喷嘴将(99m)Tc-DTPA(6 - 10微升)输送至第四代支气管。在局部沉积(9mTc-DTPA)后30分钟监测气道滞留(通过闪烁显像)和血液摄取情况。在对照血流条件下,放射性标记物输送30分钟后,21%的示踪剂留在沉积部位。在输送的示踪剂总量中,最大血液摄取量为18%(n = 3)。当支气管灌注停止时,沉积后30分钟的气道滞留增加到43%,最大血液摄取量降至输送的示踪剂总量的7%。虽然未直接测量黏液纤毛清除,但在两种血流条件下均观察到放射性标记示踪剂从沉积部位逐渐向上移动至较大气道,并有助于从沉积部位整体清除示踪剂。然而,这些结果表明,支气管灌注减少通过限制可溶性示踪剂的血管摄取而增加气道滞留。这些结果强调了气道血管系统正常灌注对于摄取专门输送至传导气道的治疗药物的重要性。