TREATMENT OF ACUTE HYPOXEMIC RESPIRATORY FAILURE

成人呼吸窘迫综合征(ARDS)是一种急性急性呼吸窘迫综合征 急性肺损伤引起的低氧性呼吸衰竭 肺血管将血浆泄漏到肺泡腔导致 肺内分流(Qs/Qt)和难治性动脉低氧血症 氧气疗法。由于没有有效的预防或特效治疗方法， 肺毛细血管渗漏尚可，这项建议旨在改善 从三个方面明确支持性治疗的原则 AHRF犬模型中相关且知之甚少的问题：1) 肺血管压力、血流、分流和水肿之间的关系。 体外膜肺氧合(ECMO)将用于减少肺活量 静脉注射油酸致急性肺损伤后的压力和流量 和经支气管内注射盐酸。一种类似的实验方法将确定 红细胞压积升高对肺水肿蓄积的影响。如果 体外反搏和红细胞压积升高不会增加水肿，但确实会改善 外周氧气输送(QO2)，两者都代表了新的治疗干预措施 在AHRF。确定急性肺损伤减轻的机制 水肿区的肺血流，ECMO也将用于 提供部分肺旁路以确定肺血管 急性肺损伤前后的压力-流量关系。2)至 探讨病理性供氧依赖的机制 高F1O2引起的狗的消耗，我们将延长我们之前的研究 通过研究局部血管床来了解有氧代谢的极限， 特别是在用室内空气或氧气通风时，肠道和后肢。 这些研究应该阐明高氧血症是否以及如何重新分布。 低效的周围平行器官系统中有限的QO2 举止。同样的方法将被用来比较有氧运动的极限 当QO2因进行性缺氧、贫血或 血流量进行性减少。3)测试是否有可能 AHRF患者由于缺氧、酸血症、 或者两者兼而有之，我们将测量左心室压力维度关系， 进展期冠脉血流量和心肌氧摄取 缺氧。我们将使用这种方法来确定 血管活性药物治疗菌血症、高氧血症和酸中毒 并确定心肌有氧代谢和阻力如何降低 后负荷改善戊巴比妥钠抑制的心肌泵功能 麻醉的狗。这些犬类实验的结果应该是 阐明影响发病的重要机制和病理生理机制 肺毛细血管渗漏的治疗及其对全身的影响 肠道、后肢和心脏，并促进临床试验，以改善 AHRF的支持性治疗。

The adult respiratory distress syndrome (ARDS) is one form of acute acute hypoxemic respiratory failure (AHRF) in which acute lung injury causes pulmonary vessels to leak plasma into alveolar spaces causing intrapulmonary shunt (Qs/Qt) and arterial hypoxemia which is refractory to O2 therapy. Since no effective prevention or specific therapy of the pulmonary capillary leak is yet available, this proposal seeks to improve the principles of supportive therapy by defining the mechanisms of three interrelated and poorly understood problems in canine models of AHRF: 1) Relationships among pulmonary vascular pressures, flow, shunt, and edema. Extracorporeal membrane oxygenation (ECMO) will be used to reduce pulmonary pressure and flow after acute lung injury induced by intravenous oleic acid and by intrabronchial HCl. A similar experimental approach will determine the effect of increased hematocrit on pulmonary edema accumulation. If ECMO and increased hematocrit do not increase edema but do improve peripheral O2 delivery (QO2), both represent new therapeutic interventions in AHRF. To determine the mechanism whereby acute lung injury reduces pulmonary blood flow in edematous areas, ECMO will also be utilized to provide partial bypass of the lung to define the pulmonary vascular pressure flow relationships before and after acute lung injury. 2) To explore mechanisms accounting for pathologic supply dependency of oxygen consumption induced in dogs by high F1O2, we will extend our prior studies of the limits of aerobic metabolism by studying regional vascular beds, specifically the gut and hind limb during ventilation with room air or O2. These studies should elucidate whether and how hyperoxia redistributes limited QO2 among peripheral parallel organ systems in an inefficient manner. The same methodology will be used to compare the limits of aerobic metabolism when QO2 is reduced by progressive hypoxia, by anemia, or by progressive reductions in blood flow. 3) To test the possibility that ventricular pumping function is depressed in AHRF due to hypoxia, acidemia, or both, we will measure left ventricular pressure dimension relationships, coronary blood flow, and myocardial oxygen extraction during progressive hypoxia. We will use this methodology to determine the effects of vasoactive drugs on bacteremia, hyperoxia, and acidosis on these limits of myocardial aerobic metabolism and to determine how a reduced resistive afterload improves depressed myocardial pumping function in pentobarbitol anesthetized dogs. The results of these canine experiments should elucidate important mechanisms influencing the pathophysiology and treatment of pulmonary capillary leak and its systemic consequences on the gut, hind limb and heart, and facilitate clinical trials to improve supportive therapy of AHRF.