Young J S, Rayhrer C S, Edmisten T D, Cephas G A, Tribble C G, Kron I L
Department of Surgery, University of Virginia Health System, Charlottesville 22906-0005, USA.
Ann Thorac Surg. 2000 Jan;69(1):224-7. doi: 10.1016/s0003-4975(99)01130-3.
Acute lung injury (ALI) is associated with pulmonary hypertension, intrapulmonary shunting, and increased microvascular permeability, leading to altered oxygenation capacity. Oleic acid (OA) creates a significant ALI that physiologically mimics human adult respiratory distress syndrome (ARDS). It has been hypothesized that pulmonary vasodilatation may improve ALI. Studies in our laboratory using this model and nitric oxide (NO) have shown that NO inhalation is detrimental and worsens the effects of OA. We studied the effect of pretreatment with a potent vasodilator, sodium nitroprusside (SNP), on ALI induced by OA in an isolated lung model. We hypothesized that pretreatment with SNP will worsen pulmonary hypertension and oxygenation in OA-induced ALI, similar to the effects seen with inhaled NO in this model.
Rabbit heart lung blocks were isolated, flushed in vivo, harvested, immediately perfused with whole blood, and ventilated with 50% oxygen. Pulmonary artery pressure was determined every 15 seconds for 90 minutes of perfusion. Oxygenation was determined by blood gas analysis of pulmonary venous effluent at 0, 20, 40, 60, and 90 minutes after initiation of OA infusion. Four groups were studied: saline control (SC), oleic acid control (OAC; 20-minute infusion of 50% OA/ethanol into pulmonary circulation), SNP control (NPC; 10 microg/ kg/min SNP infused without subsequent OA infusion), and SNP treatment (NPRx); 10 microg/kg/min SNP infused before OA/ethanol. Pulmonary artery pressure (PAP), oxygenation (arterio-venous oxygen difference [AVO2], compliance (CPL), and wet/dry lung weight were determined.
No significant differences were found between the NPRx group and SC. Pretreatment with SNP eliminated the detrimental effects of OA infusion.
Contrary to our hypothesis, pretreatment with SNP eliminates the decrease in oxygenation and increase in lung weight, and ameliorates pulmonary hypertension in our isolated lung model of OA-induced ALI.
急性肺损伤（ALI）与肺动脉高压、肺内分流及微血管通透性增加相关，进而导致氧合能力改变。油酸（OA）可引发显著的ALI，在生理上模拟人类成人呼吸窘迫综合征（ARDS）。据推测，肺血管舒张可能改善ALI。我们实验室使用该模型及一氧化氮（NO）进行的研究表明，吸入NO有害且会加重OA的影响。我们在离体肺模型中研究了强效血管舒张剂硝普钠（SNP）预处理对OA诱导的ALI的影响。我们假设，SNP预处理会加重OA诱导的ALI中的肺动脉高压和氧合障碍，类似于该模型中吸入NO的效果。
分离兔心肺标本，在体内冲洗，收获后立即用全血灌注，并用50%氧气通气。在灌注90分钟期间，每隔15秒测定一次肺动脉压。在开始输注OA后0、20、40、60和90分钟，通过对肺静脉流出液进行血气分析来测定氧合情况。研究了四组：生理盐水对照组（SC）、油酸对照组（OAC；向肺循环中输注50% OA/乙醇20分钟）、SNP对照组（NPC；输注10μg/kg/min SNP，随后不输注OA）和SNP治疗组（NPRx）；在OA/乙醇之前输注10μg/kg/min SNP。测定肺动脉压（PAP）、氧合情况（动静脉氧差[AVO2]）、顺应性（CPL）以及肺湿/干重。
NPRx组与SC组之间未发现显著差异。SNP预处理消除了输注OA的有害影响。
与我们的假设相反，在我们的OA诱导的ALI离体肺模型中，SNP预处理消除了氧合降低和肺重量增加的情况，并改善了肺动脉高压。
