Mechanisms underlying increased reactivity of pulmonary arteries contralateral to a localized high-flow anastomosis.
Mechanisms underlying increased reactivity of pulmonary arteries contralateral to a localized high-flow anastomosis.
复制标题
局部高流量吻合对侧肺动脉反应性增加的机制。
DOI：
10.1016/j.jtcvs.2010.07.007
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Jacobs,ElizabethR
中科院分区：
文献类型：
--
作者：
Pfister,Sandra;Somberg,Lewis;Lowry,Timothy;Gao,Ying;Medhora,Meetha;Jacobs,ElizabethR
结果我们的体肺分流模型显示，与同侧或对照肺动脉相比，吻合后48小时，左下叶肺动脉和主动脉之间局部分流对侧肺动脉的反应性增强。我们研究了一氧化氮，环氧合酶，脂氧合酶，或细胞色素P450的生产介导这种增强reactivity.METHODSWe创建一个左下叶肺动脉的主动脉的外科端侧吻合的贡献。48小时后，我们测试了右下叶和左下叶肺动脉环的张力，以在存在载体或一氧化氮合酶、环氧合酶、细胞色素P450或脂氧合酶抑制剂的情况下收缩血栓烷模拟物U46619。肺动脉匀浆的Western印迹法检测内皮型一氧化氮合酶或代谢花生四烯酸的亚型。用标记花生四烯酸和高效液相色谱分离检测完整肺动脉环中的类花生酸产物。结论：一氧化氮合酶、环氧合酶、细胞色素P450抑制剂不能消除高流量宿主未分流右肺动脉相对于左肺动脉的反应性增强。用2种不同的脂氧合酶抑制剂，去甲二氢愈创木酸和肉桂-3，4-二羟基-α-氰基肉桂酸酯治疗，关闭了分流和未分流肺动脉收缩力的差异。肺动脉对侧分流代谢花生四烯酸12-hydroxyeicosatetraenoic acid在更大的数量比类似的肺动脉从实验左或对照pulmonary arteries.CONCLUSIONSForty-eight hours after anesthesia，增强对侧肺动脉的反应性是部分归因于增加脂氧合酶的产品，而不是一氧化氮或其他类花生酸产品。
OBJECTIVESOur model of a systemic–pulmonary shunt exhibits enhanced reactivity of pulmonary arteries contralateral to a localized shunt between the left lower lobe pulmonary artery and aorta relative to those of ipsilateral or control pulmonary arteries 48 hours after anastomosis. We examined the contribution of nitric oxide, cyclooxygenase, lipoxygenase, or cytochrome P450 production to mediating this enhanced reactivity.METHODSWe created a surgical end-to-side anastomosis of the left lower lobe pulmonary artery to the aorta. Forty-eight hours later, we tested tension of pulmonary artery rings from the right and left lower lobes for contraction to the thromboxane mimetic U46619 in the presence of vehicle or inhibitors of nitric oxide synthase, cyclooxygenase, cytochrome P450, or lipoxygenase. Western blots of pulmonary artery homogenates were probed for endothelial nitric oxide synthase or isoforms metabolizing arachidonic acid. Eicosanoid products from intact pulmonary artery rings were detected using labeled arachidonic acid and high-performance liquid chromatography separation.RESULTSEnhanced reactivity of unshunted right pulmonary arteries over that of left pulmonary arteries from high-flow hosts was not eliminated by inhibitors of nitric oxide synthase, cyclooxygenase, cytochrome P450. Treatment with 2 different lipoxygenase inhibitors, nordihydroguaiaretic acid and cinnamyl-3,4-dihydroxy-α-cyanocinnamate, closed the difference in contractility of shunted and unshunted pulmonary arteries. Pulmonary arteries contralateral to shunts metabolized arachidonic acid to 12-hydroxyeicosatetraenoic acid in greater quantities than analogous pulmonary arteries from the experimental left or control pulmonary arteries.CONCLUSIONSForty-eight hours after anastomosis, enhanced reactivity of contralateral pulmonary arteries is attributable in part to increased lipoxygenase products as opposed to nitric oxide or other eicosanoid products.