Schley Marcus T, Casutt Matthias, Haberthür Christoph, Dusch Martin, Rukwied Roman, Schmelz Martin, Schmeck Joachim, Schüpfer Guido K, Konrad Christoph J
Department of Anaesthesiology and Operative Intensive Care Medicine, Kantonsspital, Lucerne, Switzerland.
Anesth Analg. 2009 Sep;109(3):880-5. doi: 10.1213/ane.0b013e3181ae5ef1.
Endothelin-1 (ET-1) is a mediator of lung diseases and a potent pulmonary vasoconstrictor. In addition to thromboxane A2, it participates in the formation of lung edema. Both lidocaine and mepivacaine attenuate the increase of pulmonary arterial pressure (PAP) and lung edema development. We examined the effects of procaine, bupivacaine, and ropivacaine on experimentally evoked PAP increase and ET-1 release.
PAP and lung weight were measured in isolated rat lungs during perfusion with Krebs-Henseleit hydroxyethyl starch buffer. Bupivacaine, ropivacaine, or procaine was added to the solution at concentrations of 10(-2)-10(-7) mg/kg. ET-1 levels were measured in the perfusate by enzyme-immunoassay, and thromboxane A2 levels were assayed by radioimmunoassay. N-formyl-L-leucine-methionyl-L-phenylalanine was used to activate human polymorphonuclear neutrophils.
Bupivacaine, ropivacaine, and procaine significantly attenuated increases of PAP (P < 0.05) and resulted in a reduction of lung weight in these treatment groups compared with the sham group (P < 0.05). The long-acting anesthetics bupivacaine and ropivacaine (P < 0.05), but not procaine, reduced ET-1 levels, produced low inflammation rates, and did not affect lung structures at doses from 10(-3) to 10(-6) mg/kg.
Bupivacaine and ropivacaine attenuated N-formyl-L-leucine-methionyl-L-phenylalanine-induced PAP, reduced lung edema, and diminished ET-1 release. Lidocaine and mepivacaine are more effective in reducing PAP and edema formation, but long-acting local anesthetics also inhibit ET-1 depletion and therefore have increased anti-inflammatory properties.
内皮素-1（ET-1）是肺部疾病的介质和强效肺血管收缩剂。除血栓素A2外，它还参与肺水肿的形成。利多卡因和甲哌卡因均可减轻肺动脉压（PAP）升高和肺水肿的发展。我们研究了普鲁卡因、布比卡因和罗哌卡因对实验诱发的PAP升高和ET-1释放的影响。
在用克雷布斯-亨泽莱特羟乙基淀粉缓冲液灌注离体大鼠肺的过程中测量PAP和肺重量。将布比卡因、罗哌卡因或普鲁卡因以10(-2)-10(-7)mg/kg的浓度加入溶液中。通过酶免疫测定法测量灌注液中的ET-1水平，通过放射免疫测定法测定血栓素A2水平。N-甲酰-L-亮氨酸-甲硫氨酰-L-苯丙氨酸用于激活人多形核中性粒细胞。
与假手术组相比，布比卡因、罗哌卡因和普鲁卡因显著减轻了PAP的升高（P<0.05），并导致这些治疗组的肺重量减轻（P<0.05）。长效麻醉药布比卡因和罗哌卡因（P<0.05），但不是普鲁卡因，降低了ET-1水平，产生低炎症率，并且在10(-3)至10(-6)mg/kg的剂量下不影响肺结构。
布比卡因和罗哌卡因减轻了N-甲酰-L-亮氨酸-甲硫氨酰-L-苯丙氨酸诱导的PAP，减轻了肺水肿，并减少了ET-1释放。利多卡因和甲哌卡因在降低PAP和水肿形成方面更有效，但长效局部麻醉药也抑制ET-1消耗，因此具有增强的抗炎特性。
