Konrad Christoph J, Schuepfer Guido K, Neuburger Michael, Schley Marcus, Schmelz Martin, Schmeck Joachim
Department of Anesthesiology and Operative Intensive Care Medicine, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Reg Anesth Pain Med. 2006 May-Jun;31(3):254-9. doi: 10.1016/j.rapm.2006.01.003.
Local anesthetics (LAs) possess a variety of effects that cannot be explained by the typical block of neuronal sodium channels. Antithrombotic effects of LAs are well known, but LAs also act as bactericides. Therefore, an investigation of the influence of LAs on the inflammatory response of the isolated rat lung (n = 78) to an N-formyl-l-leucin-methionyl-l-phenylalanine (FMLP) stimulus was performed.
The experiments were performed on isolated and ventilated rat lungs perfused with cell-free and plasma-free buffer. LAs (lidocaine and mepivacaine) were injected in various concentrations before application and activation of human granulocytes by FMLP. Pulmonary arterial pressure (PAP) and lung weight gain were monitored continuously. LAs in final dosages from 10(-2) to 10(-7) mg/kg body weight (n = 6 each) were injected into the pulmonary artery before treatment with FMLP (10(-6) M) to induce pulmonary arterial hypertension. Perfusate samples were taken intermittently to determine thromboxane A(2) (TX A(2)) and endothelin-1 concentrations. Microscopic analyses were performed to assess the degree of lung injury.
Pretreatment with LAs significantly reduced the FMLP-induced PAP increase (treatment group v sham group: 0.5 to 5 mm Hg v 8 mm Hg; P < .05) and the release of endothelin-1 (2.4 v 5 fmol/mL). Histologic damage seen as acute granulocytic alveolitis was reduced by lidocaine and mepivacaine, even below clinically relevant concentrations.
LA pretreatment reduces inflammatory reactions after FMLP stimulus.
局部麻醉药（LAs）具有多种无法用典型的神经元钠通道阻滞来解释的效应。LAs的抗血栓形成作用是众所周知的，但LAs也具有杀菌作用。因此，我们对LAs对离体大鼠肺（n = 78）对N-甲酰-L-亮氨酰-L-甲硫氨酰-L-苯丙氨酸（FMLP）刺激的炎症反应的影响进行了研究。
实验在灌注无细胞和无血浆缓冲液的离体通气大鼠肺上进行。在应用FMLP并激活人粒细胞之前，以不同浓度注射LAs（利多卡因和甲哌卡因）。连续监测肺动脉压（PAP）和肺重量增加。在使用FMLP（10⁻⁶ M）诱导肺动脉高压之前，将终浓度为10⁻²至10⁻⁷ mg/kg体重的LAs（每组n = 6）注入肺动脉。间歇性采集灌注液样本以测定血栓素A₂（TX A₂）和内皮素-1浓度。进行显微镜分析以评估肺损伤程度。
LAs预处理显著降低了FMLP诱导的PAP升高（治疗组与假手术组：0.5至5 mmHg对8 mmHg；P <.05）以及内皮素-1的释放（2.4对5 fmol/mL）。利多卡因和甲哌卡因减轻了表现为急性粒细胞性肺泡炎的组织学损伤，甚至在低于临床相关浓度时也是如此。
LA预处理可减轻FMLP刺激后的炎症反应。
