Boost K A, Flondor M, Hofstetter C, Platacis I, Stegewerth K, Hoegl S, Nguyen T, Muhl H, Zwissler B
Department of Anaesthesiology, Intensive Care and Pain Therapy, University Hospital of Johann Wolfgang Goethe-University Frankfurt am Main, Germany.
Acta Anaesthesiol Scand. 2007 Aug;51(7):900-8. doi: 10.1111/j.1399-6576.2007.01363.x.
Recent studies suggest that volatile anaesthetics have anti-inflammatory and preconditioning properties and that beta-adrenoceptors are involved in the signalling pathways for these effects. Concurrently, the blockade of beta-adrenoceptors has been shown to augment the release of inflammatory mediators in response to pro-inflammatory stimuli. We therefore aimed to investigate whether the beta-adrenoceptor antagonist propranolol might modulate the anti-inflammatory effects of isoflurane on the systemic and pulmonary release of pro-inflammatory cytokines in endotoxemic rats.
Forty anaesthetized and ventilated Sprague-Dawley rats were randomly treated as follows. Lipopolysaccharide (LPS) only (n = 8), endotoxemia with LPS [5 mg/kg, intravenously (i.v.)]. LPS-isoflurane (n = 8): endotoxemia and continuous inhalation of 1 minimum alveolar concentration (MAC) of isoflurane. LPS-isoflurane-propranolol (n = 8): administration of propranolol (3 mg/kg) before continuous inhalation of isoflurane and induction of endotoxemia. LPS-propranolol (n = 8): administration of propranolol (3 mg/kg) before endotoxemia without inhalation of isoflurane. Sham (n = 8): control-group only with surgical preparation. After 4 h of endotoxemia, levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-10 (IL-10) in plasma and bronchoalveolar fluid (BALF) were analysed. Release of nitric oxide (NO) and amount of inducible nitric oxide synthase (iNOS) protein in alveolar macrophages was measured by Griess assay or determined by Western Blotting, respectively.
Inhalation of isoflurane reduced the release of TNF-alpha (P < 0.05) and IL-1beta (P < 0.05) in plasma and IL-1beta (P < 0.05) in BALF. Co-administration of propranolol significantly inhibited these effects. During inhalation of isoflurane, the increased release of NO and iNOS protein from alveolar macrophages was also completely inhibited by propranolol.
Our results indicate for the first time, that blockade of beta-adrenoceptors counteracts the anti-inflammatory effects of isoflurane in endotoxemic rats.
近期研究表明，挥发性麻醉药具有抗炎和预处理特性，且β - 肾上腺素能受体参与这些效应的信号传导途径。同时，已证明β - 肾上腺素能受体的阻断会增强炎症介质对促炎刺激的释放。因此，我们旨在研究β - 肾上腺素能受体拮抗剂普萘洛尔是否可能调节异氟烷对内毒素血症大鼠全身和肺部促炎细胞因子释放的抗炎作用。
40只麻醉并通气的Sprague - Dawley大鼠随机分为以下几组。仅脂多糖（LPS）组（n = 8），静脉注射（i.v.）5 mg/kg LPS诱导内毒素血症。LPS - 异氟烷组（n = 8）：内毒素血症并持续吸入1最低肺泡浓度（MAC）的异氟烷。LPS - 异氟烷 - 普萘洛尔组（n = 8）：在持续吸入异氟烷和诱导内毒素血症之前给予普萘洛尔（3 mg/kg）。LPS - 普萘洛尔组（n = 8）：在内毒素血症之前给予普萘洛尔（3 mg/kg），不吸入异氟烷。假手术组（n = 8）：仅进行手术准备的对照组。内毒素血症4小时后，分析血浆和支气管肺泡灌洗液（BALF）中肿瘤坏死因子 - α（TNF - α）、白细胞介素 - 1β（IL - 1β）和白细胞介素 - 10（IL - 10）的水平。分别通过Griess法或蛋白质印迹法测定肺泡巨噬细胞中一氧化氮（NO）的释放和诱导型一氧化氮合酶（iNOS）蛋白的含量。
吸入异氟烷可降低血浆中TNF - α（P < 0.05）和IL - 1β（P < 0.05）以及BALF中IL - 1β（P < 0.0）的释放。普萘洛尔的联合使用显著抑制了这些作用。在吸入异氟烷期间，普萘洛尔也完全抑制了肺泡巨噬细胞中NO释放增加和iNOS蛋白的增加。
我们的结果首次表明，β - 肾上腺素能受体的阻断会抵消异氟烷对内毒素血症大鼠的抗炎作用。
