Department of Anesthesiology, University Medical Center, Regensburg, Germany.
Surgery. 2010 Apr;147(4):562-74. doi: 10.1016/j.surg.2009.10.028. Epub 2009 Dec 11.
To evaluate the possible protective effect of sympatholytic medications with respect to neutrophil function, we evaluated the influence of a nonselective beta-blocker medication on the interaction of neutrophils and epinephrine after cardiopulmonary bypass. Therefore, we studied the importance of adrenoceptors for the immunomodulation of neutrophils by catecholamines in vitro.
First, we investigated the modulation of neutrophils from healthy volunteers, after stimulation with n-formyl-l-methionyl-l-leucyl-l-phenylalanin (FMLP) in the presence of epinephrine with or without the addition of one of the following adrenergic receptor antagonists: atenolol, butoxamine, pindolol, prazosin, or RS79984. The second part included an investigation of the modulation of neutrophils from patients after operative coronary revascularization with or without extracorporeal circulation after stimulation with FMLP and addition of epinephrine. After loading with anti-CD62l or anti-CD11b antibodies or dihydrorhodamine, the expression of CD62l and CD11b and generation of oxidative free radicals were assessed by flow cytometry.
The suppression of oxidative free radical generation, inhibition of CD62l downregulation after stimulation with FMLP, and suppression of CD11b upregulation after FMLP stimulation from epinephrine were all mediated by beta(2)-adrenoceptors. After cardiac surgery with cardiopulmonary bypass, epinephrine inhibited the CD62l downregulation, the suppression of CD11b upregulation, and the generation of oxidative free radicals after FMLP stimulation. The pre-operative administration of beta-blockers abolished the immunomodulatory effects of epinephrine on CD62l and CD11b expression and the generation of oxidative free radicals.
The immunomodulatory effects of epinephrine on neutrophils remained unchanged irrespective of cardiopulmonary bypass and could contribute to the detrimental effects of epinephrine after heart surgery. The preoperative administration of nonselective beta-blockers abolished the immunomodulatory effects of epinephrine in vitro and in patients, and it enhanced the immunocompetence of neutrophils in a context of increased catecholamine levels.
为了评估交感神经抑制药物对中性粒细胞功能的可能保护作用，我们评估了非选择性β-受体阻滞剂药物对体外心肺旁路后中性粒细胞与肾上腺素相互作用的影响。因此，我们研究了儿茶酚胺对中性粒细胞的免疫调节作用中肾上腺素能受体的重要性。
首先，我们研究了来自健康志愿者的中性粒细胞在存在肾上腺素的情况下用 N-甲酰基-L-甲硫氨酸-L-亮氨酸-L-苯丙氨酸（FMLP）刺激后的调制，同时添加以下肾上腺素能受体拮抗剂之一：阿替洛尔、丁氧胺、普萘洛尔、哌唑嗪或 RS79984。第二部分包括对接受体外循环冠状动脉血运重建手术后患者的中性粒细胞进行研究，刺激后用 FMLP 和肾上腺素添加，然后进行调制。通过流式细胞术，用抗 CD62l 或抗 CD11b 抗体或二氢罗丹明负载后，评估 CD62l 和 CD11b 的表达和氧化自由基的产生。
氧化自由基产生的抑制、FMLP 刺激后 CD62l 下调的抑制以及肾上腺素刺激后 CD11b 上调的抑制均由β2-肾上腺素能受体介导。体外心肺旁路手术后，肾上腺素抑制 FMLP 刺激后的 CD62l 下调、CD11b 上调和氧化自由基的产生。术前给予β-受体阻滞剂可消除肾上腺素对 CD62l 和 CD11b 表达及氧化自由基产生的免疫调节作用。
肾上腺素对中性粒细胞的免疫调节作用在心肺旁路手术中保持不变，可能导致心脏手术后肾上腺素的有害作用。术前给予非选择性β-受体阻滞剂可消除肾上腺素的体外和体内的免疫调节作用，并增强高儿茶酚胺水平背景下中性粒细胞的免疫能力。
