Abstract
Background. 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. ...
Abstract
Background. 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. Methods. 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, 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-CD621 or anti-CD11b antibodies or dihydrorhodamine, the expression of CD621 and CD11b and generation of oxidative free radicals were assessed by flow cytometry. Results. The suppression of oxidative free radical generation., inhibition of CD621 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 CD621 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 CD621 and CD11b expression and the generation. of oxidative free radicals. Conclusion. 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 ire patients, and it enhanced the immunocompetence of neutrophils in a context of increased catecholamine levels. (Surgery 2010;147:562-74.)
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