Pharmacological suppression of the inflammatory response to cardiac surgery and perfusion

Secondary to open-heart surgery and perfusion a systemic inflammatory response (IR) develops which is noxious for the patient. It has therefore been attempted to counteract this response pharmacologically. The drugs used for this purpose are the subject of the present survey. The potential drug targets in the IR are multiple, such as for instance the kinin-kallikrein pathway, the fibrinolytic system, the complent system, neutrophils, platelets and cytokines. Glucocorticoids (methylprednisolone, dexamathasone) are strong suppressants of cytokine release caused by IR. However, their various side-effects outweigh a potential clinical benefit and these drugs cannot be generally recommended to counteract IR. Aprotinin, an inhibitor of serine proteases can be used in cardiac surgery to reduce blood loss. Aprotinin also suppresses the release of IL-8 and appears to improve recovery from the noxious sequelae of CABG, perfusion and ischaemia. Pentoxyfylline, a phosphodiesterase (PDE)-inhibitor, also displays immunomodulatory activities by inhibiting cytokine production and release. The IR in elderly CABG patients was indeed suppressed and haemodynamic parameters were improved by pentoxyfylline. Small studies claiming a beneficial effect on IR and its sequelae were reported for vesnarinone (PDE-inhibitor), colforsin (stimulator of adenylyl cyclase) and nafamostat (inhibitor of natural endopeptidase [NEP]). Finally, heparin coating of CABG-perfusion circuits has been demonstrated to be a beneficial measure, in particular when combined with the systemic administration of aprotinin. © 2002 Éditions scientifiques et médicales Elsevier SAS. Tous droits réservés.