The volatile anesthetic sevoflurane inhibits activation of neutrophil granulocytes during simulated extracorporeal circulation
Highlights
► Extracorporeal circulation (ECC) induces granulocyte activation associated with systemic inflammation. ► The volatile anesthetic sevoflurane inhibits granulocyte activation during ex vivo ECC. ► Sevoflurane has the potential to decrease the ECC-triggered inflammatory response in clinical routine.
Introduction
Extracorporeal circulation (ECC) is employed in many cardiac surgical procedures to maintain stable circulatory parameters of the patient. Therefore, ECC is an essential tool for the successful execution of cardiac operations. However, ECC is also associated with adverse side effects. These include the induction of a systemic inflammatory response caused by the contact of blood components with the artificial surfaces of the ECC circuit. ECC-associated inflammation can result in potentially life-threatening complications including dysfunction of lung, myocardium, kidney and liver, which can cause multi-organ failure and significant mortality [1], [2], [3], [4].
The mechanism of ECC-induced inflammation is multifactorial. ECC causes activation of white blood cells including neutrophil granulocytes and results in release of inflammatory mediators including cytokines [1]. Upon activation neutrophils upregulate surface expression of the Mac-1 receptor (CD11b/CD18) and release cytotoxic enzymes including polymorphonuclear (PMN) elastase from intracellular granules into their surrounding [4].
Volatile anesthetics including sevoflurane have been reported to protect the myocardium against ischemia as well as reperfusion injury in clinical [5] and experimental studies [3]. Furthermore, it has been reported that sevoflurane may have the potential to inhibit pro-inflammatory events in the setting of cardiac surgery [6]. Nevertheless, it is unclear whether routine administration of sevoflurane in concentrations employed during balanced anesthesia may also inhibit ECC-induced inflammation.
On this background, the aim of our study was to investigate whether sevoflurane administration may modulate the ECC-triggered inflammatory response during ex vivo ECC. Sevoflurane was administered via the oxygenator of the ECC circuit according to standard clinical procedures. The effect of sevoflurane on the activation of leukocytes, their interaction with platelets and on cytokine release was investigated.
Section snippets
Methods
Study and blood sampling procedures were approved by the Research and Ethics Unit of the University of Tübingen, Germany (project number 270/2010BO1, approval date: 05/02/2011). Written informed consent was obtained from all subjects before blood sampling.
Effect of ECC and sevoflurane on whole blood cell counts
Addition of the ECC priming volume to whole blood results in hemodilution. In order to investigate the extent of ECC-induced hemodilution in our experiments, whole blood counts were determined. Compared to undiluted baseline values, similar decreases of hematocrit, erythrocyte and white blood cell as well as platelet counts after start of ECC were observed for controls and sevoflurane-treated samples.
Sevoflurane treatment had no further effect on whole blood count parameters (Fig. 1A–D).
Sevoflurane decreases Mac-1 expression on granulocytes during ECC
The
Discussion
In our current study, we investigated the effect of the volatile anesthetic sevoflurane on inflammatory events during ex vivo ECC. To address this topic, we systematically analyzed blood cell counts, release of leukocyte activation markers, leukocyte–platelet binding and generation of pro-inflammatory cytokines. Our results clearly indicate that ECC induces Mac-1 expression on neutrophil granulocytes and PMN-elastase release. Notably, both ex vivo ECC-induced effects were inhibited by treatment
Conflicts of interest and sources of funding
This work was funded from internal financial resources of the Department of Anesthesiology and Intensive Care Medicine in Tübingen.
The authors report no conflicts of interest.
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Authors contributed equally to this work.