title: Cardiospecific sevoflurane treatment quenches inflammation but does not attenuate myocardial cell damage markers: a proof-of-concept study in patients undergoing mitral valve repair.
abstract: BACKGROUND
  Inflammation is considered a key mediator of complications after cardiac surgery. Sevoflurane has been shown to quench inflammation and to provide cardioprotection in preclinical studies. Clinical studies using sevoflurane confirm this effect on inflammation but do not consistently show clinical benefits. This paradox may indicate that the contribution of inflammation to postoperative sequalae is less than commonly thought or that systemic doses are too low in their local concentration. To test the latter, we evaluated the effects of intramyocardial sevoflurane delivery.
  
  
  METHODS
  Selective myocardial sevoflurane delivery was performed during aortic cross-clamping in patients undergoing valve surgery (n=11). Results were compared with a control group not receiving sevoflurane (n=10). A reference group (n=5) was added to evaluate the effects of systemic sevoflurane delivery. Paired arterial and myocardial venous blood samples were collected at various time points post-reperfusion. Inflammatory mediators and myocardial cell damage were studied.
  
  
  RESULTS
  Intramyocardial delivery was superior to systemic delivery in attenuation of interleukin-6 and interleukin-8 (-44% and -25%, respectively; both P=0.001). Myocardial and systemic sevoflurane delivery effectively suppressed surgery-related inflammatory responses including postoperative C-reactive protein levels when compared with controls [63 (47-99) (P=0.01) and 58 (56-81) (P=0.04) compared with 107 (79-144) mg litre(-1)]. Sevoflurane treatment did not reduce postoperative troponin T, creatine kinase, and creatine kinase-MB values.
  
  
  CONCLUSIONS
  This proof-of-concept study suggests that intramyocardial delivery compared with the systemic delivery of sevoflurane more strongly attenuates the systemic inflammatory response after cardiopulmonary bypass without reducing postoperative markers of myocardial cell damage.
  
  
  BACKGROUND
  Nederlands Trial Register NTR2089.
authors.affiliation: Department of Cardiothoracic Surgery, K6-S, k.a.kortekaas@lumc.nl.
authors.forename: K A
authors.initials: KA
authors.lastname: Kortekaas
authors.affiliation: Department of Cardiothoracic Surgery, K6-S.
authors.forename: A
authors.initials: A
authors.lastname: van der Baan
authors.affiliation: Department of Anaesthesiology.
authors.forename: L P H J
authors.initials: LP
authors.lastname: Aarts
authors.affiliation: Department of Cardiothoracic Surgery, K6-S.
authors.forename: M
authors.initials: M
authors.lastname: Palmen
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine and.
authors.forename: C M
authors.initials: CM
authors.lastname: Cobbaert
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine and.
authors.forename: J C M
authors.initials: JC
authors.lastname: Verhagen
authors.affiliation: Department of Anaesthesiology.
authors.forename: F H M
authors.initials: FH
authors.lastname: Engbers
authors.affiliation: Department of Cardiothoracic Surgery, K6-S.
authors.forename: R J M
authors.initials: RJ
authors.lastname: Klautz
authors.affiliation: Department of Vascular Surgery, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: J H N
authors.initials: JH
authors.lastname: Lindeman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000187:drug effects; D006348:Cardiac Surgical Procedures / Q000379:methods; D002315:Cardiopulmonary Bypass / Q000379:methods; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D008943:Mitral Valve / Q000601:surgery*; D009205:Myocarditis / Q000097:blood* / Q000188:drug therapy*; D011183:Postoperative Complications / Q000097:blood* / Q000188:drug therapy*; D011446:Prospective Studies; D000077149:Sevoflurane; D016037:Single-Blind Method
chemical_list: D018685:Anesthetics, Inhalation; D015415:Biomarkers; D002316:Cardiotonic Agents; D015850:Interleukin-6; D016209:Interleukin-8; D008738:Methyl Ethers; D000077149:Sevoflurane; D002097:C-Reactive Protein
keywords: anaesthetics volatile, sevoflurane; cardiopulmonary bypass; immune response; myocardial damage; reperfusion injury