Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery: a double-blinded, placebo-controlled, multicenter study.
BACKGROUND
Preconditioning by volatile anesthetics is a promising therapeutic strategy to render myocardial tissue resistant to perioperative ischemia. It was hypothesized that sevoflurane preconditioning would decrease postoperative release of brain natriuretic peptide, a biochemical marker for myocardial dysfunction. In addition, several variables associated with the protective effects of preconditioning were evaluated.


METHODS
Seventy-two patients scheduled for coronary artery bypass graft surgery under cardioplegic arrest were randomly assigned to preconditioning during the first 10 min of complete cardiopulmonary bypass with either placebo (oxygen-air mixture only) or sevoflurane 4 vol% (2 minimum alveolar concentration). No other volatile anesthetics were administered at any time during the study. Treatment was strictly blinded to anesthesiologists, perfusionists, and surgeons. Biochemical markers of myocardial dysfunction and injury (brain natriuretic peptide, creatine kinase-MB activity, and cardiac troponin T), and renal dysfunction (cystatin C) were determined. Results of Holter electrocardiography were recorded perioperatively. Translocation of protein kinase C was assessed by immunohistochemical analysis of atrial samples.


RESULTS
Sevoflurane preconditioning significantly decreased postoperative release of brain natriuretic peptide, a sensitive biochemical marker of myocardial contractile dysfunction. Pronounced protein kinase C delta and epsilon translocation was observed in sevoflurane-preconditioned myocardium. In addition, postoperative plasma cystatin C concentrations increased significantly less in sevoflurane-preconditioned patients. No differences between groups were found for perioperative ST-segment changes, arrhythmias, or creatine kinase-MB and cardiac troponin T release.


CONCLUSIONS
Sevoflurane preconditioning preserves myocardial and renal function as assessed by biochemical markers in patients undergoing coronary artery bypass graft surgery under cardioplegic arrest. This study demonstrated for the first time translocation of protein kinase C isoforms delta and epsilon in human myocardium in response to sevoflurane.
Julier
Karine
K
Department of Anesthesiology, University Hospital Lausanne, Switzerland.
da Silva
Rafaela
R
Garcia
Carlos
C
Bestmann
Lukas
L
Frascarolo
Philippe
P
Zollinger
Andreas
A
Chassot
Pierre-Guy
PG
Schmid
Edith R
ER
Turina
Marko I
MI
von Segesser
Ludwig K
LK
Pasch
Thomas
T
Spahn
Donat R
DR
Zaugg
Michael
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D015415:Biomarkers; D001026:Coronary Artery Bypass; D003402:Creatine Kinase / Q000097:blood; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D015716:Electrocardiography, Ambulatory; D005260:Female; D006331:Heart Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000517:prevention & control*; D006801:Humans; D007150:Immunohistochemistry; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007674:Kidney Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D011379:Prognosis; D011493:Protein Kinase C / Q000097:blood; D000077149:Sevoflurane; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood
D018685:Anesthetics, Inhalation; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D008738:Methyl Ethers; D020107:Troponin T; D000077149:Sevoflurane; D011493:Protein Kinase C; D003402:Creatine Kinase