title: Mitochondrial molecular basis of sevoflurane and propofol cardioprotection in patients undergoing aortic valve replacement with cardiopulmonary bypass.
abstract: OBJECTIVE
  Study elucidates and compares the mitochondrial bioenergetic-related molecular basis of sevoflurane and propofol cardioprotection during aortic valve replacement surgery due to aortic valve stenosis.
  
  
  METHODS
  Twenty-two patients were prospectively randomized in two groups regarding the anesthetic regime: sevoflurane and propofol. Hemodynamic parameters, biomarkers of cardiac injury and brain natriuretic peptide (BNP) were measured preoperatively and postoperatively. In tissue samples, taken from the interventricular septum, key mitochondrial molecules were determined by Western blot, real time PCR, as well as confocal microscopy and immunohisto- and immunocyto-chemical analysis.
  
  
  RESULTS
  The protein levels of cytochrome c oxidase and ATP synthase were higher in sevoflurane than in propofol group. Nevertheless, cytochrome c protein content was higher in propofol than sevoflurane receiving patients. Propofol group also showed higher protein level of connexin 43 (Cx43) than sevoflurane group. Besides, immunogold analysis showed its mitochondrial localization. The mRNA level of mtDNA and uncoupling protein (UCP2) were higher in propofol than sevoflurane patients, as well. On the other hand, there were no significant differences between groups in hemodynamic assessment, intensive care unit length of stay, troponin I and BNP level.
  
  
  CONCLUSIONS
  Our data indicate that sevoflurane and propofol lead to cardiac protection via different mitochondrially related molecular mechanisms. It appears that sevoflurane acts regulating cytochrome c oxidase and ATP synthase, while the effects of propofol occur through regulation of cytochrome c, Cx43, mtDNA transcription and UCP2.
authors.affiliation: University of Belgrade, Medical School, Dedinje Cardiovascular Institute, Belgrade, Serbia.
authors.forename: Miomir
authors.initials: M
authors.lastname: Jovic
authors.forename: Ana
authors.initials: A
authors.lastname: Stancic
authors.forename: Dragan
authors.initials: D
authors.lastname: Nenadic
authors.forename: Olivera
authors.initials: O
authors.lastname: Cekic
authors.forename: Dusko
authors.initials: D
authors.lastname: Nezic
authors.forename: Predrag
authors.initials: P
authors.lastname: Milojevic
authors.forename: Slobodan
authors.initials: S
authors.lastname: Micovic
authors.forename: Biljana
authors.initials: B
authors.lastname: Buzadzic
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Korac
authors.forename: Vesna
authors.initials: V
authors.lastname: Otasevic
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jankovic
authors.forename: Milica
authors.initials: M
authors.lastname: Vucetic
authors.forename: Ksenija
authors.initials: K
authors.lastname: Velickovic
authors.forename: Igor
authors.initials: I
authors.lastname: Golic
authors.forename: Bato
authors.initials: B
authors.lastname: Korac
mesh_terms: D025181:ATP Synthetase Complexes / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000777:Anesthetics / Q000627:therapeutic use*; D001021:Aortic Valve / Q000637:transplantation*; D001024:Aortic Valve Stenosis / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D002315:Cardiopulmonary Bypass; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000627:therapeutic use*; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D015742:Propofol / Q000627:therapeutic use*; D011446:Prospective Studies; D000077149:Sevoflurane; D019210:Troponin I / Q000235:genetics / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D000777:Anesthetics; D018031:Connexin 43; D004272:DNA, Mitochondrial; D007473:Ion Channels; D008738:Methyl Ethers; D024101:Mitochondrial Proteins; D019210:Troponin I; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D020097:Natriuretic Peptide, Brain; D000077149:Sevoflurane; D045304:Cytochromes c; D025181:ATP Synthetase Complexes; D015742:Propofol