title: Effect of preoperative oral pravastatin reload in systemic inflammatory response and myocardial damage after coronary artery bypass grafting. A pilot double-blind placebo-controlled study.
abstract: OBJECTIVE
  Statins exert pleiotropic effects that result in cardioprotective and antiinflammatory properties. There is a lack of information about the effect of preoperative reloading statin administration in surgical coronary patients regarding myocardial protection, systemic inflammatory response (SIR) attenuation and nitric oxide (NO) metabolism.
  
  
  METHODS
  Thirty consecutive dyslipidemic patients under chronic treatment with statins were randomized to orally receive pravastatin 80 mg (N.=10), 40 mg (N.=10) or placebo (N.=10) two hours before anesthetic induction for non-emergent on-pump coronary artery bypass grafting (CABG) procedures. Perioperative peripheral venous and intraoperative CS blood samples were collected for determination of drug-related adverse effects, NO metabolism and both myocardial damage and SIR biomarkers.
  
  
  RESULTS
  Pravastatin reloading resulted in a significant and dose-related intense attenuation of SIR, but no differences in cardiac damage biomarker levels were demonstrated. NO release and inducible nitric oxide synthase expression was significantly reduced in both treatment groups. Highest pravastatin doses significantly increased systemic creatine phosphokinase (CPK) concentration compared with intermediate doses but no other adverse effects were observed.
  
  
  CONCLUSIONS
  Oral pravastatin reloading before non-emergent CABG significantly attenuates postoperative SIR and systemic NO/iNOS concentrations with no effect in perioperative myocardial damage. Highest pravastatin doses increase CPK levels and must be avoided in susceptible patients.
authors.affiliation: Department of Cardiac Surgery, León University Hospital, León, Spain - marioborg@telefonica.net.
authors.forename: M
authors.initials: M
authors.lastname: Castaño
authors.forename: J M
authors.initials: JM
authors.lastname: González-Santos
authors.forename: J
authors.initials: J
authors.lastname: López
authors.forename: B
authors.initials: B
authors.lastname: García
authors.forename: J E
authors.initials: JE
authors.lastname: Centeno
authors.forename: B
authors.initials: B
authors.lastname: Aparicio
authors.forename: M J
authors.initials: MJ
authors.lastname: Bueno
authors.forename: R
authors.initials: R
authors.lastname: Díez
authors.forename: V
authors.initials: V
authors.lastname: Sagredo
authors.forename: J M
authors.initials: JM
authors.lastname: Rodríguez
authors.forename: F J
authors.initials: FJ
authors.lastname: García-Criado
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000601:surgery*; D003402:Creatine Kinase / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D010865:Pilot Projects; D017035:Pravastatin / Q000008:administration & dosage* / Q000009:adverse effects; D011300:Preoperative Care; D012307:Risk Factors; D013030:Spain; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D003402:Creatine Kinase; D017035:Pravastatin