title: Protective effects of simvastatin on coronary artery function in swine with acute infection.
abstract: BACKGROUND
  The risk for coronary events may rise during acute infection. Perturbation in coronary endothelial function emerges as one important link. We investigated whether simvastatin could protect the coronary arterial function from the adverse effects of acute infection in swine.
  
  
  METHODS
  Coronary endothelium-dependent and -independent vasomotor responses were assessed by Doppler velocimetry in 12 Chlamydia pneumoniae-infected and 6 sham-infected swine 2 weeks after intratracheal inoculation. Half of animals from the infection group were pre-treated with simvastatin (80 mg daily), while the remaining animals received placebo. The treatment was started 2 weeks prior to inoculation and continued until the end of the study. ANOVA was used for statistical calculations. Data are mean+/-S.D.
  
  
  RESULTS
  All animals inoculated with C. pneumoniae developed IgM antibodies against this organism. As compared to noninfected animals, peak-to-baseline coronary flow velocity (CFV) ratio after bradykinin was significantly decreased in infected animals regardless of statin treatment (p=0.01). Intracoronary 10(-6) M acetylcholine caused slight dilatory responses in both noninfected and infected-treated animals (CFV ratio: 1.6+/-0.2 and 1.4+/-0.2, respectively; p>0.1), while a velocity drop (CFV ratio: 0.7+/-0.1; p<0.01 versus noninfected-infected and treated), indicating constriction, was observed in infected-nontreated animals; 10(-5) M acetylcholine caused vasoconstriction in all animals, with a significantly more prolonged response in the infected-nontreated group (p<0.01). Intracoronary adenosine and SNP induced similar dilatory responses in all groups (p>0.5). There were no differences in markers of systemic inflammation (fibrinogen, amyloid, and CRP) and lipid profile (HDL, LDL and total cholesterol) between the groups (p>0.2).
  
  
  CONCLUSIONS
  Acute infection is associated with impairment of the muscarinic and kinin-related reactivity of coronary circulation. These functional abnormalities are in part prevented by simvastatin through mechanisms unrelated to lipid lowering.
authors.affiliation: Department of Pediatric Cardiology, Lund University Hospital, 22185 Lund, Sweden. petru.liuba@med.lu.se
authors.forename: Petru
authors.initials: P
authors.lastname: Liuba
authors.forename: Erkki
authors.initials: E
authors.lastname: Pesonen
authors.forename: Anders
authors.initials: A
authors.lastname: Forslid
authors.forename: Ilari
authors.initials: I
authors.lastname: Paakkari
authors.forename: Axel
authors.initials: A
authors.lastname: Kornerup-Hansen
authors.forename: Petri
authors.initials: P
authors.lastname: Kovanen
authors.forename: Markku
authors.initials: M
authors.lastname: Pentikäinen
authors.forename: Kenneth
authors.initials: K
authors.lastname: Persson
authors.forename: Grete
authors.initials: G
authors.lastname: Østergård
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000208:Acute Disease; D000818:Animals; D001920:Bradykinin / Q000502:physiology; D023521:Chlamydophila Infections / Q000188:drug therapy* / Q000503:physiopathology; D016993:Chlamydophila pneumoniae; D003324:Coronary Artery Disease / Q000382:microbiology* / Q000503:physiopathology / Q000517:prevention & control*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000382:microbiology / Q000503:physiopathology*; D019821:Simvastatin / Q000627:therapeutic use*; D013552:Swine
chemical_list: D019821:Simvastatin; D000109:Acetylcholine; D001920:Bradykinin