Protective effects of simvastatin on coronary artery function in swine with acute infection

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.

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.

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).

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.