Simvastatin: pharmacological response in experimental hyperfibrinogenaemias.

摘要

Through a disorder in the endothelial haemostatic balance, hyperfibrinogenaemia could generate endothelial dysfunction. Statins would have antiinflammatory effects on injured endothelium. OBJECTIVE: Simvastatin pharmacological response in rats with hyperfibrinogenaemias induced by laparotomies was studied. METHODS AND RESULTS: Rats were subjected to multiple injuries (MI) for 30 days (1 laparotomy/week) and for 60 days (1 laparotomy/2 weeks). Simvastatin (0.035 mg/kg) was administered orally to the 30-day multiple injuries group after the third injury for a period of 10 days. A similar dose was administered to the 60-day multiple injuries group after the second injury for a period of 45 days. Blood samples of all the groups were obtained 72 hours after the last injury. In the 30 and 60-day multiple injuries groups, a statistically significant fibrinogen increase was observed (336.6 +/- 7.5 and 358.7 +/- 9.9, respectively) compared with the control group (207.0 +/- 3.0) (p < 0.001). There were no significant differences in the plasmatic fibrinogen (PF) levels between the control and simvastatin treated groups (224.9 +/- 1.4 and 216.3 +/- 4.3, respectively). There were significant differences between the 30 or 60-day MI untreated groups compared with the 30 or 60-day multiple injuries + simvastatin treated group (p < 0.001). Endothelial denudation and intima widening were observed in the untreated injured groups, whereas in the 60 day multiple injuries group + simvastatin, a regression of histopathological lesions was observed. CONCLUSIONS: The decrease of the inflammatory component that would accompany early atherogenesis processes and the regression of the histopathological lesions after treatment could be attributed to the decreased plasmatic fibrinogen.