Simvastatin: pharmacological response in experimental hyperfibrinogenaemias

Through a disorder in the endothelial haemostatic balance, hyperfibrinogenaemia could generate endothelial dysfunction. Statins would have antiinflammatory effects on injured endothelium.

Simvastatin pharmacological response in rats with hyperfibrinogenaemias induced by laparotomies was studied.

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.

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.