Lovastatin and nitrate therapy induced changes in hemorheological parameters and in free radical mediated processes in patients with ischemic heart disease

Reactive oxygen species play an important role in the development and progr ession of atherosclerosis and ischemic heart disease, in ischemia-reperfusi on injury, in cardiac arrhythmias and finally they are able to cause impair ment in the vascular function and blood viscosity. Impaired blood rheology and its components: elevated fibrinogen and lipoprotein levels, increased h ematocrit, increased aggregability and decreased deformability of red blood cells on the other hand were also shown to contribute to the pathological processes in ischemic heart disease. In the study the effects of two drugs - lovastatin (Mevacor(R), MSD) and isosorbide-5-mononitrate (Olicard R(R), Solvay Pharma) - on hemorheological and free radical associated parameters were evaluated. The administration of 40-60 mg isosorbide-5-mononitrate onc e daily in group >>A<< did not change the plasma viscosity, but the whole b lood viscosity decreased significantly (from 5.09 +/- 0.06 to 4.72 +/- 0.06 mPas, shear rate: 90 l/s, p < 0.01) at the end of the first month. The adm inistration of 20-80 mg lovastatin daily in group >>B<< produced also a sig nificant decrease (from 11.76+/-0.21 to 10.97+/-0.19 mPas, shear rate: 4.59 l/s, p<0.05) in the whole blood viscosity while the tendency of plasma vis cosity was also slightly decreasing. The superoxide anion generation of neu trophil granulocytes increased (n. s.), the activity of erythrocyte superox ide dismutase (SOD) decreased (from 767 +/- 162 to 577 +/- 92 U/ml, p < 0.0 5) in patients treated with isosorbide-5-mononitrate for two weeks (group > >C<<). The concentration of reduced glutathione (GSH) was not altered, whil e the concentration of plasma malondialdehyde decreased significantly (from 0.73 +/- 0.06 to 0.59 +/- 0.08 nmol/ml, p < 0.05). The superoxide anion ge nerating capacity of neutrophil granulocytes decreased markedly in patients on three month long 20 mg lovastatin therapy (group >>D<<) (from 28.61 +/- 2.89 to 13.49 +/- 2.2 nmol/1.5 x 10(6) cells/min, p<0.01). The activity of erythrocyte SOD showed an increasing (n. s.), the activity of erythrocyte catalase a decreasing tendency (n. s.), and the activity of glutathione per oxidase increased significantly (from 13.92+/-0.57 to 18.61+/-0.81 U/ml, p <0.01). A marked decrease could be observed in the concentration of erythro cyte malondialdehyde (from 550 +/- 30 to 390 +/- 56 nmol/ml, p < 0.05). Our results indicate, that both lovastatin and nitrate treatment have benefici al effects on whole blood viscosity and in addition, lovastatin exerts a si gnificant amelioration of the free radical associated parameters and the an tioxidant status of the patients.