Effects of Diltiazem on Rheological Properties of Human Blood

The in vitro effects of diltiazem (DTZ), a coronary vasodilator, deacetyldiltiazem (D-M1), one of the metabolites of DTZ, and pentoxifylline (PTF) which is known to improve erythrocyte deformation, on the viscosity of platelet poor blood were compared. Furthermore the change in the viscosity of whole blood from patients with effort angina after intravenous administration of DTZ was examined ex vivo. The addition of DTZ into platelet poor blood at 37°C caused a rapid reduction in blood viscosity and an enhancement of erythrocyte deformability within 5 min, which then diminished in a time-dependent manner. Similar effects were also found by adding D-M1. On the other hand, the effects of PTF appeared after an incubation period of more than 60 min and were enhanced in a timedependent manner. These actions of PTF, but not those of DTZ and D-M1, paralleled the increase of erythrocyte adenosine-triphosphate content. DTZ and D-M1, but not PTF, had biphasic effects on the osmotic behavior of erythrocytes. Whole blood viscosity was reduced significantly during the period 5-30 min after intravenous administration of 10 mg of DTZ, which diminished with the elimination of plasma DTZ. In conclusion, the action mechanisms involved in the effect of DTZ and D-M1 on blood rheological properties appeared to be different from that of PTF. These effects of DTZ are clinically significant in improving the flow properties of blood in vascular diseases.