THE EFFECTS OF CALCIUM-CHANNEL BLOCKERS ON BLOOD FLUIDITY

Although vasodilation, direct cardiac actions, or both represent the main properties of calcium channel blockers, there are further pharmacologic effects that may be therapeutically relevant. For example, hemorrheological effects, which have been demonstrated for a variety of calcium antagonists, have received relatively little attention to date. Hemorrheology describes the mechanics of blood and its components. It is of particular interest in the context of cardiovascular disease, as it has been shown that under certain conditions (reduced pump function, impaired vasomotor reserve), parameters of blood fluidity may be crucial for tissue perfusion. Whole-blood viscosity is the dominating factor in large arteries. For geometrical reasons, plasma viscosity and the rheological properties of blood cells may become of paramount importance at the microcirculatory level. In ischemic states, erythrocytes may be depleted of ATP, which they need for maintenance of normal shape and for transformation. This results in rigidification of the red blood cell and hindrance of its passage in the microcirculatory bed. Hence, blood flow deteriorates with the consequence of further unfavorable changes in the "milieu interieur," leading to the induction of a vicious cycle. Although effects on several hemorrheological parameters, for example, whole-blood viscosity, plasma viscosity, and red cell aggregation, can be demonstrated for various calcium channel blockers, the main rheological effects of these compounds are believed to consist in the improvement of erythrocyte deformability. When the ATP-dependent calcium pump is impaired in ischemia, calcium channel blockers may inhibit the slow inward transmembrane calcium flux and prevent the accumulation of intracellular calcium.