Hemorheological efficiency of drugs, targeting on intracellular phosphodiesterase activity: in vitro study.

This in vitro study was designed to examine changes of red cell microrheological parameters (red cell aggregation and their suspension viscosity) after cell incubation with some drugs having phosphodiesterase (PDE) inhibitory activity (pentoxifylline - 25.0 microg/ml; drotaverine - 10.0 microg/ml; vinpocetine - 5.0 microg/ml; papaverine - 10.0 microg/ml; caffeine - 25.0 microg/ml; 3-isobutyl-1-methylxanthine [IBMX] - 10.0 microg/ml). Concentrations of used drugs for in vitro red cell microrheology study were the similar with those which it could be possible in blood of patient after intravenous therapeutic infusion. Red blood cells were separated from the blood by centrifugation at 1400 g for 15 min and washed 3 times with phosphate buffered saline (PBS). The washed RBCs were then resuspended in PBS at a hematocrit of approximately 40%. In each of the research sessions these RBC suspensions were divided into two aliquots and exposed to: one of the drug at 37 degrees C for 15 min; remaining aliquot (red cell suspension with PBS) was kept at 37 degrees C for 15 min and served as the control. It was found that all of used drugs decreased red cell aggregation and their suspension viscosity significantly. Since IBMX and vinpocetine are the specific inhibitor PDE activity it might be suppose that cellular PDE is molecular target in RBCs for this class of drugs. The obtained data reveals evidence that drugs, acting as PDE inhibitors, might be considered as microrheologically positive remedies.