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.

The effect of diuretics on red blood cell microrheological parameters in female hypertensive patients.

This study was designed to examine changes of hemorheological parameters and red cell aggregation particularly in essential arterial hypertension subjects receiving antihypertensive diuretic therapy. Fifty six female subjects were enrolled in this study. Thirty seven subjects (group I) were treated for four weeks with Hydrochlorothiaszide (25 mg/day); Nineteen patients (group II) were infused with dose of furosemide 40 mg i.v. Both prior to and following drug treatment for four weeks and four hours after furosemide infusion hemorheological measurements included plasma viscosity; hematocrit, total plasma protein, red cell rigidity index (Tk) and RBC aggregation indices. In addition to this protocol the erythrocytes of patients of group II were incubated with furosemide (0.03 mM; for 30 min at 37 degrees C) to study a direct furosemide effect on red cell aggregation. Treatment and infusion with each of the two drugs significantly (p<0.05) reduced blood pressure in both groups. However, the hemorheological effects of hydrochlorothiaszide therapy were not significant. The effect of furosemide infusion and red cell incubation with it led to significant RBCA elevation. These results thus suggest that the rheologic effects of saluretic diuretics therapy were not significant. Single furosemide infusion and using it in vitro resulted in strong effect of red cell aggregation increase.

The effect of simvastatin therapy on hemorheological profile in coronary heart desease (CHD) patients.

This study was designed to examine changes of hemorheological parameters in patients with CHD and hypercholesterolaemia (wide range of plasma total cholesterol level from 5.6 to 9.8 mmol.l-1) subjected to lipid lowering therapy with statins (simvastatin, 10.0-20.0 mg/day, dosage was dependent on an initial level of total cholesterol). Twenty female subjects were enrolled in this research program. Both prior to and following drug treatment for eight weeks, hemorheological measurements included plasma viscosity, high and low shear whole blood viscosity, hematocrit, RBC aggregation and rigidity. Treatment with simvastatin significantly (p<0.05) reduced total cholesterol, total triglycerides and low-density lipoprotein cholesterol (LDL-C). However, the hemorheological effects of lipid lowering therapy differed markedly between macro- and microrheological groups of parameters: plasma and whole blood viscosity were not significantly changed whereas RBC aggregation and its rigidity were decreased significantly after statin treatment. These results thus suggest that the rheologic effect of lipid lowering therapy concerned mainly the microrheological parameters: red cell aggregation and deformability.

Effects of antihypertensive therapy on hemorheological profiles in female hypertensive patients with initially low or high whole blood viscosity.

This study was designed to examine changes of hemorheological parameters in essential arterial hypertension subjects following antihypertensive drug therapy. Eighty two female subjects were enrolled, and sub-divided into two groups based upon their high shear whole blood viscosity being lower (L) or higher (H) than normal controls. Equal numbers of L and H subjects were then treated for four weeks with one of four agents: angiotensin-converting enzyme inhibitor (ACE-inhibitor, Spirapril - 6 mg/day); calcium antagonist (Isradipin - 5 mg/day); beta-1-blocker (Talinolol - 100 mg/day); diuretic (Indapamide - 1.5 mg/day). Both prior to and following drug treatment for six weeks, hemorheological measurements included plasma viscosity; high and low shear whole blood viscosity, hematocrit, fibrinogen and RBC aggregation. Treatment with each of the four drugs significantly (p<0.05) reduced blood pressure in both the L and H groups. However, the hemorheological effects of antihypertensive drug therapy differed markedly between groups: plasma and whole blood viscosity were significantly elevated in the L groups whereas these parameters were significantly decreased in the H groups. Fibrinogen levels and RBC aggregation decreased in both groups, whereas hematocrit was unaffected. These results thus suggest that the rheologic effects of antihypertensive drug therapy depend strongly on the initial, pre-treatment status of the subject, and that for some subjects, such therapy can result in adverse hemorheological alterations.