The effect of aspirin on hemorheological parameters of patients with diabetic retinopathy.

Hemorheological factors play an important role in the pathogenesis of severe complications of diabetes. The diabetic retinopathy is the leading cause of blindness in patients aged 20-65 years. In our study we investigated the effect of aspirin on the hemorheological parameters in patients with different diabetic retinopathies. Hemorheological parameters (hematocrit, fibrinogen, plasma and whole blood viscosity, red blood cell aggregation) of diabetic patients with non-proliferative (n=14, mean age: 66 years) and proliferative retinopathy (n=8, mean age: 48 years) were measured. The results between the two groups were compared: twelve patients were taking aspirin (group A), while ten patients were not (group B).Hematocrit, fibrinogen, plasma and whole blood viscosity were significantly higher (p < 0.05-0.001) in patients with diabetic retinopathy who did not take aspirin than in those who took. No significant difference was observed in red blood cell aggregation parameters between the two groups. We could not find any significant difference in the measured parameters between patients with non-proliferative and proliferative diabetic retinopathy. According to our results, all the measured hemorheological parameters were in the pathological range, although aspirin treatment could decrease these factors and thus may help to prevent the progression of severe diabetic retinopathy and perhaps blindness.

Hemorheological alterations in patients with diabetic retinopathy.

Hemorheological factors play an important role in the pathogenesis of different cardiovascular diseases. Diabetes mellitus resulting in micro- and macroangiopathies is one of the major risk factors for cardiovascular diseases. In our present study the hemorheological parameters (hematocrit, plasma fibrinogen level, plasma and whole blood viscosity, red blood cell aggregation) of 30 diabetic patients (mean age: 57 +/- 12 years) and 30 healthy volunteers (mean age: 31 +/- 10 years) were examined. The fundus appearance of patients showed diabetic retinopathy; non-proliferative stage in 22 cases, preproliferative or proliferative stage in 8 cases. The measured hemorheological parameters of the examined patients were in the pathological range and were significantly higher than those of healthy volunteers (hematocrit: p < 0.01; plasma fibrinogen: p < 0.001; plasma viscosity: p < 0.01; whole blood viscosity: p < 0.001; red blood cell aggregation: p < 0.01). In our study there was not significant difference in the hemorheologic variables of patients with different stages of retinopathy. Our results propose the importance of hemorheologic factors in the development of diabetic microangiopathy.

Red blood cell aggregation measurements in whole blood and in fibrinogen solutions by different methods.

Red blood cell (RBC) aggregation is an important component of whole blood viscosity, especially at low shear rates, and is the major cause of the non-Newtonian flow properties of normal blood. In different laboratories several methods are used to determine RBC aggregation, therefore the standardization of aggregation measurements is especially important for getting comparable results. Aggregation indices of 62 human blood samples were determined by two different methods; LORCA (Laser-assisted Optical Rotational Cell Analyzer) and Myrenne aggregometers and related to plasma fibrinogen concentration. Our results show closer correlation values between RBC aggregation and fibrinogen concentration, when RBC aggregation was measured by LORCA (p<0.001), although correlation could be revealed with Myrenne, when plasma fibrinogen level was less than 4.5 g/l. Correlation coefficient between aggregation indices measured by LORCA and Myrenne aggregometers was also closer below this fibrinogen level. In vitro examination of RBC aggregation in fibrinogen solutions showed that higher fibrinogen concentration results in higher RBC aggregation only up to a certain level similarly to that found in human whole blood samples. Our results show that plasma fibrinogen level has an important, concentration dependent effect on RBC aggregation in human blood, but above a certain level it may not cause further aggregate formation.

Hemorheological and hemodynamic parameters in patients with essential hypertension and their modification by alpha-1 inhibitor drug treatment.

Hemorheological factors play an important role in the pathogenesis of different cardiovascular diseases. The hemorheological and hemodynamic parameters in essential hypertension and their possible modification by antihypertensive treatment were examined in the following two studies. In the first study the fundus appearance and hemorheological parameters (plasma and whole blood viscosity (WBV), fibrinogen level) of 33 hypertensive patients (mean age: 55 years) were examined. The fundus appearance showed retinopathy in all the cases between stages I-III. All the measured hemorheological parameters of the examined patients were in the pathological range (WBV at 90 s(-1): 5.18 mPa s) and were significantly (p < 0.01) higher than in healthy controls (WBV at 90 s(-1): 4.18 mPa s). The hemorheological factors showed a parallel deterioration with the fundus appearance, namely their values were significantly (p < 0.01) higher in patients with a fundus appearance stage III (WBV at 90 s(-1): 6.02 mPa s) than stage I (WBV at 90 s(-1): 4.51 mPa s). These results show that there is a correlation between hemorheological parameters and fundus appearance in hypertensives, and this suggests that hemorheological factors may play a role in the development of hypertensive retinopathy. In the second study the hemorheological and hemodynamical effects of Doxazosin, a selective alpha-1-adrenoreceptor blocker agent, was examined in twenty patients (mean age: 54 years) with essential hypertension. Hemorheologic (hematocrit, fibrinogen, plasma and whole blood viscosity) and hemodynamic (cardiac output and index, total peripheral resistance) parameters and plasma lipids were determined. The measurements were carried out before the beginning of the treatment, after 1 week and after 12 weeks treatment periods. Besides significant reduction of blood pressure and total peripheral resistance (p < 0.001), a decrease in cholesterol (p < 0.001) and triglycerides (p < 0.01) levels and a beneficial effect on hemorheological parameters was detected. Fibrinogen and plasma viscosity decreased significantly (p < 0.01). Hematocrit value was also lower after one week (p < 0.001), then an increase could be seen. Whole blood viscosity showed similar changes as hematocrit, but the degree of its final increase was slighter, which was supported by the significantly lower value of corrected blood viscosity (p < 0.05). All these findings indicate that hemorheological factors may play a role in the pathogenesis and in the development of organ damages in hypertension.

[Hemorheologic factors in hypertensive and diabetic retinopathy]. / Haemorheologiai faktorok vizsgálata hypertoniás és diabeteses retinopathiában.

Hemorheological factors play an important role in the pathogenesis of different cardiovascular diseases. In the present study the fundus picture and hemorheological parameters (plasma and whole blood viscosity *WBV* by capillary viscosimetry; fibrinogen level; red blood cell aggregation by Myrenne and LORCA aggregometers) of 33 hypertensive patients (23 females, 10 males; mean age: 55 years) and 30 diabetic patients (14 females, 16 males; mean age: 57 years) and healthy controls were examined. The fundus pictures showed different forms of retinopathy in both groups. All the measured hemorheological parameters of the examined patients were in the pathological range and were significantly higher than in healthy controls. In the group of hypertensive patients hematocrit (p < 0.05), plasma fibrinogen (p < 0.01), plasma viscosity (p < 0.01) and whole blood viscosity (p < 0.01) showed a significant increase. The hemorrheological factors showed a parallel deterioration with the severity of hypertension (measured BP values) and of fundus picture, namely their values were significantly (p < 0.01) higher in patients with stage III fundus picture (WBV at 90 1/s: 6.02 mPas), than stage I hypertension (WBV at 90 1/s: 4.51 mPas). In the diabetic group hematocrit (p < 0.01), plasma fibrinogen (p < 0.001), plasma viscosity (p < 0.01), "WBV" (p < 0.001), red blood cell aggregation (p < 0.05) showed a significant increase comparing to healthy controls. These results show that there is a correlation between hemorrheological parameters and fundus picture in hypertensive and diabetic patients, and this suggests that hemorrheological factors may play a role in the development of hypertensive and diabetic retinopathy.

Scavenger effect of experimental and clinically used cardiovascular drugs.

Oxygen free radicals play an important role in several physiologic and pathophysiologic processes. In pathophysiologic circumstances they can modify and damage biologic systems. Their functional properties (exposed to high oxygen tension) place red blood cells among the most susceptible cells to the harmful effect of free radicals. Because oxygen free radicals are involved in a wide range of diseases, scavenging these radicals should be an important therapeutic approach. In this study the antioxidant capacities of experimental and clinically used cardiovascular drugs were investigated. Phenazine methosulfate was used to generate free radicals and thus harden red blood cells. Filtration technique and potassium leaking were used to detect the scavenging effect of the examined drugs. The experimental drug H-2545 provided 43% protection against phenazine methosulfate-induced changes in red blood cell filterability (p < 0.001). Although some of the examined, clinically used cardiovascular drugs (carvedilol, metoprolol, verapamil, trimetazidine) also showed significant (p < 0.05) antioxidant effect, they were less efficient than H-2545. The scavenger effect of this novel drug exceeded the antioxidant properties of vitamin E. Modification of mexiletine with a pyrroline ring significantly improved its antioxidant capacity, suggesting that this molecular segment is responsible for the antioxidant effect.