The role of hemorheological factors in cardiovascular medicine.

Cardiovascular diseases (CVD) are the most frequent cause of death throughout the world. The coronary vessel system is a special part of the circulation since there is a continuous change in blood flow, perfusion pressure and shear rate during each cardiac cycle. It is also the place of the narrowest capillaries in the human body, therefore the role of rheological alterations may be of greater importance than in the other parts of the circulatory system. During the past decades, our group has investigated hemorheological parameters (HP) in over 1,000 patients diagnosed with various forms of ischemic heart disease (IHD). In one prospective study, we measured the HP of patients with acute coronary syndrome (ACS). On admission, all examined variables were significantly worse than those of control subjects. During the hospital phase, some of the HP showed further deterioration, and HP remained in the pathologic range during the follow-up period. In another study, we showed that HP are in close correlation with the severity of coronary artery disease. In patients treated with percutaneous coronary intervention, changes in HP were very similar to those observed in subjects with ACS. In a recent study, we analyzed HP in patients undergoing CABG surgery. Our data suggest a hemorheological advantage of off-pump surgery. In another study low Hct/WBV ratio can be regarded as a risk factor of cardiac death in IHD. Our data indicate that rheological parameters are significantly altered in patients with IHD: the extent of the alterations is in excellent correlation with the clinical severity of the disease. Our findings prove that HP play a critical role in the pathogenesis of myocardial ischemia. In recent in vitro and in vivo studies we have investigated the effects of red wine on hemorheological parameters. Our results show that moderate red wine consumption has beneficial effects on hemorheological parameters which may contribute to the French paradox.

Reviewing data reduction methods for ektacytometry.

Ektacytometry quantifies erythrocyte deformability by measuring the elongation of suspended red blood cells subjected to a range of shear stresses. Raw shear stress-elongation index plots are difficult to interpret and thus data reduction methods characterizing the relationship using few parameters without loss of information and good reproducibility are essential, especially for the clinician. Two such curve fitting formulas, used widely in the literature for this purpose, are reviewed herein. The Lineweaver-Burke method overestimates maximal deformability if shear stresses below 1 Pa are applied. A modified version of the formula estimates maximal deformation more accurately but gives little weight to data at low shear stresses. Neither method is accurate if negative elongation indices are present (artifact phenomenon when measurement is performed from high to low shear stresses). The Streekstra-Bronkhorst method provides efficient data reduction though the theoretical background of the formula is incorrect. The parameters have expressive meaning; however, both maximal and minimal deformations are slightly underestimated. Moreover, parameters are biased according to the range of measured shear stresses.

The influence of on-pump and off-pump coronary artery bypass grafting on hemorheological parameters.

Conditions during coronary artery bypass grafting (CABG) performed on beating heart (off-pump) are more physiological than using extracorporeal perfusion (on-pump). The present study aims to examine the hemorheological aspects of the two techniques. Blood samples were taken from patients undergoing on-pump (n = 25) and off-pump (n = 22) CABG, upon arrival to the operating theatre, after 20 and 40 minutes during the operation, after closing the thorax, on the 1st and 2nd postoperative days, and during the 2nd and 6th month control check-ups. Hematocrit (Hct), plasma and whole blood viscosity (PV, WBV; Hevimet 40 capillary viscometer), red blood cell (RBC) aggregation (Myrenne RBC aggregometer, LORCA) and deformability (LORCA, Carat FT-1 filtrometer), and platelet aggregation (Carat TX4 aggregometer) were determined. The morphology of red blood cells was investigated by scanning electron microscopy (SEM). Hct, PV, WBV and RBC aggregation decreased significantly during the early phase of the surgery, they started to recover during the postoperative period, and reached the baseline values by the 2nd and 6th month control check-ups. These parameters were significantly lower in samples taken after 20 and 40 minutes in the on-pump group. SEM showed rather damaged and malformed cells in case of on-pump surgery. Ektacytometry showed no significant difference, but RBC deformability was impaired during on-pump surgery when measured by filtrometry. The decrease in platelet aggregation was more pronounced by the end of surgery in case of on-pump technique. During CABG rheological parameters change less when using the off-pump method, and mechanical damage of RBCs are also smaller. The off-pump technique seems to be favorable from a hemorhelogical point of view.

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.

Low hematocrit per blood viscosity ratio as a mortality risk factor in coronary heart disease.

Increased blood viscosity has not been associated with mortality risk in coronary heart disease (CHD). We aimed to investigate the predictive power of hematocrit per blood viscosity (Hct/BV) ratio as a marker of rheological oxygen carrying capacity of the blood to assess mortality risk of CHD. Elective coronary angiography was performed and CHD was proved in 109 patients in 1996 and 1997. In 78 cases (72%) complete follow up information was obtained in February 2006. During the follow up time (mean 8.9 years) 10 patients died due to cardiac cause (group C). Two patients died due to non-cardiac cause and 66 were still alive at the end of the follow up period (group NC, n=68). Mean hematocrit per blood viscosity (Hct/BV) ratio was significantly lower in group C comparing to NC (87+/-5; 93+/-9 Pa(-1)s(-1), SD, respectively, p=0.022). Other factors (body mass index, serum cholesterol, fibrinogen, hematocrit, plasma and blood viscosity, cardiac index, left ventricular ejection fraction) provided no statistical differences. Kaplan-Meier survival analysis showed only the impact of fibrinogen and Hct/BV ratio on cardiac mortality (p=0.029 and 0.009, respectively). Receiver operating characteristic curves proved only Hct/BV ratio to be able to differentiate between groups (area under curve: 0.716, p=0.028). Hct/BV ratio showed significant negative correlation with the frequency of hospital admissions (r=-0.377, p=0.03). Low Hct/BV ratio can be regarded as a risk factor of cardiac death in CHD.

Gender differences in hemorheological parameters of coronary artery disease patients.

Plasma fibrinogen concentration, plasma and whole blood viscosity (WBV) are independent risk factors of coronary artery disease (CAD). Fibrinogen seems to be a relatively stronger risk factor for women than for men, but men are more endangered by higher hematocrit (Hct) and WBV than women are. We have previously reported that a theoretically optimal Hct value can be determined using Hct/WBV ratio in healthy subjects, hyperlipidemic and Raynaud's disease patients. Our aim was to examine whether Hct/WBV ratio is differently correlated with Hct in men and women with proven CAD. In a retrospective study we analysed the hemorheological data of 162 CAD outpatients (107 men and 55 women). Coronary angiography, echocardiography and impedance cardiography were performed. Hemorheological parameters (Hct, fibrinogen level, plasma viscosity, WBV), blood picture, serum lipid concentrations were determined and Hct/WBV ratio was calculated. Mean ages of male and female patients were similar (54.9 and 55.4 years, respectively), but men had significantly higher coronary angiography score than women. Mean left ventricular ejection fraction, stroke volume index and cardiac index showed no significant differences in men and women. Similarly, lipid concentrations, fibrinogen levels and plasma viscosities demonstrated no statistical differences. However, Hct, WBV and Hct/WBV ratios were significantly higher in male than in female patients (p < 0.00001; p < 0.00001 and p < 0.005, respectively). The most striking gender difference was found in the correlation between Hct/WBV ratio and cardiac index. Men older than 56 years showed negative, women positive correlation (r = -0.485, p = 0.01; r = 0.468, p = 0.006, respectively). This study demonstrates that Hct/WBV ratio as a rheological oxygen carrying capacity parameter is positively correlated with the cardiac index as it can be expected. However, the correlation is negative in elder men indicating an unhealthy relation between hemodynamic and hemorheologic parameters.

Erythrocyte transport efficacy of human blood: a rheological point of view.

BACKGROUND: Large-scale epidemiological studies have demonstrated that both anaemia and polycytaemia are independent cardiovascular risk factors. This was substantiated by the Framingham study, which demonstrated a U-shaped relation between haemoglobin concentration and mortality. It was previously noted that delineating the corresponding haematocrit/blood viscosity ratios in the function of haematocrit provided a distribution of an inverted U-shaped curve. The peak appeared physiologically important because it denotes a healthy balance between a relatively high oxygen binding capacity and a moderately low blood viscosity. It was the aim of this study to examine the mathematical relationship between the haematocrit and haematocrit/blood viscosity ratio. MATERIALS AND METHODS: In a retrospective study, the haemorheological data of 32 healthy controls, 52 outpatients with hyperlipidaemia and 120 outpatients with Raynaud's disease were analyzed. Whole blood viscosity was measured with Hevimet 40 capillary viscometer at 37.0 degrees C and at shear rates of 10 s(-1), 90 s(-1) and 200 s(-1). RESULTS: Haematocrit/blood viscosity ratios in the function of haematocrit values showed a Gaussian association in the healthy subjects, hyperlipidaemic and Raynaud's disease outpatient groups. Peak values (i.e. the rheologically optimal haematocrit) were shear-rate and group dependent and were found at 44.3%, 43.5% and 38.3% in controls, hyperlipidaemic and Raynaud's disease patients, respectively, at a shear rate of 90 s(-1). CONCLUSIONS: This is one of the first reports in which a theoretically optimal haematocrit value was determined using the haematocrit/blood viscosity ratio. Further studies are needed to examine the potential clinical usefulness of this approach.

Hemorheological disturbances in patients with chronic cerebrovascular diseases.

Hemorheological disturbances may occur in more than 40% of patients with ischemic cerebrovascular diseases. In this study the changes of rheological factors--hematocrit, plasma fibrinogen concentration, whole blood and plasma viscosity, red blood cell aggregation and deformability were investigated in 297 patients (173 males, 124 females, mean age 60 +/- 11 years) with transient ischemic attack or chronic phase (> 3 months after onset) ischemic stroke, and in 73 healthy volunteers (35 males, 38 females, mean age 38 +/- 7 years). Hematocrit, plasma and whole blood viscosity were significantly (p < 0.0001) elevated in cerebrovascular patients compared to controls. Plasma fibrinogen concentration (p < 0.001), red blood cell aggregation (p < 0.05) and deformability (p < 0.01) were also impaired in stroke patients. Hemorheological disturbances were dominant in stroke patients with diabetes, hyperlipidemia and smoking habits. Hematocrit, plasma viscosity and red blood cell aggregation showed a significant (p < 0.025-0.001) correlation with the severity of carotid artery stenosis. We could not find any characteristic distribution of rheological parameters among the three subtypes of brain ischemia. Our results show that all of the measured rheological parameters are significantly impaired in chronic ischemic cerebrovascular disorders, especially in diabetic, smoking and alcoholic patients. They correlate with the severity of the carotid artery stenosis, but there is no association with the type of ischemic stroke.

Follow-up of hemorheological parameters and platelet aggregation in patients with acute coronary syndromes.

Pathologic hemorheological parameters and increased platelet aggregation in association with other risk factors significantly increase the possibility of the development of myocardial ischemia. Hemorheological parameters and platelet aggregation were investigated in 157 patients (mean age: 65+/-12 years) with acute coronary syndromes and in 68 healthy subjects (mean age: 36+/-6 years). Plasma fibrinogen, plasma and whole blood viscosity, red blood cell aggregation and filterability and platelet aggregation were measured in the hospital phase (after admission, on 2nd and 6th days) and monitored after discharge (at 1, 6 and 12 months). After admission all these parameters were significantly higher in patients than in control subjects (p<0.01) and almost all of them remained in the pathologic range at discharge. Some of the rheologic parameters showed a slight improvement after 1 month, but hematocrit and whole blood viscosity were higher than those after admission and of control subjects (p<0.05). After 6 and 12 months these parameters showed a small, but significant increase. Pathologically altered hemorheological parameters could be observed in patients with classical cardiovascular risk factors and significant improvement was found after elimination of them. Antiplatelet therapy was efficient in about half of the treated patients after admission; and despite a significant improvement, the proportion of ineffectively treated patients was still considerable during the follow-up. Our results support the role of abnormal hemorheological parameters in the development of myocardial ischemia and draw attention to the rheologic risk of these patients. The results of platelet aggregation measurements show the insufficiency of antiplatelet therapy at some cases and confirm the importance of guided secondary prevention.

QRS Score: a composite index of exercise-induced changes in the Q, R, and S waves during exercise stress testing in patients with ischemic heart disease.

BACKGROUND: To detect ischemic heart disease, the exercise-induced ST-segment displacement is the most frequently used ECG parameter. However, the value of this marker was proven to be limited with varying sensitivity and specificity. A new parameter, called QRS score, emerged to improve the efficacy of exercise testing. METHODS: Our study aimed at evaluating the diagnostic value of QRS score in ischemic heart disease, investigating males and females separately, and examining the effects of heart rate and antiischemic medication. QRS score and cumulative ST depression were calculated in 212 patients and correlated to the findings of the stress myocardial perfusion SPECT (197 subjects) or coronary angiography (54 subjects). RESULTS: An inverse correlation could be found between the QRS score and the results of myocardial SPECT and coronary angiography in the whole population, especially in males; females did not show a significant relationship. In patients with conclusive tests (achieving 85% of the maximal predicted heart rate) QRS score correlated significantly with the results of the stress myocardial perfusion SPECT and coronary angiography. The sensitivity, specificity, and validity of the QRS score surpassed those of the cumulative ST depression in the entire population as well as in patients with conclusive tests. The antiischemic medication did not affect correlation values. CONCLUSION: QRS score was significantly related to the extent of myocardial ischemia and the severity of coronary heart disease, thus along with the analysis of ST-segment displacement may contribute to the more precise evaluation of exercise testing.

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.

The effect of carvedilol on enhanced ADP-ribosylation and red blood cell membrane damage caused by free radicals.

OBJECTIVE: Previous studies have reported that the beta and alpha adrenoceptor blocker carvedilol has unique protective effects on free radical-induced myocardial injury. The aim of this study was to examine how carvedilol regulates reactive-oxygen-species-mediated signaling and decreases red blood cell membrane damage in heart perfusion and in a rheological model. METHODS: The ischemia-reperfusion-induced oxidative cell damage, and changes in the intracellular signaling mediated by reactive oxygen species and peroxynitrite were studied on rat hearts in a Langendorff perfusion system (n=15). The effect of carvedilol on red blood cell suspension viscosity (hematocrit: 60%) incubated with free radical generator (phenazine methosulphate) was also investigated (n=10). The measurements were performed on a capillary viscosimeter. RESULTS: In both studies a protective effect of carvedilol was found, as the decrease of red blood cell suspension viscosity and K(+) concentration in the supernatant indicated. Carvedilol significantly decreased the ischemia-reperfusion-induced free radical production and the NAD(+) catabolism and reversed the poly- and mono(ADP-ribosyl)ation. Carvedilol also decreased the lipid peroxidation and membrane damages as determined by free malondialdehyde production and the release of intracellular enzymes. The self ADP-ribosylation of isolated poly(ADP-ribose) polymerase was also significantly inhibited by carvedilol. CONCLUSION: Our results show that carvedilol can modulate the reactive-oxygen-species-induced signaling through poly- and mono(ADP-ribosyl)ation reactions, the NAD(+) catabolism in postischemic perfused hearts and has a marked scavenger effect on free radical generator-induced red blood cell membrane damage. All these findings may play an important role in the beneficial effects of carvedilol treatment in different cardiovascular diseases.

[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.

Hemorheological and oxygen free radical associated alterations during and after percutaneous transluminal coronary angioplasty.

Percutaneous transluminal coronary angioplasty (PTCA) is a frequently used method in the treatment of coronary artery disease. Coronary stenosis, endothelial injury, and ischemia-reperfusion caused by the balloon inflation and deflation during this procedure can cause several changes in blood flow. In our study 19 patients (mean age: 58 +/- 9 years) undergoing PTCA were examined. For the laboratory measurements several blood samples were taken from the femoral vein and the coronary sinus before and 30 minutes after PTCA, and from the cubital vein 1, 2, 5 days and 1, 6 months after PTCA. Among hemorheologic parameters hematocrit, plasma fibrinogen level, plasma and whole blood viscosities were measured and corrected blood viscosity value was calculated. To characterize the oxidative stress, samples were analyzed for thiobarbituric acid reactive substances (TBARS) of blood as a marker of lipidperoxidation and changes in the antioxidant system were investigated by measuring the activity of superoxide dismutase, catalase and the concentration of glutathione; superoxide generating capacity of isolated leukocytes and platelet aggregation were examined as markers of cellular activation. Plasma fibrinogen concentration increased markedly during the first and second day after PTCA (p < 0.001), which was accompanied by the elevation of plasma viscosity (p < 0.05). Plasma fibrinogen returned to the baseline at the one-month check-up visit, but there was a significant increase in its concentration by the end of the sixth month follow-up. Apparent whole blood viscosity at 90 s (-1) showed gradually increasing values up to the one- and six-month check-up visits (p < 0.01), which can partially be explained by the elevation of hematocrit. Corrected blood viscosity was significantly elevated on the fifth day already (p < 0.01), and one month later also. Superoxide production of leukocytes showed an increasing tendency (p = 0.05), and blood TBARS was elevated after one day (p < 0.05) and remained higher during the following days. Catalase activity showed significantly increasing values (p < 0.01) during the hospital phase, then at the end of the first month. SOD activity and spontaneous platelet aggregation were higher in the samples from the coronary sinus than in those from the peripheral vein before the procedure; 30 minutes after PTCA increased levels in the peripheral sample were found (p < 0.01). Our findings indicate that PTCA may cause significant changes in the hemorheologic and free radical associated parameters, which can affect the final outcome of this intervention.

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.

[The effect of carvedilol on enhanced adp-ribosylation and red blood cell membrane damage caused by free radicals]. / Carvedilol hatása a szabadgyök indukálta ADP-ribozilációra és vörösvértest membrán károsodásra.

OBJECTIVE: Previous studies have reported that the beta and alpha adrenoceptor blocker carvedilol had unique protective effect on free radical induced myocardial injury. The aim of this study was to examine how carvedilol regulates ROI-mediated signaling and decreases RBC membrane damage in heart perfusion and rheological model. METHODS: The ischemia-reperfusion induced oxidative cell damages, and changes in the intracellular signaling mediated by reactive oxygen species and peroxynitrite were studied on rats, in Langendorff heart perfusion system (n = 15). The effect of carvedilol on red blood cell suspension viscosity (hematocrit: 60%) incubated with free radical generator (phenazine methosulphate) was also investigated (n = 10). The measurements were performed on a capillary viscosimeter. RESULTS: In both studies a protective effect of carvedilol was found, as the decrease of red blood cell suspension viscosity and K+ concentration in the supernatant indicated. Carvedilol significantly decreased the ischemia-reperfusion induced free radical production and the NAD+ catabolism and reversed the poly- and mono-ADP-ribosylation. Carvedilol also decreased the lipid peroxidation and membrane damages as determined by free malondialdehyde production and the release of intracellular enzymes. The self ADP-ribosylation of isolated PARP was also significantly inhibited by carvedilol. CONCLUSION: Our results show that carvedilol can modulate the ROI-induced signaling through poly- and mono-ADP-ribosylation reactions, the NAD+ catabolism in postischemic perfused hearts and has a marked scavenger effect on free radical generator induced red blood cell membrane damage. All these findings may play an important role in the beneficial effects of carvedilol treatment in different cardiovascular diseases.

Effects of doxazosin on hemorheological, hemodynamic and lipid parameters in patients with essential hypertension.

It is known from previous studies that hemorheological parameters are altered in patients with essential hypertension. The hemorheological and hemodynamical effects of doxazosin, a selective alpha-1-adrenoreceptor blocker agent, was examined in twenty patients (mean age: 54+/-10 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 triglyceride (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).