Laszlo Czopf

University of Pécs, Fuenfkirchen, Baranya county, Hungary

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Publications (22)54.71 Total impact

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    ABSTRACT: Several beneficial effects of resveratrol (RES), a natural antioxidant present in red wine have already been described. The aim of our study was to investigate if RES had a clinically measurable cardioprotective effect in patients after myocardial infarction. In this double-blind, placebo controlled trial 40 post-infarction Caucasian patients were randomized into two groups. One group received 10 mg RES capsule daily for 3 months. Systolic and diastolic left ventricular function, flow-mediated vasodilation (FMD), several laboratory and hemorheological parameters were measured before and after the treatment. Left ventricular ejection fraction showed an increasing tendency (ns) by RES treatment. However, left ventricular diastolic function was improved significantly (p < 0.01) by RES. A significant improvement in endothelial function measured by FMD was also observed (p < 0.05). Low-density lipoprotein (LDL) level significantly decreased (p < 0.05) in the RES treated group. Red blood cell deformability decreased and platelet aggregation increased significantly in the placebo group (p < 0.05), while resveratrol treatment has prevented these unfavourable changes. Concerning other measured parameters no significant changes were observed neither in placebo nor in RES group. Our results show that resveratrol improved left ventricle diastolic function, endothelial function, lowered LDL-cholesterol level and protected against unfavourable hemorheological changes measured in patients with coronary artery disease (CAD).
    Clinical hemorheology and microcirculation 01/2012; 50(3):179-87. · 3.40 Impact Factor
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    ABSTRACT: The French paradox is based on epidemiological evidence which supports that moderate red wine consumption reduces the risk of cardiovascular diseases. A number of experimental animal studies reported favourable cardiovascular effects of alcohol-free red wine extract (AFRW). Our study was designed to determine red wine and AFRW induced changes in various hemorheological parameters. These effects may play a role in the pathophysiology of the French paradox regarding the cardiovascular protective impacts of red wine. Blood samples of healthy volunteers were mixed with red wine to achieve alcohol concentrations of 1 per thousand, 3 per thousand and 10 per thousand, respectively, with equivalent amount of AFRW or physiological saline. Blood samples were pretreated with red wine or AFRW in order to prove the protective effects on erythrocytes from impairment of deformability caused by the free radical generator phenazine methosulfate (PMS). Erythrocyte aggregation (Myrenne and LORCA), deformability (LORCA) and platelet aggregation (Carat TX4) were measured. Erythrocyte aggregation using Myrenne aggregometer was inhibited by red wine and AFRW compared to the saline treated samples. The difference reached already significance at 1 per thousand concentration at the AFRW samples (p < 0.05). Furthermore, red wine caused stronger inhibition than AFRW. The difference between the two agents became significant at 10 per thousand concentration (p < 0.05). LORCA aggregation index and threshold shear rate supported these results at the highest concentration. Erythrocyte deformability of healthy volunteers did not change significantly for any concentrations of red wine and AFRW. On the other hand AFRW at 3 per thousand concentration significantly prevented erythrocytes from impairment of deformability caused by PMS (p < 0.05). Platelet aggregation was significantly inhibited by the highest concentration of AFRW (p < 0.05). Our results show that red wine and AFRW have some beneficial effects on hemorheological parameters that may contribute to the French paradox.
    Clinical hemorheology and microcirculation 01/2010; 44(3):227-36. · 3.40 Impact Factor
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    ABSTRACT: The onset of acute myocardial infarct shows circadian and seasonal variations, that are influenced by sex, age and the changes of weather conditions as well. The purpose of our present study is to investigate whether a seasonal variation can be found in the onset of myocardial infarctions during the period under investigation, and whether certain meteorological factors (air temperature, atmospheric pressure, front movements) influence the incidence of myocardial infarction. Retrospective analysis has been carried out on patients admitted because of acute myocardial infarct in Hungary between 2000 and 2004 ( n=81.956). Data have been taken from the database of the National Health Insurance Fund Administration based on the International Classification of Diseases (ICD). Weather related data were provided by the National Meteorology Service. Regarding seasonal distribution the peak incidence period of acute myocardial infarct was spring, whereas the lowest number of events was observed during the summer months. There was a marked difference in the number of events per season ( p<0.001). A medium level negative correlation was found between the monthly average temperature and the occurrence of heart attack ( r=-0.404) during the period examined. A positive correlation was shown between front movements and the of number of events per season ( r=0.053). Our findings show that certain meteorological factors may be related to the onset of acute myocardial infarct, however, a number of other factors may also play an important role.
    Orvosi Hetilap 04/2007; 148(16):731-6.
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    ABSTRACT: Recent studies have described the incidence (approximately one in eight high-risk patients will experience a further atherothrombotic event over a 2-year period) of aspirin (acetylsalicylic acid) resistance and its possible background. The aim of this study was to compare the characteristics (risk profile, previous diseases, medications and haemorrheological variables) of patients in whom aspirin provided effective platelet inhibition with those in whom aspirin was not effective in providing platelet inhibition. 599 patients with chronic cardio- and cerebrovascular diseases (355 men, mean age 64 +/- 11 years; 244 women, mean age 63 +/- 10 years) taking aspirin 100-325 mg/day were included in the study. Blood was collected between 8:00am and 9:00am from these patients after an overnight fast. The cardiovascular risk profiles, history of previous diseases, medication history and haemorrheological parameters of patients who responded to aspirin and those who did not were compared. Platelet and red blood cell (RBC) aggregation were measured by aggregometry, haematocrit by a microhaematocrit centrifuge, and plasma fibrinogen by Clauss' method. Plasma and whole blood viscosities were measured using a capillary viscosimeter. Compared with aspirin-resistant patients, patients who demonstrated effective aspirin inhibition had a significantly lower plasma fibrinogen level (3.3 g/L vs 3.8 g/L; p < 0.05) and significantly lower RBC aggregation values (24.3 vs 28.2; p < 0.01). In addition, significantly more patients with effective aspirin inhibition were hypertensive (80% vs 62%; p < 0.05). Patients who had effective platelet aggregation were significantly more likely to be taking beta-adrenoceptor antagonists (75% vs 55%; p < 0.05) and ACE inhibitors (70% vs 50%; p < 0.05), whereas patients with ineffective platelet aggregation were significantly more likely to be taking HMG-CoA reductase inhibitors (statins) [52% vs 38%; p < 0.05]. Use of statins remained an independent predictor of aspirin resistance even after adjustment for risk factors and medication use (odds ratio 5.92; 95% CI 1.83, 16.9; p < 0.001). The mechanisms underlying aspirin resistance are multifactorial. Higher fibrinogen concentrations increase RBC aggregation and can also result in increased platelet aggregation. The higher rate of hypertension in patients with effective platelet aggregation on aspirin could explain the differences in beta-adrenoceptor antagonist and ACE inhibitor use between these patients and aspirin-resistant patients. Furthermore, an additive effect of these drugs may contribute to effective antiplatelet therapy. It is also possible that drug interactions with statins might reduce aspirin bioavailability and/or activity, thereby reducing platelet inhibition in aspirin-resistant patients.
    Drugs & Aging 02/2006; 23(7):559-67. · 2.50 Impact Factor
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    ABSTRACT: Rheological factors and increased platelet aggregation are convincingly implicated in the development of micro- and macrovascular disease associated with diabetes mellitus. The present examination has been designed to describe the effects of a standard oral glucose load on hemorheological parameters, platelet activation and aggregation in patients with normal and pathologic glucose tolerance. Oral glucose tolerance test (OGTT) was performed in 30 patients suspected to have diabetes mellitus. Hematocrit, erythrocyte aggregation, red blood cell filterability, plasma and whole blood viscosity, soluble P-selectin levels and platelet aggregation were tested paralelly with blood glucose measurements 1, 2, and 3 hours after glucose consumption. Patients were divided into two groups based on glucose tolerance. Patients with abnormal glucose tolerance (IGT/DM) showed significant elevation in red blood cell aggregability (Myrenne indices M and M1) at the 2- and 3-hour samplings (p<0.01 and p<0.001, respectively). Patients with normal glucose tolerance (NGT) showed significant elevation only in M1 index (p=0.01). Plasma viscosity decreased significantly compared to fasting values in IGT/DM patients in all samples, but remained unchanged in NGT patients. Hematocrit decreased in IGT/DM patients significantly from the 2-hour samplings on (p<0.05), in normoglycaemic patients its decrease reached a borderline significance at 3-hour measurements. No significant changes were detected in whole blood viscosity, red blood cell filterability and sP-selectin levels during OGTT in either examined groups. No examined parameters were significantly correlated to blood glucose levels at any sampling. Erythrocyte aggregation showed significant correlation with BMI (p<0.01). Our results demonstrate that after the intake of a standard amount of glucose the development of rheological alterations is not simultaneous with the elevation of blood glucose levels, and our data suggest that the observed elevation in erythrocyte aggregation during OGTT might be associated with hyperinsulinemia.
    Clinical hemorheology and microcirculation 01/2006; 35(4):517-25. · 3.40 Impact Factor
  • Atherosclerosis Supplements 01/2006; 7(3):356-356. · 4.33 Impact Factor
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    ABSTRACT: Blocking poly(ADP-ribosyl)ation of nuclear proteins protects the heart from ischemia-reperfusion injury. In addition, activation of Akt and mitogen-activated protein kinase (MAPK) cascades also plays a pivotal role in the survival of cardiomyocytes during ischemia-reperfusion; however, the potential interplay between these pathways is yet to be elucidated. We therefore tested the hypothesis whether poly(ADP-ribose) polymerase (PARP) inhibition can modulate Akt and MAPK signaling of ischemic-reperfused rat hearts. A novel PARP inhibitor, L-2286 [2-[(2-piperidin-1-yletil)thio]quinazolin-4(3H)-one] was administered during ischemia-reperfusion in Langendorff perfused rat hearts and in isoproterenol-induced myocardial infarction. Thereafter, the cardiac energy metabolism, oxidative damage, and the phosphorylation state of Akt and MAPK cascades were monitored. L-2286 exerted significant protective effect against ischemia-reperfusion-induced myocardial injury in both experimental models. More importantly, L-2286 facilitated the ischemia-reperfusion-induced activation of Akt, extracellular signal-regulated kinase, and p38-MAPK in both isolated hearts and in vivo cardiac injury. By contrast, isoproterenol-induced rapid c-Jun N-termainal kinase activation was repressed by L-2286. Here, we provide evidence for the first time that PARP inhibition beneficially modulates the cardiac Akt and MAPK signaling in ex vivo and in vivo ischemia-reperfusion models. We therefore propose that this novel mechanism may contribute to the cardioprotective properties of PARP inhibitors.
    Journal of Pharmacology and Experimental Therapeutics 11/2005; 315(1):273-82. · 3.89 Impact Factor
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    ABSTRACT: Platelet glycoprotein (GP) IIb/IIIa receptors play an inevitable role in platelet aggregation. The GP IIIa gene is polymorphic (PlA1/PlA2) and the presence of a PlA2 allele might be associated with an increased risk for acute coronary syndrome (ACS). To examine the prevalence of the PlA2 allele in patients with ACS and in subjects with or without aspirin resistance. The prevalence of the PlA2 allele was assessed in 158 patients with ACS and PlA2 compared with its prevalence in 199 healthy volunteers. The antiplatelet efficacy of aspirin was examined in all patients with ACS, as well as in 69 individuals who had suffered ischemic stroke and in 58 high-risk subjects without any known ischemic vascular events. PlA2 prevalence was significantly higher in patients with ACS (59/158) than in the control group (51/199; p < 0.05). Carriers of the PlA2 allele had a significantly higher risk of developing ACS, even after an adjustment to the risk factors (OR 5.74; 95% CI 1.75 to 18.8; p = 0.004). The occurrence of the PlA2 allele was significantly higher among patients with aspirin resistance than in subjects who demonstrated an appropriate response to the drug (allele frequencies, 0.21 vs 0.14; p < 0.05). All patients homozygous for the PlA2 allele had an inadequate platelet response to aspirin. Our results support the hypothesis that carriers of the PlA2 allele might have an increased risk for ACS. PlA2 homozygosity was associated with an inadequate response to aspirin therapy. Our data further suggest that patients with PlA2 allele homozygosity might benefit from antiplatelet therapy based on adenosine diphosphate antagonists throughout secondary treatment for prevention of ACS.
    Annals of Pharmacotherapy 06/2005; 39(6):1013-8. · 2.92 Impact Factor
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    ABSTRACT: Doxorubicin is a widely used anticancer agent, but its application is restricted by its cardiotoxic side effects. The current theory of its cardiotoxicity is based on free radical formation. The compound H-2545, having a 3-carboxamido-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole moiety, was reported to exhibit antioxidant properties and accumulate in cell membranes, scavenging free radicals at the site of formation. Therefore, we hypothesized that H-2545 could reduce the doxorubicin-induced acute deterioration of cardiac function. Langendorff-perfused rat hearts were treated with doxorubicin and/or H-2545, its metabolite H-2954, or dihydrolipoamide. High-energy phosphate levels, contractile function, lipid peroxidation, protein oxidation, and Akt phosphorylation were investigated. We also determined whether the antioxidants influenced doxorubicin toxicity on malignant cells. During perfusion with doxorubicin, the energetic and functional parameters of the myocardium were improved by adding H-2545. H-2545 significantly diminished doxorubicin-induced lipid and protein damage. On H-2545 treatment, the doxorubicin-triggered Akt phosphorylation was markedly reduced, whereas dihydrolipoamide had such an effect only at higher concentrations. H-2545 did not alter the anticancer effect of doxorubicin on malignant cell lines. We propose that the coadministration of the antioxidant H-2545 attenuates doxorubicin-induced acute cardiotoxicity without interfering with its anticancer effects. Prevention of the acute adverse effects of doxorubicin on myocardium may hinder the later development of cardiomyopathy.
    Journal of Cardiovascular Pharmacology 02/2005; 45(1):36-43. · 2.38 Impact Factor
  • International Journal of Cardiology 02/2005; 98(1):169-70. · 6.18 Impact Factor
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    ABSTRACT: von Willebrand factor is a blood glycoprotein that is required for normal hemostasis. Its level can be increased by endothelial cell damage. von Willebrand factor is a suitable marker of endothelial dysfunction. von Willebrand factor activity was determined by ELISA in patients with acute coronary syndromes, acute stroke and chronic vascular diseases, and was compared with the values of healthy controls. von Willebrand factor activity of patients in each group was significantly higher (P<0.001) than that of the control group. The values of patients with acute coronary syndrome and acute stroke were significantly higher (P<0.05 and P<0.01, respectively) than those of patients with chronic vascular diseases. von Willebrand factor activity was significantly higher in patients with acute coronary syndrome and acute stroke (P<0.05 and P<0.01, respectively) on the sixth day than on admission. By measuring von Willebrand factor activity, a considerable, significant difference could be found between healthy people and chronic and acute vascular patients. The routine measurement of von Willebrand factor activity in vascular patients as an index of endothelial dysfunction may have clinical importance, because detection of this marker can be a noninvasive way of assisting diagnosis and indicating disease progression.
    Experimental and clinical cardiology 01/2004; 9(1):31-4. · 1.10 Impact Factor
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    ABSTRACT: Cardioprotective effect of a free radical-scavenging compound (HO-3073) was examined during ischaemia-reperfusion (IR) in isolated heart perfusion system and its influence on the pro-survival Akt signalling pathway was addressed. Rat hearts were perfused according to the Langendorff method and subjected to a global 25-min ischaemia and 15, 45 and 90-min reperfusion either untreated or treated with HO-3073 (2, 5 and 10 microM) and/or wortmannin (100 nM, inhibitor of phosphatidylinositol-3-kinase). HO-3073 facilitated the recovery of myocardial energy metabolism as assessed by 31P NMR spectroscopy (creatine phosphate recovery in reperfusion was 76+/-5%, while in untreated hearts 32+/-4%). Functional performance of the hearts followed by a left ventricular balloon manometer was also markedly improved by HO-3073 administration (recovery of rate-pressure product related to normoxia was 47+/-3%, while in untreated hearts 12+/-3%). HO-3073 diminished the infarct size measured by TTC staining (29+/-6% as opposed to 64+/-7% in untreated ischaemia-reperfusion). HO-3073 also significantly attenuated lipid peroxidation (thiobarbituric acid reactive substances) and protein oxidation (protein carbonyl content) compared to untreated hearts. HO-3073 enhanced the ischaemia-reperfusion-triggered phosphorylation of Akt-1 (activation) and glycogen synthase kinase-3 beta (inactivation) as evidenced by Western blot analysis. Wortmannin co-administration neutralised the beneficial effects of HO-3073 on cardiac energetics, contractile function, infarct size, as well as Akt signalling. Our results first display that a radical-scavenging molecule possesses the ability to intensify the pro-survival functioning of phosphatidylinositol-3-kinase/Akt pathway, which is presumed to play an additive role in the cardioprotective properties of HO-3073.
    Biochemical Pharmacology 01/2004; 66(11):2263-72. · 4.58 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2004; 43(5).
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    ABSTRACT: 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.
    Clinical hemorheology and microcirculation 01/2003; 29(2):81-94. · 3.40 Impact Factor
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    ABSTRACT: 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. 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). 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. 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.
    Annals of Noninvasive Electrocardiology 11/2001; 6(4):310-8. · 1.08 Impact Factor
  • Journal of Nuclear Cardiology 01/2001; 8(6):716. · 2.85 Impact Factor
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    ABSTRACT: 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.
    Clinical hemorheology and microcirculation 01/1999; 21(3-4):209-16. · 3.40 Impact Factor
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    ABSTRACT: 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).
    Clinical hemorheology and microcirculation 01/1999; 20(1):57-61. · 3.40 Impact Factor
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    ABSTRACT: The effect of Ca-antagonist, long-acting verapamil and the selective beta-1 blocking bisoprolol were investigated and compared in the secondary prevention after myocardial infarction. Eighty-seven patients were enrolled, 27 patients were not included because of the exclusion criteria, 30 patients were treated with verapamil and 30 patients with bisoprolol. During the 540 days of follow up period treadmill ergometry and dobutamine stress-test with SPECT investigation were performed two times. Both clinically and the data of our investigations the effect of the two drugs in the secondary prevention was good, and even at the 540th day the protective effect was still excellent.
    Orvosi Hetilap 09/1997; 138(31):1939-45.
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    ABSTRACT: The peroxidative processes and individual antioxidant protection were measured in patients with different cardiovascular diseases. We concluded that monitoring of this system we were able to detect not only the actual changes of lipid peroxidation and antioxidant defence mechanisms, but additionally the therapeutic efficacy of the treatment.
    Acta chirurgica Hungarica 02/1997; 36(1-4):65-6.