Controlled reperfusion reduces hemorheological alterations in a porcine infrarenal aortic-clamping ischemia-reperfusion model.

INTRODUCTION: Restoration of blood flow after prolonged acute ischemia causes further injury to tissues. The role of increased oxidative stress is emphasized in the pathogenesis, and impairment of hemorheological factors may also hinder proper microcirculation. Controlled reperfusion at lowered pressure with diluted blood may help to decrease reperfusion injury. METHODS: Four-hour infrarenal aortic clamping was performed in 16 Yorkshire pigs. In 8 animals blood flow was restored subsequently (full reperfusion, FR), in the other 8 animals clamping was followed by an initial 30 minutes of controlled reperfusion (CR) at 60 mmHg pressure with a 1 : 1 ratio mixture of blood and reperfusion solution. Blood samples were taken before the intervention, at the end of ischemia, 15 minutes, 60 minutes, 1 day and 1 week after the start of reperfusion. Hemorheological parameters were measured. RESULTS: Hematocrit, plasma and whole blood viscosity decreased significantly during CR, these attenuated at 1 day. At 1 week whole blood and plasma viscosities were elevated in the FR group. Erythrocyte deformability did not change significantly at any measurements. Erythrocyte aggregation decreased during CR but not in FR, and was found elevated in both groups at 1 week. CONCLUSION: Our results suggest slightly improved hemorheological properties in case of controlled reperfusion compared to full reperfusion, which may help to reduce tissue damage.

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.

Antiplatelet effect of acetylsalicylic acid, metamizole and their combination - in vitro and in vivo comparisons.

BACKGROUND: Acetylsalicylic acid (ASA) plays an important role in the treatment and prevention of cardiovascular diseases. Metamizole (MET) is an analgesic and antipyretic medicine, it is not used as an antiplatelet drug. OBJECTIVES: We aimed to examine the antiplatelet effect of MET and the possible interactions between the drugs. METHODS: In our in vitro investigations different concentrations of ASA and MET solutions were added to blood. To examine the interactions MET and ASA were added together. In our in vivo crossover study intravenous MET, oral ASA or both drugs together were administered. Epinephrine and adenosine-diphosphate induced platelet aggregation was determined by optical aggregometry. RESULTS: Epinephrine-induced aggregation was completely inhibited in all ASA and MET concentrations in vitro. Lower, ineffective concentration of MET prevented the antiplatelet effect of ASA. The inhibition was completely restored when higher concentration of ASA was used or when ASA was added first. Our in vivo study showed that in the MET group rapid onset of inhibition was developed and there was no inhibition after one day. In the ASA group platelet aggregation decreased slowly but still had significant inhibitory effect after 72 hours. Combined therapy showed similar changes to the MET group. CONCLUSION: Antiplatelet effect of MET and ASA did not differ significantly in vitro. The observations may indicate a competitive interaction between the two drugs. The in vivo experiments showed that intravenously administered MET is an effective antiplatelet drug and can be considered as a therapeutic alternative, when ASA cannot be used in oral form.

Moderate red wine consumption improves hemorheological parameters in healthy volunteers.

Pieces of epidemiological evidence have supported that moderate red wine consumption reduces the risk of cardiovascular diseases (French-paradox). Our previous in vitro experiment has demonstrated favourable hemorheological effects of red wine, alcohol-free red wine extract and ethanol. Thirty-nine healthy, non-smoking male volunteers between 18-40 years were assigned into two groups: control group had drunk water, while red wine group had consumed 2 dl of red wine each day at dinner for 3 weeks. No alcohol had been drunk for one week prior to the study. Blood was obtained in the morning of the first and last day. Hematocrit (Hct), plasma (PV) and whole blood viscosity (WBV) (Hevimet 40 capillary viscometer), red blood cell (RBC) aggregation (Myrenne and LORCA aggregometer) and deformability (LORCA ektacytometer) were measured and Hct/WBV ratio was calculated to determine oxygen carrying capacity. Hct was adjusted to 40%. Hct and PV were not affected. WBV remained unchanged in controls, but it considerably decreased in the red wine group compared to the 3-week control group, while Hct/WBV ratio became significantly higher in the red wine group compared to the control (p < 0.05). RBC aggregation significantly decreased in the red wine group and became significantly lower compared to the 3-week controls (p < 0.05). Red wine significantly increased RBC deformability (p < 0.05) at high shear stress. Our results show that moderate red wine consumption has beneficial effects on hemorheological parameters which may contribute to the French-paradox.

Clinical importance of antiplatelet drugs in cardiovascular diseases.

Platelets play an important role both in normal hemostasis and in pathological thrombus formation. Several large-scale clinical studies have proved that the inhibition of platelet aggregation results in a significant decrease in mortality and morbidity of ischemic atherothrombotic events, thus antiplatelet therapy became a key pharmacological method in prevention and treatment of such cardiovascular, cerebrovascular and peripheral arterial diseases. The present paper aims to give a brief overview of the most important antiplatelet drugs, their mechanism of action and their recommended usage in cardiovascular diseases. We also discuss possible methods to monitor the effectiveness of therapy and possible causes of therapeutic failure.

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.

Relationship of adipokines and non-esterified fatty acid to the insulin resistance in non-diabetic individuals.

BACKGROUND: Altered secretion of adipokines and non-esterified fatty acid (NEFA) seems to play a pivotal role in the abdominal obesity-related insulin resistance (IR). AIM: To determine semi-quantitatively the impact of serum NEFA, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin, and resistin levels on IR measured by homeostasis model assessment (HOMA-IR). MATERIAL/SUBJECTS: Seventy-four Caucasian subjects forming 3 age-, and sex-matched groups were included into the study [Group 1 and 2: non-diabetic obese patients, no.= 25, body mass index (BMI): 28-39.9 kg/m(2), no.=25, BMI≥40 kg/m(2), respectively, and Group 3: 24 healthy, normal weight control subjects]. METHODS: Serum levels of NEFA and adipokines as well as other metabolic variables including HOMA-IR were measured. RESULTS: HOMA-IR was associated positively with BMI, waist circumference, serum NEFA, leptin, IL-6, and TNF-α levels, negatively with adiponectin, with no significant relation to resistin. In multiple regression analyses, of these factors leptin was a strong, IL-6 and adiponectin were weak independent predictors of HOMA-IR, while the others were not significant determinants of HOMA-IR. However, even together, they explained only 35-36% of variance of HOMAIR. CONCLUSIONS: Although IR has associations with many of the investigated parameters, of these, only serum level of leptin, and in lesser degree IL-6 and adiponectin are independent determinants of the severity of IR. Moreover, even together they explain only a minority of variance IR.

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.

In vitro hemorheological effects of red wine and alcohol-free red wine extract.

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.

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.

Sedimentation characteristics of leucocytes can predict bacteraemia in critical care patients.

BACKGROUND: Early detection of blood stream infection can be lifesaving, but the results of blood cultures are not usually available before 24 hours after blood sampling. An earlier indication would lead to the initiation of immediate and adequate antibiotic treatment with obvious advantages for the patient. OBJECTIVE: To evaluate the ability of leucocyte count, serum procalcitonin (PCT) concentration, erythrocyte sedimentation rate (ESR), and leucocyte antisedimentation rate (LAR) in predicting the blood culture results in critical care patients. METHODS: 39 consecutive patients with their first febrile episode were investigated prospectively. LAR was determined as the percentage of leucocytes crossing the midline of a blood column upward during one hour of gravity sedimentation. The relevance of the different variables was estimated by likelihood ratio tests and area under receiver operating characteristic curves (AUC). RESULTS: 23 patients had positive blood culture results and 16 negative. LAR was significantly higher in bacteraemic patients than in non-bacteraemic patients (p = 0.001), but leucocyte count, ESR and PCT level failed to show significant differences. Leucocyte count, PCT, and ESR yielded low discriminative values with the AUCs of 0.66, 0.64, and 0.52, respectively. LAR provided a likelihood ratio of 3.6 and an AUC of 0.80 (95% confidence interval, 0.64 to 0.95) (p = 0.002). CONCLUSIONS: The simple LAR test can predict blood culture results and support urgent treatment decisions in critical care patients in their first febrile episode.

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.

[Incidence and role of hypertension in the development and recurrence of acute myocardial infarct in a 5-year case load]. / Hypertonia gyakorisága és szerepe akut myocardialis infarctus kialakulásában és ismétlödésében osztályunk 5 éves beteganyagában.

Authors treated and checked 474 patients with acute myocardial infarction (AMI) during 5 years. The occurrence of hypertension was 37.15% of the total number of patients but this rate was 51.37% for women patients. Obesity, hyperlipidaemia and diabetes mellitus were the most frequent of the risk factors on the patients with hypertension. Asthma cardiale and acute arrhythmias were slightly more frequent early complications and cardial decompensation was a slightly more frequent late complication. The number of myocardial reinfarctions was the same both in the case of hypertensive and normotensive patients under the circumstances of parallel normalization and keeping the tension and serum cholesterol on the normal level.

Photographic recording of slit-lamp appearances of the ocular fundus.

The four methods of illumination in the use of slit-lamp biomicroscopy of the anterior segment, described first by Vogt, are equally useful in the posterior part of the eye. Examination of the ocular fundus is more difficult. In particular, photography of the central and peripheral parts of the fundus demands additional technical arrangements if all the appearances of biomicroscopy are to be recorded.

[Vasoproliferative intermediary uveitis (author's transl)]. / Vasoproliferative intermediäre Uveitis.

Dust-like opacities of the vitreous body are the main feature of all types of intermediary uveitis. In addition recurrent vitreous hemorrhages occasionally occur. They mark the vasoproliferative form of the inflammation and originate from different regions of the posterior segment of the eye; their distribution sometimes enables conclusions to be drawn concerning the site of the vasoproliferation.

Clinical studies on the mucolytic effect of mesna.

Eighty intensive care patients requiring mucolytic therapy because of pulmonary mucus retention after chest (28 cases) or thoracic (52 cases) surgery were given the drug mesna by three different methods: bronchial lavage with a mixture of mesna (5% to 10%) and lidocaine (1%) in 15 to 20 ml, 10 to 20 times a day (10 cases); instillation into the bronchial tree of 15 to 20 ml of a 5% to 10% mesna solution three to five times a day (20 cases); continuous aerosolization of four to five ampules of mesna per 24 hours with a Bennett nebulizer (50 cases). The duration of mesna therapy ranged from 2 to 21 days. The drug was found to be highly effective in all three methods; rapid fluidization of bronchial secretions was observed and aspiration of the latter was considerably facilitated. Tolerance was excellent and there were no side effects, even in cases with bronchial asthma. A particularly good effect was seen on blood-contaminated mucus. Samples of aspirated mucus were investigated by the electron spin resonance (ESR) technique to obtain structural information about the effects of mesna as compared with N-acetylcysteine. Mucolytics decrease with ESR signal, and the rate of reduction is supposed to measure the rupture of disulphide bridges and, consequently, the degree of mucus fluidization. The rate of decrease of the ESR signals is much higher after mesna.

[Circumscribed peripheral (equatorial or pre-equatorial) retinoschisis (author's transl)]. / Herdförmige periphere (äquatoriale oder prääquatoriale) Retinoschisis.

Circumscribed areas of retinoschisis along or anterior to the Equator occur mainly in elderly subjects. Diagnosis is based on biomicroscopic criteria.

[Is a microscope essential in cataract surgery? (author's transl)]. / Kataraktoperation--mit oder ohne Mikroskop?

For many ophthalmic surgical procedures a well-equipped operating microscope is indispensable. However, it is not necessary to use the microscope routinely in the removal of normal senile cataracts. While there are advantages, particularly as regards accurate suture placement, there are also disadvantages.