Barbara Sandor

Effects of Moderate Aerobic Exercise Training on Hemorheological and Laboratory Parameters in Ischemic Heart Disease Patients

Background and Design In this study we set out to determine the effects of long-term physical training on hemorheological, laboratory parameters, exercise tolerability, psychological factors in cardiac patients participating in an ambulatory rehabilitation program. Methods Before physical training, patients were examined by echocardiography, tested on treadmill by the Bruce protocol, and blood was drawn for laboratory tests. The enrolled 79 ischemic heart disease patients joined a 24-week cardiac rehabilitation training program. Blood was drawn to measure hematocrit (Hct), plasma and whole blood viscosity (PV, WBV), red blood cell (RBC) aggregation and deformability. Hemorheological, clinical chemistry and psychological measurements were repeated 12 and 24 weeks later, and a treadmill test was performed at the end of the program. Results After 12 weeks Hct, PV, WBV and RBC aggregation were significantly decreased, RBC deformability exhibited a significant increase (p<0.05). Laboratory parameters (triglyceride, uric acid, hsCRP and fibrinogen) were significantly decreased (p<0.05). After 24 weeks the significant results were still observed. By the end of the study, IL-6 and TNF-α levels displayed decreasing trends (p<0.06). There was a significant improvement in MET (p<0.001), and the BMI decrease was also significant (p<0.05). The vital exhaustion parameters measured on the fatigue impact scale indicated a significant improvement in two areas of the daily activities (p<0.05). Conclusions Regular physical training improved the exercise tolerability of patients with ischemic heart disease. Previous publications have demonstrated that decreases in Hct and PV may reduce cardiovascular risk, while a decrease in RBC aggregation and an increase in deformability improve the capillary flow. Positive changes in laboratory parameters and body weight may indicate better oxidative and inflammatory circumstances and an improved metabolic state. The psychological findings point to an improvement in the quality of life.

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.

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.

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.

Effects of Poloxamer 188 on red blood cell membrane properties in sickle cell anaemia.

Vaso‐occlusive crisis (VOC) is the main acute complication in sickle cell anaemia (SS) and several clinical trials are investigating different drugs to improve the clinical severity of SS patients. A phase III study is currently exploring the profit of Velopoloxamer in SS during VOCs. We analysed, in‐vitro, the effect of poloxamer (P188) on red blood cell (RBC) properties by investigating haemorheology, mechanical and adhesion functions using ektacytometry, microfluidics and dynamic adhesion approaches, respectively. We show that poloxamer significantly reduces blood viscosity, RBC aggregation and adhesion to endothelial cells, supporting the beneficial use of this molecule in SS therapy.

Hemorheological parameters in coronary artery disease detected by multi-slice CT

Epidemiological studies have confirmed that hemorheological parameters are primary risk factors in CAD; and their alterations in CAD have been described. We aimed to investigate both macro- and microrheological properties of blood in patients with CAD. The data of 121 patients (mean age: 58.8 ± 9.6 years) undergoing coronary CT were analyzed. Blood samples were obtained right before CT examinations. Hematocrit (Hct), plasma (PV) and apparent whole blood viscosity (WBV), red blood cell (RBC) aggregation and RBC deformability were measured. Patients were classified into four groups according to their coronary vessel state: Negative group (n = 32, mean age: 56.8 ± 11.1 years) without any coronary stenosis or atherosclerotic lesion and zero calcium-score, Non-significant group (n = 27, mean age: 59.2 ± 7.5 years) below 40% area stenosis, Singlevessel group (n = 32, mean age: 58.8 ± 8.5 years) over 40% area stenosis or history of PCI or CABG on one coronary vessel, Multi-vessel group (n = 30, mean age: 62.1 ± 8.4 years) with over 40% area stenosis or history of PCI or CABG on multiple coronary vessels. Hct was significantly (p < 0.05) higher in all CAD (Non-significant, Single-vessel, Multi-vessel) groups compared to the Negative group. WBV was significantly (p<0.05) higher in the Multi-vessel group compared to the Negative group. No significant (p > 0.05) differences were observed in PV. RBC aggregation was significantly (p < 0.05) increased in the Multi-vessel group compared to the Negative group. RBC deformability showed a decreasing tendency with the increasing number of atherosclerotic vessels. Our results indicate that hemorheological variables are deteriorated in patients with CAD established by coronary CT, which is more pronounced in severe coronary disease.

Aspirin resistance as cardiovascular risk after kidney transplantation

International surveys have shown that the leading cause of death after kidney transplantation has cardiovascular origin with a prevalence of 35–40%. As a preventive strategy these patients receive aspirin (ASA) therapy, even though their rate of aspirin resistance is still unknown. In our study, platelet aggregation measurements were performed between 2009 and 2012 investigating the laboratory effect of low-dose aspirin (100 mg) treatment using a CARAT TX4 optical aggregometer. ASA therapy was considered clinically effective in case of low (i.e., below 40%) epinephrine-induced (10 μM) platelet aggregation index. Rate of aspirin resistance, morbidity and mortality data of kidney transplanted patients (n = 255, mean age: 49 ± 12 years) were compared to a patient population with cardio- and cerebrovascular diseases (n = 346, mean age: 52.6 ± 11 years). Rate of aspirin resistance was significantly higher in the renal transplantation group (RT) compared to the positive control group (PC) (35.9% vs. 25.6%, p < 0.002). Morbidity analysis demonstrated significantly higher incidence of myocardial infarction, hypertension and diabetes mellitus in the RT group (p < 0.05). The subgroup analysis revealed significantly higher incidence of infarction and stroke in the ASA resistant RT group compared to the RT patients without ASA resistance (p < 0.05). Furthermore, the incidence of myocardial infarction and hypertension was significantly higher in the non-resistant RT group than in the group of PC patients without ASA resistance (p < 0.05). These results may suggest that the elevated rate of aspirin resistance contributes to the high cardiovascular mortality after kidney transplantation.

Toe-brachial index and exercise test can improve the exploration of peripheral artery disease

BACKGROUND AND AIMS We assumed that hand-held Doppler ultrasound (DUS) at rest was insufficient to assess the severity of peripheral artery disease (PAD). Toe pressure and transcutaneous tissue oxygen pressure were studied to prove whether these could identify more patients with severe lower limb ischemia; exercise was applied to provoke ischemia. METHODS 120 patients with PAD and 30 volunteers without PAD were recruited. DUS, transcutaneous tissue oxygen pressure (tcpO2) and toe pressure measurements were performed at rest and after exercise. The differential power of these examinations for severe limb ischemia (SLI) was determined by receiver-operating curves (ROCs) and pattern recognition by independent multicategory analysis (PRIMA). RESULTS There was an obvious significant difference between the patient and control groups at rest; after exercise; the ratio of severely impaired values (ankle-brachial index - ABI, toe-brachial index - TBI, tcpO2 measured on index forefoot) increased significantly in the patient group (p < 0.05). TBI, tcpO2, ABI measured after exercise could differentiate SLI better than the values of these tests at rest (p < 0.001). In ROC analysis, the largest area under the curve (AUC) was covered by post- (AUC: 0.860) and pre-exercise TBI (AUC: 0.785), and post-exercise tcpO2 (AUC: 0.720) (p < 0.001). Post-exercise TBI gained the best discriminant score in PRIMA. CONCLUSIONS Pre- and post-exercise non-invasive vascular tests could reveal severe limb ischemia. Toe pressure measurement and TBI should become a basic part of the vascular workup.

Hemorheological alterations in carotid artery stenosis

BACKGROUND Carotid artery stenosis (CAS) is not only an important risk factor of cerebrovascular events but it can also indicate generalized atherosclerosis. Hemorheological parameters are altered in CAS and in chronic cerebrovascular disorders as well, but it is controversial if hemorheological parameters could be markers of stenosis or atherosclerosis. METHODS 107 patients were investigated, 40% of them had stroke or TIA in case history and 48% had CAS. Routine lab parameters were determined and hemorheological variables were measured: hematocrit, plasma viscosity, whole blood viscosity, red blood cell aggregation, and deformability. RESULTS In the stenotic group whole blood viscosity and red blood cell aggregation were deteriorated (p < 0.05). Whole blood and plasma viscosity were higher and red blood cell deformability was lower in the symptomatic group (p < 0.05). Plasma viscosity and red blood cell deformability were altered in the evolving atherosclerosis group and the CAS groups compared to patients having no signs of stenosis (p < 0.05), but there was no difference among the CAS groups. CONCLUSION Although hemorheological parameters are impaired both in CAS and chronic cerebrovascular disorders, the severity of stenosis cannot be detected based on hemorheological parameters. Our investigation suggests that alteration of hemorheological parameters could indicate carotid atherosclerosis.

Lower limb ischemia and microrheological alterations in patients with diabetic retinopathy

BACKGROUND Diabetes mellitus is frequently associated with vascular pathologies and hemorheological disorders. METHODS 105 patients with diabetic retinopathy (DRP) (mean age 64.64±9.01 years, 56 males, 49 females), 35 age-matched non-diabetic (mean age 61.65±7.6 years, 14 males and 21 females) and 42 young healthy volunteers (mean age 25.52±3.32 years, 22 males, 20 females) were recruited. Lower extremity artery disease (LEAD) and microcirculatory alterations were screened by hand-held Doppler, transcutaneous partial tissue oxygen tension (tcpO2), tuning fork test, 6-minute walk test, erythrocyte aggregation and deformability. RESULTS High prevalence of LEAD was detected in diabetic population: 55.3% fulfilled the criteria of LEAD based on ankle-brachial index; severely impaired tcpO2 was measured in 18.6%. The results of non-invasive measurements of the diabetic patients were significantly worse than those of the control groups (p < 0.05). Hemorheological disturbances could be characterized by the significantly higher erythrocyte aggregation (p < 0.05) and lower erythrocyte deformability (p < 0.05) in the diabetic population. CONCLUSION Macro- and microcirculatory lower limb disorders could be revealed at high prevalence in diabetic patients with retinopathy. Measurement of tcpO2 and hemorheological variables could be useful to discover patients at higher risk for diabetic foot complications.