Impact of moderately reduced renal function on the diagnostic and prognostic value of galectin-3 in patients with exertional dyspnea.

BACKGROUND: Blood concentration of galectin-3 (Gal-3) - a biomarker of fibrosis useful in diagnostics and prognostication in heart failure (HF) - is known to be elevated in patients with renal impairment, a condition which often accompanies cardiac insufficiency. OBJECTIVES: To investigate the effect of moderately reduced renal function (estimated glomerular filtration rate (eGFR) 30-60 mL/min/1.73 m2) on the diagnostic and prognostic utility of circulating Gal-3 in patients with HF with preserved ejection fraction (HFpEF). MATERIAL AND METHODS: Clinical, biochemical and echocardiographic variables were collected at baseline in 154 patients with HFpEF: 101 with normal and 53 with moderately reduced renal function, who were followed up for 48 (24-60) months for HF hospitalization and cardiovascular (CV) death (composite endpoint). RESULTS: Patients with moderately impaired renal function were characterized by higher age, Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, Gal-3, B-type natriuretic peptide (BNP) and New York Heart Association (NYHA) class, lower hemoglobin, and more advanced left ventricular diastolic dysfunction. Older age, female sex and deeper impairment of renal performance were determinants of higher Gal-3 blood concentrations. Lower exercise capacity (lower peak VO2) was associated with higher Gal-3 level and more pronounced renal impairment. Multivariable regression analysis demonstrated the significance of renal dysfunction as a determinant of lower exercise capacity and revealed a significant interaction between Gal-3 and eGFR with respect to peak VO2. The addition of Gal-3 to the prognostic models based on clinical data improved their predictive power for the study endpoint. The Kaplan-Meier analysis revealed that the presence of moderately reduced renal function with eGFR 30-60 mL/min/1.73 m2 did not enhance the increased risk of adverse outcome associated with Gal-3 above the median. CONCLUSIONS: In patients with HFpEF, the coexistence of moderate renal dysfunction does not deteriorate the prognostic usefulness of circulating Gal-3. However, renal impairment modifies the association between Gal-3 and exercise capacity, which supports the need to adjust for kidney function when interpreting the contribution of Gal-3 to exercise intolerance in this population.

Diurnal Variability of Platelet Aggregation in Patients with Myocardial Infarction Treated with Prasugrel and Ticagrelor.

BACKGROUND: Contemporary antiplatelet treatment in acute myocardial infarction (AMI) is based on one of two P2Y12 receptor inhibitors, prasugrel or ticagrelor. The aim of this study was to compare diurnal variability of platelet reactivity between patients receiving prasugrel and ticagrelor during the initial phase of maintenance treatment after AMI. METHODS: It was a prospective, two-center, pharmacodynamic, observational study. Blood for platelet testing was sampled at four time points on day four after AMI (8:00, 12:00, 16:00, 20:00). Diurnal variability of platelet reactivity was expressed as a coefficient of variation (CV) of the above-mentioned measurements. RESULTS: 73 invasively-treated patients were enrolled (ticagrelor: n = 47, prasugrel: n = 26). CV was greater in patients treated with ticagrelor compared with prasugrel according to a VASP assay (47.8 [31.6-64.6]% vs. 21.3 [12.9-25.5]%, p < 0.001), while no statistical differences were detected when the CVs of platelet aggregation according to Multiplate were compared between ticagrelor- and prasugrel-treated patients. Ticagrelor-treated patients showed more pronounced platelet inhibition than prasugrel at 16:00 and 20:00 (VASP16:00: 20.6 ± 15.0 vs. 24.9 ± 12.8 PRI, p = 0.049; VASP20:00: 18.6 ± 17.7 vs. 26.0 ± 11.7 PRI, p = 0.002). CONCLUSIONS: Ticagrelor shows greater diurnal variability in platelet aggregation than prasugrel during the initial maintenance phase of AMI treatment, and this is due to the continuous increase of platelet inhibition after the morning maintenance dose. Both drugs provide an adequate antiplatelet effect early after AMI. Evaluation of the clinical significance of these findings warrants further investigation.

Matrix Metalloproteinase-2 Inhibition in Acute Ischemia-Reperfusion Heart Injury-Cardioprotective Properties of Carvedilol.

Matrix metalloproteinase 2 (MMP-2) is activated in hearts upon ischemia-reperfusion (IR) injury and cleaves sarcomeric proteins. It was shown that carvedilol and nebivolol reduced the activity of different MMPs. Hence, we hypothesized that they could reduce MMPs activation in myocytes, and therefore, protect against cardiac contractile dysfunction related with IR injury. Isolated rat hearts were subjected to either control aerobic perfusion or IR injury: 25 min of aerobic perfusion, followed by 20 min global, no-flow ischemia, and reperfusion for 30 min. The effects of carvedilol, nebivolol, or metoprolol were evaluated in hearts subjected to IR injury. Cardiac mechanical function and MMP-2 activity in the heart homogenates and coronary effluent were assessed along with troponin I content in the former. Only carvedilol improved the recovery of mechanical function at the end of reperfusion compared to IR injury hearts. IR injury induced the activation and release of MMP-2 into the coronary effluent during reperfusion. MMP-2 activity in the coronary effluent increased in the IR injury group and this was prevented by carvedilol. Troponin I levels decreased by 73% in IR hearts and this was abolished by carvedilol. Conclusions: These data suggest that the cardioprotective effect of carvedilol in myocardial IR injury may be mediated by inhibiting MMP-2 activation.

Relationships between Circulating Matrix Metalloproteinases, Tissue Inhibitor TIMP-2, and Renal Function in Patients with Myocarditis.

INTRODUCTION: Under physiological conditions, the myocardial extracellular matrix (ECM) is maintained by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). However, changes in the balance between MMPs and TIMPs can lead to pathological remodeling of the ECM, which contributes to cardiovascular and kidney diseases. The aim of our study was to assess levels of MMPs and TIMP-2 in patients with myocarditis and their relationship to renal function. MATERIALS AND METHODS: Forty five patients with myocarditis who underwent CMR were included, comprising 11 with concurrent chronic kidney disease (CKD). Blood samples were obtained to assess serum levels of MMP-2, MMP-3, MMP-9, and TIMP-2. RESULTS: Serum MMP-2, MMP-3, and TIMP-2 levels negatively correlated with the ejection fraction in patients with myocarditis, while MMP-3 levels correlated with longitudinal deformation (p < 0.05). Serum MMP-2, MMP-3, and TIMP-2 levels also negatively correlated with renal function, as assessed by the estimated glomerular filtration rate (eGFR) (p < 0.05). Patients with myocarditis and concurrent CKD had higher levels of MMP-2 and TIMP-2 than those without kidney damage. CONCLUSIONS: (1) We demonstrated that MMP-2, MMP-3, and TIMP-2 concentrations were related to left-ventricular ejection fraction, and MMP-3 levels correlated with longitudinal deformation, indicating MMPs play an important role in the post-inflammatory remodeling of the myocardium. (2) A negative correlation between the eGFR and MMP-2, MMP-3, and TIMP-2 and a positive correlation between creatinine and MMP-3 levels indicate the role of MMPs and TIMP-2 in renal dysfunction.

The influence of acute coronary syndrome on levels of clopidogrel active metabolite and platelet inhibition in patients with and without CYP2C19*2(681 G>A), *3(636 G>A) and ABCB1(C3435C> T) gene polymorphisms.

INTRODUCTION: Although ticagrelor and prasugrel remain the standard antiplatelet treatments in acute coronary syndrome (ACS), numerous patients still present with indications for clopidogrel use. AIM: We aimed to assess the levels of clopidogrel active metabolite and to evaluate the effect of the drug on platelet inhibition in patients with ACS as compared with those with stable coronary disease. Patients were assessed for the presence of the most common genetic polymorphisms that reduce the absorption (ABCB1) and activation (CYP2C19*2 and CYP2C19*3) of clopidogrel to exclude the effect of genetic variability on drug concentrations and activity. MATERIAL AND METHODS: This single-center, open-label, prospective study included 199 patients hospitalized due to ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) in Killip class I-III, who underwent percutaneous coronary intervention. The control group included 22 patients with stable coronary artery disease. RESULTS: The mean (SD) levels of active clopidogrel were 17.1 (12.3) ng/ml in controls and 16.4 (12.0) ng/ml in the whole study group (p < 0.68). No differences were noted in clopidogrel levels between patients with STEMI and NSTEMI (mean (SD), 17.6 (2.3) ng/ml and 15.1 (11.5) ng/ml; p < 0.45) or between STEMI and NSTEMI groups and controls (p < 0.38 and p < 0.61, respectively). No effect of ABCB1 or CYP2C19 polymorphism was observed in the study subgroups. CONCLUSIONS: We concluded that ACS does not affect the levels of clopidogrel active metabolite or platelet inhibition in patients in Killip class I-III with or without CYP2C19 or ABCB1 gene polymorphisms.

Platelet Reactivity and Response to Aspirin and Clopidogrel in Patients with Platelet Count Disorders.

BACKGROUND: Platelet reactivity and response to antiplatelet drugs, acetylsalicylic acid (ASA) and clopidogrel, in patients with thrombocytopenia and thrombocythemia can have a potentially important effect on the outcome. The effectiveness and safety of antiplatelet drugs in such patients has not been well examined. Measuring the effect of ASA and clopidogrel on platelets could help guide the therapy. Nevertheless, platelet response to antiplatelet drugs is not routinely measured in platelet count disorders and relevant evidence is scarce. AIMS: The study aimed to measure platelet reactivity and response to ASA and clopidogrel in patients with platelet count disorders. MATERIALS AND METHODS: This was a cross-sectional study of consecutive patients hospitalized in cardiology and hematology departments in the years 2018-2019. The study included patients with thrombocytopenia (PLT < 150 G/L) and thrombocythemia (PLT > 450 G/L) on ASA or dual antiplatelet therapy (DAPT; ASA plus clopidogrel). Controls included patients on antiplatelet drugs with normal platelet count. Platelet reactivity was measured in whole blood (Multiplate aggregometer, Roche, Switzerland) using arachidonic acid (AA), adenosine-5'-diphosphate (ADP), and thrombin receptor agonist peptide-6 (TRAP) as agonists. Platelet aggregation was expressed in arbitrary units (AU). AA-induced aggregation was used as a measure of response to ASA with a cut-off above 30 AU showing high on-treatment platelet reactivity to ASA (HTPR-A). ADP-induced aggregation measured response to clopidogrel with a cut-off above 48 AU for high on-treatment platelet reactivity to clopidogrel (HTPR-C). TRAP-induced aggregation measured baseline platelet reactivity not affected by oral antiplatelet drugs. RESULTS: The study included 174 patients. There were 64 patients with thrombocytopenia, 30 patients with chronic thrombocythemia, and 80 controls. All patients were on 75 mg of ASA and 32% of them additionally on 75 mg of clopidogrel due to a history of recent coronary artery angioplasty. AA- and ADP-induced aggregation was comparable between thrombocytopenic patients and controls (median (IQR) 19 (7-28) vs. 23 (15-38) for AA AU and 32 (16-44) vs. 50 (32-71) for ADP AU, respectively), while it was significantly higher in thrombocythemic patients (median (IQR) 80 (79-118) for AA AU and 124 (89-139) for ADP AU). TRAP-induced aggregation showed significantly lowest aggregation in thrombocytopenic (median (IQR) 41 (34-60) for TRAP AU) and highest in thrombocythemic patients (median (IQR) 137 (120-180) for TRAP AU). HTPR-A was frequent in thrombocythemic patients in comparison with thrombocytopenic patients and controls (60% vs. 4% vs. 15%, respectively; p < 0.0002). HTPR-C was highly common in thrombocythemic patients and least common in thrombocytopenic ones in comparison with controls (80% vs. 8% vs. 40%, respectively; p < 0.001). CONCLUSION: Chronic thrombocytopenia does not significantly affect platelet reactivity and response to ASA and clopidogrel in comparison with controls. Thrombocytosis significantly increases platelet reactivity and attenuates response to both ASA and clopidogrel.

Platelet polyphosphate level is elevated in patients with chronic primary thrombocytopenia: A preliminary study.

BACKGROUND: Platelets are key players in hemostasis. These blood cells contain different types of granules. Recently, there has been a growing interest in the role of inorganic polyphosphate (polyP) structures stored in dense granules of platelets and secreted during platelet activation. OBJECTIVES: To measure platelet polyP levels in patients with thrombocytopenia and thrombocythemia, and to examine the relationship of this indicator with platelet aggregation. MATERIAL AND METHODS: The study included 36 patients with hematological disorders (26 with primary chronic thrombocytopenia and 10 with essential thrombocythemia (ET)) and 40 healthy subjects. Platelet reactivity was measured using whole blood impedance aggregometry. The polyP levels were isolated from lysed platelets, which were obtained from citrated platelet-rich plasma. The procedure included inactivating endogenous phosphatases, removing phosphate units derived from DNA and proteins, and finally hydrolyzing them into monophosphate units. A colorimetric assay using malachite green and ammonium molybdate was performed in order to quantify polyP levels. RESULTS: The polyP concentrations were significantly higher in the patients with thrombocytopenia than in the patients with thrombocythemia or the controls. The polyP level was not correlated with the level of aggregation. CONCLUSIONS: The higher polyP levels observed in the patients with low platelet counts may indicate the existence of a compensatory mechanism that prevents excessive bleeding in such patients. Our study provides evidence of an essential role of polyP in platelet function and the coagulation process.

Response to antiplatelet therapy in patients undergoing invasive treatment due to acute coronary syndrome complicated by cardiogenic shock.

INTRODUCTION: There are limited data on platelet reactivity and response to antiplatelet drugs in patients with cardiogenic shock. AIM: To assess platelet reactivity on dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor, a novel potent P2Y12 receptor inhibitor, in patients with cardiogenic shock in the course of acute coronary syndrome (ACS) who received invasive treatment. MATERIAL AND METHODS: We enrolled 12 consecutive patients with ACS complicated by cardiogenic shock. To assess response to antiplatelet therapy during cardiogenic shock, only patients with symptoms persisting for at least 3 days and who completed a 5-day follow-up were included in the study. Patients received a loading dose of ASA (300 mg) and ticagrelor (180 mg), followed by a maintenance dose (ASA, 1 × 75 mg; ticagrelor, 2 × 90 mg). Blood samples for platelet function tests were collected. Platelet aggregation was assessed with a Multiplate whole-blood impedance aggregometer. Arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor-activating peptide (TRAP) were used as aggregation agonists. RESULTS: Response to antiplatelet therapy assessed by aggregometry showed numerically higher on-ASA platelet reactivity on day one and statistically significant higher on-ticagrelor platelet reactivity on day one in comparison with following days. There were 2 patients with high on ASA platelet reactivity and 3 with high on ticagrelor platelet reactivity, but only on the day one. CONCLUSIONS: Some patients with cardiogenic shock in the course of ACS treated invasively show a lower response to ASA and ticagrelor only on the first day after invasive treatment, with a good response on subsequent days.

Plasma YKL-40 levels correlate with the severity of coronary atherosclerosis assessed with the SYNTAX score.

Introduction YKL­40 is a protein released locally by inflammatory cells. Thus, it may constitute a biomarker of inflammatory conditions, such as atherosclerosis. Objectives The aim of the study was to determine YKL­40 levels in patients with ischemic heart disease and to analyze the correlation of this biomarker with the severity of coronary atherosclerosis. Patients and methods The study included 158 patients: 52 with stable ischemic heart disease and 67 with acute coronary syndrome: ST­segment elevation myocardial infarction (STEMI; n = 47) or non-ST­segment elevation myocardial infarction (NSTEMI; n = 20). The control group included 39 individuals without abnormalities in coronary vessels. We evaluated plasma YKL­40 levels and their correlation with the severity of coronary atherosclerosis assessed with the SYNTAX score. Results Patients with myocardial infarction had higher plasma YKL­40 levels than those with stable ischemic disease (median [range], 235.3 [161.6-366.1] ng/ml vs 61.2 [53.1-83.1] ng/ml; P <0.001) or controls (median [range], 235.3 [161.6-366.1] ng/ml vs 55.7 [51.2-75.2] ng/ml; P <0.001). No differences were found in YKL­40 concentrations between STEMI and NSTEMI patients (median [range], 263 [150.3-363.7] ng/ml and 214.9 [163.4-367.6] ng/ml, respectively; P = 0.7). The SYNTAX score in patients with ischemic heart disease correlated positively with YKL­40 concentrations (R = 0.34; P <0.001). Conclusions YKL­40 can be considered a potential biomarker of coronary atherosclerosis severity.

Determinants of the beneficial effect of mineralocorticoid receptor antagonism on exercise capacity in heart failure with reduced ejection fraction.

BACKGROUND: The determinants of the impact of mineralocorticoid receptor antagonism (MRA) on exercise tolerance in heart failure with reduced ejection fraction (HFrEF) have not been sufficiently characterised. AIM: We sought to investigate the factors associated with improvement in exercise capacity following the introduction of spironolactone to therapy in HFrEF patients, as well as to assess the association between improvement in exercise capacity and changes in cardiac functional characteristics with treatment. METHODS: In 120 patients (age 62 ± 11 years) with stable chronic HFrEF, remaining on optimal pharmacotherapy, spironolactone 25 mg/d was added to treatment. Echocardiographic assessment, including myocardial deformation, and treadmill exercise tests were performed at baseline and at six-month follow-up. RESULTS: According to the functional improvement at follow-up, patients were stratified into two groups: with increase in exercise capacity > 20% (IMPRpos, n = 68) and < 20% (IMPRneg, n = 52) of the baseline value. The IMPRpos subset demonstrated significantly larger improvement in left ventricular systolic and diastolic functions at follow-up, as assessed by global longitudinal deformation (GLS), ejection fraction, and tissue e' velocity. Functional improvement > 20% was independently predicted by diabetes (odds ratio [OR] 5.62, p = 0.011), estimated glomerular filtration rate (OR 0.95, p = 0.008), and B-type natriuretic peptide (BNP) at baseline (OR 0.54, p = 0.027), and associated with increase in GLS at follow-up (OR 1.40, p = 0.019). CONCLUSIONS: In patients with HFrEF, improvement in exercise capacity in response to the addition of spironolactone to treatment is more evident in the presence of diabetes, decreased renal function and lower BNP, and improvement in GLS is a contributor to this beneficial effect of MRA.

Contributions of Nondiastolic Factors to Exercise Intolerance in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has a complex etiology. Factors responsible for development of impaired exercise tolerance and disease progression are incompletely defined. OBJECTIVES: The authors sought to define the contributions of contractile reserve, ventriculo-arterial coupling (VAC) reserve, and chronotropic response to the progression of HFpEF. METHODS: We performed echocardiography at rest and immediately post-cardiopulmonary exercise test in 207 patients (63 ± 8 years of age) with stage C heart failure (HF) (exertional dyspnea, New York Heart Association functional class II to III, exercise capacity <80% of normal, left ventricular ejection fraction >50%, and diastolic dysfunction) and 60 patients with stage B HF (normal exercise tolerance with left ventricular hypertrophy, and/or reduced global longitudinal strain, with diastolic dysfunction). RESULTS: Symptomatic patients were grouped as stage C1 (ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity [E/e'] <13 both at rest and exercise; n = 63), C2 (E/e' >13 only at exercise; n = 118), and C3 (E/e' >13 both at rest and exercise; n = 26) HF. Exercise capacity and cardiovascular functional reserve were less impaired in stage C1 than in stages C2 and C3. Chronotropic response was more disturbed in stage C3 than C1 and C2. Changes from rest to exercise in E/e' (-0.6 ± 1.7 vs. 3.7 ± 2.8; p < 0.0001), global longitudinal strain (2.9 ± 2.0 vs. 1.6 ± 2.8; p < 0.002), VAC (-0.21 ± 0.17 vs. -0.09 ± 0.15; p < 0.0001), and in VO2-HR gradient (0.30 ± 0.07 vs. 0.26 ± 0.11; p < 0.01) were significantly different in stages B and C. CONCLUSIONS: Normal E/e' response to exertion in symptomatic HFpEF is associated with less profound impairment of exercise capacity and is accompanied by derangements of contractile state and VAC. The transition from asymptomatic to overt HFpEF is linked to diastolic, systolic, and chronotropic deficits and an increasing degree of hemodynamic disturbances in stage C HF.

Cardiac arrest during percutaneous coronary intervention in a patient 'resistant' to clopidogrel - successful 50-minute mechanical chest compression.

We report a case of 72-year-old female patient with end-stage chronic kidney disease, undergoing percutaneous coronary intervention (PCI) that resulted in a cardiac arrest caused by a thrombus mediated flow limitation in the left coronary artery. With mechanical cardiopulmonary resuscitation (CPR) PCI of the left main artery was performed successfully during 50 min cardiac arrest. The patient was discharged from the hospital without compromising cardiac function and neurological deficits.

Anticoagulant and anti-platelet activity of polyphenolic-polysaccharide preparation isolated from the medicinal plant Erigeron canadensis L.

The polyphenolic-polysaccharide preparation from Erigeron canadensis L. was isolated by multi-step process, characterized by chromatographic and spectroscopic methods, and was subjected to anion-exchange chromatography. The whole preparation demonstrated in vivo anticoagulant activity, and the effect was neutralized by protamine sulfate. It had also anti-platelet activity, limited to the cyclooxygenase pathway, induced by arachidonic acid. The plant preparation was fractionated to receive the fraction of the highest anticoagulant activity - 7-9IU/mg of heparin standard, expressed in aPTT. The influences of the plant preparation as well as its the most active fraction on thrombin and factor Xa inactivation by antithrombin, and on thrombin inhibition by heparin cofactor II, were compared. The both tested plant preparations inhibited thrombin as well as factor Xa amidolytic activities in the presence of antithrombin, but much higher concentrations were required to obtain the same effects like for unfractionated heparin. The mechanisms of anticoagulant activity in the case of the plant preparation are based on interactions with heparin cofactor II, to inactivate thrombin. Chromatographic and spectroscopic methods revealed its macromolecular polyanionic non-sulfated polyphenolic-polysaccharide conjugate, with carboxylic groups. The polysaccharide part constituted 32% of the total mass and was homogenous, with molecular mass 38kDa, containing mainly hexuronic acids, and much smaller amounts of glucose, arabinose, galactose, as well as some traces of mannose, xylose and rhamnose. Polyphenolic part, with molecular mass >12.5kDa, was rich in hydroxylic rests as well as in carboxylic groups, free and esterified. The polyphenolic-polysaccharide preparation from E. canadensis may become a new source of anticoagulant compound potentially useful in anticoagulant and anti-platelet therapy.

Aspirin failure course during exercise and its connection with soluble CD40L.

INTRODUCTION: The aspirin failure (resistance) is a still discussed and highly studied problem. This phenomenon is observed in rest, but could be precipitated by an exercise. The aspirin resistance was also linked with the inflammatory process which is a key event for the atherosclerosis development. Platelets seem to play an important role also in that setting, probably by the CD40-CD40L axis. The aim of the study was to assess the frequency of the aspirin failure induced by the exercise and the role of sCD40L in that regard. MATERIALS AND METHODS: The study included 40 patients with established coronary artery disease. The control group consisted of 10 patients without coronary artery disease matched for age. All patients and controls were on 75 mg of aspirin for at least 30 days and had treadmill testing and blood collected for measurement of sCD40L and optical platelet aggregation with ADP, collagen and arachidonic acid. Aspirin resistance was defined as a maximal aggregation with ADP and collagen exceeding 70%. RESULTS: There were 15 aspirin-resistant patients in the studied group (37%). There were significantly higher concentration of sCD40L (ng/ml) in aspirin-resistant patients in comparison with aspirin-sensitive ones before testing (7,9 +/- 2,5 vs. 5,1 +/- 3,5, p < 0,05) and on the top of it (8,1 +/- 2,9 vs. 4,5 +/- 3,9, p < 0,05). There were 3 persons who become resistant on the top of the exercise which was connected with the significant increase of sCD40L concentration in that group (from 7,6 +/- 1,9 before exercise to 10,1 +/- 2,9 on the top of the exercise, p < 0,05). There was also a positive correlation between the sCD40L level before and on the top of the exercise in an aspirin-resistant group (r = 0,48 for both, p < 0,05). Patients who were aspirin-resistant at rest had also significant elevation of platelet aggregation on the top of the exercise (ADP (%) from 90,5 +/- 8,6 to 95,0 +/- 6,5, p < 0,05 and collagen (%) from 87,8 +/- 8,7 to 92,1 +/- 8,0, p < 0,05). CONCLUSIONS: 1. Aspirin resistance phenomenon is present in about 37% patients on 75 mg aspirin daily.2. Aspirin-resistant patients have higher platelet aggregation during the exercise.3. Moderate physical exercise provokes 12% increase in the aspirin resistance phenomenon occurrence.4. Aspirin resistance is connected with higher sCD40L level at rest and exercise provoked aspirin resistance is connected with the sCD40L concentration increase.

Platelet aggregation and P-selectin levels during exercise treadmill test in patients with ischaemic heart disease.

INTRODUCTION: Coronary artery disease (CAD) is associated with higher platelet activation sometimes despite aspirin use. There are conflicting data concerning platelet activation course during physical exercise in patients on aspirin with CAD. AIM: To assess platelet activation pattern during physical exercise in patients with CAD. METHODS: The study included 35 patients (20 men, 15 women) aged 64.7+/-10 years with CAD (CCS II) on aspirin treatment (75 mg daily) and a control group of 10 healthy subjects adjusted for age and gender. Treadmill testing was performed using the Bruce protocol. Platelet aggregation was measured with optical aggregation with the agonists ADP (10 microM), collagen (2 microg/ml) and arachidonic acid (0.5 mg/ml) before and at peak exercise; P-selectin platelet and soluble expression (basal and after stimulation with thrombin) was assessed with cytofluorometry before, at peak exercise and 1 hour after. RESULTS: There were no differences in collagen and ADP aggregation between patients and the control group. There was a significant increase of ADP aggregation at peak exercise in the control group (p <0.05). There was a positive correlation between platelet aggregation before exercise and at peak exercise with ADP (r=+0.86) and with collagen (r=+0.61). There was no difference in soluble P-selectin concentration between patients and the control group. Platelet P-selectin expression without stimulation with thrombin 1 hour after exercise was significantly higher in patients than in the control group (p <0.05). CONCLUSIONS: 1. Physical exercise does not intensify platelet aggregation in patients with CAD on 75 mg aspirin daily. 2. Despite taking aspirin, platelet activation measured with the expression of platelet P-selectin increases and there is further intensification during exercise testing. 3. The concentration of soluble P-selectin in patients with CAD does not reflect the expression of platelet P-selectin.

[Influence of amlodipine on serum level of some cytokines in patients with congestive heart failure]. / Wplyw amlodypiny na stezenie wybranych cytokin u chorych na przewlekla niewydolnosc krazenia.

Recent studies showed higher plasma levels of several cytokines, such as interleukines or tumour necrosis factor in patients with congestive heart failure. Cytokines play a very important role in pathogenesis of congestive heart failure, because they impair contractility of heart muscle and cause damage of endothelium and myocytes due to their proinflammatory effects. One of the treatment modalities of heart failure might be administration of drugs inhibiting production of cytokines. The study was undertaken to evaluate whether beneficial effects of amlodipine in congestive heart failure are due to inhibition of synthesis of cytokines. The plasma levels of interleukine 6 (IL-6), tumour necrosis factor (TNF-alpha), neuropeptide Y (NPY) and endothelin-1 (ET-1) were determined in patients with congestive heart failure (NYHA II and III) before and after 30 days of treatment with amlodipine. 40 patients with congestive heart failure (CHF) treated in the Department of Cardiology of Medical University in Wroclaw participated in this study. In all patients CHF developed in the course of ischaemic heart disease and coexisting hypertension. Patients were divided into 2 groups dependingly on the NYHA classification. The first group consisted of 24 patients in II NYHA class, the other one--of 16 patients in III NYHA class. At 8 am, on the second day after admission and before treatment with amlodipine blood samples were taken from examined patients to determine plasma levels of IL-6, TNF-alpha, NPY and ET-1. Then patients were administered amlodipine at the dose of 5-10 mg per day. The next blood samples were taken on 5th and 30th day of treatment. Plasma levels of TNF-alpha, IL-6, NPY and ET-1 were estimated with radioimmunoassay using Medgerix kits. Our findings showed that plasma levels of TNF-alpha, IL-6, NPY and ET-1 in patients with CHF are increased. 30-days treatment with amlodipine caused significant decrease of TNF-alpha and IL-6 levels, but did not influence the plasma levels of NPY and ET-1. Amlodipine causes improvement of circulatory efficiency assessed according to NYHA classification. Treatment with amlodipine may be an additional way of therapy in CHF.