Gray matter volume in relation to cardio-vascular stiffness.

BACKGROUND: Hemodynamic disturbances are associated with aging as well as the chronic process of left ventricular and arterial stiffening. This process can influence gray matter volume and thereby contribute to brain atrophy. We performed a comprehensive assessment of left ventricular and arterial function as well as central hemodynamics. These data were correlated with gray matter volume (GMV) as evaluated by magnetic resonance imaging (MRI). METHODS: GMV and aortic stiffness were estimated using MRI. Left ventricular end-systolic elastance or stiffness (Ees), arterial elastance (Ea) and total arterial compliance (TAC) were determined by echocardiography. Central hemodynamics were assessed using pulse wave analysis. RESULTS: Seventy-five healthy subjects (42 women, 33 men, mean age of 58 years) were recruited. The clinical analyses showed that GMV correlates significantly and inversely with age (r=-0.37, P=0.001), end-systolic LV stiffness (r=-0.39, P=0.0009), augmentation pressure (r=-0.48, P<0.0001), arterial elastance (r=-0.27, P=0.02) and aortic stiffness (r=-0.23, P=0.04), as determined by aortic pulse wave velocity (aPWV). GMV correlated significantly with total arterial compliance (r=0.23, P=0.04). Stepwise forward multiple regression analysis revealed that 35% of variance (P<0.0001) in GMV is attributed to aPWV, Ees and AP. CONCLUSIONS: Left ventricular end-systolic stiffness, augmentation of central arterial pressure and aortic stiffness are associated independently and negatively with GMV. These associations suggested that brain atrophy is influenced by hemodynamic factors.

Selenium reverses Pteridium aquilinum-induced immunotoxic effects.

We have previously shown that bracken fern (Pteridium aquilinum) has immunomodulatory effects on mouse natural killer (NK) cells by reducing cytotoxicity. Alternatively, it has been demonstrated that selenium can enhance NK cell activity. Therefore, the aims of the present study were to evaluate if ptaquiloside, the main toxic component found in P. aquilinum, is responsible for the immunotoxic effects observed in mice, and if selenium supplementation could prevent or even reverse these effects. Male C57BL/6 mice were administered the P. aquilinum extract by daily gavage for 30 days, and histological analyses revealed a significant reduction in splenic white pulp area that was fully reversed by selenium treatment. In addition, mice administered ptaquiloside by daily gavage for 14 days demonstrated the same reduction of NK cell activity as the P. aquilinum extract, and this reduction was prevented by selenium co-administration. Lastly, non-adherent splenic cells treated in vitro with an RPMI extract of P. aquilinum also showed diminished NK cell activity that was not only prevented by selenium co-treatment but also fully reversed by selenium post-treatment. The results of this study clearly show that the immunosuppressive effects of P. aquilinum are induced by ptaquiloside and that selenium supplementation can prevent as well as reverse these effects.

Arterial stiffness in relation to subclinical atherosclerosis.

BACKGROUND: Increased arterial stiffness or arteriosclerosis, represents a physiological part of ageing. Atherosclerosis is a process that does not affect the arterial bed uniformly but has a variable local distribution and is frequently superimposed on stiffened vessels. We therefore addressed the question of whether any correlation exists between the general characteristics of arterial stiffness or wave reflection and subclinical atherosclerosis as assessed by carotid intima-media thickness (IMT) in a sample of healthy subjects. METHODS: A total of 116 healthy subjects (mean age 55 years, 43 female) were evaluated. Arterial stiffness and wave reflection was assessed with the use of digital volume pulse analysis (DVP) and pulse wave analysis (PWA). Subclinical atherosclerosis was assessed by measurement of IMT. RESULTS: Stiffness Index (SI(DVP)), the measure of general arterial stiffness correlated significantly with IMT (r = 0.37, P < 0.01). IMT correlated significantly with age (r = 0.5, P < 0.0001), waist to hip ratio (WHR) (r = 0.39, P < 0.0001) and mean blood pressure (BPmean) (r = 0.4, P < 0.0001). IMT did not correlate with measures of wave reflection. SI(DVP) correlated significantly with age (r = 0.32, P < 0.005), WHR (r = 0.36, P < 0.0001), BPmean (r = 0.36, P < 0.0001) and measurements of wave reflection. However analysis of a model which included variables that significantly influenced SI(DVP) and IMT, such as age, WHR and mean BP showed that arterial stiffness is not independently associated with subclinical atherosclerosis. CONCLUSIONS: The indices of subclinical atherosclerosis, arterial stiffness and wave reflection, indicate different aspects of vascular status in otherwise healthy subjects.

Cardiovascular complications associated with biological therapies for breast cancer.

BACKGROUND: With increasing number of breast cancer survivors, treatment-associated toxicities are gaining importance because they may decrease quality of life and shorten expected survival. Biological treatment strategies are less toxic than conventional chemotherapy. However, practically all biological therapies for breast cancer induce cardiovascular complications. In the case of targeted therapies mechanisms of cardiotoxicity and strategies to manage cardiovascular disorders have not been completely defined. METHODS: Articles were found by searching PubMed and abstract databases of several oncological meetings. This review summarizes the risks and mechanisms of cardiovascular complications associated with biological agents used in treatment of breast cancer. RESULTS/CONCLUSION: Introduction of biological therapies has resulted in reduction of morbidity and mortality of breast cancer patients in recent years. However, all biological strategies bring a risk of cardiotoxicity and despite progress in the knowledge and management of cardiovascular complications there are still many unaswered questions.

Myocardial perfusion SPECT with dipyridamole stress test in cardiac syndrome X.

UNLABELLED: Cardiac syndrome X defines patients with typical anginal chest pain, a positive exercise ECG stress test and angiographically normal coronary arteries. AIM of this study was to evaluate the role of myocardial perfusion SPECT with dipyridamole stress in the diagnosis of cardiac syndrome X. PATIENTS, METHODS: 68 patients with syndrome X aged 32 to 60 years were subjected to myocardial imaging using (99m)Tc-MIBI according to the two-days protocol: at rest and after dipyridamole infusion. Semiquantitative evaluation of the images was based on the assessment of (99m)Tc-MIBI uptake in 17 myocardial segments using a 5-points scale (0 point -- normal uptake, 4 points -- no uptake). Scores obtained in each segment were summed up, constituting the summed rest score (SRS) and summed stress score (SSS). RESULTS: Mean SRS was 7.9 +/- 4.8 and mean SSS was 7.2 +/- 4.4 (non-significant difference). Individual comparison of SRS and SSS values revealed three patterns of scintigraphic images: 1) in 25 patients (36.8%), a paradoxical improvement of perfusion at stress images was found, 2) in 23 patients (33.8%), the myocardial perfusion deteriorated after dipyridamole, 3) in 20 patients (29.4%), no significant change of the myocardial perfusion between rest and stress images occurred. CONCLUSIONS: In cardiac syndrome X, myocardial SPECT with dipyridamole stress shows different patterns of myocardial perfusion that reflects heterogeneity of this pathology.

The influence of growth hormone (GH) therapy on cardiac performance in patients with childhood onset GH deficiency.

OBJECTIVE: There is accumulating evidence that growth hormone (GH) plays an important role in the maintenance of normal cardiac growth and function. Abnormalities in left ventricular diastolic function and impairment of systolic function have also been reported in patients with GHD. In this study, we investigated the effects of 12 months GH replacement therapy on cardiac functional indices measured by echocardiography, the ECG stress test and SPECT imaging. DESIGN: Sixteen patients with childhood onset GHD (age 42.3+/-13.1 years, 10 males) were investigated before, and after, 12 months of GH treatment at a dosage of 0.02 IU/kg/day (7 microg/kg/day). The GH administration resulted in serum IGF-I levels within the normal range in all the patients. The following investigations were performed initially and after 12 months: electrocardiography, systolic and diastolic blood pressure, heart rate measurement, a complete Doppler-echocardiographic examination, treadmill exercise test and Technetium-99m sestamibi single-photon emission computer tomography (SPECT) imaging at rest and after exercise. RESULTS: Echocardiography showed improvement in left ventricular systolic function after GH treatment. End-systolic volume fell from 29.9+/-12.4 to 24.4+/-6.9 ml (p<0.05) and the ejection fraction increased from 56.2+/-7.2% to 63.2+/-6,1% (p<0.01). Left ventricular diameter and wall thickness did not change after GH treatment, although systolic increase in interventricular septum thickness (IVS%) and systolic increase in posterior wall thickness (PWT%) increased significantly (IVS% 52.2+/-31.9% vs. 67.3+/-30.4% and PWT% 48.7+/-20.2% vs. 58.0+/-17.7%, p<0.01, p<0.01, respectively). Contractile function, measured at midwall level, improved as left ventricular midwall fractional shortening (MWS) increased (16.11+/-6.55 vs. 23.30+/-5.89 %, p<0.01) and stress-corrected MWS increased between the examinations performed before and after 12 months of GH treatment (90.97+/-36.66 vs. 133.10+/-32.84 %, p<0.01). Diastolic function did not change, as assessed by early diastolic flow (E), diastolic flow secondary to atrial contraction (A), or the E/A ratio. The LV-mass index did not change significantly after GH treatment (78.4+/-22.1 vs. 81.9+/-21.1g/m(2)). After 12 months of GH treatment the myocardial performance index (MPI) decreased significantly from 0.483+/-0.146 at baseline to 0.410+/-0.086 at the end of the study (p<0.05). There was a trend towards an increase in exercise duration and capacity after GH treatment but the differences did not reach levels of statistical significance. SPECT imaging basally and after 12 months showed normal myocardial perfusion at rest and after exercise in all the patients. In conclusion, GH replacement therapy in adults with GHD demonstrated the beneficial effects on cardiac functions.

Augmentation index, pulse pressure amplification and superoxide anion production in patients with coronary artery disease.

BACKGROUND: Free oxygen radicals appear to be involved in several processes that contribute to atherogenesis and increased arterial stiffness. METHODS: The aim of our study was to evaluate arterial stiffness and the production of superoxide anions by activated polymorphonuclear neutrophils (PMN) obtained from patients with stable coronary artery disease (CAD). Thirty four consecutive patients were studied (21 men, 13 women, mean age 58 years) who underwent coronary angiography. Arterial stiffness was assessed by pulse wave analysis using a validated system (Sphygmocor Mx, AtCor Medical). Superoxide anion production by activated neutrophils was determined by a spectrophotometric method involving the measurement of cytochrome C reduction. The extent of coronary narrowing was estimated by calculation of the Gensini score. RESULTS: Superoxide anion production by stimulated PMN showed a significant positive correlation with the augmentation index (AIx) and a significant negative correlation with pulse pressure amplification (PPA), (r=0.4, p=0.02; r=-0.5 and p=0.0026 respectively). In multivariable analyses, after adjustment for age, gender and Gensini score, superoxide anions and BMI were significant predictors of AIx (R2=57.37%, p=0.001) and PPA (R2=49.04%, p=0.008). Superoxide anion production was significantly higher in the middle (52.0+/-5.8 nmol O2-/2.5x10(6) PMN/30 min) and upper teriles (62.7+/-5.6) of AIx in comparison with the first tertile 31.8+/-4.1 (p< or =0.05, p< or =0.001). Moreover, superoxide anion production in the highest tertile of PPA was significantly lower (35.6+/-4.3 nmol O2-/2.5x10(6) PMN/30 min) than that in the tertile (60.8+/-6.2, p< or =0.05). Neither the augmentation index nor pulse pressure amplification correlate with the severity of coronary atherosclerosis as indicated by the Gensini score. CONCLUSIONS: markers of arterial stiffness, AIx and pulse pressure amplification correlate with superoxide anion production but not with the severity of atherosclerosis in coronary arteries.

Dipyridamole inhibits hydroxylamine augmented nitric oxide (NO) production by activated polymorphonuclear neutrophils through an adenosine-independent mechanism.

Polymorphonuclear neutrophils (PMN) are thought to play a role in reperfusion injury and ischemia. These effects are partly mediated by toxic oxygen species (superoxide anion, hydrogen peroxide and hydroxyl radical) acting at the level of the endothelium. It was demonstrated recently that the superoxide anion reacts with nitric oxide (NO) and that interaction leads to the generation of highly toxic peroxynitrite. Several drugs were tested so far in order to affect PMN function. It was demonstrated that dipyridamole (2,6-bis-diethanolamino-4,8-dipiperidinopyrimido-(5,4-d)-pyrimidine) can influence neutrophil function by inhibiting adenosine uptake. However, this action can not fully explain all of the observed effects of dipyridamole action on PMN metabolism. The aim of our study was to evaluate the influence of dipyridamole on nitric oxide production by activated polymorphonuclear neutrophils. Incubation of PMNs with hydroxylamine (HA) and phorbol myristate acetate (PMA) generated nitrite (36.4+/-4.2 nmol/h 2x10(6) PMN), dipyridamole at 100 micromol/l, 50 micromol/l and 10 micromol/l caused a considerable drop in nitrite production (11.8+/-1.8, 19.7+/-2.7 and 27.4+/-3.2 nmol/h, respectively). Neither adenosine nor the adenosine analogue could mimic the dipyridamole effect. Moreover theophylline, an adenosine inhibitor could not reverse the dipirydamole action on PMN metabolism. We also found that dipyridamole inhibited hydrogen peroxide release from neutrophils. Catalase that scavenges hydrogen peroxide also largely abolished nitric oxide release from PMN. It is evident that dipyridamole inhibits hydroxylamine-augmented nitric oxide production by activated polymorphonuclear neutrophils through an adenosine-independent mechanism.

Prospective evaluation of hydroperoxide plasma levels and stable nitric oxide end products in patients subjected to angioplasty for coronary artery disease.

BACKGROUND: Oxidative stress appears to be involved in several processes that contribute to atherogenesis and restenosis following vascular intervention. METHODS: The aim of our study was to evaluate prospectively the plasma concentrations of a hydroperoxide (ROOH) and nitric oxide end product (NO(x)) in patients subjected to coronary angioplasty (PTCA) and routine control angiography 6 months after the initial procedure. We prospectively studied 48 consecutive patients (39 men, nine women, mean age 52 years) with stable angina who underwent successful elective angioplasty. A vascular segment was considered successfully treated when the residual luminal narrowing in the dilated segment immediately after angioplasty was <50%. Angiographic follow-up was obtained in all of the patients. Plasma samples were drawn at baseline (before angioplasty) and serially after angioplasty (1, 3 and 6 months afterwards). Hydroperoxides were determined by the FOX II assay (ferrous oxidation in xylenol orange, Pierce Rockford, IL). Nitrate was converted in the presence of NO3 reductase. The Griess reagent was used for the measurement of NO2. RESULTS: The overall angiographic restenosis rate was 35%. There were no significant differences in clinical variables between the patients with or without restenosis. The baseline levels (0.8+/-0.09 vs. 0.6+/-0.2 micromol/l) as well as the concentrations of authentic lipid hydroperoxide in plasma after 1 month (0.7+/-0.09 vs. 1.0+/-0.2 micromol/l) and 6 months (0.8+/-0.1 vs. 1.0+/-0.2 micromol/l) were similar in both groups. Three months after the angioplasty a significant increase in the ROOH level was noticed in the patients with restenosis (0.9+/-0.1 vs. 1.4+/-0.2, P=0.04). Plasma levels of NO(x) were similar in both groups at baseline (23.6+/-2.1 vs. 22.7+/-2.6 micromol/l) and 1 month after procedure (24.4+/-2.2 vs. 23.4+/-3.3 micromol/l). However, in patients with restenosis significant decreases in stable NO end products were observed 3 and 6 months after PTCA (18.1+/-1.5 vs. 13.3+/-1.7, P=0.04; 14.2+/-1.0 vs. 8.7+/-1.3, P=0.02, respectively). CONCLUSIONS: In patients with angiographic restenosis a significant increase in lipid peroxidation accompanied by a reduction in the stable end products of nitric oxide in plasma is observed several months after PTCA.

Effects of magnetic resonance imaging on polymorphonuclear neutrophil adhesion.

BACKGROUND: Limited research has been performed concerning the effects of MR imaging on the immune system. In this study the influence of MR imaging exposure on polymorphonuclear neutrophil (PMN) adhesion was evaluated. MATERIAL AND METHODS: In vivo and in vitro studies were performed in 10 patients undergoing an MR imaging procedure, PMN adhesion to a plastic surface, as well as the expression of adhesion molecules beta 2-integrins CD11b, CD18, and L-selectin on the surface of PMN were estimated. RESULTS: Exposure to MR imaging significantly increased adhesion of isolated PMNs to plastic surfaces. PMNs from blood samples obtained from patients undergoing MR imaging as well as from blood samples placed beside patients during MR imaging did not differ from controls in adhesion to plastic surfaces. Similarly, plasma from three tested samples did not change control PMN adhesion to plastic surface. Expression of beta 2-integrins (CD11, CD18) was significantly increased in samples left beside patients during MR imaging, while significantly decreased in samples obtained from patients after MR imaging exposure when compared to control samples. Expression of the surface adhesion molecule L-selectin on the surface of PMN decreased significantly in blood samples left beside patients during MR imaging. CONCLUSION: The results indicate that the PMN adhesion properties increase under the influence of MR imaging exposure. This phenomenon may be the result of direct stimulation of polymorphonuclear neutrophils by the exposure to MR imaging.

Hydrogen peroxide and superoxide anion production by polymorphonuclear neutrophils in patients with chronic periapical granuloma, before and after surgical treatment.

Chronic periapical granuloma represents a localized tissue injury with well established signs of systemic immunological reactions. The aim of the study was to investigate changes in superoxide anion and hydrogen peroxide production by polymorphonuclear neutrophils (PMN) in patients with chronic periapical granuloma before and after surgical treatment. The affected teeth were extracted from 20 patients with chronic periapical lesions. Blood samples were obtained at admission, before extraction and on day 14. PMNs were isolated from blood samples and superoxide anion (O2-) and hydrogen peroxide (H2O2) production were estimated without stimulation and after stimulation of the cells with opsonized zymosan. Similar procedures were performed with blood samples obtained from 20 healthy controls. Superoxide anions as well as hydrogen peroxide production by unstimulated cells obtained from patients before treatment were significantly higher in comparison with controls. Fourteen days after extraction O2- production by unstimulated cells was higher than the controls and significantly lower in comparison to PMNs obtained before treatment, while H2O2 production was not significantly higher when compared to controls and significantly lower in comparison with PMNs obtained before extraction. The results obtained strongly imply the termination of a generalized inflammatory response after elimination of local inflammation by tooth extraction.

The influence of short-term treatment with simvastatin on the inflammatory profile of patients with hypercholesterolaemia.

BACKGROUND: Treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors can reduce cardiovascular mortality of patients with atherosclerosis. This effect is probably due not only to a decrease in concentration of cholesterol, but also to non-lipid-involving mechanisms elicited by the action of statin drugs. OBJECTIVE: To investigate the influence of short-term therapy with simvastatin on markers of inflammation and oxidation processes in patients with hypercholesterolaemia. DESIGN: We administered 20mg simvastatin daily for 12 weeks to 19 patients with hypercholesterolaemia (250-400 mg/dl). Peripheral blood samples for evaluation of plasma concentrations of thiobarbituric acid reactive substances (malonaldehyde), stable metabolites of nitric oxide (NOx) and interleukin 6 (11-6) were taken before and after the therapy. RESULTS: Plasma levels of malonaldehyde decreased significantly (from 4.533+/-0.428 versus 3.690+/-0.310 micromol/l, P = 0.04) during the study period. Similarly, there was a significant decrease in the plasma concentrations of NOx (from 33.477+/-4.352 micromol/l versus 25.919+/-2.561 micromol/l, P = 0.02). There were significant positive correlations between concentrations of total cholesterol and NOx in plasma (r = 0.4397, P = 0.008) and of low-density lipoprotein and NOx (r = 0.3987, P = 0.02). The plasma level of interleukin 6 remained unchanged by the intervention (1.837+/-0.200 versus 1.820+/-0.169 pg/ml, P = 0.54). CONCLUSIONS: Short-term therapy with simvastatin decreases the plasma concentrations of markers of peroxidation of lipids and of stable metabolites of nitric oxide in hypercholesterolaemic patients, but leaves levels of interleukin 6 unaffected.

Stimulation of neutrophil activation during coronary artery bypass grafting: comparison of crystalloid and blood cardioplegia.

BACKGROUND: During myocardial ischemia, activation of polymorphonuclear neutrophils (PMNs) results in the production of free oxygen radicals, which increase myocardial injury. It has been shown that PMNs also produce nitric oxide. It is not clear whether PMNs become activated as a result of their direct contact with ischemic/reperfused myocardium or if PMN activation and free oxygen radical production are effects of specific stimuli released during coronary artery bypass grafting (CABG). The aim of the current study was to evaluate plasma-mediated neutrophil stimulation and production of superoxide anion (O2) and nitric oxide in patients undergoing CABG, and to verify whether crystalloid and blood cardioplegia can modify such stimulation. METHODS: Coronary sinus, peripheral arterial, and venous plasma samples were collected from 50 patients who underwent CABG and were divided into 2 equal groups which received either crystalloid or blood cardioplegia: directly before myocardial ischemia and aortic cross-clamping; at the beginning of reperfusion after aortic clamp release; and 30 minutes after reperfusion. O2 and nitric oxide production by PMN was evaluated by standard methods. RESULTS: There was a significant (p < 0.05) increase in O2 production by PMN incubated with plasma obtained from the coronary sinus immediately after reperfusion in patients receiving crystalloid cardioplegia compared to blood cardioplegia. No difference was observed in plasma stimulation of nitric oxide production by PMN in the 2 groups of patients at different times during the procedure. CONCLUSIONS: Cardioplegia may affect release of neutrophil-oriented stimuli from ischemic myocardium and modify neutrophil activation during coronary artery bypass grafting.

The influence of treatment of hypercholesterolemic patients with simvastatin on plasma chemotactic activity and adherence of neutrophils.

BACKGROUND: there is some evidence to indicate that statins may affect the function of immune and inflammatory cells. This study investigates the influence of short term treatment with simvastatin on plasma chemotactic activity and adherence of polymorphonuclear neutrophils in hypercholesterolemic patients. METHODS AND RESULTS: 20 hypercholesterolemic patients (250-400 mg/dl) were given simvastatin (20 mg daily for 12 weeks). Peripheral blood samples were taken before and after 4 and 12 weeks of the therapy. The percentage of neutrophils adhering to plastic surface coated with albumin was significantly higher when cells were incubated with plasma obtained after 12 weeks of treatment with simvastatin in comparison with plasma collected before the therapy (unstimulated neutrophils: 5.945+/-0.475% vs. 8.155+/-0.96%, P=0.0477, stimulated neutrophils: 39.09+/-4.540% vs. 29.18+/-3.702%, P=0.032). There was a significant negative correlation between adherence of stimulated neutrophils and total cholesterol levels ((r)=-0.2796, 95% CI -0. 4999 to -0.02526, r(2)=0.07817, P=0.032). Migration of neutrophils towards plasma obtained after 12 weeks of treatment with simvastatin was significantly higher than towards plasma collected before the therapy (7.038+/-1.127 vs. 4.505+/-0 618 P=0.0475). CONCLUSION: treatment of hypercholesterolemic patients with simvastatin increases the chemotactic activity of plasma and augments the adherence of human neutrophils.

Stimulation of neutrophil integrin expression during coronary artery bypass grafting: comparison of crystalloid and blood cardioplegic solutions.

OBJECTIVES: This study was designed (1) to evaluate the influence of plasma obtained from patients undergoing coronary artery bypass grafting on L-selectin, CD11b, and CD18 expression on human neutrophils and (2) to determine the influence of the use of crystalloid or blood cardioplegia during bypass grafting on plasma-mediated expression of adhesion molecules on polymorphonuclear neutrophils. PATIENTS AND METHODS: Patients undergoing coronary artery bypass grafting were divided into 2 groups to receive crystalloid or blood cardioplegic solutions. Peripheral vein, radial artery, and coronary sinus blood samples were drawn at aortic crossclamping, aortic crossclamp release, and 30 minutes after reperfusion. Human neutrophils were incubated with patients' plasma, and the expression of CD11b, CD18, and L-selectin was determined with flow cytometry. RESULTS: In patients receiving crystalloid cardioplegic solutions, plasma samples collected from the coronary sinus at aortic clamp release and 30 minutes thereafter induced significantly higher expression of neutrophil CD11b and CD18 than plasma samples obtained from a peripheral vein or artery at the same time points. The expression of L-selectin on polymorphonuclear neutrophils was significantly reduced with plasma obtained 30 minutes after reperfusion as compared with samples collected at aortic crossclamp release. In the group receiving blood cardioplegia, no significant differences in CD11b, CD18, or L-selectin expression were found. CONCLUSIONS: (1) Ischemia/reperfusion after coronary artery bypass grafting is associated with the release of factors capable of neutrophil activation from myocardium into the circulating blood. (2) The release of soluble stimuli for neutrophils during bypass grafting may be modified by the cardioplegic solution.

Effects of trimetazidine on clinical symptoms and tolerance of exercise of patients with syndrome X: a preliminary study.

BACKGROUND: Trimetazidine diminishes angina and improves tolerance of exercise of patients with ischemic heart disease, and has no influence on blood pressure and heart rate. OBJECTIVE: To determine the effect of trimetazidine on angina symptoms and exercise tolerance in patients with syndrome X. METHODS: We investigated the effect of trimetazidine on the clinical symptoms and tolerance of exercise of 34 patients (20 women and 14 men, aged 32-60 years) with syndrome X (angina pectoris, positive result of exercise test, and normal coronary angiogram). The exercise test was performed before initiation of oral administration of trimetazidine therapy (20 mg three times a day) and 1 and 6 months thereafter. RESULTS: We obtained negative results of exercise treadmill tests for four patients (11.76%) after 1 month and five patients (14.71%) after 6 months of trimetazidine treatment. There was also a decrease in the incidence of effort angina after 6 months of treatment (26 patients or 76.47% before treatment versus 13 patients or 38.23% after 6 months of treatment). The drug had no significant influence on the heart rate and blood pressure. The duration for which patients could exercise was significantly prolonged by 1 month (652.9 +/- 206.2 versus 563.4 +/- 190.4 s, P = 0.0047) and 6 months (650.3 +/- 207.8 s, P = 0.0094) of treatment with trimetazidine. CONCLUSION: Treatment with trimetazidine decreases signs of angina during exercise and improves tolerance of exercise of patients with syndrome X.

Plasma-mediated stimulation of neutrophil superoxide anion production during coronary artery bypass grafting: role of endothelin-1.

BACKGROUND: Activation of polymorphonuclear neutrophils (PMN) and subsequent release of free oxygen radicals, including the superoxide anion (O2-) has been shown to result in postischaemic myocardial dysfunction during coronary artery bypass grafting (CABG). Several neutrophil-oriented stimuli are known to be released from myocardium during ischaemia and reperfusion. Release of endothelin-1 has been documented during CABG. The aim of the current study was to evaluate plasma-mediated neutrophil stimulation and to verify whether endothelin-1, known to be a stimulus for PMN, is involved in plasma-mediated stimulation of PMN during coronary artery bypass grafting. METHODS: Plasma samples from peripheral artery, peripheral vein, and coronary sinus were obtained from 21 patients undergoing CABG before aortic clamping (global ischaemia), immediately after beginning reperfusion, and 30 min after reperfusion as well as from healthy controls. Plasma was incubated with PMN isolated from healthy donors preincubated in the presence of saline or specific endothelin-1 receptor antagonist (ET-A). PMN O2- production was measured spectrophotometrically. RESULTS: Plasma samples taken from the coronary sinus at the beginning of reperfusion were capable of higher stimulation of neutrophil superoxide anion production (24.2 +/- 2.0 nmol/5 x 10(6)PMN/30 min) than plasma obtained before reperfusion (15.6 +/- 1.5; p < 0.05) or plasma taken from peripheral artery (17.1 +/- 1.7; p < 0.05). Preincubation of PMN with endothelin-1 receptor antagonist decreased superoxide anion production by cells exposed to plasma taken from coronary sinus at the beginning of reperfusion (17.6 +/- 2.0, p < 0.05). CONCLUSIONS: Transcardiac release of soluble stimuli for PMN occurs as a result of myocardial ischaemia during CABG. Endothelin-1 may be involved in the plasma-mediated stimulation of neutrophil superoxide anion production.