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ABSTRACT: We investigated the effects of resveratrol on rat portal vein (RPV) contractility without endothelium. Contractions were produced by electrical field stimulation of perivascular nerves (EFS), norepinephrine (NE), adenosine 5'-triphosphate (ATP), high K(+) solution and by calcium chloride (CaCl(2) ) in Ca(2+) -free and high K(+) , Ca(2+) -free solution. The EFS-evoked contractions were more sensitive to resveratrol and to NS1619-selective openers of big calcium-sensitive (BK(Ca) ) channels, than NE-evoked contractions. Effects of resveratrol on the ATP-evoked contractions were weak. Blockers of BK(Ca) channels partly inhibited the effect of resveratrol only in EFS-contracted preparations. Western blotting showed that RPV expressed K(Ca) 1.1 protein. Inhibitors of ATP- and voltage-sensitive K(+) channels did not modify the effects of resveratrol. None of the antagonists of K(+) channels affected the resveratrol inhibition of NE-evoked contractions and effect of high concentrations of resveratrol on the EFS-evoked contractions. Resveratrol more potently inhibited CaCl(2) than potassium chloride contractions of RPV. Thus, BK(Ca) channels partly mediate the inhibitory effect of resveratrol on the neurogenic contractions of RPV. The smooth muscle Ca(2+) channels and/or Ca(2+) mobilizing through cells might be involved in the effects of resveratrol on the contractility of RPV. Our results are important for better understanding the impact of resveratrol on the portal circulation. Copyright © 2013 John Wiley & Sons, Ltd.
Phytotherapy Research 01/2013; · 2.09 Impact Factor
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ABSTRACT: Despite a myriad of causes, pericardial diseases present in few clinical syndromes. Acute pericarditis should be differentiated from aortic dissection, myocardial infarction, pneumonia/pleuritis, pulmonary embolism, pneumothorax, costochondritis, gastroesophageal reflux/neoplasm, and herpes zoster. High-risk features indicating hospitalization are: fever >38 °C, subacute onset, large effusion/tamponade, failure of non-steroidal anti-inflammatory drugs (NSAIDs), previous immunosuppression, trauma, anticoagulation, neoplasm, and myopericarditis. Treatment comprises 10-14-days NSAID plus 3 months colchicine (2 × 0.5 mg; 1 × 0.5 mg in patients <70 kg). Corticosteroids are avoided, except for autoimmunity, as they facilitate the recurrences. Echo-guided pericardiocentesis (±fluoroscopy) is indicated for tamponade and effusions >2 cm. Smaller effusions are drained if neoplastic, purulent or tuberculous etiology is suspected. In recurrent pericarditis, repeated testing for autoimmune and thyroid disease is appropriate. Pericardioscopy and pericardial/epicardial biopsy may clarify the etiology. Familial clustering was recently associated with tumor necrosis factor receptor-associated periodic syndrome (TNFRSF1A gene mutation). Treatment includes 10-14 days NSAIDs with colchicine 0.5 mg bid for up to 6 months. In non-responders, low-dose steroids, intrapericardial steroids, azathioprine, and cyclophosphamide can be tried. Successful management with interleukin-1 receptor antagonist (anakinra) was recently reported. Pericardiectomy remains the last option in >2 years severely symptomatic patients. In constriction, expansion of the heart is impaired by the rigid, chronically inflamed/thickened pericardium (no thickening ~20 %). Chest radiography, echocardiography, computerized tomography, magnetic resonance imaging, hemodynamics, and endomyocardial biopsy indicate the diagnosis. Pericardiectomy is the only treatment for permanent constriction. Predictors of poor survival are prior radiation, renal dysfunction, high pulmonary artery pressures, poor left ventricular function, hyponatremia, age, and simultaneous HIV and tuberculous infection.
Heart Failure Reviews 08/2012; · 3.20 Impact Factor
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ABSTRACT: The heart has traditionally been considered as a static organ without capacity of regeneration after trauma. Currently, the more and more often asked question is whether the heart has any intrinsic capacities to regenerate myocytes after myocardial infarction. The aim of this study was to present the existence of the preserved muscle fibers in the myocardial scar following myocardial infarction as well as the presence of numerous cells of various size and form that differently reacted to the used immunohistochemical antibodies.
Histological, histochemical and immunohistochemical analyses of myocardial sections taken from 177 patients who had died of acute myocardial infarction and had the myocardial scar following myocardial infarction, were carried out. More sections taken both from the site of acute infarction and scar were examined by the following methods: hematoxylin-eosin (HE), periodic acid schiff (PAS), PAS-diastasis, Masson trichrom, Malory, van Gieson, vimentin, desmin, myosin, myoglobin, alpha actin, smoth muscle actin (SMA), p53, leukocyte common antigen (LCA), proliferating cell nuclear antigen (PCNA), Ki-67, actin HHF35, CD34, CD31, CD45, CD45Ro, CD8, CD20.
In all sections taken from the scar region, larger or smaller islets of the preserved muscle fibers with the signs of hypertrophy were found. In the scar, a large number of cells of various size and form: spindle, oval, elongated with abundant cytoplasm, small with one nucleus and cells with scanty cytoplasm, were found. The present cells differently reacted to histochemical and immunohistochemical methods. Large oval cells showed negative reaction to lymphocytic and leukocytic markers, and positive to alpha actin, actin HHF35, Ki-67, myosin, myoglobin and desmin. Elongated cells were also positive to those markers. Small mononuclear cells showed positive reaction to lymphocytic markers. Endothelial and smooth muscle cells in the blood vessel walls were positive to CD34 and CD31, and smooth muscle cells to SMA. Oval and elongated cells were positive to PCNA and Ki-67. The preserved muscle fibers in the scar were positive to myosin, myoglobin and desmin as well as elongated and oval cells. Other cells were negative to these markers.
Our findings speak that myocardial regeneration is maybe possible and develops in human ischemic heart damages and that the myocardium is not a static organ without capacity of cell regeneration.
Vojnosanitetski pregled. Military-medical and pharmaceutical review 07/2012; 69(7):581-8. · 0.18 Impact Factor
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Milan A. Nedeljkovic,
Miodrag Ostojic,
Nebojsa Lalic,
Branko Beleslin,
Ivana Nedeljkovic,
Katarina Lalic,
Miljko Ristic,
Vojislav Giga,
Lazar Angelkov,
Miloje Tomasevic, Vladimir Kanjuh
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ABSTRACT: A 55-year-old man, with a history of medically uncontrolled coronary vasospasm, presented for evaluation of chest pain 6 months
after implantation of left internal mammary artery. Due to recurrent episodes of vasospastic angina and serious complications
of coronary spasm (ventricular fibrillation, myocardial infarction), a stent had previously been implanted in the proximal
part of left anterior descending artery at the site of angiographically and ergonovine-proven coronary spasm, with subsequent
in-stent restenosis.
Ein 55-jähriger Patient mit therapeutisch unkontrollierbaren koronaren Vasospasmen wurde 6 Monate nach Implantation der linken
A. mammaria interna zur Abklärung von Brustschmerzen vorstellig. We - gen der wiederholten vasospastischen Anfälle und Komplikationen
mit Kammerflimmern und Myokardinfarkt war zuvor ein Stent in die proximale LAD implantiert worden mit nachfolgender In-Stent-
Restenose, nachdem angiographisch und mittels Ergonovintest schwere Koronarspasmen festgestellt worden waren.
Herz 04/2012; 34(7):564-566. · 0.92 Impact Factor
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Saso Rafajlovski,
Radoje Ilić,
Branko Gligić, Vladimir Kanjuh,
Vujadin Tatić,
Andjelka Ristić,
Slobodan Obradović,
Dragan Dincić,
Nenad Ratković,
Radoslav Romanović,
Jasna Karić,
Nemanja Djenić,
Snjezana Vukotić
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ABSTRACT: Primary heart tumors are very rare. They can be benign and malignant. Benign ones make about two thirds of all heart tumors. However, they are benign only by their biologic characteristics, but potentially malignant by their localization. About three forths of benign tumors are myxomas. Their growth is usually slow and they can be for a long time silent, particularly if they do not compromise vital functional parts of the heart. Myxomas grow in the atria, mostly in the left one and very rarely in the ventricles.
We presented two patients with myxomas in the left, and, in the right atrium which are representative samples of the most common localization of heart myxoma considering previous knowledge of these tumors. Analysis of the clinical course in the two presented patients with characteristic localizations showed general characteristics of the clinical course of heart myxoma. The patients did not have characteristic symptoms for a rather long period of time and the findings obtained by standard examinations did not raise suspicion of heart tumor. Pulmonary symptomatology in one patient and cardial in the other, when tumor had already occupied almost the entire atrium, suggested necessity of cardiologic examination. Indication for operation was in both patients confirmed after performed echocardiography, computed tomography of the thorax and angiography with ventriculography. The size of the removed atrial tumors and their localization explained some of the patients' troubles, but it was also amazing that they had not caused more serious problems. Operation as the only method of treatment was successful in both female patients and its effect was permanent. At annual controls neither recurrence of the tumor nor troubles possibly associated with it were observed.
Patients with heart myxoma usually pass through asymptomatic or oligosymptomatic phase, but when troubles become manifested, they do not much differ from those due to other causes. For this reason this tumor can be diagnosed just when complications caused by its localization and growth develop. Modern cardiologic diagnostics, primarily preventive non-invasive echocardiography, enables timely diagnosis and removal of the tumor because only then it may take a name benign tumor.
Vojnosanitetski pregled. Military-medical and pharmaceutical review 03/2012; 69(3):270-6. · 0.18 Impact Factor
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ABSTRACT: The ATP-sensitive K(+) channels opener (K(ATP)CO), P1075 [N-cyano-N'-(1,1-dimethylpropyl)-N″-3-pyridylguanidine], has been shown to cause relaxation of various isolated animal and human blood vessels by opening of vascular smooth muscle ATP-sensitive K(+) (K(ATP)) channels. In addition to the well-known effect on the opening of K(ATP) channels, it has been reported that vasorelaxation induced by some of the K(ATP)COs includes some other K(+) channel subtypes. Given that there is still no information on other types of K(+) channels possibly involved in the mechanism of relaxation induced by P1075, this study was designed to examine the effects of P1075 on the rat renal artery with endothelium and with denuded endothelium and to define the contribution of different K(+) channel subtypes in the P1075 action on this blood vessel. Our results show that P1075 induced a concentration-dependent relaxation of rat renal artery rings pre-contracted by phenylephrine. Glibenclamide, a selective K(ATP) channels inhibitor, partly antagonized the relaxation of rat renal artery induced by P1075. Tetraethylammonium (TEA), a non-selective inhibitor of Ca(2+)-activated K(+) channels, as well as iberiotoxin, a most selective blocker of large-conductance Ca(2+) -activated K(+) (BK(Ca)) channels, did not abolish the effect of P1075 on rat renal artery. In contrast, a non-selective blocker of voltage-gated K(+) (K(V)) channels, 4-aminopyridine (4-AP), as well as margatoxin, a potent inhibitor of K(V)1.3 channels, caused partial inhibition of the P1075-induced relaxation of rat renal artery. In addition, in this study, P1075 relaxed contractions induced by 20 mM K(+) , but had no effect on contractions induced by 80 mM K(+). Our results showed that P1075 induced strong endothelium-independent relaxation of rat renal artery. It seems that K(ATP), 4-AP- and margatoxin-sensitive K(+) channels located in vascular smooth muscle mediated the relaxation of rat renal artery induced by P1075.
Basic & Clinical Pharmacology & Toxicology 01/2012; 111(1):24-30. · 2.18 Impact Factor
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ABSTRACT: The drug nicorandil is a vasodilator approved for the treatment of angina. In addition to its well-known effect on the opening of ATP-sensitive K (KATP) channels, nicorandil-induced vasorelaxation also involves the opening of Ca-activated K channels. The aim of this study was to investigate the effects of nicorandil on the isolated human internal mammary artery (HIMA) and the human saphenous vein (HSV) and to define the contribution of different K channel subtypes in the nicorandil action on these arterial and venous grafts. Our results show that nicorandil induced a concentration-dependent relaxation of HSV and HIMA rings precontracted by phenylephrine. Glibenclamide, a selective KATP channels inhibitor, partially inhibited the response to nicorandil in both HSV and HIMA. Iberiotoxin, a most selective blocker of large-conductance Ca-activated K (BKCa) channels, partly antagonized relaxation of HIMA. A nonselective blocker of voltage-gated K channels, 4-aminopyridine caused partial inhibition of the nicorandil-induced relaxation of HSV but did not antagonize relaxation of HIMA induced by nicorandil. Margatoxin, a potent inhibitor of KV1.3 channels, did not abolish the effect of nicorandil on HSV and HIMA. Our results showed that nicorandil induced strong endothelium-independent relaxation of HSV and HIMA contracted by phenylephrine. It seems that KATP and 4-aminopyridine-sensitive K channels located in the smooth muscle of HSV mediated relaxation induced by nicorandil. In addition, KATP and BKCa channels are probably involved in the nicorandil action on HIMA.
Journal of cardiovascular pharmacology 12/2011; 58(6):602-8. · 2.83 Impact Factor
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ABSTRACT: Myxoma is the most common benign primary cardiac neoplasm, and usually originates from the left atrial septum. Early diagnosis of cardiac myxomas depends on a high index of a clinical suspicion. Surgical management must be done as soon as possible after diagnosis. The aim of this retrospective study was to present diagnostics and treatment outcome data of 61 patients with cardiac myxoma treated in the Military Medical Academy, Belgrade during a 49-years period.
Intra-hospital diagnosis was established in all the patients by the cardiologist. Diagnostic methods were various, in dependence on the examination period and suspected diagnosis.
Within a 49-years period (1961-2009) heart myxoma was diagnozed and treated in 61 patients in the Military Medical Academy, Belgrade. Most of the operated patients were females (38 or 62.3%). The operated patients were 19-68 years old. Average age of all the patients was 47.9%. The great majority of them (98.4%) had atrial, and only one operated patient had ventricular myxoma. In 13 (21.3%) of the patients heart myxoma was found out accidentally due to no previous cardiologic symptomatology. In most patients (27.44%) symptomatology was presented as thromboembolic disease. Because of the suspected ventricular myxoma in one patient, the patient was operated on, but Hodgkin's lymphoma was found out which, according to the subsequent course of the disease, could be justifiably recognized as primary heart lymphoma. This study presented brief descriptions of the course of the disease in 4 patients with myxomas in each of the cardiac cavities.
The only diagnostic difficulty in cardiac myxoma is due to its asymptomatic and oligosymptomatic presence within the longer period of time, namely, its growth period. Echocardiography should be the standard method of cardiologic examination of these patients, which could considerably contribute to early diagnosis and treatment of heart myxoma. Surgical extirpation of myxoma is the only and very successful therapeutic method.
Vojnosanitetski pregled. Military-medical and pharmaceutical review 10/2011; 68(10):851-5. · 0.18 Impact Factor
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Ljiljana Gojkovic-Bukarica,
Natasa Savic,
Miodrag Peric,
Jasmina Markovic-Lipkovski,
Sanja Cirovic, Vladimir Kanjuh,
Jelena Cvejic,
Milica Atanackovic,
Aleksandar Lesic,
Marko Bumbasirevic,
Helmut Heinle
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ABSTRACT: In order to discover an agent that can prevent spasm of the human radial artery, the aim of our study was to evaluate the effect of the K(+) channel opener, pinacidil, on contractions in the radial artery. Contractions of the radial artery were evoked by exogenously applied noradrenaline or by electrical field stimulation (EFS, 20Hz, neurogenic). Pinacidil induced concentration-dependent inhibition of both EFS- and noradrenaline-evoked contractions of the radial artery. Glibenclamide, a selective blocker of ATP-sensitive K(+) channels (Kir6.x containing subunit) antagonized in the same manner the pinacidil-induced inhibition of neurogenic contractions and contractions evoked by exogenous noradrenaline. The inhibition of pinacidil relaxation by tetraethylammonium (TEA), a blocker of Ca-sensitive K(+) (K(Ca)) channels, was more pronounced in EFS-contracted preparations. A blocker of voltage-sensitive K(+) (K(V)) channels, 4-aminopyridine (4-AP), inhibited pinacidil relaxation only in EFS-contracted preparations. In order to test the presence of different K(+) channels, immunohistochemistry of K(+) channels expression in the radial artery was performed. The vascular wall of the human radial artery showed variable positivity with the following applied antibodies: Kv1.2, Kv1.3, Kir6.1, and K(Ca)1.1. The antibodies against Kv1.6, Kv2.1, and Kir6.2 channel subunits were completely negative. These results suggest that the inhibitory effect of pinacidil on contractions of the human radial artery might be postsynaptic and associated with opening of smooth muscle Kir6.1-containing K(ATP) channels. TEA- and 4-AP-sensitive K(+) channels may also contribute to pinacidil effect in the human radial artery.
European journal of pharmacology 03/2011; 654(3):266-73. · 2.59 Impact Factor
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Milan A Nedeljkovic,
Miodrag Ostojic,
Nebojsa Lalic,
Branko Beleslin,
Ivana Nedeljkovic,
Katarina Lalic,
Miljko Ristic,
Vojislav Giga,
Lazar Angelkov,
Miloje Tomasevic, Vladimir Kanjuh
[show abstract]
[hide abstract]
ABSTRACT: A 55-year-old man, with a history of medically uncontrolled coronary vasospasm, presented for evaluation of chest pain 6 months after implantation of left internal mammary artery. Due to recurrent episodes of vasospastic angina and serious complications of coronary spasm (ventricular fibrillation, myocardial infarction), a stent had previously been implanted in the proximal part of left anterior descending artery at the site of angiographically and ergonovine-proven coronary spasm, with subsequent in-stent restenosis.
Herz 11/2009; 34(7):564-6. · 0.92 Impact Factor
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ABSTRACT: After reviewing the general characteristics of lipids (LDL-C, VLDL-C, HDL-C) and atherothrombosis, including the I-VIII degrees of its histopathological arterial lesions (with contributions of J. E. Edwards and R. Virmani), the authors described the P. Libby's data on lipoprotein-associated phospholipaseA2 (Lp-PLA2) and its two inflammatory mediators: lysophosphatidylcholine and oxidized nonesterified fatty acids. They are involved in plaque progression and vulnerability. Lp-PLA2 is an emerging proinflammatory marker. The new drug darapladib inhibits Lp-PLA2 and acts against inflammation. LDL-C is present in the atherosclerotic plaque from the circulating blood in arterial lumen (through the dysfunctional endothelium) and vasa vasorum as well as after the decomposition of foam cells (monocytes-phagocytes, smooth muscle and dendritic cells) and outpoured erythrocytes (its membranes) after hemorrhage. The blood from the arterial lumen can also enter the atherosclerotic plaque through the lesions in its fibrous cap (erosion, fissure, rupture). Atherosclerosis as a disease or as an inevitable accompaniment of aging ("the senescence hypothesis"). The familial hypercholesterolemia is usually due to mutation of just one gene--a defective LDL-C receptor gene on chromosome 19. The accelerated and severe atherosclerosis very resistant to therapy occurs. The patients with homozygous familial hypercholesterolemia can die of myocardial infarction in early childhood. Therapeutic decrease of LDL-C and increase of HDL-C slows down the evolution of atherosclerosis, stabilizes the atherosclerotic plaques, and even brings about their partial regression. Statins, niacin, ezetimibe, LDL-C apheresis, and surgery: shunt between the portal and inferior caval veins, liver transplantation, and partial ileal bypass. The elevated LDL-C is the most established risk factor for atherosclerosis with impact on coronary heart disease mortality of 26%, and it should be the primary target of preventive and therapeutic efforts.
Medicinski pregled 02/2009; 62 Suppl 3:7-14.
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ABSTRACT: Recently it has been suggested that resveratrol relaxes different isolated arteries. The present study addressed the question whether different ion channels are involved in the endothelium-independent mechanism of vasodilatation induced by resveratrol. For that purpose, we tested the action of resveratrol on the rat mesenteric artery without endothelium. Resveratrol induced concentration-dependent relaxation of rat mesenteric artery. Among the K(+)-channel blockers, 4-amynopiridine (4-AP) moderately antagonized the resveratrol-induced relaxation, while glibenclamide, tetraethylammonium chloride, charybdotoxin, margatoxin, and barium chloride did not inhibit resveratrol-induced vasorelaxation. In rings, precontracted with 100 mM K(+), the relaxant responses to resveratrol were highly significantly shifted to the right compared to those obtained in rings precontracted with phenylephrine, but resveratrol-induced maximal relaxation was only slightly affected. In order to minimize the influence of K(+) channels and voltage-gated Ca(2+) channels (VGCCs) in vascular smooth muscle, the third contraction was made by 100 mM K(+) in the presence of nifedipine. The relaxant response to resveratrol was abolished. Thus, the mechanism of vasorelaxation induced by resveratrol probably involves activation of 4-AP-sensitive K(+) channels. Its ability to completely relax the mesenteric artery precontracted with K(+)-rich solution suggests that K(+) channel-independent mechanism(s) are involved in its vasorelaxant effect. It seems that interaction with VGCCs plays a part in this K(+) channel-independent effect of resveratrol.
Journal of Pharmacological Sciences 10/2008; 108(1):124-30. · 2.08 Impact Factor
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Milan A Nedeljkovic,
Miodrag C Ostojic,
Branko D Beleslin,
Ivana Nedeljkovic,
Natasa Milic,
Vladan Vukcevic,
Sinisa Stojkovic,
Jovica Saponjski,
Dejan Orlic,
Ana Djordjevic-Dikic,
Jelena Stepanovic,
Vojislav Giga,
Zorica Petrasinovic,
Aleksandra Arandjelovic,
Biljana Beleslin, Vladimir Kanjuh
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ABSTRACT: Serum cholesterol is positively associated with the risk of developing coronary heart disease. The aim of this study was to determine the relation between response of coronary arteries to ergonovine provocation and lipid profile in patients with nonsignificant coronary artery disease.
105 patients (46 male, 59 female, mean age 52 +/- 8 years) with chest pain syndrome and nonsignificant coronary artery stenosis (< 50% diameter stenosis) were analyzed. Ergonovine test was performed at the end of diagnostic catheterization. Coronary spasm was defined as total or near total obstruction of the coronary artery. By quantitative coronary arteriography, changes of minimal luminal diameter (MLD) during ergonovine provocation were evaluated. Total cholesterol, LDL and HDL cholesterol, and triglycerides were measured.
There was a significant negative correlation between resting MLD and LDL cholesterol (r = -0.215; p = 0.034), and a significant positive correlation between MLD decrease provoked by ergonovine and total cholesterol (r = 0.275; p = 0.006), as well as LDL cholesterol (r = 0.284; p = 0.004), but not for HDL cholesterol and triglycerides (p = NS [not significant]).
In patients with nonsignificant coronary artery stenosis evaluated by ergonovine provocation, there was not only a significant negative correlation between MLD and LDL cholesterol, but also a positive correlation between coronary vasoconstriction induced by ergonovine provocation and both total and LDL cholesterol.
Herz 06/2007; 32(4):329-35. · 0.92 Impact Factor
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ABSTRACT: To assess the effects of chorionic villus sampling (CVS) on fetal heart rate (FHR).
A prospective longitudinal study was conducted among 300 patients undergoing transabdominal CVS between 8 and 13 weeks of gestation. Duration of the procedure, number of needle passes, sample weight, maternal age, fetal gender, and FHR response to CVS were recorded.
The FHR before but not after CVS was inversely correlated with gestational age (r = -0.406, p < 0.001). Conversely, following CVS, no correlation was observed between FHR and gestational age (r = -0.06, p = 0.27). The difference between FHR after CVS and that obtained before CVS (delta FHR) increased with increasing gestational age at sampling (r = 0.372, p < 0.0001), decreased with increasing specimen weight (r = -0.16, p = 0.01) and increased with increasing maternal age (r = 0.22, p < 0.0001). Duration of the procedure, fetal gender and number of needle passes did not affect delta FHR. Multiple logistic regression indicated that gestational age at CVS and maternal age but not the other variables significantly affected delta FHR and together they accounted for over 22% of the variance (R(2) = 0.224, p < 0.0001).
In summary, our results suggest that acute fetal hemodynamic changes accompany CVS and that these changes vary with gestational age.
Journal of Maternal-Fetal and Neonatal Medicine 04/2007; 20(4):285-8. · 1.50 Impact Factor
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ABSTRACT: Introduction: Brain natriuretic peptide (BNP) has a role in control of cardiovascular and renal functions. Objective The objective was to assess the predictive value of BNP levels for development of heart failure in patients with permanent pacemakers. Method In patients with implanted DDD pacemakers, BNP levels were measured at rest and after exercise testing, on DDD and VVI modes. There were 42 patients (25 males; 59.5%), without symptoms or signs of coronary disease or heart failure, and with normal echocardiograms. According to BNP levels, the patients were divided into three groups: with BNP levels lower than 80 pg/ml, BNP ranging from 81-150 pg/ml, and BNP levels over 151 pg/ml. Results In the first group (27 patients), BNP levels were significantly higher on VVI compared to DDD mode, both at rest and after exercise (p<0.01), with all BNP levels within normal range. In the second group (5 pts), BNP levels at rest were also significantly higher on VVI than on DDD mode, p<0.05. After exercise, these values were also higher on VVI compared to DDD mode, but without statistical significance. The third group (10 pts) as a whole had higher BNP values on VVI compared to DDD mode, with no statistical significance. In patients from this group who later developed heart failure, BNP levels were found to be significantly lower on DDD as opposed to VVI mode at rest, p<0.05, and even higher significance was found after exercise, p<0.01. After 6-year follow-up, 2 out of 5 patients from the second group developed dilated cardiomyopathy, and 8/10 patients in the third group experienced heart failure with LV EF 34.1±10%, LV EDD 6.1±0.42 cm, LV ESD 4.8±0.45 cm. Five of these patients died within the follow-up period. Conclusion The increased BNP levels can be valuable for early screening of patients with higher risk of heart failure. In patients with increased BNP at the time of pacemaker implantation, DDD pacing is a modality of choice.
Srpski Arhiv za Celokupno Lekarstvo. 01/2007;
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ABSTRACT: Resveratrol, a phenolic substance present in grapes and a variety of medical plants, has been reported to induce vasorelaxation, however the mechanisms are uncertain. In this paper we investigate the possible participation of K(+) channels in the endothelium-independent vasodilatation of rat aorta induced by resveratrol. Resveratrol induced concentration-dependent relaxation of rings with endothelium and without endothelium. We used different potassium channel inhibitors to determine whether the K(+) channels mediated endothelium-independent relaxation of rat aorta induced by resveratrol. Highly selective blocker of ATP-sensitive K(+) channels, glibenclamide, as well as non-selective blockers of K(+) channels, tetraethylammonium, did not block resveratrol-induced relaxation of rat aortic rings. Charybdotoxin, a blocker of calcium-sensitive K(+) channels did not affect the resveratrol-induced relaxation. 4-Aminopiridine, non-selective blocker of voltage-gated K(+) (Kv) channels, and margatoxin that inhibits Kv1 channels abolished relaxation of rat aortic rings induced by resveratrol. In conclusion, we have shown that resveratrol potently relaxed rat aortic rings with denuded endothelium. It seems that 4-aminopiridine and margatoxin-sensitive K(+) channels located in the smooth muscle of rat aorta mediated this relaxation.
Basic & Clinical Pharmacology & Toxicology 12/2006; 99(5):360-4. · 2.18 Impact Factor
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ABSTRACT: Secondary or metastatic tumors in the heart occur more frequently than primary ones, and, according to the published series, their frequency found in autopsic material ranges from 1.6% to 20.6%. Metastatic tumors in the heart are rarely clinically symptomatic, and, therefore, they are rarely diagnosed within the lifetime. They are mostly diagnosed at autopsy. The aim of this study was to analyze the frequency of metastatic tumors of the heart, their primary localization, as well as the localization of the metastases found in the autopsic material within the period 1972-2004.
During the autopsy of the patients died of metastatic tumors, we microscopically and macroscopically analyzed all the organs and tissues to determine the metastases of primary tumors in other organs, especially in the heart and pericardium.
Within the period from 1972-2004, 11 403 autopsies were performed. In 2 928 (25.6%) out of 11 403 autopsies, the presence of malignant tumor was diagnosed, and in 79 (2.7%) of these cases, metastasis of the heart was found out. Only in 5 of the cases, the presence of metastasis in the heart was diagnosed during the lifetime. The most frequent metastases in the heart were caused by pulmonary carcinoma (18 cases), leukemia and malignant lymphoma (8 cases, each), then pancreatic and breast carcinoma, while the metastases of other carcinomas were rather rare. In 40 (60.76%) cases, the metastasis was localized in the myocardium, but more often in the left ventricle, in 24 (30.38%) cases in the pericardium, in 4 cases in the epicardium and in the 3 of them in the mitral and tricuspid valve. Only in one case of renal carcionoma, metastasis was found in the right atrium and it occurred by spreading (dissemination) through the lumen of the inferior vena cava.
Metastatic tumors of the heart are rather rare, and rarely clinically symptomatic, and, thus, rarely diagnosed during life. The methods of choice for the diagnosis of the metastasis in the heart are echocardiography, computerized tomography, magnetic resonance imaging, cytological analysis of the pericardial effusion and biopsy. The treatment includes surgery, chemotherapy and radiotherapy.
Vojnosanitetski pregled. Military-medical and pharmaceutical review 01/2006; 62(12):915-20. · 0.18 Impact Factor
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ABSTRACT: Although Rudolf Virchow considered arteriosclerosis an inflammatory disease in his book Cellular Pathology publisched in 1858, the opinion that it was a degenerative arterial disease as a civilization disease prevailed. Nowadays, a great attention has been paid to the inflammatory process in the patogenesis of arteriosclerosis and particularly in the destabilization and rupture of plaque.
To find out whether T and B lymphocytes, lipid macrophages, vascular smooth muscle and mast cells as well as plaque destabilization and rupture are present in ruptured arteriosclerotic plaque in the coronary arteries.
Histochemical and immunochemical analyses of 68 ruptured arteriosclerotic plaques from the coronary arteries were performed. Microscopic examination revealed the presence of inflammation elements in all of them. The following histochemical and immunochemical methods were applied: Masson's trichrome, actins, vimentin, CD3, CD43, CD68, CD20, CD45 and chlorine acetyl esterase. The control group included 10 arteriosclerotic plaques from the coronary arteries with fibrous cap, but without inflammation cells.
Rupture of the arteriosclerotic plaque fibrous cap, with thinned and torn collagen fibers, was found in all of the 68 arteriosclerotic plaques. In 57 out of 68 analysed plaques, the increased number of T-lymphocytes, lipid macrophages, vascular smooth muscle and mast cells particularly on the plaque rupture site were found. In the remaining 11 specimens, mast cells were present in a somewhat smaller number. In the control group with the stable plaque, inflammation cells were not observed.
Our results pointed out that the inflammatory elements, which might exert an effect upon the arteriosclerotic plaque destabilization, and rupture had been present in the ruptured arteriosclerotic plaque.
Vojnosanitetski pregled. Military-medical and pharmaceutical review 10/2005; 62(9):649-53. · 0.18 Impact Factor
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ABSTRACT: According to the data from immunological, biological and molecular researches, there is a close association between the undifferentiated carcinoma of nasopharyngeal type (UCNT) and Epstein-Barr virus (EBV). To use IgA EA antibody as a serological marker in our patients with nasopharyngeal carcinoma from a clinical viewpoint.
91 patients were followed in the period from 1989-1998. In 11 of the patients the antibody titre serum for the early antigen of EBV virus were determinated before the treatement, and in 24 of the patients 3 years after the treatement. There were three control groups of patients: 20 voluntary blood donors, 26 patients with squamocellular laryngeal carcinoma, and 10 patients with squamocellular nasopharyngeal carcinoma.
In the group of 11 patients with UCNT before the treatment, the value of anti-EA IgA titre was 31.09, and in the patients after the treatement anti-EA IgA antiody titre was 14.56. In the control groups of patients the results were: in the blood donors 5.00; in the group with the diagnosis of squamocellular laryngeal carcinoma, the titre was 5.00; in the patients with squamocellular nosopharyngeal carcinoma, the titre anti-EA IgA was 5.36.
These results were statisticly highly significant (p < 0.01). Our research clearly showed that anti-EA IgA EBV marker could be useful in diagnosing, differential diagnosing and prognosing as well.
Vojnosanitetski pregled. Military-medical and pharmaceutical review 10/2005; 62(10):739-44. · 0.18 Impact Factor
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ABSTRACT: INTRODUCTION. Resynchronisation therapy with biventricular permanent pacing stimulation is one method of treating patients with systolic heart failure, with echocardiograph signs of ventricular asynchrony and a prolonged QRS of longer than 120 milliseconds. This method has been accepted in most medical centers around the world and was instigated in our Pacemaker Centre in December 2001, 3 months after FDA approval for human use. OBJECTIVE. The aim of the study was to present this new procedure and the results obtained from our own group of patients. METHOD. A multi-site, biventricular pacemaker, with a special electrode for left-half heart stimulation was implanted in the coronary sinus of 17 patients who had suffered systolic heart failure (12 male and 5 female, average age 59.9 years). For all of them, the duration of the QRS interval was longer than 120 ms, with left bundle branch morphology, and an ejection fraction below 30%. All the patients were NYHA class II or III. Prior to and after the implantation, a 12-channel ECG and ECHO were carried out, a b-minute hall walk test was performed, additionally, the total walked distance on a flat surface was measured, the general condition of the patient was evaluated, the number of medications being taken was noted, as was the number of days of hospitalization. RESULTS. The average time from diagnosis to implantation was 22 months, and the average post-operative follow-up was 14 months. Two of the patients died 10 and 7 months after the implantation, due to a new myocardial infarction and refractory heart failure. In addition, one patient did not show any improvement after the implantation of the multi-site pacemaker (there were three "non-responder" patients). All the other patients felt much better: decreased NYHA class for I - II class, increased left ventricle ejection fraction, reduced use of diuretics, increased b-minute hall walk distance and general walk distance on a flat surface, and decreased number of days of hospitalization. CONCLUSION. Resynchronisation heart failure therapy in the majority of patients with systolic left ventricular dysfunction and a prolonged QRS interval considerably improves cardiac function, in addition to reducing symptoms and hospital stays.
Srpski Arhiv za Celokupno Lekarstvo. 01/2005;
