Prolonged clopidogrel application reduces tissue factor expression after percutaneous coronary intervention in the porcine model.

Background: Late thrombotic events are important complications associated with intracoronary brachytherapy (ICBT) using ionizing radiation (IR) or with antiproliferative treatment modalities such as drug-eluting stents (DES). The mechanism mediating these thrombotic events is not well understood. This study assessed the effect of prolonged clopidogrel treatment on tissue factor (TF) expression in coronary arteries and on the circulating TF level after percutaneous transluminal coronary angioplasty /ICBT in a porcine coronary model.

Effect of interleukin-15 on the course of myocarditis in Coxsackievirus B3-infected BALB/c mice.

Objective: Cytokines have an important role in both the initiation and perpetuation of viral myocarditis. Because a causative therapy of myocarditis is not yet well established and immunomodulation is a promising approach, the influence of interleukin (IL)-15, a proinflammatory cytokine, on the course of experimental myocarditis in Coxsackievirus B3 (CVB3)-infected mice was examined.

Methods: Hearts from CVB3-infected (n=14), sham-infected (n=14) and CVB3-infected BALB/c mice treated with IL-15 (n=6) or a competitive IL-15 fusion protein (n=6) were analyzed for hemodynamic function, cellular infiltrates and myocardial collagen content.

Complex porcine model of atherosclerosis: induction of early coronary lesions after long-term hyperlipidemia without sustained hyperglycemia.

Background: The incidence of coronary artery disease (CAD) is still increasing in industrialized countries and it is even higher in diabetic patients. For experimental studies investigating the pathophysiology of CAD, the use of an animal model comparable with the pathological situation in patients is crucial.

Objective: To develop a model of advanced coronary atherosclerosis with induction of hyperlipidemia and hyperglycemia in domestic pigs.

Association of cytokines with endothelium dependent flow mediated vasodilation (FMD) of systemic arteries in patients with non-ischemic cardiomyopathy.

Background: Aim of this study was to elucidate the relation between localised inflammatory heart disease and endothelial dysfunction in the peripheral circulation, considering circulating cytokines as a potential link.

Methods: In 38 patients with non-ischemic heart disease, myocardial biopsies were examined for myocardial inflammation (immunohistology) and virus persistence (PCR). Cytokines (sIL-4, IFN-g, IFN-b, IFN-a, sIL-12p7, TNF-a) were measured by ELISA in venous serum.

Correlation of epicardial and systemic flow-mediated vasodilation in patients with atypical angina but no evidence of atherosclerotic disease.

Background: Atypical angina represents a diagnostic challenge and can be observed in the absence of significant coronary atherosclerosis. Endothelial dysfunction is a relevant marker of prognosis, considering cardiovascular events. The aim of the present study was to compare flow-mediated vasodilation (FMD) in systemic peripheral and epicardial coronary arteries.

Prolonged application of clopidogrel reduces inflammation after percutaneous coronary intervention in the porcine model.

Objective: We determined the effect of prolonged treatment with clopidogrel on C-reactive protein (CRP) concentrations and blood thrombogenicity after percutaneous transluminal coronary angioplasty followed by intracoronary brachytherapy in the porcine model. ANIMAL MODEL: All 48 pigs received antiplatelet therapy, including aspirin (325 mg, daily) and clopidogrel (300 mg, loading dose) 1 day before PCI, followed by a daily dose of clopidogrel (75 mg/day) in addition to aspirin. During PCI, one of two balloon-injured arteries was randomly assigned to receive immediate radiation treatment.

Mechanisms of late lumen loss after antiproliferative percutaneous coronary intervention using beta-irradiation in a porcine model of restenosis.

Background: The short-term results for the prevention of coronary restenosis after intravascular brachytherapy (IVBT) and use of drug-eluting stents (DESs) are excellent. The long-term results either lack or present with late complications (e.g.

Nf-kappab and AP-1 activation is associated with late lumen loss after porcine coronary angioplasty and antiproliferative beta-irradiation.

Objective: Despite the success of antiproliferative therapies, restenosis remains a common problem after percutaneous transluminal coronary angioplasty (PTCA). Longer-term clinical results of brachytherapy (intracoronary radiation), the lack of long-term clinical results after implantation of drug eluting stents, and the occurrence of late thrombosis after both procedures leave room for skepticism. Neointimal proliferation is not substantially inhibited at late time points after brachytherapy, and late lumen loss with a "catch-up" proliferation can occur.

Immunomodulation by interleukin-4 suppresses matrix metalloproteinases and improves cardiac function in murine myocarditis.

Immune response is critically involved in determining the course of viral myocarditis and immunomodulation. Different cytokines may have either deleterious or protective effects. Following acute Coxsackievirus B3 infection, intramyocardial inflammation is associated with altered myocardial matrix metalloproteinase (MMP) expression and left ventricular dysfunction.

Coronary vasospasm-induced acute diastolic dysfunction in a patient with Raynaud's phenomenon.

We present the case of a patient with severe dyspnea and Raynaud's phenomenon. We could clarify, using invasive techniques including left ventricular conductance catheterization and coronary ergonovine provocation, that isolated diastolic dysfunction induced by coronary vasospasm were responsible for the symptoms. Systolic function was not affected.

Adventitial VEGF165 gene transfer prevents lumen loss through induction of positive arterial remodeling after PTCA in porcine coronary arteries.

Negative arterial remodeling still plays an important role in the pathogenesis of coronary restenosis even in the era of interventional stenting (e.g. arterial narrowing occurs proximal and distal of a stented segment).

An isoform shift in the cardiac adenine nucleotide translocase expression alters the kinetic properties of the carrier in dilated cardiomyopathy.

Background: Impaired mitochondrial ADP/ATP transport and altered adenine nucleotide translocase (ANT) isoform expression characterized by enhanced ANT1 and decreased ANT2 expression have been implicated in the pathophysiology of dilated cardiomyopathy (DCM). It is still unknown whether restricted ANT function results from exogenous factors, or mutations in the ANT genes, or whether the imbalance in the isoform composition causes the reduced ADP/ATP transport. We performed DNA mutation screening of ANT genes and analyzed the kinetic properties of ANT protein isolated from DCM hearts and controls in a reconstituted system excluding natural environmental influences.

Differential aspects of endothelial function of the coronary microcirculation considering myocardial virus persistence, endothelial activation, and myocardial leukocyte infiltrates.

Background: Viral cardiomyopathy resulting from myocardial virus persistence can be associated with inflammatory immune responses that involve the myocardium and coronary blood vessels. The aim of this study was to investigate the differential impact of myocardial virus persistence and inflammation on endothelial function of the coronary microcirculation.

Methods And Results: In 71 patients with nonischemic cardiomyopathy, myocardial biopsies were examined for virus persistence (by polymerase chain reaction) and inflammation (by immunohistology).

Endothelium-dependent flow-mediated vasodilation of systemic arteries is impaired in patients with myocardial virus persistence.

Background: Myocardial virus persistence is frequently observed in patients with cardiomyopathy. Endothelial dysfunction in patients with cardiomyopathy is associated with inflammatory immunoresponses in myocardial biopsies. The aim of this study was to investigate the impact of myocardial virus persistence on endothelial function.

[Antiplatelet strategies in the acute and chronic therapy of cardiovascular disease].

Atherothrombotic diseases and especially coronary and cerebrovascular diseases are the most important causes of death in western countries. Besides the prevention and treatment of cardiovascular risk factors like hyperlipidemia, smoking and arterial hypertension along with improvements in the catheter-based interventional therapy, the treatment of cardiovascular diseases with platelet aggregation inhibitors improved the the patients' long-term outcome and mortality. The effect of acetylsalicylic acid (ASA) as an inhibitor of the cylooxygenase is well studied and proven in numerous major studies.

Hemodynamic characterization of left ventricular function in experimental coxsackieviral myocarditis: effects of carvedilol and metoprolol.

Background: Carvedilol, a vasodilating nonselective beta-adrenoceptor antagonist, but not metoprolol, a selective beta1-adrenoceptor antagonist, has been shown to increase the production of cardiac antiinflammatory cytokines in experimental myocarditis. However, the hemodynamic consequences of these differences had not been investigated until today. Therefore, we determined the effects of carvedilol and metoprolol on left ventricular function in a murine model of coxsackievirus B3 (CVB3)-induced myocarditis.

The humoral immune response in viral heart disease: characterization and pathophysiological significance of antibodies.

Several lines of evidence suggest a viral infection as the initiating event for the development of myocarditis (MC). Especially enteroviruses like coxsackie B3 virus have been shown to induce MC in humans and strains of MC-prone mice after an infection. The further course of the disease is, however, determined not only by the viral infection but also by the host's immune system.

Effect of adventitial VEGF(165) gene transfer on vascular thickening after coronary artery balloon injury.

Objective: Experimental studies have provided evidence that neovascularization is an important feature of plaque growth, and angiogenic gene therapy may, therefore, increase plaque growth. This study examined the effect of local (peri)adventitial vascular endothelial growth factor165 (VEGF) gene transfer on vascular thickening after coronary balloon injury.

Methods: Two coronary arteries of 15 pigs were subjected to balloon injury followed by either (peri)adventitial VEGF165 or beta-galactosidase (LacZ) plasmid/liposome-mediated gene transfer via needle injection catheter.

Leukocyte CD15 expression and platelet activation in the coronary sinus after coronary intervention.

Markers associated with coronary restenosis must be identified to develop therapeutic strategies for improving the clinical outcome. We studied whether adhesion proteins on leukocytes and platelets from coronary sinus blood were associated with restenosis after coronary intervention in patients with stable coronary artery disease. Adhesion proteins on platelets and leukocytes were measured by flow cytometry.

Interferon-beta treatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction.

Background: Viral infections are important causes of myocarditis and may induce cardiac dysfunction and finally lead to dilated cardiomyopathy. We investigated whether interferon (IFN)-beta therapy is safe and may achieve virus clearance and prevent deterioration of left ventricular (LV) function in patients with myocardial virus persistence.

Methods And Results: In this phase II study, 22 consecutive patients with persistence of LV dysfunction (history of symptoms, 44+/-27 months) and polymerase chain reaction-proven enteroviral or adenoviral genomes were treated with 18x10(6) IU/week IFN-beta (Beneferon) subcutaneously for 24 weeks.

[Mechanisms of extracellular matrix remodeling in dilated cardiomyopathy].

Background: The mechanisms underlying myocardial remodeling during heart failure have historically been attributed as the consequence of intrinsic changes in cardiac myocytes. Nevertheless, over the last several years, it has become increasingly evident that disruption of extracellular matrix (ECM) homeostasis is also a deciding factor for the progression of myocardial failure.

Pathogenetic Mechanisms: Collagens, the chief components of extracellular matrix, are a tightly regulated family of proteins that determine the structural and functional integrity of heart.

Analysis of the coxsackievirus B-adenovirus receptor gene in patients with myocarditis or dilated cardiomyopathy.

Myocarditis and dilated cardiomyopathy (DCM) are common causes of morbidity and mortality in children and adults, most commonly due to infection with coxsackievirus B or adenovirus. Increased expression of the common human coxsackievirus B-adenovirus receptor (CAR) has been reported in patients with DCM. We investigated the CAR gene in patients with acquired or familial myocarditis/DCM for mutations/polymorphisms.

Collagen degradation in a murine myocarditis model: relevance of matrix metalloproteinase in association with inflammatory induction.

Objective: Myocardial collagen degradation is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinase (TIMPs). The possible relevance of MMPs in association with the inflammatory induction was investigated in a murine coxsackievirus B3 myocarditis model.

Methods: Hearts from viral infected and sham-infected BALB/c mice were analyzed by semi-quantitative RT-PCR, picrosirius red staining, Western blot analysis, and immunohistochemistry.

Endothelial dysfunction of peripheral arteries in patients with immunohistologically confirmed myocardial inflammation correlates with endothelial expression of human leukocyte antigens and adhesion molecules in myocardial biopsies.

Objectives: The aim of this study was to investigate whether myocardial inflammation (MC) and endothelial activation are associated with clinically detectable endothelial dysfunction.

Background: In patients with MC, immunohistologic evaluation of myocardial biopsies demonstrates a cellular infiltrate of lymphocytes in the myocardium and endothelial activation, as indicated by enhanced expression of human leukocyte antigen (HLA)-1, HLA-DR and intercellular adhesion molecule (ICAM)-1. This chronic inflammatory process may be associated with endothelial dysfunction.