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Biomedical subjects

Gerasimos Filippatos

Publications and source records attributed to Gerasimos Filippatos.

30 records · Page 2Linked to original sources
PubMed2005

Levosimendan for the treatment of acute heart failure syndromes.

Levosimendan is a novel calcium-sensitising agent that has been shown to have beneficial inotropic, metabolic and vasodilatory effects in the treatment of acute and advanced chronic heart failure. Levosimendan binds to troponin-C in cardiomyocytes and, thereby, improves cardiac contractility without disturbing the metabolic status of the heart and increasing myocardial oxygen demand or provoking fatal cardiac arrhythmias. Levosimendan also opens ATP-sensitive potassium channels, causing peripheral arterial and venous dilatation, and increasing coronary flow reserve. When it is given as a short-term therapy, levosimendan enhances cardiac output, reduces systemic vascular resistance and lowers pulmonary capillary wedge pressure. Clinical outcomes were significantly reduced in decompensated or postmyocardial infarction heart failure patients who received levosimendan, compared with those on dobutamine or placebo. Recent investigations focusing on the anti-inflammatory and antiapoptotic actions of levosimendan in the failing heart indicate that improvement of cardiac contractile performance is closely related with the drug-induced reduction of circulating pro-inflammatory cytokines and apoptosis inducers. The most common adverse effects of levosimendan treatment are hypotension and headache. Overall, levosimendan represents an effective and safe option for the treatment of decompensated heart failure patients.

Acute Disease↗
PubMed2004

Facilitating internal cardioversion of chronic atrial fibrillation with ibutilide--predictors of atrial defibrillation-threshold decrease.

BACKGROUND: Internal atrial cardioversion has been successfully used in the treatment of atrial fibrillation. The object of this study was to depict the effect of ibutilide on sinus rhythm restoration and internal atrial defibrillation threshold in patients with chronic atrial fibrillation. MATERIAL/METHODS: Twenty-four patients (14 men and 10 women, mean age 63.16+/-8.55 years) with chronic atrial fibrillation were cardioverted using a single-lead system. The distal coil of the defibrillator catheter was placed in the coronary sinus and the proximal coil at the junction of the superior vena cava and the high right atrium. Synchronized biphasic shocks were applied using a step-up protocol from 1 to 30 joules until sinus rhythm was restored. In all patients with successful cardioversion, atrial fibrillation was reinduced and second cardioversion was attempted after intravenous administration of 1 mg ibutilide. RESULTS: Successful internal cardioversion was achieved in 22 (91.6%) and 23 (95.83%) patients before and after ibutilide administration, respectively. The amount of energy given was reduced from 13.89+/-11.44 to 8.28+/-9.64 joules (p=0.0001). Variables associated with the reduction of the defibrillation threshold after ibutilide administration were: duration of the last episode of atrial fibrillation (p=0.008), time since the first episode of atrial fibrillation (p=0.002), body mass index (p=0.01), ejection fraction (p=0.025), male gender (p=0.001), and diameter of the left atrium (p=0.028). CONCLUSIONS: Internal atrial defibrillation after ibutilide administration is a safe and effective method for sinus rhythm restoration, with concurrent significant reduction of the atrial defibrillation threshold.

Aged↗
PubMed2004

Fas induces apoptosis in human coronary artery endothelial cells in vitro.

BACKGROUND: Published work suggests that some types of endothelial cells undergo apoptosis in response to ligation of the receptor Fas (CD95, APO1) but other types are resistant. Because heterogeneity among endothelial cells from different tissues, has been demonstrated, the purpose of this study was to determine, if Fas ligation and/or activation by human Fas ligand induces apoptosis and caspase activities, in cultured human coronary artery endothelial cells, and the differences between TNF-a and FAS induced apoptosis in these cells. RESULTS: Cultured human coronary artery endothelial cells (HCAEC) were exposed to the monoclonal Fas-activating antibody CH-11, to purified recombinant human Fas ligand, to the Fas-neutralizing antibody ZB4, or to purified recombinant human TNF-alpha. Apoptosis was detected by assessment of chromatin condensation and nuclear fragmentation and by assay of the enzymatic activities of Caspase 1 and Caspase 3 with membrane-permeable substrates applied to intact cells. Fas protein was detected by immunoblotting of HCAEC lysates. Apoptosis was induced in HCAEC by purified Fas ligand or by the monoclonal activating antibody CH-11 at concentrations of 25 or 200 ng/ml, but not by nonspecific isotype-matched immunoglobulins. The apoptotic index elicited by either Fas activator was equal to that induced by TNF-a (3.0-3.6-fold versus control, p < 0.01). The Fas-neutralizing antibody ZB4 abrogated HCAEC apoptosis induced by CH-11, but had no inhibitory effect on apoptosis in response to TNF-a. Fas ligation significantly increased the activities of both Caspase 1 and Caspase 3 at 20 hours of stimulation (1.7- and 2.0-fold versus control, both p < 0.05); in contrast, purified TNF-a increased the activity of Caspase 3 but not Caspase 1 (2.1-fold, p < 0.05). Western blotting of HCAEC lysates with antibody CH-11 identified a single immunoreactive protein of 90 kDa. CONCLUSIONS: Cultured human coronary artery endothelial cells express functional Fas capable of inducing apoptosis in response to either purified Fas ligand or receptor-activating monoclonal antibodies, at levels equal to those inducible by purified TNF-alpha. Immunologic studies and differential kinetics of caspase activation suggest that Fas and TNF-alpha induce apoptosis in HCAEC by signaling pathways that are distinct but equal in potency.

Apoptosis↗
PubMed2004

Effect of atrial pressure increase on sinus node automaticity.

There is evidence suggesting that atrial electrophysiological properties may be changed by an acute increase in atrial pressure. The aim of the present study was to investigate the effect of alteration, in atrial pressure on sinus node recovery time. Twelve patients (8 men and 4 women, mean age 61.3 +/- 14.1 years) were included in this study. None of the patients had organic heart disease. Sinus node recovery time (SNRT) was measured following atrial pacing and atrioventricular (AV) pacing at sequential cycle lengths of 600, 545, 500, 461, 428, and 400 ms with two different AV intervals (150, 0 ms). Peak and minimal atrial pressure increased significantly from 8.5 +/- 2.8 to 20.1 +/- 2.9 mmHg (11.56 +/- 3.8 to 27.3 +/- 3.9 cmH2O) ( P=0.001) and from 2.06 +/- 1.69 to 5.33 +/- 2.9 mmHg (2.8 +/- 2.29 to 7.2 +/- 3.9 cmH2O), respectively (P=0.002) during AV interval modification. Sinus node recovery time did not change despite the increase in atrial pressure. Autonomic blockade had no effect on SNRT. This study demonstrates that atrial pressure increase does not significantly affect sinus node automaticity expressed by SNRT.

Adult↗
PubMed2004

Temporary assist device for postcardiotomy cardiac failure.

Postcardiotomy left ventricular failure (LVF) complicating a cardiac surgical procedure is usually managed with intraaortic balloon pump (IABP) counterpulsation. We report two cases of postcardiotomy LVF unresponsive to inotropic support and IABP counterpulsation that were managed successfully with the use of the TandemHeart percutaneous ventricular assist device (pVAD) (CardiacAssist, Pittsburgh, PA). The TandemHeart pVAD appears to be safe and effective as a bridge to recovery in the treatment of postcardiotomy cardiac failure.

Aged↗
PubMed2004

Apoptosis in lung injury and remodeling.

The mode of cell death termed apoptosis, sometimes referred to as programmed cell death, is as critical a determinant of cell population size as is cell proliferation. Although best characterized in cells of the immune system, apoptosis is now known to be a key factor in the maintenance of normal cell turnover within structural cells in the parenchyma of virtually every organ. Recent interest in apoptosis in the lung has sparked a surge of investigations designed to determine the roles of apoptosis in lung development, injury, and remodeling. Of particular recent interest are the roles of apoptosis in disease pathogenesis and resolution, in which the concept of apoptosis as a "programmed" cell death, i.e., genetically determined, is often more accurately viewed as "inappropriate cell suicide" with regard to its extent and/or timing. Data accumulating over the past decade have made clear the complexity of the control of lung cell apoptosis; concepts of the regulation of apoptosis originally determined in classical cell culture models are often, but not always, applicable to structural cells. For this reason, each of the many cell types of the lung must be studied as a potentially new subject with its own idiosyncrasies yet to be discovered. In light of the large volume of literature now available, this article focuses on the roles of apoptosis in three pathophysiological contexts: acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. Each section presents key data describing the evidence for apoptosis in the lung, its possible relevance to disease pathogenesis, and proposed mechanisms that might suggest potential avenues for therapeutic intervention.

Animals↗
PubMed2003

Inhibition of amiodarone-induced lung fibrosis but not alveolitis by angiotensin system antagonists.

Earlier work in this laboratory showed that amiodarone induces apoptosis in alveolar epithelial cells by a mechanism inhibitable by angiotensin system antagonists. A variety of recent studies suggests a critical role for alveolar epithelial cell apoptosis in the pathogenesis of lung fibrosis. On this basis we hypothesized that amiodarone-induced alveolar epithelial cell apoptosis and lung fibrosis in vivo might be inhibitable by the angiotensin converting enzyme inhibitor captopril or the angiotensin receptor antagonist losartan. Amiodarone-induced lung fibrosis was induced in male Wistar rats by oral administration over six months. Replicate groups of rats received captopril or losartan in addition to amiodarone. Apoptosis was detected by increased total lung activity of caspase 3 and in situ end labeling (ISEL) of fragmented DNA. Collagen was localized and quantitated by the picrosirius red technique. Alveolar epithelial cell apoptosis was detected in amiodarone-treated animals as early as three weeks after the start of amiodarone administration; by six months exposure, the incidence of alveolar epithelial cell apoptosis was significantly reduced by coadministration of captopril or losartan. Alveolar wall collagen accumulation also was significantly attenuated by captopril (100%) or losartan (74%), but neither agent blunted the accumulation of alveolar macrophages evoked by amiodarone (5.3-fold at 6 months). Lung neutrophil content was unchanged by amiodarone treatment for three weeks or six months. These results indicate that amiodarone induces alveolar epithelial cell apoptosis in vivo that is inhibitable by angiotensin antagonists. They also support the hypothesis that blockade of angiotensin formation or function attenuates amiodarone-induced lung fibrosis irrespective of the severity of alveolitis.

Amiodarone↗
PubMed2003

Blockade of apoptosis by ACE inhibitors and angiotensin receptor antagonists.

Inhibitors of angiotensin converting enzyme (ACE-Is) and angiotensin (ANG) receptor antagonists were originally developed to aid in the management of hypertension. As the use of these agents was extended to the management of heart failure and other cardiovascular diseases, studies of tissue remodeling suggested that blockade of ANGII function might play a role in the regulation of cell death by apoptosis. Experiments with cultured cells confirmed that ANGII is an inducer of apoptosis in well differentiated cell types isolated from the heart, kidneys, lungs and other organs. More recent evidence with animal models strongly suggests that ACE-Is and ANG receptor antagonists, in addition to affecting hemodynamics, also influence disease progression through direct inhibition of ANG-induced apoptosis. This manuscript reviews the evidence supporting this view, discusses its potential relevance to disease pathogenesis and offers new hypotheses regarding novel uses of ACE-Is and ANG receptor antagonists in the control of cell death.

Angiotensin II↗
PubMed2003

Chemokines in cardiovascular remodeling: clinical and therapeutic implications.

Chemokines are newly discovered molecules that mediate the migration of leukocytes into inflammed tissues and control the inflammatory reactions in various immune-mediated diseases. Both in animal models and in human specimens, chemokine expression is associated with atherosclerotic lesion development and vascular remodeling and restenosis after angioplasty. Furthermore, recent studies have demonstrated that chemokines play an important role in the pathophysiology of acute coronary syndromes, post-infarction left ventricular remodeling and chronic heart failure. The capacity to control activation and movement of inflammatory cells suggests that chemokines and their receptors might provide novel targets for therapeutic intervention in a number of conditions characterized by chronic inflammation, including cardiovascular diseases. The present review summarizes current knowledge regarding the potential pathogenic role of chemokines in major cardiovascular disorders, as well as the modulation of the chemokine network as a novel, interesting therapeutic modality in this field.

Animals↗
PubMed2002

Cytokines and anti-cytokine therapeutic approaches to chronic heart failure.

Recent investigations have shown that, in addition to neurohormonal system overactivation, another class of biologically active molecules, termed cytokines, is also overexpressed in the setting of chronic heart failure and participates actively in the progression of the syndrome. In this article, we present recent experimental and clinical data describing the pathophysiological role of cytokines in left ventricular remodeling, endothelial dysfunction, and peripheral myopathy characterizing the progression of chronic heart failure, as well as novel therapeutic approaches aimed at attenuating the deleterious effects of cytokines on the cardiovascular system.

Journal Article↗