Epicardial Tissue Research Articles

Tcf21+ epicardial cells adopt non-myocardial fates during zebrafish heart development and regeneration

Recent lineage-tracing studies have produced conflicting results about whether the epicardium is a source of cardiac muscle cells during heart development. Here, we examined the developmental potential of epicardial tissue in zebrafish during both embryonic development and injury-induced heart regeneration. We found that upstream sequences of the transcription factor gene tcf21 activated robust, epicardium-specific expression throughout development and regeneration. Cre recombinase-based, genetic fate-mapping of larval or adult tcf21(+) cells revealed contributions to perivascular cells, but not cardiomyocytes, during each form of cardiogenesis. Our findings indicate that natural epicardial fates are limited to non-myocardial cell types in zebrafish.

Prominent isovolumic relaxation flow in a patient with cardiac tamponade.

We present herein the case of a 72-year-old man who presented with orthopnea and was diagnosed with cardiac tamponade due to carcinomatous pericarditis. Pulsed Doppler echocardiogram showed prominent isovolumic relaxation flow (IVRF) directed from the cardiac base toward the apex. Such flow is rare in pericardial effusion and may be due to enhanced early diastolic untwisting, sphericalization of apex, and restriction of wall motion by epicardial fibrous tissue. We describe herein a rare case of prominent IVRF with interesting underlying mechanisms.

Tumormarker im Perikarderguss bei malignen und nichtmalignen Perikardergüssen

The differential diagnosis of pericardial effusion is often challenging because different etiologies can be discussed. Of particular therapeutic and prognostic importance is the definitive differentiation of malignant pericardial effusion from benign effusions. The definitive diagnosis of malignant pericardial effusion is established by a positive cytological examination of the pericardial fluid. However, pericardial fluid cytology, although specific has variable sensitivity. Tumor markers are often investigated after pericardiocentesis but their utility as an aid for the diagnosis of malignant pericardial effusion is not well established. The aim of this study was to measure the concentrations of the tumor markers CEA, CA 19-9, CA 72-4, SCC and NSE in malignant and non-malignant pericardial effusions and to assess their diagnostic utility in differentiating malignant from benign pericardial effusion. We investigated the pericardial fluid of 29 patients with proven malignant pericardial effusion and 25 patients with non-malignant pericardial effusion. The etiology of the pericardial effusion was defined by pericardial cytology, epicardial histology and PCR for cardiotropic viruses from pericardial and epicardial tissue acquired by pericardioscopy. The group with non-malignant pericardial effusion comprised 15 patients with autoreactive effusion and 10 patients with viral pericardial effusion. We analyzed the following tumor markers in the pericardial fluid: carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, carbohydrate antigen (CA) 72-4, squamous cell carcinoma (SCC) antigen and neuron-specific enolase (NSE). Of the tumor markers tested the mean concentrations of the CEA, CA 72-4 and CA 19-9 were significantly higher in malignant pericardial effusions than in non-malignant effusions (CEA 450.66 ±1620.58 µg/l vs. 0.72 ±1.49 µg/l, p<0.001; CA 19-9 1331.31 ±3420.87 kU/l vs. 58.85 ±17.53 kU/l, p=0.04; CA 72-4 707.90 ±2397.55 kU/l vs. 0.48 ±2.40 kU/l, p<0.001). ROC curve analysis showed that pericardial fluid CA 72-4 yielded an area under the curve (AUC) of 0.85 (95% confidence interval 0.74-0.95), followed by CEA with 0.80 (95% confidence interval 0.68-0.92). Pericardial fluid CA 72-4 levels >1.0 kU/l had 72% sensitivity (95% confidence interval 53%-87%) and 96% specificity (95% confidence interval 80%-99.9%) and CA 72-4 levels >2.5 kU/l had 69% sensitivity (95% confidence interval 49%-85%) and 96% specificity (95% confidence interval 80%-99.9%) in differentiating malignant pericardial effusions from effusions due to benign conditions. Malignant pericardial effusions are associated with significantly higher pericardial concentrations of the tumor markers CEA, CA 72-4 and CA 19-9. Of the tested tumor markers, measurement of CA 72-4 levels in pericardial fluid offered the best diagnostic accuracy. Based on our data evaluation of every patient with unexplained pericardial effusion and negative pericardial fluid cytology should include the measurement of pericardial fluid CA 72-4 levels. Under these circumstances the elevation of pericardial fluid CA 72-4 levels should include malignancy as a probable diagnosis.

Pericardial Myxoid Liposarcoma in a Common Eland ( Taurotragus oryx)

A pericardial myxoid liposarcoma was diagnosed in a common eland (Taurotragus oryx) based on gross, microscopical and immunohistochemical findings. The pericardial and epicardial tissues were soft and uniformly thickened. Microscopically, the neoplastic mass consisted of stellate cells embedded in a myxoid matrix. These cells contained cytoplasmic vacuoles stained by oil red O. Immunohistochemical analysis showed the neoplastic cells to express vimentin and S-100.

NADH as an Endogenous Marker of Cardiac Tissue Injury at the Site of Radiofrequency Ablation

Atrial fibrillation (AF) remains the most commonly occurring cardiac arrhythmia; its incidence is associated with a lower quality of life including a higher rate of morbidity & mortality. Percutaneous left atrial catheter ablation for the purpose of eliminating AF has become a common treatment option and is currently being investigated for superiority over medical therapy in a large clinical trial. RFA produces lesions that can block the spread of electrical activity from the sites of abnormal activity including pulmonary veins. Today, there are limited means for real time monitoring of tissue injury during the RFA procedure. To address this need, we explored the fluorescence of endogenous NADH as a possible live marker of tissue injury during the ablation procedure. Studies were conducted in blood-free and blood-perfused isolated rat hearts. Epicardial RFA lesions were seen as areas of low NADH fluorescence which encompassed both irreversible and reversibly damaged tissue. Their size significantly exceeded TTC negative staining (TTC - Triphenyl Tetrazolium Chloride, a redox indicator used to differentiate between metabolically active and inactive tissues). Real-time monitoring of NADH fluorescence allowed visualization of gaps of viable tissue between the RFA lesions. Dual recordings of NADH and epicardial electrical activity linked these gaps to the occurrence of post-ablation reentries. We conclude that fluorescence of endogenous NADH can assist visualization of injured epicardial tissue near the tip of the RFA catheter lesions.

Effect of dronedarone on Na+, Ca2+ and HCN channels

Previous studies showed that amiodarone causes state-dependent inhibition of Na(+) channels thereby mediating an atrial-selective drug effect. The aim of the present study was to investigate the impact of the new antiarrhythmic compound dronedarone on Na(+), Ca(2+) and hyperpolarization-activated cyclic nucleotide-gated ion channels. Monophasic action potentials (MAP) and effective refractory period (ERP) were studied in arterially perfused left atria and ventricular wedge preparations of the pig. Fast Na(+) and Ca(2+) currents in isolated guinea pig ventricular myocytes as well as human HCN4 channels expressed in Chinese hamster ovary (CHO) cells were investigated with the patch-clamp technique. In left atrial epicardial tissue, dronedarone (3μM) had no effect on the MAP duration, but the drug caused a significant prolongation of the ERP from 145 ± 9 to 184 ± 17ms (n = 6; p < 0.05). In guinea pig ventricular myocytes, dronedarone exhibited a state-dependent inhibition of the fast Na(+) channel current with an IC(50) of 0.7 ± 0.1μM, when the holding potential (V (hold)) was -80mV. The maximal block at the highest concentration used was 77 ± 8%. In contrast, when V (hold) was -100mV, inhibition with 10μM dronedarone was only 9 ± 3% (n = 7). Dronedarone blocked Ca(2+) currents elicited by rectangular pulses at V (hold) = -40mV with an IC(50) value of 0.4 ± 0.1μM (maximal block by 10μM dronedarone, 80 ± 6%), whereas at V (hold) = -80mV, 10μM dronedarone blocked only 20 ± 6% (n = 4) of the current. Applying an action potential clamp (V (hold) = -80mV) yielded an IC(50) of 0.4 ± 0.3μM. Human HCN4 channels expressed in CHO cells were blocked by dronedarone with an IC(50) of 1.0 ± 0.1μM. Inhibition of fast Na(+) and Ca(2+) channels by dronedarone depends on the cell's resting membrane potential (state-dependent block) favouring an atrial-selective mode of action. Besides fast Na(+) and Ca(2+) channels, dronedarone also inhibits HCN4 currents. This might contribute to the clinically observed reduction in heart rate seen in patients in sinus rhythm after dronedarone treatment.

Epicardial Lipomatous Hypertrophy Mimicking Pericardial Effusion

HomeCirculation: Cardiovascular ImagingVol. 4, No. 1Epicardial Lipomatous Hypertrophy Mimicking Pericardial Effusion Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsFree AccessResearch ArticlePDF/EPUBEpicardial Lipomatous Hypertrophy Mimicking Pericardial EffusionCharacterization With Cardiovascular Magnetic Resonance Christopher A. Miller, MRCP and Matthias Schmitt, MD, PhD Christopher A. MillerChristopher A. Miller From the Cardiovascular Magnetic Resonance Unit, North West Regional Cardiac Centre, University Hospital of South Manchester, Manchester, United Kingdom. Search for more papers by this author and Matthias SchmittMatthias Schmitt From the Cardiovascular Magnetic Resonance Unit, North West Regional Cardiac Centre, University Hospital of South Manchester, Manchester, United Kingdom. Search for more papers by this author Originally published1 Jan 2011https://doi.org/10.1161/CIRCIMAGING.110.957498Circulation: Cardiovascular Imaging. 2011;4:77–78IntroductionA 62-year-old man with no history of cardiac disease was referred because of exertional dyspnea. His body mass index was elevated at 29 kg/m2, and a large cutaneous lipoma was present on his abdominal wall. Transthoracic echocardiography was performed and initially reported to demonstrate a moderate-sized global pericardial effusion (Figure 1 and Movies 1 and 2). Consideration was given to pericardiocentesis; however, subsequent review suggested that the appearances may have been due to pericardial thickening (Movie 3). Cardiovascular magnetic resonance (CMR) imaging was performed for clarification.Download figureDownload PowerPointFigure 1. Echocardiographic images. Parasternal long-axis (A) and short-axis (B) views showing the echolucent zone surrounding the heart that was mistaken for a pericardial effusion (asterisk, dashed line). LV indicates left ventricle; RV, right ventricle; LA, left atrium; and Ao, aorta.A thick layer of epicardial tissue, measuring up to 29 mm deep, was seen to surround the myocardium on balanced steady-state free precession (SSFP) cine images (Figure 2 and Movie 4). On both SSFP and half-Fourier single-shot fast spin-echo images, signal intensity was high, indeed identical to that from subcutaneous fat. Using a spatial modulation of magnetization sequence (“tagging”), the epicardial tissue appeared to be adherent to the myocardium (Movie 5). The interatrial septum was also markedly thickened (23 mm), with sparing of the fossa ovalis, and had the same high signal intensity (Figure 2C). Fast spin-echo images with a fat-saturation inversion recovery prepulse (which significantly reduces, or “nulls,” the signal from fat) confirmed the epicardial and interatrial septal tissue to be fat (Figure 3). A diagnosis of epicardial lipomatous hypertrophy with concomitant lipomatous hypertrophy of the interatrial septum was made. The pericardium itself was thin and of normal appearance, with no evidence of pericardial effusion; indeed, the contrast provided by the fat allowed for unusually good delineation of the pericardium, highlighting its cranial extension.Download figureDownload PowerPointFigure 2. Cardiovascular magnetic resonance SSFP images. Left ventricular outflow tract (A), short-axis (B), 4-chamber (C), and coronal (D) images showing extensive epicardial lipomatous hypertrophy (asterisk) and lipomatous hypertrophy of the interatrial septum (double dagger). The pericardium (arrows) has a normal appearance, and its cranial extension is particularly evident (D) due to the contrast provided by the fat. RA indicates right atrium; PA, pulmonary artery.Download figureDownload PowerPointFigure 3. Cardiovascular magnetic resonance fat saturation images. In the corresponding fat-saturation fast spin-echo 4-chamber (A, corresponding to Figure 2C) and coronal (B, corresponding to Figure 2D) views, the signal from the epicardial (asterisk) and atrial septal (double dagger) lipomatous hypertrophy is “nulled,” confirming its fatty composition.Cardiac lipomatosis is characterized by the accumulation of nonencapsulated mature adipose tissue caused by hyperplasia of lipocytes. The etiology is unknown, but it may be associated with obesity and advancing age.1 The most frequent manifestation is lipomatous hypertrophy of the interatrial septum. Massive epicardial lipomatous hypertrophy is less well documented. Although histologically benign, it has been reported to cause cardiac tamponade, requiring decompressive pericardiectomy.2 In the presented case, cine imaging demonstrated normal right heart and caval appearances, phase contrast imaging with velocity encoding demonstrated normal systemic venous inflow, and on real-time, free-breathing imaging, ventricular septal motion was seen to be normal, all of which suggested reassuring cardiac filling physiology.The case highlights the possibility of mistaking epicardial lipomatous hypertrophy for pericardial effusion on transthoracic echocardiography. The tissue characterization provided by CMR allowed the diagnosis to be made, avoiding the need for invasive investigation or unnecessary intervention. The functional data provided by CMR suggested that the epicardial lipomatous hypertrophy was not affecting cardiac function.DisclosuresNone.FootnotesThe online-only Data Supplement is available at http://circimaging.ahajournals.org/cgi/content/full/CIRCIMAGING.110.957498/DC1.Correspondence to Dr Christopher Miller, Cardiovascular Magnetic Resonance Unit, North West Regional Cardiac Centre, University Hospital of South Manchester, Southmoor Road, Wythenshawe, Manchester, UK. E-mail [email protected]org.uk

Heterogeneous memory in restitution of action potential duration in pig ventricles

BackgroundRestitution of action potential duration and memory importantly affect electrical stability in ventricles. Studies have reported heterogeneous restitution among different regions of the ventricles. However, existence of heterogeneity in memory is not as well investigated. MethodsTransmembrane potentials were recorded in endocardial and epicardial tissues from both ventricles of farm pigs. Pacing protocols with sinusoidally changing diastolic intervals were used to reveal hysteresis in restitution, from which quantitative measures of memory were calculated. ResultsLarger measures of hysteresis were observed in the endocardium than the epicardium (P < .05): loop thickness (in milliseconds), 26.9 vs 16.2; overall tilt, 0.376 vs 0.249; and loop area (in square milliseconds), 7288 vs 4146. Except for overall tilt, no significant differences in these measures were observed between ventricles. ConclusionHeterogeneity in memory exists in pig ventricles. Because regions with the steepest restitution may also have the largest memory, our results suggest that heterogeneity in memory should also be factored in when predicting electrical stability.

Paroxysmal β-adrenergic Receptor-mediated Alterations in Ventricular Repolarization at Rapid Heart Rates During Inhibition of Delayed Rectifier Currents

The contribution of the slow component of the delayed rectifier current (IKs) to ventricular repolarization is increased during rapid heart rates and prolonged repolarization. The objective was to characterize physiologically relevant paroxysmal beta-adrenergic receptor-mediated alterations on ventricular repolarization under these conditions. Paced guinea pig hearts were perfused with (1) control, (2) sparfloxacin (IKr inhibitor), or (3) sparfloxacin and HMR 1556 (IKs inhibitor). The mean +/- standard error of the mean epicardial action potential duration at 90% repolarization (APD90) increased from baseline with IKr inhibition (12.9% +/- 4.7%) and dual IKr/IKs inhibition (25.1% +/- 5.3). Paroxysmal isoproterenol (0.01 and 1.0 nM) significantly decreased APD90 in the presence of IKr inhibition but was attenuated with the addition of IKs inhibition. Spontaneous episodes of polymorphic ventricular tachycardia were observed with isoproterenol during dual IKr and IKs inhibition. The endocardial expression of KCNQ1 increased greater than 2-fold after exposure to IKr and dual IKr/IKs inhibition relative to control but was not altered in epicardial tissue. The beta-adrenergic receptor-mediated decrease in APD90 during IKr inhibition is reversed in the presence of IKs inhibition at rapid heart rates. IKs may serve as an important compensatory mechanism to protect against adrenergically induced arrhythmias when the repolarization reserve is depleted.

Reexcitation mechanisms in epicardial tissue: Role of Ito density heterogeneities and INa inactivation kinetics

Dispersion of action potential repolarization is known to be an important arrhythmogenic factor in cardiopathies such as Brugada syndrome. In this work, we analyze the effect of a variation in sodium current ( I Na) inactivation and a heterogeneous rise of transient outward current ( I to) in the probability of reentry in epicardial tissue. We use the Luo–Rudy model of epicardial ventricular action potential to study wave propagation in a one-dimensional fiber. Spatial dispersion in repolarization is introduced by splitting the fiber into zones with different strength of I to. We then analyze the pro-arrhythmic effect of a variation in the relaxation time and steady-state of the sodium channel fast inactivating gate h. We quantify the probability of reentry measuring the percentage of reexcitations that occurs in 200 beats. We find that, for high stimulation rates, this percentage is negligible, but increases notably for pacing periods above 700 ms. Surprisingly, with decreasing I Na inactivation time, the percentage of reexcitations does not grow monotonically, but presents vulnerable windows, separated by values of the I Na inactivation speed-up where reexcitation does not occur. By increasing the strength of L-type calcium current I CaL above a certain threshold, reexcitation disappears. Finally, we show the formation of reentry in stimulated two-dimensional epicardial tissue with modified I Na kinetics and I to heterogeneity. Thus, we confirm that while I to dispersion is necessary for phase-2 reentry, altered sodium inactivation kinetics influences the probability of reexcitation in a highly nonlinear fashion.

Early Constrictive Epicarditis After Coronary Artery Bypass Surgery

A patient with constrictive pericarditis early after coronary bypass surgery is presented. At reoperation a dense inflammatory process was encountered on the epicardial surface of the heart with minimal pericardial thickening. Crosshatching of the epicardial scar tissue produced an immediate and durable clinical response.

Focal and Linear Endocardial and Epicardial Catheter‐Based Cryoablation of Normal and Infarcted Ventricular Tissue

This study of a chronic porcine postinfarction model examined whether linear epicardial cryoablation was capable of creating large, homogenous lesions in regions of the myocardium including scarred ventricle. Endocardial and epicardial focal cryolesions were also compared to determine if there were significant differences in lesion characteristics. Eighty focal endocardial and 28 focal epicardial cryoapplications were delivered to eight normal caprine and four normal porcine ventricular myocardium, and 21 linear cryolesions were applied along the border of infarcted epicardial tissue in a chronic porcine infarct model in six swines. Focal endocardial cryolesions in normal animals measured 9.7+/-0.4 mm (length) by 7.3+/-1.4 mm (width) by 4.8+/-0.2 mm (depth), while epicardial lesions measured 10.2+/-1.4 mm (length) by 7.7+/-2 mm (width) by 4.6+/-0.9 mm (depth); P > 0.05. Linear epicardial cryolesions in the chronic porcine infarct model measured 36.5+/-7.8 mm (length) by 8.2+/-1.3 mm (width) by 6.0+/-1.2 mm (depth). The mean depth of linear cryolesions applied to the border of the infarct scar was 7+/-0.7 mm, as measured by magnetic resonance imaging. Cryoablation can create deep lesions when delivered to the ventricular epicardium. Endocardial and epicardial cryolesions created by a focal cryoablation catheter are similar in size and depth. The ability to rapidly create deep linear cryolesions may prove to be beneficial in substrate-based catheter ablation of ventricular arrhythmias.

Accessory Atrioventricular Pathways

By definition, accessory atrioventricular pathways are aberrant muscle bundles that connect the atrium to a ventricle outside of the regular atrioventricular conduction system. Clinically, they may manifest as substrates for ventricular preexcitation. The first accessory pathway in a patient who suffered from Wolff-Parkinson-White syndrome was described in 1943 by Wood, Wolferth, and Geckler.1 Shortly after, Ohnell created a reconstruction of an accessory pathway that very elegantly showed the close proximity of the pathway to the fibrous attachment of the mitral valve and its relationship with the sulcus coronarius (Figure, A).2 Subsequent histological studies have demonstrated unequivocally that these pathways are the anatomic substrates for the classical Wolff-Parkinson-White variety of preexcitation. Figure. A, Ohnell’s depiction of an accessory bundle in the left atrioventricular groove.2 Reprinted with permission from Blackwell Publishing. B, Histological section stained with Masson’s trichrome (fibrous tissue in green and myocardium in red) to show an accessory left-sided pathway (arrow) skirting the mitral annulus. C, Histological section showing a broad right-sided accessory pathway (arrow) that is formed by a myocardial pouch extending from the right atrial appendage to the ventricle and ultimately traced to a small right ventricular vein. This pathway is some distance from the fibrous annulus of the tricuspid valve. *Valvar annulus. Article p 1508 Accessory atrioventricular pathways are found most often in the parietal atrioventricular junctional areas, including the paraseptal areas. They breach the insulation provided by the fibrofatty tissues of the atrioventricular groove (sulcus tissue) and the hingelines (fibrous annulus) of the valves. They are rarely found in the area of fibrous continuity between the aortic and mitral valves because in this area, there is usually a wide gap between the atrial myocardium and ventricular myocardium to accommodate the aortic outflow tract. On the left parietal side, the accessory pathways tend …

Adaptive processing of contrast enhanced ultrasonic diagnostic images

A method is described for automatically and accurately defining tissue borders within ultrasound imaging. A preferred embodiment described provides for accurately delineating endocardial and epicardial tissue borders during ultrasound imaging of the heart using contrast agents. The inventive method requires first defining a set of threshold values corresponding to various imaging depths and correlated within the image. The invention further uses the set of threshold values and a maximization function to accurately identify the tissue boundaries.

Spatial-temporal filter effect in a computer model study of ventricular fibrillation / Räumlicher und zeitlicher Filtereffekt in einer Computermodellstudie zum Herzkammerflimmern

Prediction of countershock success from ventricular fibrillation (VF) ECG is a major challenge in critical care medicine. Recent findings indicate that stable, high frequency mother rotors are one possible mechanism maintaining VF. A computer model study was performed to investigate how epicardiac sources are reflected in the ECG. In the cardiac tissues of two computer models - a model with cubic geometry and a simplified torso model with a left ventricle - a mother rotor was induced by increasing the potassium rectifier current. On the epicardium, the dominant frequency (DF) map revealed a constant DF of 23 Hz (cubic model) and 24.4 Hz (torso model) in the region of the mother rotor, respectively. A sharp drop of frequency (3-18 Hz in the cubic model and 12.4-18 Hz in the torso model) occurred in the surrounding epicardial tissue of chaotic fibrillatory conduction. While no organized pattern was observable on the body surface of the cubic model, the mother rotor frequency can be identified in the anterior surface of the torso model because of the chosen position of the mother rotor in the ventricle (shortest distance to the body surface). Nevertheless, the DFs were damped on the body surfaces of both models (4.6-8.5 Hz in the cubic model and 14.4-16.4 Hz in the torso model). Thus, it was shown in this computer model study that wave propagation transforms the spatial low pass filtering of the thorax into a temporal low pass. In contrast to the resistive-capacitive low pass filter formed by the tissue, this spatial-temporal low pass filter becomes effective at low frequencies (tens of Hertz). This effect damps the high frequency components arising from the heart and it hampers a direct observation of rapid, organized sources of VF in the ECGs, when in an emergency case an artifact-free recording is not possible.

In Vitro Effects of Acute Amiodarone and Dronedarone on Epicardial, Endocardial, and M Cells of the Canine Ventricle

Amiodarone (AM) is an antiarrhythmic agent widely used in the treatment of ventricular and supraventricular arrhythmias. Dronedarone (DR) is a new compound with a pharmacological profile similar to that of AM, but iodine free. We previously demonstrated that chronic AM treatment reduces transmural dispersion of repolarization (TDR) in the canine heart. We used standard microelectrode technique to evaluate the effects of acute AM (100 microM) and DR (30 microM) on epicardial (EPI), endocardial (ENDO), and M region tissues obtained from the left ventricular wall of the canine heart. Amiodarone (100 microM, 120 min of exposure) produced little change in the action potential duration of ENDO and EPI tissues, but it shortened the action potential of M cells, especially at slow rates, leading to a decrease in TDR. Similar results were observed with DR. Acute AM (100 microM) and DR (30 microM) eliminated d-sotalol-induced early afterdepolarizations (EADs) and triggered activity in 3 of 3 and 2 of 6 M cell preparations, respectively. The reduction of TDR and the elimination of EAD-induced triggered activity differentiates AM and DR from other class III agents. These effects may explain the efficacy and low arrhythmogenicity of acute AM and suggest a potential safe use of DR as an antiarrhythmic agent.

Regulated addition of new myocardial and epicardial cells fosters homeostatic cardiac growth and maintenance in adult zebrafish

The heart maintains structural and functional integrity during years of continual contraction, but the extent to which new cell creation participates in cardiac homeostasis is unclear. Here, we assessed cellular and molecular mechanisms of cardiac homeostasis in zebrafish, which display indeterminate growth and possess an unusual capacity to regenerate after acute cardiac injury. Lowering fish density in the aquarium triggered rapid animal growth and robust cardiomyocyte proliferation throughout the adult ventricle, greater than that observed during slow animal growth or size maintenance. Rapid animal growth also induced strong expression of the embryonic epicardial markers raldh2 (aldh1a2) and tbx18 in adult epicardial tissue. Pulse-chase dye labeling experiments revealed that the epicardium recurrently contributes cells to the ventricular wall, indicating an active homeostatic process. Inhibition of signaling by Fibroblast growth factors (Fgfs) decreased this epicardial supplementation of the ventricular wall in growing zebrafish, and led to spontaneous ventricular scarring in animals maintaining cardiac size. Our results demonstrate that the adult zebrafish ventricle grows and is maintained by cardiomyocyte hyperplasia, and that epicardial cells are added to the ventricle in an Fgf-dependent fashion to support homeostasis.

A Review of Clinical Trials with Eptifibatide in Cardiology

Glycoprotein (GP) IIb/IIIa receptor antagonists inhibit the binding of ligands to activated platelet GP IIb/IIIa receptors and, therefore, prevent the formation of platelet thrombi. Additional antithrombin therapy should be given in connection with GP IIb/IIIa administration. Eptifibatide is a small heptapeptide, which is highly selective and rapidly dissociates from its receptor after cessation of therapy. In clinical trials (IMPACT-II and ESPRIT) concomitant administration of eptifibatide to patients undergoing percutaneous coronary intervention (PCI) reduced thrombotic complications. In the PURSUIT trial, in patients with non-ST-elevation acute coronary syndromes, eptifibatide, compared to placebo, significantly reduced the primary endpoint of death and nonfatal myocardial infarction at 30 days. In patients with STEMI eptifibatide has been studied as an adjunct to fibrinolysis and primary PCI; it improved epicardial flow and tissue reperfusion. Current studies are evaluating eptifibatide as upstream therapy in high-risk patients with NSTE-ACS, in the EARLY-ACS and in comparison with abciximab in patients with primary PCI in the EVA-AMI trial.

Multilayer radial systolic strain can identify subendocardial ischemia: An experimental tissue Doppler imaging study of the porcine left ventricular wall

This study investigates whether subendocardial ischemia can be detected by measuring multilayer radial systolic strain from epicardial tissue Doppler imaging. In 10 anesthetized open-chest pigs an extracorporeal shunt from the proximal brachiocephalic to the left anterior descending coronary artery was constricted in steps. Color microsphere injections and short axis Tissue Velocity Imaging (TVI) recordings were performed with open shunt, with a non-significant stenosis, and with 2 steps of shunt flow reduction. With open shunt and no transmural flow gradient, there was a gradient of peak ejection strain with high values subendocardially for both 4 and 2 layer measurements. For 2 layer measurement strain was 56.0+/-10.5% subendocardially and 22.0+/-5.2% subepicardially. A non-significant stenosis, not altering transmural flow distribution, reduced strain to 40.3+/-5.4% in the endocardial half-layer. With reduced shunt flow resulting in subendocardial ischemia, peak ejection strain decreased further, primarily in inner wall layers, and postsystolic strain became evident. At severe stenosis (52.4+/-1.8% shunt flow reduction) strain was reduced to 3.8+/-3.6% in the subendocardium and 0.0+/-2.6% in the subepicardium. Evaluation of myocardial function with multilayer radial systolic strain has a potential for detecting subendocardial ischemia.

The role of eptifibatide in patients undergoing percutaneous coronary intervention

Glycoprotein (GP) IIb/IIIa receptor antagonists inhibit the binding of ligands to activated platelet GP IIb/IIIa receptors and, therefore, prevent the formation of platelet thrombi. They have been extensively studied in patients undergoing percutaneous coronary intervention (PCI). Eptifibatide, one of the approved GP IIb/IIIa inhibitors, is a small heptapeptide that is highly selective and rapidly dissociates from its receptor after cessation of therapy. In clinical studies, concomitant administration of eptifibatide in patients undergoing elective PCI reduced thrombotic complications in the IMPACT-II (Integrilin to Minimize Platelet Aggregation and Prevent Coronary Thrombosis II) and ESPRIT (Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy) trials. In the PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) trial, which included 10,948 patients with non-ST-elevation acute coronary syndromes, eptifibatide significantly reduced the primary end point of death and non-fatal myocardial infarction at 30 days compared with placebo. In patients with ST-segment elevation myocardial infarction (STEMI), eptifibatide has been studied as adjunct to primary PCI and improved epicardial flow and tissue reperfusion. Studies are now evaluating eptifibatide in high-risk patients with non-ST elevation acute coronary syndromes (NSTE-ACS) and a planned early invasive strategy in the EARLY-ACS (Eptifibatide Administration prior to Diagnostic Catherization and Revascularization to Limit Myocardial Necrosis in Acute Coronary Syndrome) trial and in patients with primary PCI for STEMI in comparison to abciximab in the EVA-AMI (Eptifibatide versus Abciximab in Primary PCI for Acute Myocardial Infarction) trial. After the completion of these trials, the value of eptifibatide in patients undergoing PCI in different indications can be determined.