Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ENDOCARDIUM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources
PubMed1995

Endocardial mapping of ventricular tachycardia in the intact human ventricle. III. Evidence of multiuse reentry with spontaneous and induced block in portions of reentrant path complex.

OBJECTIVES: This study was conducted to characterize the functional nature of the reentrant tract responsible for ventricular tachycardia due to ischemic heart disease. BACKGROUND: A zone of slow conduction forming the return path is though to form a critical component of the reentrant mechanism in ventricular tachycardia. Despite its importance, detailed knowledge of the return path is rare in clinical studies. METHODS: Multielectrode arrays were used intraoperatively to obtain unipolar and high gain bipolar recordings of left ventricular endocardium in patients undergoing map-directed surgical ablation of ventricular tachycardia. A total of 224 local electrograms were analyzed for each tachycardia. RESULTS: Of 10 consecutive patients undergoing intraoperative cardiac mapping, detailed recording of the return tracts of eight ventricular tachycardias were obtained in three patients. The recordings demonstrated that return tracts can be complex and extensive, with multiple paths of entry and exit. Potential and actual alternate paths were observed. Spontaneous and induced block occurred within portions of the complex. Intermittent block in one of two paths of entry resulted in intermittent cycle length changes of the tachycardia without a change in configuration. Block in one exit path resulted in a shift to alternative exit paths, with dramatic changes in ventricular activation and tachycardia configuration. Termination of the tachycardia could result from block close to the entrant or exit portion of the return tract. Different tachycardias were seen to share common portions of a return tract. CONCLUSIONS: These observations enlarge and extend our knowledge of the functional repertoire of complex reentrant tracts that occur in infarct-related ventricular tachycardia. The use of common portions of a reentrant tract by several tachycardias is confirmed. Utilization of alternate pathways can account for changes in configuration and cycle length. Spontaneous and induced block can occur at points of entry and exit in a reentrant tract and may identify optimal targets for ablation attempts. Further advances will require greater emphasis on diastolic activation mapping.

Cardiac Pacing, Artificial↗
PubMed1990

Extensive endocardial resection for recurrent ventricular tachyarrhythmias.

Twenty-two consecutive patients underwent elective map-guided extensive endocardial resection (EER) for recurrent ventricular tachyarrhythmias (VT) of whom 20 were male. The ages ranged from 43 to 74 years (mean 57). All arrhythmias were ischaemic in origin. The mean ejection fraction was 29%. The presenting arrhythmias were ventricular tachycardia in 14, ventricular fibrillation (VF) alone in 1 and ventricular tachycardia and VF in 7. Useful additional intraoperative mapping was obtained in 19 patients. Under cardioplegic arrest, the scarred left (22) and where indicated right (4) ventricular endocardium was extensively resected. Resection of scarred papillary muscles was avoided and where indicated, localised cryoablation was performed: 21/22 had concomitant aneurysmectomy and/or coronary artery bypass grafting. There was 1 (4.5%) operative death. All survivors (95.5%) underwent postoperative electrophysiological studies at around 1 week. None had inducible arrhythmias. There were 3 (13.5%) late cardiac deaths, all due to primary cardiac failure without recurrence of arrhythmia. Of 17 (77%) long-term survivors, 16 (94%) are VT-free on no anti-arrhythmic medication at a mean follow-up of 37.2 months. One developed a new arrhythmia at 1 year which is controlled on medication. EER offers a high rate of success in ablating VT in association with a low operative mortality and good prospect of VT-free long-term survival.

Adult↗
PubMed2006

In vivo and in vitro Ah-receptor activation by commercial and fractionated pentabromodiphenylether using zebrafish (Danio rerio) and the DR-CALUX assay.

The present study addresses the toxicity of a commercial pentabrominated diphenylether (PeBDE) flame retardant mixture, DE-71, in a model aquatic vertebrate. Four weeks' exposure of juvenile zebrafish (Danio rerio) to water-borne DE-71 resulted in dose-dependent induction of CYP1A immunoreactivity, predominantly in the endocardium and the endothelium of larger blood vessels, such as ventral aorta and branchial arteries, as well as the larger hepatic and pancreatic blood vessels. To investigate the impact of possible contaminating PBDD/Fs in the DE-71 product, the study was repeated after DE-71 had been fractionated into a non-planar (cleaned PBDEs) and a planar fraction (PBDD/Fs). Zebrafish were exposed under similar conditions to the planar and cleaned DE-71 fractions, and to uncleaned DE-71. In addition, the above fractions were chemically analyzed and tested in a reporter gene assay (DR-CALUX) for their aromatic hydrocarbon-receptor (AhR) stimulating potencies. A relatively strong CALUX response was detected from the planar DE-71 fraction (19.7ng TCDD equivalent (TEQ)/g DE-71), coinciding with a strong induction of CYP1A immunoreactivity in zebrafish. CYP1A immunoreactivity in zebrafish exposed to uncleaned DE-71 was intense, although the CALUX response was 10-fold less compared to the planar fraction. Only weak CYP1A immunoreactivity was found in fish exposed to cleaned DE-71, and none in control animals; no CALUX response was detected in cleaned DE-71. The present findings indicate that chemical impurities of the commercial PeBDE product account for AhR-mediated effects. Analytical isolation of a planar fraction from the commercial product increased the in vitro (DR-CALUX) signal 10 times. Immunohistochemistry showed a strong tissue specific reaction to DE-71 in vivo at these relatively low TEQ levels regardless of chemical pretreatment of the mix, reflecting the sensitivity of CYP1A induction in juvenile zebrafish to AhR agonists.

Animals↗
PubMed2004

Instant myocardial blood flow monitor: its calibration and assessment of flow capacity of the intracoronary shunt tube.

BACKGROUND: We developed a new instant regional myocardial blood flow (RMBF) monitor utilizing the thermal diffusion method in which the RMBF value is presented as the value inversely proportional to the thermocouple voltage output (1/V). The purposes of this study were (1) to validate the accuracy of RMBF measurement by the instant RMBF monitor in comparison with the colored microsphere method for calibration; (2) to investigate influences of it on the RMBF; and (3) to assess changes in RMBF caused by the shunt tube insertion. METHODS: Twenty pigs were used for this study: 4 for comparison between the instant RMBF meter and the colored microsphere method, 4 for validation of reproducibility, and 6 for measurement of RMBF during shunt tube. RESULTS: The relation between RMBF values obtained by the colored microsphere method and 1/V values by instant RMBF monitor was colored microsphere = 140,992 (1/V)--231 in epicardial layer (R2 = 0.819) and colored microsphere = 111,381 (1/V)--165 in endocardial layer (R2 = 0.693). The correlation coefficient and R2 values between RMBF values measured by both methods were 0.985 and 0.839 in epicardial layer, and 0.963 and 0.679 in endocardial layer, respectively. The RMBF at each layer did not change after the attachment of the monitor. Fifteen minutes after shunt tube insertion, RMBF measured by the colored microsphere method decreased to 31.1% (p = 0.0001) and 33.7% (p = 0.0001) in epicardium and endocardium, respectively, and no difference was observed from the value measured by the instant RMBF monitor. CONCLUSIONS: This instant RMBF monitor can provide instantaneous and continuous information of RMBF without requiring tissue examination.

Animals↗
PubMed2005

Transmural dispersion of repolarization as a key factor of arrhythmogenicity in a novel intact heart model of LQT3.

BACKGROUND: Congenital and acquired long QT syndrome (LQTS) are caused by abnormalities of ionic currents underlying ventricular repolarization. For a better understanding of the mechanisms by which functional electrical instability at the level of the whole heart leads to torsade de pointes (TdP), a novel model of LQT3 was developed and the role of transmural dispersion of repolarization for the development of proarrhythmia was evaluated. METHODS AND RESULTS: In 11 Langendorff-perfused rabbit hearts, veratridine (0.1-0.5 microM), an inhibitor of sodium channel inactivation, led to a concentration-dependent increase in QT-interval and simultaneously recorded monophasic ventricular action potentials (MAPs) (p<0.05) and thereby mimicked LQT3. Veratridine reproducibly induced early afterdepolarizations (EADs) and TdP after lowering potassium concentration. In bradycardic (AV-blocked) hearts, the increase in MAP duration showed marked regional differences. It was significantly more pronounced on the left endocardium as compared to left or right epicardium. This resulted in a significant increase in dispersion of repolarization (24% at 0.1 microM, 92% at 0.25 microM, 208% at 0.5 microM; p<0.01). Left ventricular transmural dispersion of repolarization increased significantly more than interventricular dispersion (104 to 33 ms at 0.5 microM veratridine; p<0.05). CONCLUSION: By inhibition of sodium channel inactivation, veratridine mimics LQT3 in this intact heart model. In bradycardic, hypokalemic hearts, it reproducibly induced EADs and TdP in the setting of significantly increased left ventricular transmural dispersion of repolarization. Based on these experimental data, reduction of transmural dispersion of repolarization may be considered an important target for the prevention of TdP in patients with LQT3.

Action Potentials↗
PubMed2005

Near-threshold field stimulation: intramural versus surface activation.

OBJECTIVE: The mechanism by which an electric field terminates arrhythmias continues to puzzle investigators. Existing experimental methods provide information about epicardial manifestations of electrical cardioversion, yet little is known about field effects deep inside the myocardium. Here we combine specially designed optical mapping experiments and computer modeling to separate the intra-myocardial and surface field effects. METHODS: We used isolated coronary perfused and superfused slabs of pig right ventricular wall (n=6) stained with di-4-ANNEPS. A uniform transmural field was produced via two parallel planar (5 x 5 cm) transparent mesh electrodes aligned with the endocardial and epicardial surfaces. Low-intensity shocks (< or =3.3 V/cm) were applied during diastole. The electrical activity under both electrodes was recorded simultaneously using two CCD cameras at 800 frames/s. Shock responses were also simulated using a bidomain Luo-Rudy model. RESULTS: We discovered that during the near-threshold diastolic field stimulation, when surface polarization should be dominant, the early activation occurs not at the cathodal surface, as might be expected, but deep inside the myocardium. Comparison of epi- and endocardial activation delays suggests that the sites of early activation are located closer to the endocardium. Our experimental observations could be reproduced computationally by assuming large resistive heterogeneities inside the myocardial wall. CONCLUSIONS: Surface polarization plays a minor role during field stimulation. Intramural virtual electrodes produced even by weak fields are sufficiently strong to initiate intra-myocardial excitation. Significant heterogeneities in tissue resistivity may explain the strength of the virtual electrodes.

Animals↗
PubMed2004

Assessment of left ventricular function with contrast echocardiography.

Echocardiography continues to be the primary noninvasive imaging modality for the assessment of cardiac structure and function because of significant advances in ultrasound imaging technology over the last two decades, yet quantification of the LV function has remained an elusive goal. The introduction of contrast agents has represented a major advance in clinicians' ability to visualize the endocardium and to assess LV function accurately, particularly in patients who have poor acoustic windows. Ongoing and future refinements in imaging technology used with contrast enhancement have placed automated quantification of LV function on the brink of widespread clinical use.

Contrast Media↗
PubMed2006

Color encoding of endocardial motion improves the interpretation of contrast-enhanced echocardiographic stress tests by less-experienced readers.

BACKGROUND: We hypothesized that color encoding of endocardial motion could aid less-experienced readers in detection of wall-motion abnormalities at rest and stress in patients with poor acoustic windows. METHODS: Color-encoded images (color kinesis) were obtained at rest and peak dobutamine stress in 4 standard views during intravenous infusion of contrast agent in 117 patients with poorly visualized endocardium. In 101 of 117 patients (86%), in whom contrast enhancement allowed endocardial tracking, images were reviewed by two expert readers without color overlays. Each reader graded regional wall motion as normal, abnormal, or uninterpretable, and their consensus grades served as a gold standard. The same images were then reviewed and graded with and without color overlays by 3 cardiology fellows. The accuracy of the interpretation was calculated against the gold standard separately for the 3 vascular territories (left anterior descending, left circumflex, and right coronary arteries) and averaged for the 3 fellows. RESULTS: With the addition of color encoding: (1) the number of uninterpretable segments decreased by 55% at rest and 61% at peak stress; and (2) all 3 fellows reached higher levels of accuracy in all 3 vascular territories both at rest (6%-82% average) and at stress (73%-80%). CONCLUSION: The addition of color encoding of wall motion to contrast-enhanced images obtained in patients with poor acoustic windows during stress tests improves the interpretation of regional left ventricular function by less-experienced readers.

Dobutamine↗
PubMed2004

Sympathetic nerve sprouting after orthotopic heart transplantation.

BACKGROUND: Although many studies have documented sympathetic re-innervation in transplanted hearts (allografts) using chemical, imaging, and electrophysiologic methods, little histopathologic proof of this process exists. METHODS AND RESULTS: We used immunohistochemical techniques with antibodies to S-100 protein, to growth-associated protein 43 (GAP43), and to tyrosine hydroxylase (TH) to detect nerves in the left ventricles in allografts from 29 consecutive recipients. Reasons for transplantation included ischemic heart disease (IHD, n=16), non-ischemic dilated cardiomyopathy (DCM, n=12), and both (n=1). We assessed nerve densities (nerves/mm2) with respect to time after transplantation in the endocardium; in the mid-myocardium; and around intramyocardial blood vessels, scars, foci of rejection, and Quilty lesions. Six normal hearts were used for comparison. As in normal hearts, all 29 allografts had epicardial nerve trunks that extended into the mid-myocardium around blood vessels. Although the total number of nerves (S100-positive) progressively decreased over time, GAP43-positive nerves around the blood vessels increased with time (p <0.005). We also observed abundant TH-positive nerves. The density of S100-positive nerves around blood vessels was greater in those undergoing transplantation for IHD (113 +/- 88) than in those with prior DCM (54 +/- 49, p <0.05). Nerve density in each area varied greatly. CONCLUSIONS: Heterogeneous sympathetic nerve sprouting and re-innervation occurred around blood vessels in the allografts. The magnitude of nerve sprouting increased with time and varied greatly from patient to patient. Patients with IHD had greater nerve sprouting and re-innervation than did those with DCM.

Adult↗
PubMed2004

Epicardial but not endocardial premature stimulation initiates ventricular tachyarrhythmia in canine in vitro model of long QT syndrome.

OBJECTIVES: To explore the mechanism, we tested the hypothesis that premature epicardial stimulation transiently increased the dispersion of repolarization leading to VT. BACKGROUND: Premature stimulation initiated ventricular tachycardia (VT) when applied to the epicardium but not to the endocardium in a canine model of long QT syndrome (LOTS). METHODS: We optically mapped action potentials (APs) on the cut-exposed transmural surfaces of isolated wedges of canine ventricular walls perfused with anemone toxin II (ATX-II), which produced type 3 LQTS with an asymmetrical transmural profile of repolarization that was earliest in the epicardium and latest in deep subendocardium. RESULTS: Earliest excitable epicardial stimulation triggered VT in 5 of 18 wedges receiving > or =5 nmol/L ATX-II by direct activation of epicardium, which delayed repolarization in the still refractory midmyocardium and further enhanced the dispersion of repolarization. These VTs were initiated 197 +/- 72 ms (n = 10) after the premature stimulation, from focal regions of earliest repolarization downstream to the steepest local spatial gradients of repolarization, and maintained by new focal activation and reentry. Transmural differences in the cycle lengths of activations altered conduction pathways and resulted in torsades de pointes-like polymorphic VT. In contrast, VTs were not initiated by endocardial stimulation at the same premature intervals or when ATX-II was < or =2.5 nmol/L. Failed VT initiation was associated with significantly lower maximum local gradient of repolarization. CONCLUSIONS: Heterogeneic repolarization in LQTS provides a transmural asymmetrical substrate for the earliest excitable epicardial, but not endocardial, stimulation to further delay midmyocardial repolarization and produce a steep spatial gradient of repolarization potential initiating torsades de pointes-like polymorphic VT.

Action Potentials↗
PubMed2006

Value of high-density endocardial and epicardial mapping for catheter ablation of hemodynamically unstable ventricular tachycardia.

BACKGROUND: Percutaneous epicardial mapping has been used for ablation of recurrent ventricular tachycardia (VT). OBJECTIVES: The purpose of this study was to use a combined epicardial and endocardial mapping strategy to delineate the myocardial substrate for recurrent VT in both ischemic (n = 12) and nonischemic cardiomyopathy (n = 8), and to define the role of epicardial ablation. METHODS: Electroanatomic mapping was performed in 20 patients. High-density voltage maps were obtained by acquiring both endocardial and epicardial electrograms. Electrograms derived from six patients with structurally normal hearts were used as controls. A total of 26 VTs were targeted in the 20 patients. RESULTS: Most VTs (23/26 [88.5%]) were hemodynamically unstable. In patients with ischemic cardiomyopathy, the extent of endocardial scar was greater than epicardial scar. A definable pattern of scar could not be demonstrated in nonischemic cardiomyopathy. Pathologic examination of explanted hearts in two patients with nonischemic cardiomyopathy demonstrated that low-voltage areas were not always predictive of scarred myocardium. A substrate-based approach was used for catheter ablation. Catheter ablation was performed on the endocardium in all patients; additional epicardial delivery of radiofrequency energy was required in 8 (40%) of 20 patients for successful ablation. During follow-up (12 +/- 4 months), 15 (75%) of 20 patients have been arrhythmia-free. CONCLUSION: Patients with ischemic cardiomyopathy tend to have a larger endocardial than epicardial scar. Use of epicardial and endocardial electroanatomic mapping to define the full extent of myocardial scars allows successful catheter ablation in patients with hemodynamically unstable VTs.

Adult↗
PubMed2006

Anatomic characterization of endocardial substrate for hemodynamically stable reentrant ventricular tachycardia: identification of endocardial conducting channels.

BACKGROUND: Detailed anatomic characterization of endocardial substrate of ventricular tachycardia (VT) is limited. OBJECTIVES: The purpose of this study was to determine the endocardial dimensions and local electrogram voltage characteristics of the reentrant circuit. VT-related conducting channels corresponding to zones of slow conduction may be identified. METHODS: Electroanatomic mapping was performed in 26 patients with uniform VT. Entrainment mapping was performed in 53 VTs, of which 19 entrance, 37 isthmus, 48 exit, and 32 outer loop sites were identified. The color display of voltage maps was adjusted to identify conducting channels associated with VT circuits. A conducting channel was defined as a path of multiple orthodromically activated sites within the VT circuit that demonstrated an electrogram amplitude higher than that of surrounding areas as evidenced by voltage color differences. RESULTS: Forty-seven (84%) of 56 entrance or isthmus sites were located within dense scar (<0.5 mV). Nearly all exits (92%) were located in abnormal endocardium (<1.5 mV), with more than half (54%) located in the border zone (0.5-1.5 mV). VT-related conducting channels was identified in 18 of 32 VTs with detailed mapping (average length 32 +/- 22 mm). The voltage threshold in the conducting channels ranges from 0.1 to 0.7 mV (mean 0.33 +/- 0.15 mV). CONCLUSION: (1) Most entrance and isthmus sites of hemodynamically stable VT are located in dense scar, whereas exits are located in the border zone. (2) VT-related conducting channels may be identified by careful voltage threshold adjustment. These findings have important implications regarding strategies for substrate-based VT ablation.

Adult↗
PubMed2006

Characterization of the relationship between preshock state and virtual electrode polarization-induced propagated graded responses resulting in arrhythmia induction.

BACKGROUND: Studies have demonstrated that failed defibrillation shocks often are followed by an electrically quiescent period (isoelectric window); however, the underlying mechanisms remain incompletely understood. We recently suggested a new mechanism termed "virtual electrode polarization-induced propagated graded responses" (VEPiPGRs) that might play a role in the origin of the global postshock activation following the isoelectric window. OBJECTIVES: The purpose of this study to elucidate the circumstances under which VEPiPGR activations originate for shocks given to paced right ventricular preparations. Specifically, we examined the dependence of VEPiPGRs on coupling interval (CI) and shock polarity and whether VEPiPGRs emerge preferentially on the epicardium or the endocardium. METHODS: Simultaneous endocardial and epicardial activity in isolated right ventricular preparations (n = 4) was imaged optically following shocks of strength +/-5A. All VEPiPGRs were analyzed, and the time T from shock end to activation onset was recorded (isoelectric window is the smallest T among activations that propagated globally). RESULTS: VEPiPGR activations occurred for CIs in the range from 80 to 150 ms. Average duration of T was 64.5 +/- 18.15 ms, with T decreasing as CI increased (Tmax = 82 ms, Tmin = 46 ms, linear-fit slope = -0.675). The average earliest CI at which cathodal (+5A) shocks resulted in VEPiPGRs was 87 ms compared with 116 ms for anodal (-5A) shocks. All VEPiPGR activations emerged first on the epicardium in a focal pattern, and all induced ventricular fibrillation. CONCLUSION: The global activation that terminates the isoelectric window could result from VEPiPGRs that find an exit pathway. VEPiPGRs originate at the sites of maximum action potential abbreviation by the shock, always on the epicardium for the preparation used here.

Action Potentials↗
PubMed2006

Fabry's disease cardiomyopathy: echocardiographic detection of endomyocardial glycosphingolipid compartmentalization.

OBJECTIVES: We sought to identify echocardiographic hallmarks of Fabry's disease cardiomyopathy (FC). BACKGROUND: The recognition of FC from other forms of left ventricular hypertrophy (LVH) by noninvasive imaging techniques is not yet available, and diagnosis, mostly in the absence of systemic manifestations, still relies on genetic and invasive studies. METHODS: Forty consecutive patients (mean age 39 +/- 15 years, 22 men and 18 women) with an established diagnosis of Fabry's disease were submitted to echocardiographic evaluation. Control population consisted of 40 consecutive patients with hypertrophic cardiomyopathy (HCM), 40 hypertensive patients with echocardiographic evidence of LVH, and 40 age- and gender-matched healthy subjects with no LVH. All HCM patients and FC with LVH and/or cardiac symptoms underwent cardiac catheterization with left ventricular endomyocardial biopsy. RESULTS: Echocardiography showed in 83% of FC patients (95% of FC patients with LVH) a binary appearance of endocardial border absent in all HCM, hypertensive, and healthy subjects. The sensitivity and specificity of this echocardiographic feature in detecting Fabry patients in study population were 94% and 100%, respectively. Comparison of echocardiographic with histologic and ultrastructural findings showed the binary appearance to reflect an endomyocardial glycosphingolipids compartmentalization, consisting of thickened glycolipid-rich endocardium, free glycosphingolipid subendocardial storage, and an inner severely affected myocardial layer with a clear subendocardial-midwall layer gradient of disease severity. CONCLUSIONS: Echocardiographic binary appearance of left ventricular endocardial border, reflecting endomyocardial glycosphingolipids compartmentalization, represents a sensitive and specific diagnostic hallmark of Fabry's disease cardiomyopathy.

Adolescent↗
PubMed2006

Cellular basis for trigger and maintenance of ventricular fibrillation in the Brugada syndrome model: high-resolution optical mapping study.

OBJECTIVES: We examined how repolarization and depolarization abnormalities contribute to the development of extrasystoles and subsequent ventricular fibrillation (VF) in a model of the Brugada syndrome. BACKGROUND: Repolarization and depolarization abnormalities have been considered to be mechanisms of the coved-type ST-segment elevation (Brugada-electrocardiogram [ECG]) and development of VF in the Brugada syndrome. METHODS: We used high-resolution (256 x 256) optical mapping techniques to study arterially perfused canine right ventricular wedges (n = 20) in baseline and in the Brugada-ECG produced by administration of terfenadine (5 micromol/l), pinacidil (2 micromol/l), and pilsicainide (5 micromol/l). We recorded spontaneous episodes of phase 2 re-entrant (P2R)-extrasystoles and subsequent self-terminating polymorphic ventricular tachycardia (PVT) or VF under the Brugada-ECG condition and analyzed the epicardial conduction velocity and action potential duration (APD) restitutions in each condition. RESULTS: Forty-one episodes of spontaneous P2R-extrasystoles in the Brugada-ECG were successfully mapped in 9 of 10 preparations, and 33 of them were originated from the maximum gradient of repolarization (GR(max): 176 +/- 54 ms/mm) area in the epicardium, leading to PVT (n = 12) or VF (n = 5). The epicardial GR(max) was not different between PVT and VF. Wave-break during the first P2R-extrasystole produced multiple wavelets in all VF cases, whereas no wave-break or wave-break followed by wave collision and termination occurred in PVT cases. Moreover, conduction velocity restitution was shifted lower and APD restitution was more variable in VF cases than in PVT cases. CONCLUSIONS: Steep repolarization gradient in the epicardium but not endocardium develops P2R-extrasystoles in the Brugada-ECG condition, which might degenerate into VF by further depolarization and repolarization abnormalities.

Action Potentials↗
PubMed2005

Primary endocardial malignant spindle-cell sarcoma in the right atrium of a dog resembling a malignant peripheral nerve sheath tumour.

An unusual malignant spindle-cell sarcoma in the right atrium of a 7-year-old male hunting terrier is described. The neoplasm arose from the endocardium, protruded into the lumen of the right atrium, was covered with endothelium, and showed local invasive growth into the atrial wall. The tumour was composed of interlacing bundles of spindle cells, sometimes arranged in whorls resembling the Antoni type A pattern. The extracellular matrix showed abundant reticulin fibres. Immunohistochemistry revealed an intense labelling of tumour cells for vimentin, and a partial labelling for neuron-specific enolase, S100 protein, and Melan-A. The morphology of the tumour indicated a primary malignant peripheral nerve sheath tumour, resembling a neoplasm described in rats.

Animals↗
PubMed2005

Brugada syndrome and ischemia-induced ST-segment elevation. Similarities and differences.

INTRODUCTION: ST-Segment elevation is a common electrocardiogram (ECG) manifestation of acute transmural myocardial ischemia in leads facing the injury. Acute myocardial ischemia involving the right-ventricular (RV) outflow tract is known to induce a Brugada-like ECG. In this paper, we examined the electrophysiological bases for the similarities between the ECG characteristics of the Brugada syndrome model induced by terfenadine (5 mumol/L) and the ECG manifestations of the acute transmural no-flow ischemia model. METHODS: For both experimental simulations, we used isolated arterially perfused canine RV wedge preparations to record transmembrane action potentials (AP) from endocardium and epicardium together with a transmural pseudo-ECG (ECG); basic cycle length=400 to 2000 ms. RESULTS: In the presence of a prominent Ito-mediated AP notch, no-flow ischemia causes true ST-segment elevation because of selective depression and loss of the AP dome at some epicardial sites. In the absence of a prominent AP notch, ischemia ultimately produces an apparent ST-segment elevation, which is secondary to a prolongation of the R wave caused by marked transmural conduction delays. Similarly, in the Brugada syndrome model generated in preparations displaying a large epicardial Ito, ST-segment elevation was due to loss of the epicardial AP dome at some sites but not at others. Transmural conduction delay giving the appearance of ST-segment elevation is also observed in the Brugada model in preparations exhibiting smaller AP notch. In both models, propagation of the dome from the site at which it is maintained to a site at which it is lost may result in closely coupled phase 2 reentrant extrasystoles. CONCLUSION: Our results suggest that Ito can modulate the electrocardiographic manifestation of acute ischemia as well as that of the Brugada syndrome, and that both clinical entities are the result of a similar electrophysiological substrate.

Action Potentials↗
PubMed2005

Mechanisms underlying arrhythmogenesis in long QT syndrome.

Long QT syndrome is a disease of delayed ventricular repolarization. It manifests clinically as recurrent syncope and sudden cardiac death caused by an atypical form of polymorphic ventricular tachycardia known as torsades de pointes (TdP). Evidence obtained from the studies using the rabbit left and right ventricular wedge preparations indicates that the development of TdP is relying not only on the genesis of an R-on-T trigger, but also on the formation of a functional reentrant substrate. When ventricular endocardial or subendocardial repolarization is prolonged either because of gene mutations or by drugs that reduce the net repolarization current, cell membrane potential fluctuates during phase 2 of the action potential phase 2 because of reactivation of L-type calcium current, that is, the appearance of phase 2 early afterdepolarization (EAD). In the rabbit left ventricular wedge, QT prolongation and EAD due to pure IKr inhibition are accompanied by a disproportional increase in transmural dispersion of repolarization (TDR). Early afterdepolarization in endocardium or subendocardium is able to produce new action potentials in cells with a relatively short action potential duration (eg, ventricular epicardium) probably via an electrotonic effect when TDR is large enough. This, in turn, results in an R-on-T extrasystole that is capable of initiating TdP. Enhanced TDR is essential not only for the genesis of the first initiating beat of TdP by facilitating the propagation of EAD, but also for the maintenance of TdP by serving as a functional reentrant substrate.

Action Potentials↗