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Morphological changes in endocardium subjected to global ischaemia.

To provide insight into the effects of severe ischaemia on endocardium, the sequence of morphological changes which develop in the endocardium of the isolated rat heart subjected to 0-12 hours of global ischaemia at 37 degrees C was examined. A progression of changes occurred. Following one or more hours of ischaemia crater-like depressions and blebs appeared on the luminal surfaces of ventricular endothelial cells, with margination and clumping of nuclear chromatin, loss of glycogen granules, swelling of mitochondria, and the development of subendothelial membrane-bound dilatations of myocytes. Following two or more hours of ischaemia there was progressive separation of endothelial cells along their intercellular boundaries and desquamation of an increasing proportion of these cells. In regions of desquamation the surface was initially smooth due to persistence of the lamina densa of the basal lamina, but after longer periods of ischaemia the surface became rough with exposure first of the subendothelial connective tissue fibres (4 hours) and eventually of cardiac muscle cells (12 hours).

Animals↗

Tpeak-Tend interval as an index of global dispersion of ventricular repolarization: evaluations using monophasic action potential mapping of the epi- and endocardium in swine.

UNLABELLED: The ECG interval from the peak to the end of the T wave (Tpeak-Tend) has been used as an index of transmural dispersion of ventricular repolarization (DVR). The correlation between the Tpeak-Tend interval and the global DVR, however, has not been well-evaluated. METHODS: Monophasic action potentials (MAPs) were recorded from 51+/-10 epicardial and 64 +/- 9 endocardial sites in the left ventricles of 10 pigs, and from 41+/-4 epicardial and 53+/-2 endocardial sites in the right ventricles of 2 of the 10 pigs using the CARTO mapping system. The end of repolarization times over the epi- and endocardium were measured, and the end of repolarization dispersions over the epicardium (DVR-epi), over the endocardium (DVR-endo) and over both (DVR-total) were calculated. The QTpeak, QTend and Tpeak-Tend intervals as well as the QTpeak and QTend dispersions were obtained from the simultaneously recorded 12-lead ECG. RESULTS: The maximal Tpeak-Tend intervals (57+/-7 ms) were consistent with the DVR-total (58+/-11 ms, p>0.05), and significantly correlated with the DVR-total (r=0.64, p<0.05). However, the mean Tpeak-Tend intervals (44+/-5 ms), and Tpeak-Tend intervals from lead II (41+/-6 ms) and V5 (43+/-5 ms) were all significantly smaller than and poorly correlated with the DVR-total, as were the QTpeak and QTend dispersions (15+/-2 ms vs. 21+/-4 ms). CONCLUSION: The maximal Tpeak-Tend interval may be used as a noninvasive estimate for the global DVR, but not the QTpeak and QTend dispersions, nor the mean Tpeak-Tend interval and that from a single lead.

Action Potentials↗

Role of the endocardium in the inotropic action of UD-CG-212 CL.

UD-CG-212 CL is a metabolite of pimobendan (UD-CG-115 BS), a non-glycosidic, non-adrenergic positive inotropic agent. In the present study we investigated the effect of UD-CG-212 CL on cat papillary muscles in the presence or absence of an intact endocardial endothelium. The endocardium was damaged by a very short detergent treatment. We demonstrated that, in muscles with an intact endocardial endothelium, UD-CG-212 CL induced a moderate, but significant inotropic effect resembling the changes induced by adrenoceptor agonists. Addition of an alpha- and or beta-blocker reduced this positive inotropic effect. The effect induced by UD-CG-212 CL, was completely abolished after the endocardial endothelium was damaged. We conclude that the endocardium played a modulatory role in the action of UD-CG-212 CL through the release of various factors with inotropic activity.

Adrenergic alpha-Antagonists↗

In vivo validation of the coincidence of the peak and end of the T wave with full repolarization of the epicardium and endocardium in swine.

OBJECTIVES/BACKGROUND: Previous in vitro studies have suggested full repolarization of the epicardium coincides with the peak of the T wave (T(peak)) and that of the M cells coincides with the end of the T wave (T(end)). However, in vivo validation of the theory is lacking. METHODS: Monophasic action potentials (MAPs) were recorded using the CARTO mapping system from 51 +/- 10 epicardial sites and 64 +/- 9 endocardial sites of the left ventricle in 10 pigs and from 41 +/- 4 epicardial sites and 53 +/- 2 endocardial sites of the right ventricle in two of the 10 pigs. End of repolarization (EOR) times over the epicardium (EOR(epi)), endocardium (EOR(endo)), and over both (EOR(total)) were obtained. QT(peak) and QT(end) intervals were measured from simultaneously recorded 12-lead ECG. RESULTS: Minimal and maximal EOR(total) were observed in the left ventricle in all pigs. Minimal EOR(total) was on the epicardium in five pigs, and maximal EOR(total) was on the endocardium in nine pigs. Minimal, mean, and maximal QT(peak) intervals all were significantly smaller than maximal EOR(epi) (322 +/- 23 ms, P <.01). No significant difference was found between maximal QT(end) interval (338 +/- 30 ms) and maximal EOR(endo) (339 +/- 24 ms, difference = 1 +/- 19 ms, P =.92), between maximal QT(end) interval and maximal EOR(total) (341 +/- 24 ms, difference = 2 +/- 18 ms, P =.69), or between minimal QT(peak) interval (283 +/- 28 ms) and minimal EOR(total) (282 +/- 20 ms, difference = 0 +/- 15 ms, P =.95). CONCLUSIONS: In in vivo pig models, T(peak) does not coincide with full repolarization of the epicardium but coincides well with the earliest EOR, whereas the T(end) corresponds with the latest EOR. These findings suggest that not only the transmural gradients but also the apicobasal repolarization gradients contribute to genesis of the T wave.

Action Potentials↗

Effects of multipolar electrode radiofrequency energy delivery on ventricular endocardium.

This study examined the effects of radiofrequency energy applied in a bipolar fashion with single as compared with multiple sequential applications at the canine endocardium. In this closed-chest model, radiofrequency energy (750 kHz) was delivered between two adjacent poles of an electrode catheter. Single applications were performed at distinct sites in the left (n = 30) and right ventricles (n = 29) of 13 normal dogs. A multiple sequential technique, which enlarges the ablated endocardial surface, was applied in the left (n = 13) and right ventricles (n = 4) of seven normal dogs and six dogs with remote myocardial infarction. Single applications (199 +/- 200 joules) resulted in lesions with a volume of 0.12 +/- 0.06 cm3 (range 0.03 to 0.31 cm3) and an endocardial surface area of 0.29 +/- 0.15 cm2 (range 0.06 to 0.63 cm2). Changes at the catheter/tissue interface led to a rise in impedance, restricting further enlargement of the necrosis. Sequential delivery of radiofrequency energy between poles 1 and 2, 2 and 3, and 3 and 4 of a quadripolar electrode catheter repeated 9 to 11 times in slightly different positions allowed a cumulative energy of 6571 +/- 3857 joules to be applied to the endocardium, resulting in a lesion volume of 0.84 +/- 0.38 cm3, with an endocardial lesion surface area of 3.7 +/- 1.2 cm2 (range 2.9 to 5.1 cm2). Histologically, all radiofrequency lesions were restricted to the endocardium/subendocardium with a small border zone of injury. Aggressive stimulation techniques did not induce ventricular tachycardia in any of the dogs before and 19 +/- 11.4 days after multiple sequential ablations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mechanical compliance of the endocardium.

Radio-frequency (RF) ablation is an accepted treatment for cardiac arrhythmias related to abnormal focal cardiac substrate. The penetration depth of the electrode into the endocardium affects lesion size, a critical determinant of success of RF ablation. We measured the relation between the mechanical compliance and the penetration depth of RF ablation catheter electrode at frequently ablated areas of the endocardium and examined the influence of time after death on mechanical properties of the tissue. We measured force versus time for eight insertion depths of the catheter electrode into full-thickness endocardial samples derived from the mitral valve annulus, the left ventricular free wall and the tricuspid valve annulus. We varied the time after death at 15, 40 min, 3, 8, and 18 h and repeated our measurements. At 15 min after death, the first 0.5mm penetration depth caused the fastest relaxation at 55 s. Force decay decreased dramatically at 15 min after death as the penetration depth increased from 0.5 to 4mm. We used the force data sampled at 60s after insertion to approximate the elasticity. We observed the relations between the force versus the insertion depth. The force increased by a factor of 5 for the mitral valve annulus and 8 for the left free wall from 15 min to 18 h. We derived coefficients of a second-order polynomial equation relating the force data to insertion depth with R(2)>0.99.

Animals↗

Electrophysiologic properties differ in the ventricular endocardium and epicardium of the Japanese monkey.

We measured action potential duration (APD) from the endocardium (Endo) and epicardium (Epi) of the left ventricular free wall in Japanese monkey hearts and found that the APD of Endo is significantly longer than that of Epi at a stimulus cycle length of 1500 msec in normal Tyrode solution (control condition). We then hypothesized that shorter APD of Epi results from greater outward pump current and that the difference in the current may be due to a difference in membrane Na,K-ATPase activity between Endo and Epi. If this were the case, interventions which alter the Na,K-pump activity should alter electrophysiologic characteristics in the endocardium and the epicardium to different degrees. An application of ouabain (10(-6) M), an inhibitor of Na,K-ATPase, produced greater shortening of APD and greater depolarization of the resting potential in Endo as compared with Epi. Shortening of stimulus cycle length shortened the APD more markedly in Endo than Epi, resulting in a significantly longer APD in Epi than Endo at a stimulus cycle length of 200 msec. The hyperpolarization and the APD shortening produced when the tissues were returned to 5.4 mM K+ Tyrode solution from K+-free medium were also more marked in Endo than in Epi. Such findings suggest that endocardial cells are more liable to accumulate Na ions intracellularly and K ions extracellularly when the Na, K-pump is suppressed by ouabain or K+-free perfusion, presumably due to lower activity of Na, K-ATPase in Endo compared to Epi.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Ultrastructure of atrial and ventricular endocardium and cardiac capillary endothelium of the pike.

The endocardium of the pike Esox lucius L. consists of an attenuated squamous endothelium, a sparse population of subendothelial cells, and varying amounts of collagen. Fibroblasts are not found in the endocardium, and the collagen is probably produced by the endothelium. Capillary and endocardial endothelium differ structurally in several aspects. Plasmalemmal vesicles are far more abundant in capillary endothelium, while the amount of ribosomes and endoplasmic reticulum is much smaller. Golgi complexes are well developed in endocardial cells, but not in capillary endothelia mainly have a transport function, while the endocardial endothelium is also largely concerned in protein synthesis.

Animals↗

Xenopus Smad3 is specifically expressed in the chordoneural hinge, notochord and in the endocardium of the developing heart.

The Smads are intracellular signalling molecules that transduce signals from receptors for members of the TGF-beta superfamily to the nucleus. We have cloned the Xenopus orthologue of Smad3 (XSmad3). It is 94.6% identical to human Smad3 at the amino acid level. It is expressed as a maternal mRNA which disappears after stage 10.5, but reappears at the early tailbud stages. It is much less abundant than XSmad2 at the early developmental stages. From Stage 27 onwards XSmad3 is expressed with XSmad2 throughout the head region and in the somitic region. Strikingly however, XSmad3 alone is specifically expressed in the chordoneural hinge, the notochord and in the developing heart. Closer analysis reveals that XSmad3 is specifically expressed in the endocardium but not in the myocardium or pericardium. The chordoneural hinge staining persists at least until stage 40 whereas the staining in the endocardium peaks at approximately stage 32/33.

Amino Acid Sequence↗

Global repolarization sequence of the ventricular endocardium: monophasic action potential mapping in swine and humans.

The aim of this study was to evaluate the global sequence of repolarization over the ventricular endocardium. Disturbances in myocardial repolarization are associated with the genesis of arrhythmias. However, little is known about the global sequence of repolarization. Monophasic action potentials (MAPs) were recordedfrom 61 +/- 18 LV and/or RV sites in ten healthy pigs and from 43 +/- 15 LV or RV sites in eight patients using the CARTO system. Local activation time (AT), end-of-repolarization (EOR) time, and MAP duration were calculated and three-dimensional global maps of AT, EOR, and MAP duration constructed. LV maps were obtained from all ten pigs and RV maps from three pigs. Five RV maps and five LV maps were obtained from the eight patients. (1) EOR sequence was recognizable in 12 of 13 pig maps and in all the patient maps. (2) EOR followed the sequence of activation in 12 of 13 pig maps and 8 of 10 patient maps. (3) The longest MAPs were recorded in or near the earliest activation area, and the shortest ones in or near the latest activation area in all the pig maps and in nine often and eight often patient maps, respectively. (4) In all maps, MAP duration and AT were negatively correlated, and EOR and AT positively correlated. In conclusion, repolarization gradients exist over the pig and the human ventricular endocardium. The activation sequence is a determinant for the repolarization sequence. The magnitude of the progressive MAP shortening with progressively later activation, relative to local AT, is a critical factor governing the direction and pattern of the EOR.

Action Potentials↗

Prominent I(Ks) in epicardium and endocardium contributes to development of transmural dispersion of repolarization but protects against development of early afterdepolarizations.

INTRODUCTION: Previous studies from our laboratory demonstrated (1) a much larger I(Ks) and (2) inability to induce early afterdepolarization (EAD) activity in epicardial and endocardial cells versus M cells. This study tests the hypothesis that these two characteristics are interrelated. METHODS AND RESULTS: Standard and floating microelectrode techniques were used to record transmembrane activity from the canine left ventricular epicardial, M, and endocardial regions in isolated tissue slices and arterially perfused wedge preparations. The I(Kr) blocker E-4031 (1 to 10 microM) caused prominent prolongation of action potential duration (APD) and induced EADs in tissues isolated from the M region, but not those from epicardium or endocardium, causing a large transmural dispersion of APD. In contrast, the I(Ks) blocker chromanol 293B (10 to 30 microM) produced moderate prolongation of APD without EADs in all three tissue types. The combination of E-4031 (1 microM) and chromanol 293B (30 microM) resulted in profound prolongation of APD and the development of EADs in all three tissue types. In the perfused wedge, neither E-4031 nor chromanol 293B alone could induce EADs. In combination, the two drugs caused significant prolongation of APD and EADs in all three transmural regions. CONCLUSION: Our results support the hypothesis that a prominent I(Ks) is responsible for the ability of epicardium and endocardium to resist some but not all of the arrhythmogenic effects of I(Kr) block. The data highlight the critical importance of I(Ks) in the canine heart and the significant role of electrotonic interactions in minimizing the development of an arrhythmogenic substrate when repolarization reserve is reduced.

Action Potentials↗

Atypical manifestation of a cytoplasmic antineutrophil cytoplasmic antibody (PR3-ANCA)-associated vasculitis with involvement of aortic intima and parietal endocardium.

The traditional classification of vasculitis, based on the size of affected vessels, has meanwhile been extended by using antineutrophil cytoplasmic antibodies (ANCAs) as seromarkers in the differential diagnosis of different types of vasculitis. We report an autopsy case of fulminant generalized vasculitis positive for C-ANCA (1:320) and anti-proteinase 3 (PR3) antibodies (>100 U/mL) in a 63-year-old man. The unusually broad histologic spectrum included periarteritis nodosa-like lesions in medium-sized vessels and leucocytoclastic vasculitis in small vessels, as well as capillaritis. In addition, the left atrial and ventricular endocardium and the intima of the aorta thoracalis were patchily involved in the inflammatory process. Glomerulonephritis and/or immune complexes were not detectable by electron microscopy or immunohistochemistry. To the best of our knowledge, involvement of the aortic intima ("intimitis") and the parietal endocardium has not been described in PR3-ANCA-positive vasculitis to date.

Antibodies, Antineutrophil Cytoplasmic↗

Endoventriculoplasty using autologous endocardium for anterior left ventricular aneurysms.

BACKGROUND: There is currently consensus that endoventriculoplasty is the treatment of choice for an anterior left ventricular aneurysm. We describe here a new technique of endoventriculoplasty using autologous endocardium for left ventricular anterior aneurysm. METHOD: From 1990 until 2003, 49 patients underwent endoventriculoplasty using autologous pericardium at the Thoraxcenter of the University Hospital of Groningen in the Netherlands (28 patients) and at the Department of Cardio Thoracic Surgery of the University Hospital of Pisa in Italy (21 patients). Mean logistic EuroSCORE and mean ejection fraction were 15.7 +/- 6.7 and 31 +/- 9 %, respectively. RESULTS: Overall 30-day mortality was 4.1 %. Causes of in-hospital mortality were low output syndrome (1 patient) and ventricular fibrillation (1 patient). Postoperative complications were myocardial infarct (4.1 %), low output syndrome (6.1 %), renal failure (4.1 %), neurological events (2.0 %), atrial fibrillation (14.3 %), ventricular fibrillation or tachycardia (6.1 %), ARDS (4.1 %), re-operation for bleeding (4.1 %), and major wound infection (2.0 %). CONCLUSION: Our analysis shows that endoventriculoplasty with autologous endocardium is a safe procedure and improves the outcome in high-risk patients with ventricular aneurysm.

Aged↗

A computer simulation of radio-frequency ablation of the endocardium.

A computer simulation of radio-frequency (RF) ablation of the endocardium is performed. The objective is to quantify some of the parameters affecting lesion growth, and to obtain theoretical data which can be used as a guide to maximize the lesions obtained with the procedure. The model under consideration consists of a block of heart tissue with the catheter electrode making contact at a right angle on one side (endocardium) and a large grounded electrode on the other side. An RF electrical current flows between the electrodes, heating the tissue. The simulations provide information on the time evolution of the tissue temperature, lesion dimension and tissue resistance. A first set of calculations is based on an applied RF voltage that maintains the maximum tissue temperature at 100 degrees C. The results reveal that: 1) the lesions achievable by RF ablation are considerably larger than those obtained with a hot-tip catheter of the same size; 2) increasing the electrode radius enlarges the lesion because of an associated increase in contact surface area; 3) an increase in electrode length also enlarges the lesion because of the larger convective losses to the blood flow; 4) a large difference in temperature may exist between the electrode and the tissue because of the cooling effect of the blood flow; and 5) the lesions grow as long as power is applied. Other simulations in which the RF voltage is constant show that the lesions can be enlarged by lowering the applied voltage while increasing the duration. Agreement and discrepancies between the simulations and reported experimental results are identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Repolarization differences between guinea pig atrial endocardium and epicardium: evidence for a role of Ito.

It has long been known that ventricular epicardial action potential duration (APD) is shorter than endocardial, and recent evidence suggests that a larger transient outward current (Ito) in epicardium is responsible for the difference. To evaluate possible corresponding regional variations in atrial tissue, we studied guinea pig atrial epicardial and endocardial action potentials using standard microelectrode techniques. Epicardial APD was consistently shorter than endocardial, but the difference was greatly diminished by rapid pacing or early premature activation, situations in which Ito availability should be limited. 4-Aminopyridine (4-AP), at concentrations (0.5 mM) producing specific Ito blockade, increased APD significantly in atrial epicardium without affecting endocardium. The effect of 4-AP on APD was most marked at slow rates, at which Ito would be greatest, and was negligible at rapid rates or during premature activation, during which Ito would be largely inactivated. At larger concentrations (5 mM) 4-AP caused an equalization of epicardial and endocardial APD. The equimolar substitution of strontium for calcium did not affect APD at slow rates and increased APD (particularly in endocardium) at rapid rates, suggesting that the Ito underlying endocardial-epicardial differences was unlikely to be calcium dependent. We conclude that epicardial-endocardial differences in APD, well documented in ventricular tissue, can also occur in atrial tissue and that the underlying ionic mechanisms appear to be similar.

4-Aminopyridine↗

Thrombomodulin and tissue factor pathway inhibitor in endocardium of rapidly paced rat atria.

BACKGROUND: Atrial fibrillation (AF) is well known as one of the cardiogenic causes for thromboembolism. Although decreased flow and hypercoagulable state of the blood in the fibrillating atrium have been emphasized as the underlying mechanisms, endocardial dysfunction in maintaining the local coagulation balance could also contribute to the thrombogenesis in AF. METHODS AND RESULTS: The paroxysmal AF model was created by rapid atrial pacing in anesthetized rats. To test the hypothesis that AF induces local coagulation imbalance by disturbing the atrial endocardial function, the gene expression of intrinsic anticoagulant factors, thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI), were determined by means of ribonuclease protection assay, Western blotting, and immunohistochemistry. Rapid atrial pacing for 8 hours significantly decreased TM and TFPI mRNA levels in the left atrium but not in the ventricle, leading to the downregulation of their immunoreactive proteins. Immunohistochemical analysis revealed that TM and TFPI were expressed predominantly in the endocardial cells of the normal atrium, presumably preventing local blood coagulation, and that rapid atrial pacing induced the loss of TM and TFPI expression in the endocardium, leading to deficiency in anticoagulant barriers between the atria and the blood. CONCLUSIONS: Rapid atrial pacing acutely downregulated the gene expression of TM and TFPI in the atrial endocardium, thereby inducing local coagulation imbalance on the internal surface of the atrial cavity. These results would support the validity of supplement of anticoagulant molecules deficient in AF.

Animals↗

Bmx tyrosine kinase is specifically expressed in the endocardium and the endothelium of large arteries.

BACKGROUND: The growth and differentiation of endothelial cells are regulated by signal transduction through tyrosine protein kinases. Recently, a novel cytoplasmic tyrosine kinase gene, Bmx (Bone Marrow tyrosine kinase gene in chromosome X), was identified in human bone marrow RNA and found to be expressed predominantly in myeloid hematopoietic cell lineages. Our preliminary analyses indicated that the Bmx gene was also highly expressed in human heart. METHODS AND RESULTS: Mouse Bmx cDNA was isolated, sequenced, and found to encode a polypeptide approximately 91% identical to the human Bmx tyrosine kinase. Northern blotting and in situ hybridization of tissue sections indicated that Bmx mRNA is specifically expressed in the endocardium of the developing heart as well as in the endocardium of the left ventricle and in the endothelium of large arteries in adult mice. A weak signal was seen also in coronary arterial endothelium. CONCLUSIONS: Bmx shows a unique specificity of expression among tyrosine kinase genes and may be involved in signal transduction in endocardial and arterial endothelial cells. The results suggest that specific signal transduction mechanisms are present in such endothelia.

Amino Acid Sequence↗

Permeability of rat atrial endocardium, epicardium, and myocardium to large molecules. Stretch-dependent effects.

Atrial distension, which stimulates atrial natriuretic peptide secretion by atrial myocytes, also stretches nonmuscle cells. In a noncontracting in vitro preparation of combined right and left atria we demonstrated by electron microscopy that, at 37 degrees C, transition from zero pressure to a physiological distending pressure of 5.1 mm Hg rapidly rendered atrial endocardial endothelium permeable to the macromolecular probes horseradish peroxidase (HRP; M(r), approximately 40,000) and wheat germ agglutinin-HRP (M(r), approximately 70,000); each probe was introduced at the atrial cavitary endocardial surface. Stretch-dependent permeabilization was also demonstrable in spontaneously contracting atria, was reversed by removing the distending pressure, and was unaffected by varying external Ca2+ concentration from 0.2 to 1.4 mM or by experimental perturbations that markedly decrease ANP secretory rates. Although transendocardial HRP and wheat germ agglutinin-HRP passage required stretch, native ferritin (M(r), = 500,000) could traverse unstretched endocardium. Probes were detected in noncoated endocardial vesicles and intercellular junctions between endocardial cells, but the relative contributions of vesicular transcytosis and paracellular diffusion could not be determined. Although HRP entered plasmalemmal caveolae of myocytes in stretched atria, myocytes did not internalize HRP by fluid-phase endocytosis. Distending pressure also caused apparent flow reversal in thebesian blood vessels, with retrograde transfer of HRP across the endocardium into the myocardium. HRP and ferritin presented at the external surface of the epicardium (visceral pericardium) were endocytosed by mesothelial cells, entered junctions between mesothelial cells, and readily crossed the epicardium of both stretched and unstretched preparations.

Animals↗