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At least 19 recordsLinked to original sources

PubMed1996

Variants of preexcitation--specialized atriofascicular pathways, nodofascicular pathways, and fasciculoventricular pathways: electrophysiologic findings and target sites for radiofrequency catheter ablation.

INTRODUCTION: In the present report, the electrophysiologic findings in patients with different types of variants of preexcitation, i.e., atriofascicular, nodofascicular, and fasciculoventricular fibers, and the results of radiofrequency catheter ablation using different target sites are described. METHODS AND RESULTS: Twelve patients (mean age 36 +/- 17 years) with variants of the preexcitation syndromes underwent electrophysiologic study and radiofrequency catheter ablation. The atrial origin of atriofascicular pathways remote from the normal AV node was assessed by application of late atrial extrastimuli that advanced ("reset") the timing of the next QRS complex without anterograde penetration into the AV node. In patients with atriofascicular pathways, ablation of the accessory pathway or the retrograde fast AV node pathway was attempted. Ablation of the atriofascicular pathways was guided by a stimulus-delta wave interval mapping in the first five patients and by recording of atriofascicular pathway activation potentials in the next five patients. A nodofascicular pathway was suggested if VA dissociation occurred during tachycardia and if atrial extrastimuli failed to reset the tachycardia without anterograde penetration into the AV node. A fasciculoventricular connection was suggested if the proximal insertion of the accessory pathway was found to arise from the His bundle or bundle branches. The PR interval was expected within normal limits during sinus rhythm and the QRS complex to be slightly prolonged with a discrete slurring of the R wave, suggesting a small delta wave. Ten of the 12 patients had evidence for atriofascicular pathways and one patient each for a nodofascicular and fasciculoventricular pathway. In six patients, the atriofascicular pathways were successfully ablated, and in two patients, the retrograde fast AV node pathway. In one patient, a concealed right posteroseptal accessory AV pathway served as the retrograde limb and was successfully ablated. The nodofascicular pathway was shown to be a bystander during AV node reentrant tachycardia. After successful fast AV node pathway ablation resulting in marked PR prolongation, no preexcitation was present during sinus rhythm because of the proximal insertion of the nodofascicular pathway distal to the delay producing parts of the AV node. The proximal insertion of the fasciculoventricular pathway was suggested to arise distal to the AV node at the site of the penetrating AV bundle. The earliest ventricular activation at the His-bundle recording site indicated the ventricular insertion of this accessory connection into the ventricular summit. The fasciculoventricular connection gave rise to a fixed ventricular preexcitation and served as a bystander during orthodromic AV reentrant tachycardia incorporating a left-sided accessory AV pathway. CONCLUSION: The majority of patients with variants of the preexcitation syndrome present with specialized atriofascicular pathways that seem to originate from remnants of the specialized AV ring tissue. Nodofascicular and fasciculoventricular pathways exist and may give rise to preexcitation, although their functional role in participation of clinical arrhythmias still needs to be elucidated. In the present study, both a fasciculoventricular pathway and a nodofascicular pathway acted as a bystander.

Adolescent↗

PubMed2004

Agonist-induced internalization of leukotriene B(4) receptor 1 requires G-protein-coupled receptor kinase 2 but not arrestins.

The leukotriene B(4) (LTB(4)) receptor (BLT1) becomes desensitized upon repeated agonist stimulation. Little is known, however, about BLT1 internalization, which follows desensitization in most G-protein-coupled receptors (GPCR). In the current study, transiently expressed BLT1 readily internalized, after LTB(4) stimulation, in RBL-2H3 cells that express high levels of endogenous GPCR kinase 2 (GRK2) but did not in COS-7 or human embryonic kidney (HEK) 293 cells, which do not overexpress GRK. The internalization of BLT1 could be blocked in RBL-2H3 cells by coexpressing dominant-negative (DN) GRK2 K220R and could be promoted in HEK293 cells by coexpressing wild-type (WT) GRK2. Coexpression of WT or DN nonvisual arrestins had no effect on BLT1 internalization. Moreover, upon stimulation with LTB(4), BLT1 did not induce arrestin-green fluorescence protein redistribution in either cell type, even in the presence of overexpressed GRK2. Coimmunoprecipitation experiments confirmed that BLT1 could associate with GRK2 but not with arrestins. A C-tail-truncated mutant of BLT1 lost the capacity to internalize and associate with GRK2 upon exposure to LTB(4), suggesting that the C-tail was required for receptor internalization and association with GRK2. Taken together, our results indicate that the C terminus of BLT1 plays a pivotal role in receptor internalization and GRK2 association. Moreover, ligand-induced BLT1 internalization is dependent on GRK2 but independent of arrestins. This may allow differential, cell-type-specific signaling in response to LTB(4), depending on GRK expression levels.

Animals↗

PubMed2002

Differential effects of adenosine on antegrade fast pathway, antegrade slow pathway, and retrograde fast pathway in atrioventricular nodal reentry.

Adenosine has a potent negative dromotropic effect. However, comparative effects of adenosine on the three pathways of atrioventricular (AV) nodal reentry remain unclear. In this study, we sought to determine the effects of adenosine on the antegrade fast, antegrade slow, and retrograde fast pathway conduction in patients with AV nodal reentrant tachycardia (AVNRT). Twenty patients with common slow-fast AVNRT (mean cycle length 360 +/- 49 ms) were studied. The effects of adenosine on the antegrade slow pathway and on the retrograde fast pathway conduction were determined during sustained AVNRT and constant right ventricular pacing at identical cycle lengths (mean 360 +/- 49 ms), respectively. Incremental doses of adenosine were rapidly administered: initial dose of 0.5 mg, followed by stepwise increases of 0.5 or 1.0 mg given at 5-min intervals until termination of AVNRT or second-degree ventriculoatrial block occurred. After the antegrade slow pathway conduction was selectively and completely ablated by radiofrequency catheter ablation, the effect of adenosine on the antegrade fast pathway conduction was evaluated. The dose-response curve of adenosine and the dose of adenosine required to produce AV or ventriculoatrial block among the representative three conduction pathways were compared. The dose-response curve for the effect of adenosine on the antegrade fast pathway lies to the left and upward to that of the effect of adenosine on the antegrade slow pathway which in turn lies to the left and upward to that of the retrograde fast pathway. The mean dose of adenosine required to produce conduction block at antegrade fast, antegrade slow, and retrograde fast pathways were 1.4 +/- 0.5, 4.2 +/- 1.6, and 8.5 +/- 2.6 mg, respectively (p < 0.01). Adenosine has a differential potency to depress antegrade fast, antegrade slow, and retrograde fast pathway conduction in patients with AVNRT. The depressant effect of adenosine on the antegrade fast pathway is more potent than that on the antegrade slow pathway which in turn is more potent than that on the retrograde fast pathway conduction.

Adenosine↗

PubMed1998

Two steroidogenic pathways present in the chicken ovary: theca layer prefers delta 5 pathway and granulosa layer prefers delta 4 pathway.

It has been suggested that there is a shift in steroidogenic pathways of the theca layer from delta 5 to delta 4 during follicular maturation in the chicken ovary. However, the preferred steroid metabolic pathway in the theca and granulosa layers of small and preovulatory follicles has not been identified. Therefore, the goal of our study was to identify the preferred steroidogenic pathways used by these follicles. Previously, we found that small follicles that had not entered the follicular hierarchy did not use cholesterol but did use pregnenolone (P5) to produce testosterone and estradiol. For this reason, P5 was used as the substrate for steroid production in the present study. The theca layer of small follicles (2-4 mm in diameter), and the theca and granulosa layers of the fifth largest (F5), third largest (F3), and largest (F1) preovulatory follicles were isolated from the chicken ovary 22 hr before ovulation. The granulosa layer of small follicles was excluded from the study because it is steroidogenically incompetent. Tissues were incubated with [3H]-P5 for 1 hr at 37 degrees C. Production of steroid metabolites was determined on the basis of comparison with known steroid standards using two-dimensional thin layer chromatography (2D-TLC). Conversion of [3H]-P5 to [3H]-DHEA was greater than that of [3H]-P4 in the theca layer of small and preovulatory follicles. Even though the amount of [3H]-P4 was less than that of [3H]-DHEA, theca cells from F3 and F1 follicles did produce [3H]-P4. In contrast to the theca layer, conversion of [3H]-P4 was greater than that of [3H]-DHEA in the granulosa layer of preovulatory follicles. Conversion of [3H]-P5 to [3H]-DHEA by the granulosa layer gradually decreased as the follicle matured and approached ovulation. We conclude that both delta 5 and delta 4 pathways are functional in theca and granulosa cells. However, in contrast to earlier speculation, the theca layer preferentially metabolizes steroids via the delta 5 pathway regardless of the maturational stage of the follicle, whereas the granulosa layer of preovulatory follicles preferentially metabolizes steroids via the delta 4 pathway.

Animals↗

PubMed2004

Different regulatory pathways of endometrial connexin expression: preimplantation hormonal-mediated pathway versus embryo implantation-initiated pathway.

Transformation of the endometrium into the receptive phase is under the control of ovarian steroid hormones and is modulated by embryonic signals during implantation. We have previously shown that this differentiation process is accompanied by a suppression of gap junction connexins (Cx) 26 and 43 before implantation followed by a local induction of both connexins in the implantation chamber. In the present study, we demonstrate that connexin gene expression in the rodent endometrium is regulated via two distinct signaling pathways during these different stages of early pregnancy. During preimplantation, transcription of connexins can be induced by estrogen via an estrogen receptor (ER)-dependent pathway. Additionally, Cx26 and Cx43 are induced by embryonic signals during implantation and delayed implantation as well as during artificially induced decidualization. In contrast to the estrogen-induced expression, this embryonic/decidual-associated induction of Cx26 and Cx43 could not be blocked by antiestrogen, thus pointing to another regulatory pathway independent of the ER. Studies in ERalpha and ERbeta knockout mice confirmed these different pathways, demonstrating that in the endometrium, estrogen-mediated Cx26 gene induction, but not induction during decidualization, is dependent on functional ERalpha. To evaluate potential embryonic signals regulating Cx26 expression, uteri of pseudopregnant animals were incubated with different mediators in an organ-culture model, showing that catechol estrogen and mediators of the inflammatory cascade such as prostaglandin F(2alpha) and interleukin-1beta are able to induce Cx26 expression through the ER-independent pathway. Thus, the present study demonstrates that endometrial expression of Cx26 and Cx43 is induced via estrogen and ERalpha during preimplantation but then utilizes an ER-independent signaling pathway during embryo implantation and decidualization.

Animals↗

PubMed2000

Anatomical evidence for two spinal 'afferent-interneuron-efferent' reflex pathways involved in micturition in the rat: a 'pelvic nerve' reflex pathway and a 'sacrolumbar intersegmental' reflex pathway.

We labeled interneurons in the L1-L2 and L6-S1 spinal cord segments of the rat that are involved in bladder innervation using transneuronal retrograde transport of pseudorabies virus (PRV) in normal animals and in animals with selected nerve transections. Preganglionic neurons were identified using antisera against choline acetyltransferase (ChAT). In some experiments we labelled parasympathetic preganglionic neurons (PPNs) in the L6-S1 spinal cord by retrograde transport of Fluorogold from the major pelvic ganglion. We identified bladder afferent terminals using the transganglionic transport of the anterograde tracer cholera toxin subunit b. We present anatomical evidence for two spinal pathways involved in innervation of the bladder. First, in the intact rat, afferent information from the bladder connects, via interneurons in L6-S1, to the PPNs that provide the efferent innervation of the bladder. The afferent terminals were located mainly in close apposition to interneurons located dorsal to the retrogradely labeled PPNs. Second, using L6-S1 ganglionectomies or L6-S1 ventral root rhizotomies we limited viral transport to the sympathetic pathways innervating the bladder. This procedure also labelled interneurons (but not PPNs) with PRV in the L6-S1 spinal cord in a location very similar to those described in the intact rat. These interneurons also receive bladder afferent terminals but we propose that they project to sympathetic preganglionic neurons, most of which are in the L1-L2 spinal segments. Based on this anatomical evidence, we propose the existence of two spinal reflex pathways involved in micturition: a pathway limited to a reflex arc in the pelvic nerve (presumably excitatory to the detrusor muscle); and a pathway involving the pelvic nerve and sympathetic nerve fibers, some of which may travel in the hypogastric (presumably inhibitory to the detrusor muscle).

Animals↗

PubMed1999

Comparison of the downstream pathways for degradation of nitrobenzene by Pseudomonas pseudoalcaligenes JS45 (2-aminophenol pathway) and by Comamonas sp. JS765 (catechol pathway).

Nitrobenzene is degraded by Pseudomonas pseudoalcaligenes JS45 via 2-aminophenol to 2-aminomuconic semialdehyde, which is further degraded to pyruvate and acetaldehyde. Comamonas sp. JS765 degrades nitrobenzene via catechol to 2-hydroxymuconic semialdehyde. In this study we examined and compared the late steps of degradation of nitrobenzene by these two microorganisms in order to reveal the biochemical relationships of the two pathways and to provide insight for further investigation of their evolutionary history. Experiments showed that 2-hydroxymuconate, the product of the dehydrogenation of 2-hydroxymuconic semialdehyde, was degraded to pyruvate and acetaldehyde by crude extracts of Comamonas sp. JS765, which indicated the operation of a classical catechol meta-cleavage pathway. The semialdehyde dehydrogenases from Comamonas sp. JS765 and P. pseudoalcaligenes JS45 were able to metabolize both 2-amino- and 2-hydroxymuconic semialdehyde, with strong preference for the physiological substrate. 2-Aminomuconate was not a substrate for 4-oxalocrotonate decarboxylase from either bacterial strain. The close biochemical relationships among the classical catechol meta-cleavage pathway in Comamonas sp. JS765, 2-aminophenol meta-cleavage pathways in P. pseudoalcaligenes JS45, and an alternative 2-aminophenol meta-cleavage pathway in Pseudomonas sp. AP-3 suggest a common evolutionary origin.

Aminophenols↗

PubMed2000

Insulin-like growth factor-I-dependent signal transduction pathways leading to the induction of cell growth and differentiation of human neuroblastoma cell line SH-SY5Y: the roles of MAP kinase pathway and PI 3-kinase pathway.

IGF-I regulates cell growth, differentiation, and survival in many cultured nerve cell lines. The present study was undertaken in the human neuroblastoma cell line, SH-SY5Y, to elucidate whether there are differences in the IGF-dependent signal transduction pathways that stimulate proliferation compared to those that induce differentiation. Quiescent SH-SY5Y cells were treated with IGF-I in the presence or absence of PD98059 (an inhibitor of MEK, a MAP kinase kinase) or LY294002 (an inhibitor of PI 3-kinase). Cell growth was assessed by measuring [3H]thymidine incorporation into DNA and cell number. Cell differentiation was assessed by measuring mRNA levels of NPY and neurite outgrowth. IGF-I both induced cell proliferation and differentiation. It stimulated tyrosine phosphorylation of the type I IGF receptor (IGF-IR) beta-subunit, IRS-I, IRS-2, and Shc, and these changes were associated with activation of Erk and Akt. PD98059 inhibited activation of Erk and LY294002 repressed activation of Akt in response to IGF-I, but did not affect tyrosine phosphorylation of the IGF-IR, IRS-1, IRS-2, or Shc. Each PD98059 and LY294002 inhibited IGF-I-dependent cell proliferation in a concentration-dependent manner. In contrast, each of these inhibitors only partially depressed NPY gene expression induced by IGF-I and slightly inhibited IGF-I-mediated neurite outgrowth; however, when both PD98059 and LY294002 were present, IGF-I-dependent NPY gene expression and neurite outgrowth were abolished completely. These results suggest that in these nerve cells, 1) the IGF-I signals through the MAP kinase pathway and PI-3 kinase pathway are independently essential to induce IGF-I-dependent growth, and 2) alternate activation of the MAP kinase pathway and PI 3-kinase pathway is sufficient for the cells to undergo IGF-I-dependent differentiation.

Adaptor Proteins, Signal Transducing↗

PubMed1995

Pathways, pathway tubes, pathway docking, and propagators in electron transfer proteins.

The simplest views of long-range electron transfer utilize flat one-dimensional barrier tunneling models, neglecting structural details of the protein medium. The pathway model of protein electron transfer reintroduces structure by distinguishing between covalent bonds, hydrogen bonds, and van der Waals contacts. These three kinds of interactions in a tunneling pathway each have distinctive decay factors associated with them. The distribution and arrangement of these bonded and nonbonded contacts in a folded protein varies tremendously between structures, adding a richness to the tunneling problem that is absent in simpler views. We review the pathway model and the predictions that it makes for protein electron transfer rates in small proteins, docked proteins, and the photosynthetic reactions center. We also review the formulation of the protein electron transfer problem as an effective two-level system. New multi-pathway approaches and improved electronic Hamiltonians are described briefly as well.

Electron Transport↗

PubMed2005

TDP-mycaminose biosynthetic pathway revised and conversion of desosamine pathway to mycaminose pathway with one gene.

Analysis of the tylosin gene cluster in Streptomyces fradiae uncovered an ORF, tyl1a, homologous to a hexose 3,4-isomerase found in Aneurinibacillus thermoaerophilus. Inclusion of the tyl1a gene along with other mycaminose biosynthetic genes (tylB, tylM1, tylM2, tylM3) identified in previous studies in an in vivo expression system successfully reconstituted the mycaminose pathway. Expression of tyl1a alone in the S venezuelae KdesI mutant converted a desosamine pathway to a mycaminose pathway. These results strongly support the role of Tyl1a as a TDP-4-keto-6-deoxy-d-glucose 3,4-isomerase.

Anti-Bacterial Agents↗

PubMed2001

The folding pathway of alpha-lactalbumin elucidated by the technique of disulfide scrambling. Isolation of on-pathway and off-pathway intermediates.

The technique of disulfide scrambling permits reversible conversion of the native and denatured (scrambled) proteins via shuffling and reshuffling of disulfide bonds. Under strong denaturing conditions (e.g. 6 m guanidinium chloride) and in the presence of a thiol initiator, alpha-lactalbumin (alphaLA) denatures by shuffling its four native disulfide bonds and converts to an assembly of 45 species of scrambled isomers. Among them, two predominant isomers, designated as X-alphaLA-a and X-alphaLA-d, account for about 50% of the total denatured structure of alphaLA. X-alphaLA-a and X-alphaLA-d, which adopt the disulfide patterns of (1-2,3-4,5-6,7-8) and (1-2,3-6,4-5,7-8), respectively, represent the most unfolded structures among the 104 possible scrambled isomers (Chang, J.-Y., and Li, L. (2001) J. Biol. Chem. 276, 9705-9712). In this study, X-alphaLA-a and X-alphaLA-d were purified and allowed to refold through disulfide scrambling to form the native alphaLA. Folding intermediates were trapped kinetically by acid quenching and analyzed quantitatively by reversed phase high pressure liquid chromatography. The results revealed two major on-pathway productive intermediates, two major off-pathway kinetic traps, and at least 30 additional minor transient intermediates. Of the two major on-pathway intermediates, one takes on a native-like alpha-helical domain, and the other comprises a structured beta-sheet, calcium binding domain. The two major kinetic traps are apparently stabilized by locally formed non-native-like structures. Overall, the folding mechanism of alphaLA is essentially congruent with the model of "folding funnel" furnished with a rather intricate energy landscape.

Disulfides↗

PubMed1989

Two pathways for inducing interleukin 2 production in MOLT 16 cells, a human leukemic T-cell line: interleukin 1 pathway and interleukin 1-independent pathway.

Phytohemagglutinin (PHA)-stimulated MOLT 16 cells (a human leukemic T cell line, at a concentration of 2 x 10(6) cells/ml) secreted 6 U/ml of interleukin 2 (IL 2) into the culture supernatant during 24 h culture. When interleukin 1 (IL 1) (5 U/ml) or IL 1-producing cells such as human T cell leukemia virus-1 (HTLV-1)-transformed T cell line, C5/MJ, and myelomonocytic cell line, THP-1-O, were added to the MOLT 16 culture at a concentration of 4 x 10(5) cells/ml, far greater IL 2 production (greater than 65 U/ml) was observed. The activity of soluble IL 1 and membrane-associated IL 1 produced by these accessory (A) cells was completely neutralized by the treatment with anti-human IL 1 antibody. In sharp contrast, MOLT 16 cells co-cultured with BALL-1 cells (a human leukemic B cell line) resulted in comparable increases in IL 2 production (175 U/ml), although no IL 1 or IL 1-like activity was detected either in the supernatants or in the cell lysates of BALL-1 cells. An augmentation of IL 2 production was also induced with paraformaldehyde-fixed BALL-1 cells, and this augmentation could not be inhibited by anti-human IL 1 antibody. These data indicate that MOLT 16 provides a model for determining pathways for activating T cells leading to IL 2 production in response to mitogens. Two pathways have been described in the report: one involving secreted or membrane-associated IL 1, and a second independent pathway which involves contact of surface membranes in the presence of PHA.

Antigens, Surface↗

PubMed2005

Prolongation of the fast pathway effective refractory period during cryoablation in children: a marker of slow pathway modification.

BACKGROUND: The fast pathway effective refractory period (ERP) has been reported to decrease after slow pathway modification with radiofrequency (RF) energy. How the fast pathway ERP changes during the ablation application has not been reported with either RF or cryoenergy. OBJECTIVES: Using the unique features of cryotherapy, this study assesses the short-term changes in fast pathway ERP during cryomodification of the slow pathway and examines whether these changes are a useful marker for successful slow pathway modification in children. METHODS: Nineteen pediatric patients (median age 15.1 years, range 9.6-19.6 years; weight 60.7 kg, range 35.6-130.2 kg) with anterograde dual AV nodal physiology underwent slow pathway modification with catheter-based cryoablation. Programmed stimulation was performed during cryoapplications after reaching -25 degrees C to assess fast pathway and slow pathway conduction. Data were analyzed from 59 of 237 cryoapplications where the fast pathway ERP was measured more than once (n = 13 patients). RESULTS: For 23 of 59 applications where the slow pathway was modified, the fast pathway ERP significantly increased during cryotherapy (Delta = 33.5 ms, P <.0001). The magnitude of fast pathway ERP prolongation during cryotherapy was larger when the slow pathway was modified than when there was no effect on slow pathway conduction (33.5 +/- 30.5 vs 5.8 +/- 18.9 ms, P =.0005). Prolongation of fast pathway ERP by >/=20 ms had 70% sensitivity and 72% specificity for predicting slow pathway modification. Following termination of cryoapplications, which resulted in slow pathway modification, the fast pathway ERP had significantly decreased from baseline (difference 44.5 ms, P <.0001). The effect on fast pathway ERP was not related to changes in cycle length during (R(2) = 0.04, P = .045) or after ablation (R(2) = 0.13, P = .012). CONCLUSION: The fast pathway ERP prolongs during cryoapplications that result in slow pathway modification and shortens after termination of cryoapplications. The magnitude of fast pathway ERP prolongation during cryoapplication may be useful as a marker for successful slow pathway modification.

Adolescent↗

PubMed1988

New catheter technique for recording left free-wall accessory atrioventricular pathway activation. Identification of pathway fiber orientation.

The ability to record accessory atrioventricular (AV) pathway activation consistently may be uniquely beneficial in improving pathway localization, identifying anatomic relations, and providing insight into unusual conduction properties. For the purpose of recording left AV accessory pathway activation, an electrode catheter was specially designed for use in the coronary sinus. The orthogonal catheter has three sets of four electrodes spaced evenly around the circumference. Electrograms were recorded at low gain (less than 1 cm/mV) between adjacent electrodes on the same set (interelectrode distance, 1.5 mm, center to center). This provides a recording dipole perpendicular to the atrioventricular groove to enhance recording of accessory pathway activation while minimizing overlapping atrial or ventricular potentials. The orthogonal electrode catheter was used in the electrophysiological study of 48 consecutive patients with 59 left AV accessory pathways. The catheter could be advanced along the coronary sinus beyond the site of earliest retrograde atrial activation in 49 of the 59 accessory pathways. Activation potentials were recorded from 45 of the 49 (92%) accessory pathways accessible to the catheter (5 of 5 anterior, 8 of 8 anterolateral, 15 of 16 lateral, 5 of 5 posterolateral, 5 of 5 posterior, and 7 of 10 posteroseptal). Accessory pathway potentials were validated by dissociating them from both atrial and ventricular activation by programmed-stimulation techniques. During surgery, accessory pathway potentials were identified from orthogonal catheter electrodes in the coronary sinus in 14 of 16 accessory pathways (12 patients). Epicardial mapping confirmed the location of the accessory pathway, and direct pressure over the orthogonal catheter electrode that recorded the accessory pathway potential resulted in transient conduction block in nine of the 14 accessory pathways. Orthogonal electrode maps of the coronary sinus identified an oblique course in 39 of 45 recorded accessory pathways. Thirty-two of 38 left free-wall accessory pathways were oriented with atrial insertion 4-30 mm (median, 14 mm) proximal (posterior) to the ventricular insertion. In the remaining six free-wall accessory pathways, the lateral excursion could not be determined because either only the atrial end of the accessory pathway was recorded or activation of multiple pathway fibers prevented tracking of individual strands. The seven recorded posteroseptal pathways exhibited accessory pathway potentials throughout an 8-18-mm (median, 10 mm) length of the proximal coronary sinus, but fiber orientation was difficult to determine.(ABSTRACT TRUNCATED AT 400 WORDS)

Atrioventricular Node↗

PubMed1997

Time-dependent change in fast pathway refractoriness after slow pathway ablation in atrioventricular node reentrant tachycardia. Mansfield Polaris Investigators.

OBJECTIVE: To determine the time course of change in fast pathway refractoriness after slow pathway ablation. BACKGROUND: Antegrade fast pathway refractoriness has been observed to shorten in patients undergoing slow pathway ablation for atrioventricular (AV) node reentrant tachycardia. The time course and mechanism of this observation have not been explained. METHODS: Twenty-eight patients with AV node reentrant tachycardia and dual AV node pathways undergoing slow pathway ablation had the fast pathway effective refractory period (ERP) assessed immediately before, and at 0, 15, 30 and 45 mins after slow pathway ablation (Group 1). Twenty-five additional patients with AV node reentry and dual pathways involved in a multicentre protocol evaluating the Mansfield Polaris LE catheter underwent assessment of fast pathway refractoriness before and after slow pathway ablation, and at a routine three-month follow-up electrophysiology study (Group 2). RESULTS: In Group 1, antegrade fast pathway ERP fell from 394 ms before ablation to 334 ms immediately after slow pathway ablation, increased to 348 ms within 15 mins and was 353 ms at 45 mins (ANOVA P < 0.001). Retrograde fast pathway ERP fell from 325 ms before ablation to 294 ms at 45 mins (P = 0.02). In Group 2, antegrade fast pathway ERP fell from 390 ms before ablation to 337 ms after ablation, and rose to 362 ms at three months (P = 0.01). Retrograde fast pathway ERP also fell from 347 ms to 319 ms after ablation (P = 0.01), and remained unchanged at three months. CONCLUSION: Slow pathway ablation results in an immediate and sustained change in antegrade and retrograde first pathway refractoriness. There are immediate reversible and long term nonreversible components to this phenomenon. The latter finding may be related to loss of electrotonic inhibition of the fast pathway by the slow pathway.

Adult↗

PubMed2005

Critical pathway effectiveness: assessing the impact of patient, hospital care, and pathway characteristics using qualitative comparative analysis.

OBJECTIVE: To qualitatively describe patient, hospital care, and critical pathway characteristics that may be associated with pathway effectiveness in reducing length of stay. DATA SOURCES/STUDY SETTING: Administrative data and review of pathway documentation and a sample of medical records for each of 26 surgical critical pathways in a tertiary care center's department of surgery, 1988-1998. STUDY DESIGN: Retrospective qualitative study. DATA COLLECTION/ABSTRACTION METHODS: Using information from a literature review and consultation with experts, we developed a list of characteristics that might impact critical pathway effectiveness. We used hypothesis-driven qualitative comparative analysis to describe key primary and secondary characteristics that might differentiate effective from ineffective critical pathways. PRINCIPAL FINDINGS: " All 7 of the 26 pathways associated with a reduced length of stay had at least one of the following characteristics: (1) no preexisting trend toward lower length of stay for the procedure (71 percent), and/or (2) it was the first pathway implemented in its surgical service (71 percent). In addition, pathways effective in reducing length of stay tended to be for procedures with lower patient severity of illness, as indicated by fewer intensive care days and lower mortality. Effective pathways tended to be used more frequently than ineffective pathways (77 versus 59 percent of medical records with pathway documents present), but high rates of documented pathway use were not necessary for pathway effectiveness. CONCLUSIONS: Critical pathway programs may have limited effectiveness, and may be effective only in certain situations. Because pathway utilization was not a strong predictor of pathway effectiveness, the mechanism by which critical pathways may reduce length of stay is unclear.

Baltimore↗

PubMed1994

Effects of partial and complete ablation of the slow pathway on fast pathway properties in patients with atrioventricular nodal reentrant tachycardia.

INTRODUCTION: The purpose of this study was to prospectively compare the effects of complete and partial ablation of slow pathway function on the fast pathway effective refractory period (ERP). METHODS AND RESULTS: The subjects were 20 patients (mean age 43 +/- 13 years) with atrioventricular nodal reentrant tachycardia (AVNRT), no structural heart disease, and easily inducible AVNRT. Autonomic blockade was achieved with propranolol (0.2 mg/kg) and atropine (0.04 mg/kg). After elimination of AVNRT and during autonomic blockade, the presence of residual slow pathway function was determined by the presence of a single AV nodal echo and/or dual AV nodal physiology. After autonomic blockade and before ablation, the mean fast pathway ERP was 319 +/- 44 msec and the mean slow pathway ERP was 251 +/- 31 msec. After slow pathway ablation and during autonomic blockade, 7 patients had residual slow pathway function and 13 did not. Complete loss of slow pathway function was associated with a shortening of the fast pathway ERP from 334 +/- 35 msec to 300 +/- 62 msec (P < 0.01), while the fast pathway ERP did not change significantly in patients with residual slow pathway function (291 +/- 29 msec vs 303 +/- 38 msec, respectively; P = 0.08). A shortening of 30 msec or more in the fast pathway ERP was observed in 11 of 13 patients who did not have residual slow pathway function, compared to 0 of 7 patients with residual slow pathway function (P < 0.001). CONCLUSION: Shortening of the fast pathway ERP after successful ablation of AVNRT is dependent upon complete loss of slow pathway function. This observation is consistent with electrotonic inhibition of the fast pathway by the slow pathway.

Adult↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗