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The Deoxyxylulose Phosphate Pathway for the Biosynthesis of Plastidic Isoprenoids: Early Days in Our Understanding of the Early Stages of Gibberellin Biosynthesis.

The identification of a novel pathway for isopentenyl diphosphate synthesis by Rohmer, Arigoni and colleagues in the early 1990's has led to a reappraisal of terpenoid biosynthesis in many organisms. It is now apparent that in plants there are two biosynthetic routes to isopentenyl diphosphate-the classical mevalonate pathway in the cytosol and the deoxyxylulose phosphate pathway in plastids. Sesquiterpenoids and sterols are predominantly synthesized in the cytosol by the mevalonate pathway whereas monoterpenoids, diterpenoids, the phytol side-chain of chlorophyll, carotenoids, and the nonaprenyl side-chain of plastoquinone-9 are synthesized within plastids by the deoxyxylulose phosphate pathway. Our assumptions that the early stages of gibberellin biosynthesis are plastid-localized has led to several attempts to demonstrate that the deoxyxylulose phosphate pathway is the biosynthetic route to gibberellins. Although definitive evidence is still not available there is a growing body of evidence, mostly from transgenic plants and from the use of the inhibitor, fosmidomycin, that gibberellins are synthesized from deoxyxylulose phosphate-derived isopentenyl diphosphate. However, there is evidence that a small amount of cross-talk between the two pathways may occur, implying that the pathways are not totally autonomous. Implications for the regulation of the early stages of gibberellin biosynthesis are discussed.

Journal Article↗

The role of a swelling-activated taurine transport pathway in the regulation of articular chondrocyte volume.

Swelling articular chondrocytes by reducing osmolarity stimulates a taurine transport pathway, which is implicated in regulatory volume decrease (RVD) in various cell types. The present study investigated factors controlling the activity of this pathway in chondrocytes, in particular (1) the effects of the acute (seconds) and chronic (hours) exposure of chondrocytes to anisotonic media, and (2) whether there is a role for metabolites from the arachidonic acid cascade in activating the taurine transport pathway. For in situ and isolated chondrocytes, the point at which swelling-activated [14C]taurine efflux was stimulated (the "set-point") corresponded closely to the osmolarity of the incubation medium (180, 280 or 380 mosmol/l). However, the volume of chondrocytes isolated into these media and measured by confocal microscopy was not different ( congruent with 645 microm3). Activity of the swelling-activated taurine transport pathway was inhibited by REV5901 (an inhibitor of steps of the arachidonic acid cascade; K0.5 8+/-4 microM), NDGA (a general lipoxygenase inhibitor; K0.5 28+/-5 microM), or MK886 (an inhibitor of the 5-lipoxygenase-activating protein; 91% inhibition at 10 microM), but weakly by the more potent 5-lipoxygenase inhibitor REV5901 para (K0.5 350+/-100 microM). Addition of the leukotriene (LT) B4 or D4 receptor antagonists, CP-105,696 and L660,711 respectively, or of the leukotrienes LTB4, LTC4, LTD4 and LTE4 or lipoxins (hepoxylin A3 or B3) had no effect on the activity of the pathway in isotonic or hypotonic media. The role of the pathway in RVD was determined in isolated calcein-loaded chondrocytes using fluorescence imaging. RVD was observed and inhibited by REV5901 (50 microM) and by NDGA (75 microM). The data show that despite chronic exposure of chondrocytes to anisotonic media, the cells maintain a pre-determined volume that is the "set-point" for the activation of the taurine transport pathway following acute hypotonic challenge. This pathway appears to play a role in chondrocyte RVD, but its activation does not involve metabolites of the arachidonic acid cascade.

Biological Transport↗

The Hopscotch Jak kinase requires the Raf pathway to promote blood cell activation and differentiation in Drosophila.

Cytokines regulate the development and differentiated functions of hematopoietic cells by activating multiple signaling pathways, including the Jak-Stat pathway, the PI3-kinase pathway, and the Ras/Raf pathway. While the Jak-Stat interaction has been extensively studied, the relationship between this pathway and other cytokine-induced signaling pathways is not fully understood. In Drosophila melanogaster, mutations that result in hyperactivity of the Jak kinase Hopscotch (Hop) cause an activation of the larval blood cell encapsulation response, including blood cell aggregation and differentiation of plasmatocytes into apparent lamellocytes. Here, we demonstrate that Hop requires the activity of the Raf pathway to promote the activation response of larval plasmatocytes, and provide evidence to suggest that the Hop and D-Raf proteins physically interact. We also show that basal level activity of the Raf pathway is required for the accumulation of circulating blood cells.

Animals↗

Oxidative stress in Schizosaccharomyces pombe: different H2O2 levels, different response pathways.

Schizosaccharomyces pombe triggers different signalling pathways depending on the severity of the oxidative stress exerted, the main ones being the Pap1 and the Sty1 pathways. The Pap1 transcription factor is more sensitive to hydrogen peroxide (H(2)O(2)) than the MAP kinase Sty1 pathway, and is designed to induce adaptation, rather than survival, responses. The peroxiredoxin Tpx1 acts as a H(2)O(2) sensor and the upstream activator of the Pap1 pathway. Therefore, sensitivity to H(2)O(2) depends on this thioredoxin peroxidase. In order to achieve maximal activation of the MAP kinase pathway, the concentration of H(2)O(2) needs to be at least fivefold higher than that to fully activate Pap1. Tpx1 is a H(2)O(2) scavenger, thus its peroxidase activity is essential for aerobic growth. As described for other eukaryotic peroxiredoxins, high doses of H(2)O(2) temporarily inactivate Tpx1 and delay Pap1 activation, whereas the Sty1 pathway remains fully functional under these conditions. As part of the Sty1-dependent transcriptional response, the expression of Srx1 is induced and this reductase re-activates the over-oxidised Tpx1. Therefore, the antioxidant pathways of the fission yeast are perfectly designed so that the transcriptional programs triggered by the different signalling pathways never overlap.

Amino Acid Transport Systems↗

Multiple pathways for acetate assimilation in Streptomyces cinnamonensis.

In most bacteria acetate assimilation is accomplished via the glyoxylate pathway. Isocitrate lyase (ICL) and malate synthase (MS) are two key enzymes of this pathway, which results in the net generation of one molecule of succinyl-CoA from two acetyl-CoA molecules. Genetic and biochemical data have shown that genes encoding these key enzymes are present in streptomycetes, yet there has been no clear demonstration of the importance of these genes to acetate assimilation. In fact, for Streptomyces collinus an alternative butyryl-CoA pathway has been shown to be critical for growth on acetate as a sole carbon source. Crotonyl-CoA reductase (CCR) is a key enzyme in this pathway and catalyzes the last step of the conversion of 2-acetyl-CoA molecules to butyryl-CoA. In Streptomyces cinnamonensis C730.1, it has been shown that CCR and this butyryl-CoA pathway provide the majority of methylmalonyl-CoA and ethylmalonyl-CoA for monensin A biosynthesis in an oil-based fermentation medium. We have cloned a MS homologue gene from this strain. Reverse transcription and direct enzyme assays demonstrated that neither this nor other MS genes were expressed during fermentation in an oil-based fermentation of either the C730.1 or L1 strain (a ccr mutant). Similarly, no ICL activity could be detected. The C730.1 but not the L1 strain was able to grow on acetate as a sole carbon source. The Streptomyces coelicolor aceA and aceB2 genes encoding ICL and MS were cloned into a Streptomyces expression plasmid (a derivative of pSET152) to create pExIM1. Enzyme assays and transcript analyses demonstrated expression of both of these proteins in C730.1/pExIM1 and L1/pExIM1 grown in an oil-based fermentation and tryptic soy broth media. Nonetheless, L1/pExIM1, like L1, was unable to grow on acetate as a sole carbon source, and was unable to efficiently generate precursors for monensin A biosynthesis in an oil-based fermentation, indicating that the additional presence of these two enzyme activities does not permit a functional glyoxylate cycle to occur. UV mutagenesis of S. cinnamonensis L1 and L1/pExIM1 led to mutants which were able to grow efficiently on acetate despite a block in the butyryl-CoA pathway. Analysis of enzyme activity and monensin production from these mutants in an oil-based fermentation demonstrated that neither the glyoxylate cycle nor the butyryl-CoA pathway function, suggesting the possibility of alternative pathways of acetate assimilation.

Acetates↗

Breast cancer risk associated with genotypic polymorphism of the genes involved in the estrogen-receptor-signaling pathway: a multigenic study on cancer susceptibility.

The reproductive hormone, estrogen, contributes to the development of breast cancer by binding to the estrogen receptor (ER) in the nucleus, triggering cell growth and tumor promotion. In addition to its role in regulating target genes and signaling pathways involved in cell cycle progression, the ER-signaling pathway may regulate the expression of chromatin-remodeling gene, Metastasis-associated 3 (MTA3), or interact with chromatin-remodeling protein, Metastasis-associated 1 (MTA1). The invasion-suppressor gene, E-Cadherin (E-Cad), has recently been identified as a downstream target gene regulated by the ER-MTA3 pathway via the transcriptional repressor, Snail, and the ER-MTA3-Snail-E-Cad pathway has therefore been evoked to explain the clinical observation that ER expression in breast cancer is generally associated with a better clinical outcome. Since E-Cad may play an initiating role during breast tumorigenesis, we hypothesized that this ER-signaling pathway may also determine susceptibility to breast cancer, and examined this in a multigenic case-control study of 468 incident breast cancer patients and 470 healthy controls by genotyping the single nucleotide polymorphisms (SNPs) in five genes (ER, MTA3, Snail, E-Cad, and MTA1) in the ER-signaling pathways. Support for this hypothesis came from the observations that (a) with the exception of Snail, which interacted differently with reproductive risk factors in relation to breast cancer risk, there was a joint effect of the SNPs of these genes and estrogen-related risk factors (age at first full-term pregnancy and obesity, measured by the body mass index) on breast cancer risk (p < 0.05); (b) a trend toward increased risk of developing breast cancer was seen in women harboring a greater number of putative high-risk genotypes of these genes in ER-signaling pathways; (c) this association between risk and the number of putative high-risk genotypes was stronger and more significant in women thought to have experienced higher estrogen level, i.e., obese women; and (d) the risk effect conferred by obesity was only significant in women with a higher number of putative high-risk genotypes of the ER-signaling genes. These epidemiological findings highlight the role of newly identified novel ER-related pathways in breast cancer development and provide a more comprehensive picture of the tumorigenic effect of estrogen in breast cancer development.

Breast Neoplasms↗

Effect of isoproterenol on the anterograde refractory period of the accessory pathway in patients with the Wolff-Parkinson-White syndrome.

To evaluate the effect of beta adrenergic stimulation on the duration of the anterograde refractory period of the accessory pathway, isoproterenol was infused in seven patients with the Wolff-Parkinson-White syndrome. In two patients the effect of isoproterenol was studied during long-term oral amiodarone administration. To avoid rate-related changes induced by isoproterenol, the anterograde refractory period of the accessory pathway was determined using the single test stimulus method at identical basic cycle lengths. Isoproterenol shortened the anterograde refractory period of the accessory pathway in six of the seven patients studied. In two of the three patients with an initial anterograde refractory period of the accessory pathway of equal to or less than 290 ms, shortening measured 30 ms. In three patients having an anterograde refractory period of the accessory pathway of more than 290 ms, isoproterenol abbreviated these values by 30, 60 and 80 ms, respectively. The greatest amount of shortening was observed in patients having the longest initial values for the anterograde refractory period of their accessory pathway. In the two patients receiving oral amiodarone therapy, isoproterenol shortened the anterograde refractory period of the accessory pathway by 180 and 60 ms, respectively, indicating that the effect of isoproterenol can not be prevented by long-term oral amiodarone administration. Our observations may be of importance in patients with the Wolff-Parkinson-White syndrome and atrial fibrillation. They suggest that beta adrenergic stimulation induced by hypotension or anxiety may result in shortening of the anterograde refractory period of the accessory pathway, leading to increased ventricular rates during atrial fibrillation.

Adult↗

Quintuple pathways participating in three distinct types of atrioventricular reciprocating tachycardia in a patient with Wolff-Parkinson-White syndrome.

Electrophysiologic studies were performed in a patient with recurrent supraventricular tachyarrhythmias. Sinus and paced atrial beats had QRS complexes characteristic of atrioventricular (A-V) conduction through a manifest left lateral accessory pathway (Wolff-Parkinson-White syndrome, type A). Three distinct types of A-V reciprocating tachycardia and three different modes of retrograde atrial activation were demonstrated. Type 1 tachycardia involved the slow A-V nodal pathway and a second (left lateral or left paraseptal) accessory A-V pathway capable of retrograde conduction only. Type 2 tachycardia was of the slow-fast A-V nodal pathway type. Type 3 tachycardia involved in heretofore undescribed circuit in that retrograde conduction occurred through an accessory A-V pathway with long retrograde conduction times and anterograde conduction through both the manifest left lateral accessory A-V pathway and fast A-V nodal pathway. Premature ventricular beats delivered late in the cycle of this tachycardia advanced (but did not change) the retrograde atrial activity without affecting the timing of the corresponding anterograde H deflection. In summary, this patient had five (three accessory and two intranodal) pathways participating in three different types of A-V reciprocating tachycardia; the recurrence of these were prevented with oral amiodarone therapy.

Aged↗

Value of the ajmaline-procainamide test to predict the effect of long-term oral amiodarone on the anterograde effective refractory period of the accessory pathway in the Wolff-Parkinson-White syndrome.

In patients with the Wolff-Parkinson-White syndrome, intravenous ajmaline (50 mg administered over 3 minutes) or procainamide (10 mg/kg body weight administered over 10 minutes) is helpful in defining the duration of the anterograde effective refractory period of the accessory pathway. In this study the value of the ajmaline-procainamide test to predict the effects on the anterograde effective refractory period of the accessory pathway of long-term oral amiodarone were assessed. Thirty-six patients with the Wolff-Parkinson-White syndrome were studied. Twenty-four (Group A) had a negative result of the ajmaline-procainamide test and a mean duration of the anterograde effective refractory period of the accessory pathway of 237 +/- 24 ms. Twelve (Group B) had a positive result in the ajmaline-procainamide test (disappearance of preexcitation during sinus rhythm after administration of ajmaline and procainamide) and a duration of the anterograde effective refractory period of the accessory pathway of 284 +/- 25 ms (p less than 0.05 versus values in Group A). Amiodarone prolonged the anterograde effective refractory period of the accessory pathway by 53 +/- 35 ms in patients in Group A to 290 +/- 37 ms (p less than 0.001) and by 100 +/- 85 ms in patients in Group B to 384 +/- 94 ms (p less than 0.001). The difference in mean increase between both groups was not significant. In most patients (83%) in Group A amiodarone prolonged the anterograde effective refractory period of the accessory pathway to 260 to 330 ms. However, in most patients (83%) in Group B, amiodarone prolonged the anterograde effective refractory period of the accessory pathway to greater than or equal to 330 ms (p less than 0.01). Thus, an ajmaline-procainamide test is of value in predicting the results of oral amiodarone on the anterograde effective refractory period of the accessory pathway.

Adolescent↗

Surgical treatment of accessory atrioventricular pathways and symptomatic tachycardia in children and young adults.

Twenty-seven patients aged 21 years or younger (mean 15) with symptomatic tachycardia underwent operation for ablation of an accessory atrioventricular pathway. Six patients had associated Ebstein's malformation of the tricuspid valve. Supraventricular tachycardia had been present for a mean of 5 years. At electrophysiologic study, 4 patients were found to have 2 accessory pathways. Left ventricular free wall pathways were found in 14 patients, right ventricular free wall pathways in 10 and septal pathways in 6. Successful initial ablation of all the pathways was achieved in 26 of the 27 patients. No patient died perioperatively and none had persistent complete heart block. During a mean follow-up of 11 months, no patient had recurrence of an arrhythmia related to the accessory pathway. Thus, the surgical treatment of children and young adults with accessory atrioventricular pathways and symptomatic supraventricular tachycardia is safe and effective. For these patients, unless the tachycardia can be easily controlled with a minimal number of drugs and adverse effects, surgical ablation should be considered early in the clinical course.

Adolescent↗

Radiofrequency catheter ablation of accessory pathways: a learning experience.

Success rates of approximately 90% have recently been reported with radiofrequency catheter ablation of accessory pathways. This study determined whether this success could be repeated using a conservative approach generally limiting fluoroscopy time to 1 hour. Consecutive patients referred for management of arrhythmias associated with accessory atrioventricular pathways were included over a 9-month period. Ablation was attempted in 75 patients with 84 pathways. Overall success rate (including second attempts in 9 patients) was 60 of 84 accessory pathways (71%). Success rates for the first 3 months (n = 23) were 52%, the second 3 months (n = 23) 60% and the last 3 months (n = 38) 90%. Success rate varied with pathway location, with left lateral pathways having the best early success rates. Mean fluoroscopy time for successful procedures of 33 +/- 21 minutes was shorter than the time for unsuccessful procedures of 63 +/- 24 minutes (p = 0.001). There were no major complications and no patients with successful procedures (n = 53) have had recurrence of accessory pathway conduction or reciprocating tachycardia (follow-up 1 to 10 months). A conservative approach can yield success rates approaching 90% in a short time. The absence of major complications supports earlier reports suggesting that radiofrequency catheter ablation of accessory pathways is a reasonable first-line therapy in the Wolff-Parkinson-White syndrome.

Adolescent↗

Metabolism of inhaled dihalomethanes in vivo: differentiation of kinetic constants for two independent pathways.

Dihalomethanes are metabolized by two major pathways: an oxidative, cytochrome P-450-mediated pathway that has been previously thought to yield only CO, and a glutathione (GSH)-dependent one that yields CO2. Both give 2 mol of halide ion. We studied the kinetic properties of the two pathways in vivo by exposing male rats to various inhaled concentrations of CH2Cl2,CH2F2, CH2FCl, CH2BrCl, and CH2Br2 and determining end-exposure carboxyhemoglobin (HbCO) and plasma bromide (where appropriate). Closed atmosphere gas uptake studies were employed for CH2F2, CH2FCl, CH2Cl2, and CH2BrCl metabolism. A physiologically based kinetic model was used to determine kinetic constants based on gas uptake or plasma bromide data and these constants were used to predict HbCO concentrations. Oxidation was high affinity, low capacity. The maximum metabolic rates for this pathway with CH2Br2, CH2BrCl, and CH2Cl2 were, respectively, 72, 54, and 47 mumol metabolized/kg/hr. CH2FCl did not undergo significant oxidative metabolism and appears more like CH3C1 than a dihalomethane in its metabolic reactivity. The GSH pathway was low affinity, but high capacity and could be described as a single first-order process at all accessible exposure concentrations. The rate constant for this first-order GSH-dependent pathway was related as CH2BrCl greater than CH2Cl2 congruent to CH2FCl greater than CH2Br2 greater than CH2F2. Presumably bromide is a preferred leaving group but steric hindrance in the initial reaction with GSH is important with CH2Br2. We also studied the effects of pyrazole (which inhibits microsomal oxidation) and 2,3-epoxypropanol (which depletes GSH) on dihalomethane metabolism. Pyrazole abolished CO production from CH2Br2, CH2BrCl, and CH2Cl2. GSH depletion did not change the yield of halide ion from the high-affinity pathway; it did increase the steady-state HbCO concentrations with CH2Cl2 and CH2ClBr, but not with CH2Br2. The putative formyl chloride (FC) intermediate from CH2Cl2 or CH2BrCl appears to have a longer life than the formyl bromide from CH2Br2 and a significant portion of the FC (congruent to 20-30%) may react with other cellular nucleophiles instead of spontaneously decomposing to CO. This portion of the oxidative pathway probably yields CO2.

1-Propanol↗

Transesophageal versus intracardiac atrial stimulation in assessing anterograde conduction properties of the accessory pathway in Wolff-Parkinson-White syndrome.

Electrophysiologic intracardiac and noninvasive transesophageal testing, used to evaluate parameters of anterograde conduction across the accessory pathway, the refractory period and shortest atrial cycle length with 1:1 conduction over the pathway, were compared to assess the reliability of the noninvasive technique in identifying patients with Wolff-Parkinson-White syndrome, at risk of rapid ventricular response during atrial fibrillation when this arrhythmia is not inducible. Sixteen patients with Wolff-Parkinson-White syndrome were submitted both to invasive and transesophageal atrial stimulation. We evaluated both the functional and effective refractory periods of the accessory pathway, using the same drive cycle length, and the shortest cycle length with 1:1 atrioventricular conduction over the accessory pathway. There were no differences between the parameters obtained by intracardiac atrial stimulation and by transesophageal atrial stimulation. The two approaches correlated well: mean functional refractory periods of the accessory pathway were 285 +/- 42 msec and 289 +/- 32 msec, respectively (NS, r = 0.88); mean effective refractory periods of the accessory pathway were 267 +/- 41 msec and 271 +/- 32 msec, respectively (NS, r = 0.89); mean shortest cycle lengths with 1:1 conduction over the accessory pathway were 255 +/- 48 msec and 255 +/- 44 msec, respectively (NS, r = 0.94). These data demonstrate the reliability of transesophageal atrial stimulation in estimating the parameters for anterograde conduction across an accessory pathway. These results, and the already documented ability of transesophageal atrial stimulation to induce atrial fibrillation, suggest this noninvasive technique should be taken as a first approach in screening patients with Wolff-Parkinson-White syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Differential effect of intravenous procainamide on anterograde and retrograde accessory pathway refractoriness.

Although procainamide may markedly impair or abolish anterograde conduction over an accessory atrioventricular (AV) pathway, orthodromic AV reentry may remain inducible. This difference may be related to a systemic differential effect of procainamide on anterograde and retrograde accessory pathway refractoriness. To examine this phenomenon, an infusion of procainamide producing five incremental blood levels over 75 min was administered to 15 patients with the Wolff-Parkinson-White syndrome. At each procainamide level, accessory pathway effective refractory period and accessory pathway block cycle length were determined in the anterograde and retrograde directions. At baseline, there were no significant differences between anterograde and retrograde accessory pathway effective refractory periods (282 +/- 7 vs. 266 +/- 9 ms, p = 0.08) and block cycle lengths (288 +/- 15 vs. 283 +/- 9 ms, p = 0.66). The concentration of procainamide resulting in 50% prolongation of accessory pathway refractoriness was less in the anterograde direction than in the retrograde direction (27.5 [log concentration -4.56 +/- SE 0.13] vs. 64.6 [-4.19 +/- 0.11] mumol/liter, p = 0.02). Similarly, the concentration of procainamide resulting in 50% prolongation of accessory pathway block cycle length in the anterograde direction (25.1 [-4.60 +/- 0.13] mumol/liter) was less than in the retrograde direction (52.5 [-4.28 +/- 0.07] mumol/liter, p = 0.01). The probability of persistence of accessory pathway conduction in the anterograde direction was less than in the retrograde direction by Kaplan-Meier analysis (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Adenosine-induced atrioventricular block: a rapid and reliable method to assess surgical and radiofrequency catheter ablation of accessory atrioventricular pathways.

Adenosine has been shown to inhibit anterograde and retrograde conduction through the atrioventricular (AV) node while having little or no effect on accessory pathway conduction. Its rapid onset of action and short half-life make it particularly suitable for repetitive measurements. In this study, the utility of adenosine was tested in assessing completeness of accessory pathway ablation. Sixteen patients with an accessory pathway were studied (eight surgical ablations, eight catheter ablations with radiofrequency energy). Before ablation, no accessory pathway was sensitive to adenosine. Twelve patients with pre-excitation showed high grade AV node block with maximal pre-excitation on the administration of adenosine during atrial pacing. Four patients with a concealed accessory pathway demonstrated high grade AV block without evidence of latent anterograde accessory pathway conduction. Preablation ventriculoatrial (VA) block was not observed in any of the 16 patients in response to adenosine during ventricular pacing. Immediately after accessory pathway ablation, all patients developed AV and VA block with the administration of adenosine during atrial and ventricular pacing, respectively. These findings were confirmed during follow-up study 1 week later. Atrioventricular block during atrial and ventricular pacing with adenosine affords a reliable and immediate assessment of successful pathway ablation.

Adenosine↗

Curative percutaneous catheter ablation using radiofrequency energy for accessory pathways in all locations: results in 100 consecutive patients.

Patients with accessory pathway-mediated supraventricular tachycardia have typically been treated with drugs or surgery. Although catheter ablation using high voltage direct current shocks has been used to treat patients with drug-refractory supraventricular tachycardia, there are associated disadvantages, including damage due to barotrauma as well as the need for general anesthesia. Recently, transcatheter radiofrequency energy has evolved as an alternative to direct current shock or surgery to ablate accessory pathways. Percutaneous catheter ablation of 109 accessory pathways with use of radiofrequency energy was attempted in 100 consecutive patients. Patient age ranged from 3 to 67 years. The patients had been treated for recurrent tachycardia with a mean of 2.7 +/- 0.2 antiarrhythmic agents that either proved ineffective or caused unacceptable side effects. In seven patients previous attempts at accessory pathway ablation with use of direct current shock had been unsuccessful. Forty-five (41%) of the pathways were left free wall, 43 (40%) were septal and 21 (19%) were right free wall. Eighty-nine (89%) of the 100 patients had successful radiofrequency ablation at the time of hospital discharge. In all but 12 patients the ablation was accomplished in a single session. Complications attributable to the procedure, but not to the ablation itself, occurred in four patients (4%). No patient developed atrioventricular block or other cardiac arrhythmias. Over a mean follow-up period of 10 months, nine patients had some return of accessory pathway conduction; a repeat ablation procedure was successful in all five patients in whom it was attempted. It is concluded that a catheter ablation procedure using radiofrequency energy can be performed on accessory pathways in all locations. The procedure is effective and safer, less costly and more convenient than cardiac surgery and can be considered as an alternative to lifelong medical therapy in any patient with symptomatic accessory pathway-mediated tachycardia.

Adolescent↗

Slow pathway ablation in patients with atrioventricular node reentrant tachycardia and a prolonged PR interval.

OBJECTIVES: We sought to assess the safety and efficacy of selective slow pathway ablation using radiogfrequency energy and a transcatheter technique in patients with a prolonged PR interval and atrioventricular (AV) node reentrant tachycardia. BACKGROUND: Although both fast and slow AV node pathways can be ablated in patients with AV node reentrant tachycardia, slow pathway ablation, by obviating the risk of AV block, appears to be safer. However, the safety and efficacy of selective slow pathway ablation using transcatheter radiofrequency energy in patients with a prolonged PR interval during sinus rhythm are unclear. METHODS: The seven study patients with a prolonged PR interval (mean +/- SD 237 +/- 26 ms) comprised three women and four men with a mean age of 31 +/- 15 years. The slow pathway was targeted in all seven patients at the posterior/inferior interatrial septal aspect of the tricuspid annulus. Two patients presented with the uncommon variety of AV node reentrant tachycardia after initial fast pathway ablation; in the remaining five patients, the AV node reentrant tachycardia was of the common variety. RESULTS: A single radiofrequency pulse at 30 W successfully abolished the slow pathway in both the anterograde and the retrograde direction in the two patients with uncommon AV node reentrant tachycardia. A mean of 5 +/- 3 radiofrequency pulses were required in the remaining five patients with reentrant tachycardia of the common variety. The postablation PR interval and AH interval remained unchanged. The shortest cycle length of 1:1 AV conduction was prolonged significantly (from 327 +/- 31 to 440 +/- 59 ms, p < 0.01, as was the AV node effective refractory period (from 244 +/- 35 to 344 +/- 43 ms, p < 0.01). During a mean follow-up interval of 20 +/- 6 months, no patient developed symptoms suggestive of AV node reentrant tachycardia or had evidence of second- or third-degree AV block. CONCLUSIONS: These data suggest that the AV node slow pathway can be ablated in patients with AV node reentrant tachycardia who demonstrate a prolonged PR interval during sinus rhythm.

Adolescent↗

Surgical approach to anterior septal accessory pathways in 20 patients with the Wolff-Parkinson-White syndrome.

Right anterior septal accessory pathways in the Wolff-Parkinson-White syndrome are generally defined by electrophysiological criteria, the most important being that earliest retrograde atrial activation during AV reciprocating tachycardia occurs at the anterior medial segment of the tricuspid annulus (His bundle catheter). The purpose of our study is to describe intraoperative mapping in 20 patients with anterior septal accessory pathways, and to assess if intraoperative mapping contributes to the operative approach. At surgery, all patients had identical early ventricular activation during pre-excitation at the infundibulum. However, two groups could be identified on the basis of retrograde atrial epicardial activation during AV reciprocating tachycardia or right ventricular pacing. Group 1 comprised 16 patients with earliest activation at the interatrial septum adjacent to the His bundle. Epicardial dissection failed to affect accessory pathway conduction. The accessory pathway was only ablated when a discrete endocardial approach to the atrial septum was used. Group 2 comprised 4 patients with early atrial activation "paraseptally" in the right coronary fossa. These accessory pathways were ablated by an epicardial approach without using cardiopulmonary bypass. We conclude that right anterior septal accessory pathways as defined by electrophysiological criteria can be divided into two groups on the basis of the atrial activation sequence: (1) right septal accessory pathways in the septal para-Hissian region and (2) right anterior 'paraseptal' accessory pathways. This classification is of practical importance because the latter can be ablated using an epicardial approach without the need for cardiopulmonary bypass or atriotomy.

Adolescent↗