Two pathways of proton transfer reaction to (triphos)Cu(η(1)-BH4) via a dihydrogen bond [triphos = 1,1,1-tris(diphenylphosphinomethyl)ethane].

The interaction of the η(1)-tetrahydroborate copper(i) complex (triphos)Cu(η(1)-BH4) () with proton donors [CF3CH2OH (TFE), (CF3)2CHOH (HFIP), (CF3)3COH (PFTB), PhOH, p-NO2C6H4OH (PNP), p-NO2C6H4N[double bond, length as m-dash]NC6H4OH (PNAP), CF3OH] was a subject of a combined IR spectroscopic and theoretical investigation. Spectral (Δν) and thermodynamic (ΔH) parameters of dihydrogen bond (DHB) formation were determined experimentally. The terminal hydride ligand (characterized by the basicity factor Ej(BH) = 0.87 ± 0.01) is found to be a site of proton transfer which begins with nucleophilic substitution of BH4(-) by the alcohol oxygen atom on the copper center (BH pathway). The activation barrier computed for (CF3)2CHOH in CH2Cl2 - ΔG = 20.6 kcal mol(-1) - is in good agreement with the experimental value (ΔG = 20.0 kcal mol(-1)). An abnormal dependence of the reaction rate on the proton donor strength found experimentally in dichloromethane is explained computationally on the basis of the variation of the structural and energetic details of this process with the proton donor strength. In the second reaction mechanism found (CuH pathway), DHB complexes with the initial ROH coordination to the bridging hydride lead to B-Hbr bond cleavage with BH3 elimination. "Copper assistance" via the CuO interaction is not involved. This mechanism can be evoked to explain the occurrence of proton transfer in coordinating solvents.

Crown compounds for anions: sandwich and half-sandwich complexes of cyclic trimetric perfluoro-o-phenylenemercury with polyhedral closo-[B10H10]2- and closo-[B12H12]2- anions.

It has been shown by IR and NMR spectroscopy that cyclic trimeric perfluoro-o-phenylenemercury (o-C6F4-Hg)3 (1) is capable of binding closo-[B10H10]2- and closo-[B12H12]2- anions to form complexes [[(o-C6F4Hg)3](B10-H10)]2- (2), [[(o-C6F4Hg)3]2(B10H10)]2-(3), [[(o-C6F4Hg)3](B12H12)]2- (4), and [[(o-C6F4Hg)3]2(B12H12)]2- (5). According to IR data, the bonding of the [B10H10]2- and [B12H12]2- ions to the macrocycle in these complexes is accomplished through the formation of B-H-Hg bridges. Complexes 2, 3, and 5 have been isolated in analytically pure form and have been characterized by spectroscopic means. X-ray diffraction studies of 3 and 5 have revealed that these compounds have unusual sandwich structures, in which the polyhedral di-anion is located between the planes of two molecules of 1 and is bonded to each of them through two types of B-H-Hg bridges. One type is the simultaneous coordination of a B-H group to all three Hg atoms of the macrocycle. The other type is the coordination of a B-H group to a single Hg atom of the cycle. According to X-ray diffraction data, complex 2 has an analogous but half-sandwich structure. The obtained complexes 2-5 are quite stable; their stability constants in THF/acetone (1:1) at 20 degrees C have been determined as 1.0 x 10(2)Lmol(-1), 2.6 x 10(3)L(2)mol(2), 0.7 x 10(2)Lmol(-1), and 0.98 x 10(3)L(2)mol(-2), respectively.

Recalls and safety alerts involving pacemakers and implantable cardioverter-defibrillator generators.

CONTEXT: Unanticipated pacemaker and implantable cardioverter-defibrillator (ICD) generator malfunctions sometimes warrant recall by the US Food and Drug Administration (FDA). Despite increasingly frequent device implantation, pacemaker and ICD recalls and safety alerts (advisories) remain poorly characterized. OBJECTIVES: To determine pacemaker and ICD generator advisory rates in the United States, to identify trends in these rates, and to examine their clinical and financial implications. DESIGN AND SETTING: Analysis of weekly FDA Enforcement Reports issued between January 1990 and December 2000 to identify all advisories involving pacemaker or ICD generators in the United States. Recalls and safety alerts involving lead malfunctions were not included. MAIN OUTCOME MEASURES: Number of pacemakers and ICD generators in the United States subject to FDA recall or safety alert in 1990-2000; annual pacemaker and ICD advisory rates in the United States in 1990-2000; and estimated cost of device advisories. RESULTS: During the study period, 52 advisories (median [25th and 75th percentiles], 4 [4 and 7] per year) involving 408 500 pacemakers and 114 645 ICDs (523 145 total devices) were issued. Hardware malfunctions (35 advisories affecting 280 641 devices) and computer errors (10 advisories affecting 216 533 devices) accounted for 95% of device recalls. Implantable cardioverter-defibrillators were recalled more frequently than pacemakers (mean [SD], 16.4 [1.6] vs 6.7 [0.8] advisories per 100 person-years; P<.001). Between 1995 and 2000, the annual advisory rate increased for both pacemakers (P for trend <.001) and ICDs (P for trend =.02). An estimated 1.3 million device checks and analyses and 36 187 device replacements resulted from the advisories and cost approximately $870 million. CONCLUSIONS: Pacemaker and ICD recalls and safety alerts occur frequently, affect many patients, and appear to be increasing in number and rate. With the growing number of device implants and expanding indications for device therapy, the number of patients affected by device advisories will likely continue to increase.

A novel indication for transvenous lead extraction: upgrading implantable cardioverter defibrillator systems.

UNLABELLED: Technological advances have resulted in the development of dual chamber pacemaker/defibrillator systems with smaller pectoral 'active cans'. Patients now have the option of upgrading from abdominal to pectoral or from single to dual chamber devices. In addition, due to the potential complications which may arise with abandoned ICD leads, extraction of preexisting leads may be preferable. METHODS AND RESULTS: Twenty consecutive patients (11 males), underwent lead extraction and upgrade, either from an abdominal to a pectoral, or from a single to a dual chamber device. The mean age was 62+/-18 years and mean implant duration was 50+/-14 months. Indications for extraction included lead fracture/malfunction (13), ERI/EOL (2), new SVT/VT (2), long charge times (2), and impending erosion (1). An initial attempt was made to remove the lead with gentle traction. If excessive scar tissue prohibited extraction, then a laser sheath was employed. Reimplantation proceeded following standard protocol. Clinical success was achieved in all patients. Eleven of thirty leads were removed with traction. The remaining 19 leads required removal with the laser sheath. All ICD reimplants were placed in the left pectoral position, of which 10 were dual chamber. The mean defibrillation threshold was 9.5+/-5.8 Joules. There were no procedure related perforations or deaths. At follow up (13+/-10 mos. ) there were no infections, lead malfunctions or venous thromboses. There were two deaths, both from intractable heart failure. CONCLUSIONS: This study demonstrates that, when indicated, ICD leads can be safely extracted and systems successfully upgraded to take advantage of new technology.

The utility of intracardiac echocardiography in interventional electrophysiology.

With the mounting of an ultrasound transducer on the end of a percutaneously placed catheter, intracardiac echocardiography is now possible. It has become clear that endocardial anatomy plays a critical role in a variety of cardiac arrhythmias. The ability to visualize this anatomy, and it's relationship to mapping and ablation catheters, may greatly enhance the safety and efficacy of catheter ablation procedures.

Abg1: a novel gene up-regulated by abscisic acid in guard cells of Vicia faba L.

A novel gene (abg1) was isolated by differential display RT-PCR from guard cells of Vicia faba L. Abg1 transcript accumulated in guard cells that were incubated with 5 microM S(+)-ABA for 1 h. The full-length abg1 cDNA was 753 bp, which included a 513 bp coding region. The deduced 17.8 kDa protein shared sequence similarity with several desiccation-related proteins reported in plants.

Initial experience with larger laser sheaths for the removal of transvenous pacemaker and implantable defibrillator leads.

BACKGROUND: In a previous randomized trial, the 12F laser sheath removed pacing leads via the implant vein more successfully than traditional mechanical tools alone. Two larger sizes of laser sheath, the 14F and 16F models, were developed to extract defibrillator leads and large-diameter pacing leads implanted for the chronic. These devices use pulsed ultraviolet laser light to core though fibrotic tissue grown over the lead body to free the lead from the vasculature. A mandatory prospective registry studied the safety and effectiveness profiles of the larger laser sheaths vis-à-vis the 12F laser sheath. METHODS AND RESULTS: In this study, 863 patients underwent extraction of 1285 leads at 52 sites. Patients treated with the 14F device tended to have older leads than the 12F population; the 16F population, which comprised mostly defibrillator patients, were younger, had younger leads, and were more often male than the 12F population. Clinical success (extracting the entire lead or the lead body minus the distal electrode) was observed in 91% to 92% of cases for all device sizes. The overall complication rate was 3.6%, with 0.8% perioperative mortality. Incidence of complications was independent of laser sheath size. CONCLUSIONS: The 14F and 16F laser sheaths offer an extraction option for larger long-term transvenous pacemaker and defibrillator leads that is as safe and effective as the 12F laser sheath.

Presence and significance of the left atrionodal connection during atrioventricular nodal reentrant tachycardia.

It has been suggested that the anatomic substrates of dual atrioventricular nodal pathways are likely to be the atrionodal connections. During atrioventricular nodal re-entrant tachycardia (AVNRT) or ventricular pacing (VP), an earliest retrograde atrial activation in the coronary sinus (CS) distal to the ostium (CS breakthrough) would suggest the presence of an exit from a left atrionodal connection. The aim of the study was to evaluate the incidence of such an atrial retrograde activation in the CS during AVNRT and VP. The retrograde atrial activation was recorded during typical AVNRT (38 patients, 27 women, mean age 44 +/- 18 years) by a multipolar catheter in the CS, a decapolar catheter in the His bundle position, and a deflectable quadripolar catheter along the tricuspid annulus anterior to the CS ostium. In 31 patients the retrograde atrial activation was recorded also during VP at a similar cycle length. A CS breakthrough was found in 18 patients during AVNRT (47%) and in 13 patients during VP (42%). Presence or absence of CS breakthrough was concordant between AVNRT and VP in 90% of the patients. A CS breakthrough, suggesting a left-sided atrionodal connection, is frequently recorded both during AVNRT and VP. In patients with a CS breakthrough pattern, the absence of correlation between the His bundle to the earliest CS retrograde atrial electrogram interval and AVNRT cycle length, or any other atrial activation times recorded in the posterior and anterior region of the Koch's triangle, would suggest that the left-sided atrionodal connection is a bystander during typical AVNRT.

Pacemaker lead extraction with the laser sheath: results of the pacing lead extraction with the excimer sheath (PLEXES) trial.

OBJECTIVES: The purpose of this study was to evaluate the safety and effectiveness of pacemaker lead extraction with the excimer sheath in comparison to nonlaser lead extraction. BACKGROUND: Fibrotic attachments that develop between chronically implanted pacemaker leads and to the venous, valvular and cardiac structures are the major obstacles to safe and consistent lead extraction. Locking stylets and telescoping sheaths produce a technically demanding but effective technique of mechanically disrupting the fibrosis. However, ultraviolet excimer laser light dissolves instead of tearing the tissue attachments. METHODS: A randomized trial of lead extraction was conducted in 301 patients with 465 chronically implanted pacemaker leads. The laser group patients had the leads removed with identical tools as the nonlaser group with the exception that the inner telescoping sheath was replaced with the 12-F excimer laser sheath. Success for both groups was defined as complete lead removal with the randomized therapy without complications. RESULTS: Complete lead removal rate was 94% in the laser group and 64% in the nonlaser group (p = 0.001). Failed nonlaser extraction was completed with the laser tools 88% of the time. The mean time to achieve a successful lead extraction was significantly reduced for patients randomized to the laser tools, 10.1 +/- 11.5 min compared with 12.9 +/- 19.2 min for patients randomized to nonlaser techniques (p < 0.04). Potentially life-threatening complications occurred in none of the nonlaser and three of the laser patients, including one death (p = NS). CONCLUSIONS: Laser-assisted pacemaker lead extraction has significant clinical advantages over extraction without laser tools and is associated with significant risks.

Evaluation of outpatient initiation of antiarrhythmic drug therapy in patients reverting to sinus rhythm after an episode of atrial fibrillation.

The safety of a method of outpatient antiarrhythmic drug loading utilizing a continuous loop event recorder was evaluated. The findings suggest that the standard 2-day hospital admission for drug loading is not necessary in all patients and a method of outpatient loading may be equally safe.

Initial experience with a steerable intracardiac echocardiographic catheter.

INTRODUCTION: Intracardiac echocardiography (ICE) has been used to guide radiofrequency catheter ablation procedures and transseptal punctures. The ability to position current ICE catheters is limited. In this study, we report on the initial experience with a steerable ICE catheter in a canine model and in man. METHODS: In a canine model, we compared the image quality and maneuverability of a 9 French (Fr), 9 MHz ICE catheter and a custom 9 Fr, 9 MHz steerable ICE catheter. Imaging was attempted at 7 intracardiac sites. Non-steerable catheter positioning was attempted with the catheter alone or with the curved, long 10 Fr vascular sheath. Steerable catheter positioning was attempted with the catheter alone after the vascular sheath was withdrawn into the inferior vena cava. The steerable ICE catheter was also used to help guide catheter ablation in a patient with right ventricular outflow tract (RVOT) tachycardia. RESULTS: The steerable ICE catheter was easily positioned at all 7 predetermined sites without the need for a long vascular sheath. In contrast, the non-steerable catheter was much more difficult to position. Image quality was similar for both catheters; depths of imaging were 4-8 cm, depending on catheter location. Multiple image planes could be achieved at a single site with tip deflection of the steerable catheter. In man, the steerable catheter was easily positioned to the RVOT. ICE imaging was helpful in positioning the ablation catheter below the pulmonic valve and ensuring good electrode-tissue contact during energy delivery. CONCLUSION: Steerability improved maneuverability and added multiple image planes compared to a non-steerable ICE catheter. Steerability may enhance the utility of ICE in guiding catheter ablation procedures.

Initial experience with a laser sheath to extract chronic transvenous implantable cardioverter-defibrillator leads.

This is the first study of the use of a laser sheath to remove chronic transvenous implantable cardioverter-defibrillator leads. A 16Fr laser sheath was used to extract 14 leads from 11 patients, 6 of whom had undergone failed previous extraction attempts using conventional tools.

Comparative study of fluoroscopy and intracardiac echocardiographic guidance for the creation of linear atrial lesions.

BACKGROUND: Recently, attempts have been made to cure atrial fibrillation by creating multiple linear atrial lesions with radiofrequency energy. Intracardiac echocardiography (ICE) offers imaging of endocardial anatomy and the ablation electrode-tissue interface not available with standard fluoroscopy. This study sought to prospectively compare fluoroscopic with ICE guidance for the creation of linear atrial lesions in a canine model. METHODS AND RESULTS: The creation of 3 linear atrial lesions was attempted in each of 10 dogs, half guided by fluoroscopy alone and half by ICE. Coil-tissue contact was prospectively graded. After ablation, animals were euthanized, and the location and continuity of lesions were evaluated. ICE guidance led to a higher percentage of successful applications (P=0.02) and mean achieved temperature (P=0. 004). The contact scores of excellent, fair, and poor correlated well with successful energy delivery, mean temperature, and efficiency of heating (P<0.0001). In 25% of the blinded energy deliveries, the location, as determined by the ablation operator, differed from that of ICE. Pathological evaluation revealed improved lesion formation in the ICE-guided compared with the ICE-blinded group. Lesions were found outside the target areas in the ICE-blinded but not the ICE-guided group. CONCLUSIONS: Compared with fluoroscopy, ICE guidance improved targeting, energy delivery, and lesion formation in this canine model. This study suggests that ICE guidance improves lesion formation and prevents energy delivery to potentially dangerous sites.

Nonfluoroscopic transseptal catheterization: safety and efficacy of intracardiac echocardiographic guidance.

INTRODUCTION: Recently, there has been a revival in the use of transseptal catheterization due to the development of balloon mitral valvuloplasty and radiofrequency catheter ablation. Complications of transseptal puncture, although rare, can be serious and life-threatening. In the present study, we evaluated the use of intracardiac echocardiography (ICE) as the sole imaging modality to guide transseptal puncture and catheterization. METHODS AND RESULTS: In each animal, 10 transseptal punctures were performed guided solely by ICE. The standard approach to transseptal catheterization using a Brockenbrough needle and long vascular sheath was used except for the use of ICE instead of fluoroscopy. A 6.2-French/12.5-MHz and 9-French/9-MHz ICE catheter was used for imaging. At the end of each study, pathologic evaluation was performed. Transseptal puncture was performed safely, guided solely by ICE, in each of 100 attempts (five attempts guided by each ICE catheter in 10 dogs). While the fossa ovalis was easily visualized with both ICE catheters, the 9-French/9-MHz catheter offered an enhanced field of view. On pathologic evaluation, there was no evidence of perforation of either the right or left atrium outside of the fossa ovalis. CONCLUSION: Both ICE catheters used in this trial allowed for excellent visualization of the fossa ovalis and safe transseptal puncture. Intracardiac echocardiography may be a better imaging modality than fluoroscopy for guiding transseptal catheterization, especially in less experienced hands.

Chronic atrial lead explantation using a staged percutaneous laser and open surgical approach.

We report a staged approach to the explantation of a passive fixation atrial lead 4 years after implantation in a patient with extracardiac J wire protrusion. The body of the lead, from the venous entry site to the proximal electrode, was freed from extensive fibrous binding using an investigational Excimer laser lead extraction sheath. The distal end and J wire were freed and the lead was removed at thoracotomy. This staged approach offered a safe and effective method for the removal of a heavily fibrosed chronic endocardial lead.

Hybrid pharmacologic and ablative therapy: a novel and effective approach for the management of atrial fibrillation.

INTRODUCTION: Maintenance of sinus rhythm in patients with recurrent atrial fibrillation is often difficult to achieve with pharmacologic therapy. Complex catheter ablative procedures are being developed, but efficacy and safety issues remain to be clarified. We hypothesized that combined pharmacologic and simple ablative therapies in a targeted subset of patients will improve success in the treatment of atrial fibrillation. METHODS AND RESULTS: We identified 13 patients (mean age 61.5 +/- 16.2 years) with atrial fibrillation who converted to electrocardiographic atrial flutter during antiarrhythmic drug treatment. Surface ECG suggested "typical" atrial flutter in 11 patients and "atypical" atrial flutter in 2. Intracardiac mapping and entrainment studies revealed 9 patients had counterclockwise isthmus-dependent atrial flutter, and the remaining 4 had complex activation patterns, suggesting the presence of multiple wavefronts. All 9 patients with typical atrial flutter underwent successful ablation. None of the 4 patients with complex activation patterns had successful ablation. Patients were followed for recurrences of atrial arrhythmias via clinic visits, record review, and interviews. In patients who underwent successful ablation and continued on antiarrhythmic drugs, 88.9% remain in sinus rhythm after a mean follow-up of 14.3 +/- 6.9 months (range 1 to 28). CONCLUSION: In patients who experience conversion of atrial fibrillation to atrial flutter during antiarrhythmic drug treatment, ablation and continuation of pharmacologic therapy is a safe and effective means of achieving and maintaining sinus rhythm.

Coronary sinus pacing prevents induction of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is due to reentry, and its incidence has been shown to decrease after dual-site atrial or biatrial pacing. We investigated whether a simpler pacing approach via the distal coronary sinus (CSd) could eliminate AF inducibility by high right atrial (HRA) extrastimuli (APDs). We based our hypothesis on our previous observation that AF inducibility by HRA APDs was associated with conduction delays to the posterior triangle of Koch, whereas AF was never induced with CSd APDs, which were associated with minimal intra-atrial conduction delays. METHODS AND RESULTS: Programmed electrical stimulation was performed from the high right atrium and CSd, and bipolar recordings were obtained from the high right atrium, His bundle, posterior triangle of Koch, and coronary sinus. In 13 patients (age, 44+/-18 years), AF was reproducibly induced with a critically timed HRA APD (220+/-22 ms) delivered during HRA pacing. AF was not induced in any of the patients when HRA APDs were delivered during CSd pacing at the same critical coupling intervals. Coronary sinus APDs delivered during HRA pacing also were not associated with AF induction. The APD coupling interval measured at the posterior triangle of Koch during CSd pacing was significantly prolonged compared with the one measured during HRA pacing and AF induction (381+/-58 versus 263+/-37 ms; P<.0001). CONCLUSIONS: We propose that CSd pacing suppresses the propensity of HRA APDs to induce AF by limiting their prematurity at the posterior triangle of Koch and not allowing local conduction delay and local reentry to occur.

Differences in the phosphate oxygen requirements for self-cleavage by the extended and prototypical hammerhead forms.

The hammerhead self-cleaving motif occurs in a variety of RNAs that infect plants and consists of three non-conserved helices connected by a highly conserved central core. A variant hammerhead, called the extended hammerhead, is found in satellite 2 transcripts from a variety of caudate amphibians. The extended hammerhead has the same core as the prototypical hammerhead, but has unusually conserved sequence and structural elements in its peripheral helices. Here we present the results of a thiophosphate substitution interference analysis of the pro-Rp phosphate oxygen requirements in the two hammerhead forms. Five pro-Rp phosphate oxygens, all in the central core, were found to be important for self-cleavage by the prototypical hammerhead. A similar set of core positions were important for self-cleavage by the extended hammerhead, but five non-core positions were also found to be important. Thiosubstitution at one of these positions had the most severe effect on self-cleavage observed in this analysis. Mn2+ did not alleviate this negative effect, indicating that this position was not part of a divalent cation binding site. We propose that novel tertiary interactions in the extended hammerhead help form the same catalytic core structure as that used by the prototypical plant virus hammerhead.

Slow AV nodal pathway ablation utilizing a unique temperature controlled radiofrequency energy system.

Thirty-nine consecutive patients with symptomatic AV nodal reentrant tachycardia (AVNRT) underwent temperature guided slow AV nodal pathway ablation (group 1). Forty-three consecutive patients undergoing nontemperature guided slow AV nodal pathway ablation late in our experience compose the control population (group 2). Slow pathway ablation was achieved in all patients of both groups. The mean fluoroscopy and ablation times for group 1 were significantly shorter than for group 2 (26.1 +/- 14.9 vs 33.9 +/- 18.9 min, P < 0.05; 19.9 +/- 12.1 vs 30.9 +/- 23.3 min, P < or = 0.02). There were no episodes of coagulum formation in group 1, while there were 15 episodes (7.1% of energy applications) in group 2 (P = 0.0006) despite a significantly higher applied power in group 1 (53.4 +/- 25.1 vs 35.6 +/- 9.5W, P = 0.0001). Successful energy applications were associated with significantly higher temperatures than unsuccessful applications in group 1 (55.6 degrees +/- 5.8 degrees C vs. 52.9 degrees +/- 6.8 degrees C, P < or = 0.03). The minimum temperature required for successful ablation was 48 degrees C for two patients (5%) and was > or = 50 degrees C for the remainder of patients (37/39 [95%]). The catheter ablation system used in this study was safe, effective, and prevented coagulum formation while delivering relatively high power. In addition, shorter ablation times and radiation exposure were seen with this system. Although successful energy applications and the production of junctional rhythm were associated with higher achieved temperatures, temperature alone did not predict either endpoint. Future prospective, randomized trials are needed to confirm these findings and further evaluate the value of temperature monitoring.