Localization of the Origin of Arrhythmias for Ablation: From Electrocardiography to Advanced Endocardial Mapping Systems

Radiofrequency catheter ablation techniques have had a dramatic impact on the treatment of a variety of cardiac arrhythmias. However, catheter ablation of complex arrhythmias, such as intra-atrial reentry, ventricular tachycardias, and atrial fibrillation, continues to pose a major challenge. This stems from limitations of fluoroscopy and conventional catheter-based mapping techniques that limit the accurate anatomic localization of complex arrhythmogenic substrates. In this article, ECG features of complex arrhythmias are reviewed, which may facilitate the planning of an ablation procedure. The physical principles of the newly available catheter-based endocardial mapping techniques and their clinical applicability for treatment of complex arrhythmias are discussed. The role of intracardiac echocardiography to facilitate mapping and ablation is reviewed.     

Synthesis of biologically active analogs of the dodecapeptide α-factor mating pheromone of Saccharomyces cerevisiae

A number of dodecapeptides with the sequence YIIKGVFWDPAC were synthesized using solid phase peptide synthesis. The purity of the crude cleavage product was found to be directly related to the cysteine protecting group and the conditions employed for cleavage of the peptide from the resin. When 4-methyl-benzyl cysteine was used, complete deprotection was only achieved with low-high HF conditions at temperatures of 10°-25°, whereas milder conditions could be used for dodecapeptides containing ethyl cysteine or acetamidomethyl cysteine. In several syntheses the biological activity of the crude cleavage product greatly exceeded the biological activity of a purified major peptide component. The high activity found in the crude cleavage peptide was probably due to minor peptide side products in which the cysteine sulfur was alkylated by hydrophobic species during HF treatment. Two dodecapeptides, YIIKGV-FWDPAC and YIIKGFWDPAC(Ethyl), had significant α-factor activity against MATα strains of Saccharomyces cerevisiae. These peptides represent the first synthetic analogs with α-factor activity.     

Marihuana-Induced Embryotoxicity in the Rabbit

Marihuana-Induced Embryotoxicity in the Rabbit. ROSENKRANTZ,H., GRANT, R. J., FLEISCHMAN, R. W., AND BAKER, J. R. (1986).Fundam. Appl. Toxicol. 7,236-243. Few teratogenic studies inanimals have been performed simulating marihuana smoking inman. An inhalation marihuana teratology study was conductedin albino rabbits utilizing a modified automatic smoking machineoriginally developed for rats and mice. Appropriate numbersof dams were exposed to 4 puffs (0.14 mg/kg), 8 puffs (0.72mg/kg), or 16 puffs (1.44 mgkg) once daily during gestationDays 6 to 18, and sacrificed on Day 28. Control dams were /exposedto 12 puffs of placebo cigarettes or sham-treated for a similarduration in the absence of any smoke. Consistency of smoke wasmonitored by cigarette weights, total paniculate matter, concentrationsof carbon monoxide (CO), and tetrahydrocannibinol (THC) in smoke,carboxyhemoglobin levels, and plasma THC levels. Except fora transient decrease in dam respiration rates, other gross toxicsigns were absent. Reproductive parameters of mothers were generallynormal except for a dose-related embryotoxicity predominantlyassociated with early resorptions. Despite twice the numberof embryo/fetal deaths, there were no marihuana soft tissueor skeletal defects. A correlation between dam demises and COlevels among placebo-exposed animals was related to greaterquantities of CO being generated during placebo combustion.It has been shown in the rabbit that marihuana is embryotoxicand not a teratogen at plasma THC levels found in human females.     

Improved Short-Term Outcomes of Primary Coronary Stenting Compared to Primary Balloon Angioplasty in Acute Myocardial Infarction at Experienced Centers: The PAMI Study Group Experience

To study the additive benefits of routine stent implantation in patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) at experienced centers, we compared the outcomes of the 982 patients undergoing PTCA for acute myocardial infarction (AMI) in the Primary Angioplasty in Myocardial Infarction-2 (PAMI-2) trial (only 1% of whom were stented) to the 312 patients in the PAMI Stent Pilot Trial (236 [76%] of whom were stented). The inclusion and exclusion criteria, PTCA methodology, and definitions used were prespecified to be identical between the two trials. Compared to the primary PTCA approach in PAMI-2, the strategy of stenting all eligible lesions in the PAMI Stent Pilot Trial was associated with reduced rates of in-hospital death (0.6% vs 2.7%, P = 0.03), reinfarction (1.3% vs 4.6%, P = 0.008), recurrent ischemia (3.5% vs 11.6%, P < 0.0001), target vessel revascularization (7.3% vs 11.4%, P = 0.04), and a shorter hospital stay (6.4 ± 4.4 vs 7.1 ± 6.2 days, P = 0.01). By multiple logistic regression analysis in 1,294 patients, stent implantation versus PTCA only was the strongest predictor of freedom from the composite in-hospital end point of death, reinfarction, or target vessel revascularization (TVR) (8.3% vs 15.0%, multivariate odds ratio = 0.4, P < 0.0001). These data strongly suggest that despite the excellent results achieved when primary PTCA is performed by experienced operators, the short-term outcomes of mechanical reperfusion can be further improved by a primary stent strategy.     

EFFECT OF GLUCOSE CONCENTRATION ON THE INTRATHECAL SPREAD OF 0.5% BUPIVACAINE

We have studied the effects of intrathecal injection of 0.5%bupivacaine in solutions containing different concentrationsof glucose (0.33%, 0.83% and 8%) in three groups of 10 patients.The mean maximum extent of sensory block was significantly higherwith 8% glucose (T3.6) than with 0.83% glucose (T7.2) or 0.33%glucose (T9.5). Administration of solutions containing 0.33%glucose produced a greater variability in upper level of sensoryblock (11 dermatomes) than the two other concentrations (sixdermatomes each). The rate of onset of sensory block to T12was fastest with solutions containing 8% glucose. Complete motorblock of the legs was produced in every patient. ^*Department of Anaesthetics, Ninewells Hospital & MedicalSchool, Dundee DD1 9SY     

Mutations in Conserved Amino Acids in the KCNQ1 Channel and Risk of Cardiac Events in Type-1 Long-QT Syndrome

Background: Type-1 long-QT syndrome (LQT1) is caused by mutations in the KCNQ1 gene. The purpose of this study was to investigate whether KCNQ1 mutations in highly conserved amino acid residues within the voltage-gated potassium channel family are associated with an increased risk of cardiac events.
Methods and Results: The study population involved 492 LQT1 patients with 54 missense mutations in the transmembrane region of the KCNQ1 channel. The amino acid sequences of the transmembrane region of 38 human voltage-gated potassium channels were aligned. An adjusted Shannon entropy score for each amino acid residue was calculated ranging from 0 (no conservation) to 1.0 (full conservation). Cox analysis was used to identify independent factors associated with the first cardiac event (syncope, aborted cardiac arrest, or death). Patients were subcategorized into tertiles by their adjusted Shannon entropy scores. The lowest tertile (score 0–0.469; n = 146) was used as a reference group; patients with intermediate tertile scores (0.470–0.665; n = 150) had no increased risk of cardiac events (HR = 1.19, P = 0.42) or aborted cardiac arrest/sudden cardiac death (HR = 1.58, P = 0.26), and those with the highest tertile scores (>0.665; n = 196) showed significantly increased risk of cardiac events (HR = 3.32, P <0.001) and aborted cardiac arrest/sudden cardiac death (HR = 2.62, P = 0.04). The increased risk in patients with the highest conservation scores was independent of QTc, gender, age, and beta-blocker therapy.
Conclusions: Mutations in highly conserved amino acid residues in the KCNQ1 gene are associated with a significant risk of cardiac events independent of QTc, gender, and beta-blocker therapy.     

Inadvertent Detection of 60-Hz Alternating Current by an Implantable Cardioverter Defibrillator

LEE, S.W., et al. : Inadvertent Detection of 60-Hz Alternating Current by an Implantable Cardioverter De-fibrillator. A patient with an ICD received therapies from his ICD while exercising in an indoor swimming pool. Interrogation of the ICD revealed inappropriate detection of 60-Hz alternating current artifact and delivery of ICD therapies.     

Nonsurgical Electrical Ablation of Tachycardias: Importance of Prior in Vitro Testing of Catheter Leads

Nonsurgical electrical ablation of tachycardia pathways or foci has been attempted or carried out using a variety of temporary pacing catheter leads. To determine the ability of such leads to withstand the high energies used in such procedures, 34 leads were suspended in saline, and subjected to repeated electrical shocks. Small (4 French) temporary pacing leads made by a variety of manufacturers tolerated multiple shocks up to 100 joules; above this level, failures became increasingly common, although usually the failure mode was benign with respect to patient care implications. Testing of 6, 7, and 8 French leads revealed considerable inter-and intra-manufacturer differences in the ability to withstand higher energy shocks, reflecting differences in materials and fabrication techniques. It is concluded that careful in vitro lead testing is required prior to using identical models in humans for arrhythmia ablation procedures.