Temporal Electrogram Analysis: Algorithm Development

PAUL, V.E., ET AL.: Temporal Electrogram Analysis: Algorithm Development. The automatic discrimination of physiological from pathological tachycardias by rate criteria alone lacks adequate specificity. Tachycardia detection algorithms based upon morphological analysis of the endocardial electrogram have been attributed high specificity although their specificity has not been proven. A previous study had shown temporal electrogram analysis TEA) to be an algorithm of high sensitivity in the detection of ventricular arrhythmias despite low computational demands. In this study, the specificity and potential for automatic implementation have been assessed. Manual adjustment of thresholds for individual patients gave a maximum potential sensitivity of 97% (26/27 arrhythmias correctly recognized as non-sinus). The use of automatic setting of thresholds reduced sensitivity to 81%. The specificity of the algorithm, as assessed by exercise testing, was only 60%.     

Endothelial dysfunction:EDCF revisited

Endothelial cells can initiate contraction(constriction)of the vascular smooth muscle cells that surround them.Such endothelium-dependent,acute increases in contractile tone can be due to the withdrawal of the production of nitric oxide,to the production of vasoconstrictor peptides(angiotensin II,endothelin-1),to the formation of oxygen-derived free radicals(superoxide anions)and/or the release of vasoconstrictor metabolites of arachidonic acid.The latter have been termed endothelium-derived contracting factor(EDCF)as they can contribute to moment-to-moment changes in contractile activity of the underlying vascular smooth muscle cells.To judge from animal experiments,EDCF-mediated responses are exacerbated when the production of nitric oxide is impaired as well as by aging,spontaneous hypertension and diabetes.To judge from human studies,they contribute to the blunting of endothelium-dependent vasodilatations in aged subjects and essential hypertensive patients.Since EDCF causes vasoconstriction by activation of the TP-receptors on the vascular smooth muscle cells,selective antagonists at these receptors prevent endothelium-dependent contractions,and curtail the endothelial dysfunction in hypertension and diabetes.     

Use of an Autologous Blood Recovery System during Emergency Pericardiocentesis in the Electrophysiology Laboratory

Introduction: Emergency pericardiocentesis during electrophysiology procedures is often associated with significant aspiration of pericardial blood, requiring transfusion. We sought to assess the feasibility of urgent use of an autologous blood recovery system in the electrophysiology laboratory to autotransfuse blood aspirated from the pericardium.
Methods and Results: We retrospectively analyzed Mayo Clinic electrophysiology records for patients who had ablation procedure-related pericardial effusions requiring emergency pericardial drainage during an 8-month period. An autologous blood recovery system was used during pericardiocentesis to separate and clean packed red blood cells from the pericardial aspirate. These cells were returned acutely to the patient intravenously. The procedural safety, aspirated and autotransfused volumes, and efficacy of this approach were evaluated. During the study period, nine patients underwent pericardial drainage with autotransfusion using a cell-salvage instrument during electrophysiology procedures. The mean aspirated volume was 1,078 mL, with a mean autotransfused volume of 390 mL. For four patients, all with aspirated volumes of 1,100 mL or less, autotransfusion alone was sufficient to maintain hemodynamic stability and avoid allogeneic transfusion. One patient required surgical intervention because of ongoing pericardial bleeding. The ablation procedure was completed after aspiration in two patients. No procedural complications related to the use of the cell-salvage system occurred. 
Conclusion: Autologous blood recovery during pericardiocentesis is safe, convenient, and feasible. With early use it may decrease or eliminate the need for allogeneic blood transfusion and, in selected cases, may permit completion of the ablation procedure.     

Problems associated with use of the benzyloxymethyl protecting group for histidines Formaldehyde adducts formed during cleavage by hydrogen fluoride 1

The use of N^α-tert.-butyloxycarbonyl-N^π benzyloxymethylhistidine in peptide synthesis resulted in significant levels of several different side products attributable to the generation of formaldehyde during the hydrogen fluoride cleavage reaction. Methylated impurities in a decapeptide were isolated and identified. These methylated impurities were attributed to the use of the benzyloxymethyl protecting group for the histidines, since the impurities did not form when the dinitrophenyl protecting group was used. Also, peptides containing benzyloxymethyl-protected histidines in addition to N-terminal cysteines quantitatively yielded their respective N-terminal thiazolidine derivatives upon isolation from standard hydrogen fluoride cleavage mixtures. Thiazolidine ring formation was circumvented by including in the cleavage reaction a formaldehyde scavenger such as cysteine hydrochloride or resorcinol.     

His Bundle Ablation with the Laser Thermal Probe ("Hot Tip"): A Feasibility Study

Successful percutaneous ablation of the bundle of His requires accurate localization together with delivery of the minimum effective energy to avoid unwanted effects. The energy output from laser sources can be controlled very precisely but is not easily directed to the bundle of His using conventional fiber optics. The laser thermal probe ("hot tip") consists of an optical fiber and a terminal metal cap that is rapidly heated during energy delivery. When applied to cadaver hearts at energies of 100-150 joules (10 watts for 10-15 seconds) the 2.0-mm diameter peripheral artery probe was able to damage the bundle of His without extensive surrounding damage. The right ventricular free wall and interventricular septum were perforated during some applications at these energies leaving a tract with a diameter of less than 2.0 mm. The atrioventricular (AV) membranous septum, Foramen Ovale, right atrial appendage, and septal leaflet of the tricuspid valve were more resistant at these energy levels and perforations were always less than 1.0 mm in diameter. The probe was modified for use during electrophysiological studies and good quality unipolar electrograms were recorded from the metal cap confirming that the probe could be accurately positioned adjacent to the bundle of His. The laser thermal probe deserves further study as a "self directing" ablation tool.     

Closed Loop Control of Rate Adaptive Pacing: Clinical Assessment of a System Analyzing the Ventricular Depolarization Gradient

Closed loop control of rate adaptive pacing has theoretical advantages over current rate responsive pacemakers. The first available system (which senses the ventricular depolarization gradient) has been evaluated in ten patients. The pacing response to a variety of exercise and nonexercise stimuli was assessed. Response to isotonic exercise was prompt and proportional to the exertion involved while isometric exercise and mental stress produced obvious but more gradual increases in pacing rate. In seven patients, comparison between the intrinsic P wave and pacing rate showed a high correlation during exercise (r = 0.91) and mental activity (r = 0.87). Postural changes induced a paradoxical response. Closed loop rate responsive pacing based upon analysis of the ventricular depolarization gradient produces a fast and appropriate rate response to most physiological stimuli.     

High Density Endocardial Mapping of Shifts in the Site of Earliest Depolarization During Sinus Rhythm and Sinus Tachycardia

BETTS, T.R., et al. : High Density Endocardial Mapping of Shifts in the Site of Earliest Depolarization During Sinus Rhythm and Sinus Tachycardia. Previous mapping studies of sinus rhythm suggest faster rates arise from more cranial sites within the lateral right atrium. In the intact, beating heart, mapping has been limited to epicardial plaques or single endocardial catheters. The present study was designed to examine shifts in the site of the earliest endocardial depolarization during sinus rhythm and sinus tachycardia using high density activation mapping. Noncontact mapping of the right atrium during sinus rhythm was performed on ten anesthetized swine. Recordings were made during sinus rhythm, phenylephrine infusion, and isoproterenol infusion. The hearts were then excised and the histological sinus node identified. The mean minimum and maximum cycle lengths recorded were   355 ± 43   and   717 ± 108 ms   . A median of three (range two to five) sites of earliest endocardial depolarization were documented in each animal. With increasing heart rate the site of earliest endocardial depolarization remained stationary until a sudden shift in a cranial or caudal direction, often to sites beyond the histological sinoatrial node. The endocardial shift was unpredictable with considerable variation between animals; however, faster rates arose from more cranial sites   (r = 0.46, P = 0.023)   . There was no difference in the mean cycle length of sinus rhythm originating from specific positions on the terminal crest   (r = 0.44, P = 0.17)   . Cranial sites displayed a more diffuse pattern of early depolarization than caudal sites. In the porcine heart the relationship between heart rate and site of earliest endocardial depolarization shows considerable variation between individual animals. These findings may have implications for clinical mapping and ablation procedures. (PACE 2003; 26[Pt. I]:874–882)     

Oncogene-mediated propagation of tracheal epithelial cells from two cystic fibrosis fetuses with different mutations. Characterization of CFT-1 and CFT-2 cells in culture

Abstract. Primary tracheal epithelial cells obtained from two fetuses with cystic fibrosis (CF) were successfully transfected with a plasmid vector recombined with the large T oncogene of SV40. The resulting tracheal cells were propagated in culture for up to 25 passages and retained the mutations of the CF genes carried by the two fetuses, one heterozygous for the S549N and N1303K substitutions (CFT-I cells), and the other homozygous for the most common deletion ΔF508 (CFT-2 cells). The transfected cells: (a) expressed the SV40 large T oncogene, as determined by immunofluorescence and Northern blot analysis; (b) retained typical epithelial morphology, as assessed by the presence of microvilli, desmosomes, gap junctions, and cytokeratin expression; (c) were fully responsive to the cAMP-stimulating agents isproterenol, forskolin and vasoactive intestinal peptide for cAMP production and PKA activation; (d) do not produce any tumour in the athymic nude mice; (e) were diploid and tetraploid with a normal chromosomal complement at early passages, and (f) exhibited the abnormal regulation of chloride conductance characteristic of CF.
These results indicate that CFT-1 and CFT-2 cells constitute a suitable model for: (a) comparison of the maturation and function of the CFTR protein mutated in the two nucleotide-binding domains; (2) analysis of the biochemical defect in CF epithelial airway cells, (c) development of new therapeutic agents, and correction of the CF defect by gene replacement therapy in vitro .