Noninvasive Recording of His-Purkinje System (HPS) Activity in Man on Beat-To-Beat Basis

Since 1969 His bundle electrography has been used for diagnosis and for the study of cardiac electrophysiology. This method has employed the catheterization technique and has allowed the continuous recording of electrical activity of the specialized cardiac conduction system in every beat. Such investigation, because of its invasive nature, cannot be considered a routine test; it requires expensive instrumentation, it has physiological and technical limitations that include discomfort, a slight morbidity risk and a rather limited recorded area within the heart. In 1973 a method was developed for a noninvasive recording of the electrical activity within the P-R segment of the electrocardiogram measured from the body surface. This method which employs the signal averaging technique delivers even less medical information than intracardiac measurement. The shortcomings of this averaging method include inability to detect beat-to-beat changes in the true signal. Such a method is not useful in transient arrhythmia detection and a "short acting" drug influence examination. The technical approach to the beat-to-beat noninvasive recording of the HPS activation signal as measured from the body surface has been proposed. Using a specially positioned electrode system, a low noise multiple parallel input amplifier and a computer for sampling, processing and plotting of the measured signal, we have obtained an output curve corresponding to the continuous beat-to-beat HPS activity.     

Transesophageal Programmed Atrial Pacing as a Method of Selecting Patients with Sick Sinus Syndrome for Permanent Atrial Pacing

Many recent studies have shown transesophageal programmed atrial pacing (TP) as a very practical, safe and convenient way for assessment of sinus node function and AV conduction. On the other hand, permanent atrial pacing is known to be superior to ventricular pacing due to arrhythmogenic and hemodynamic reasons. This is the reason why we decided to use TP as a method of choosing patients with sick sinus syndrome (SSS) for permanent atrial pacing. Sixty-three patients with symptomatic (58) and asymptomatic (5) SSS in a variety of clinical situations were examined in this way. The following electrophysiological features were examined: sinus cycle length, sinus node recovery time as well as corrected time, secondary pause after overdrive stimulation, sinoatrial conduction time, Wenckebach point, induction of supraventricular arrhythmias by S1, S2, S3 programmed stimulation and burst pacing. Patients with abnormal parameters were examined once more after intravenous atropine 0.2 mg/kg to evaluate parasympathetic component. Standard 12-lead ECG was performed in ail, and Holter monitoring in most of patients.
Twenty-six patients were candidates for permanent AAI pacing. Failures occurred in eight patients usually due to low P wave amplitude and electrode instability. Eighteen patients received AAI pacing systems: eight with brady-tachycardia syndrome, nine with brady-arrhythmia and one with sinoatrial block. In the follow-up of 5–28 months in one patient occurred high degree AV block (11°) during digitalis therapy. Reduction of doses made this block disappear. Examination of Wenckebach point and possibility of inducation of supraventricular lachyarrhythmias in cases of atrial overexcitability are particularly useful in selecting patients for AAI pacing. (PACE, Vol 11 November Part II 1988)     

Circadian and Sex-Dependent QT Dynamics

The dynamic QT relationship between the QT and RR intervals in normal individuals, including sex differences, has not been well examined. The aim of this Holter monitor-based study was to assess circadian and sex-related variations in QT dynamics in healthy subjects. The study population consisted of 50 healthy volunteers (mean age = 32 ± 6 years, 25 men), in whom 24-hour digital Holter monitoring and QT interactive, beat-by-beat analyses were performed. The mean lengths of QT and RR intervals were measured from the 24-hour recordings. In order to assess QT dynamics, QT/RR linear regression was performed, and the slope was calculated over 24 hour and for day and night periods, and both genders separately. In the whole population, the mean QT interval was 356.5 ± 19.2 ms and RR interval was 785.9 ± 80.7 ms. The mean value of the slope over 24 hour was 0.17 ± 0.03, though significantly steeper during the day (0.13 ± 0.03) than at night (0.09 ± 0.03, P < 0.001). The analysis of QT/RR dynamics over 24 hour revealed a significantly steeper slope in women (0.18 ± 0.03) than in men (0.16 ± 0.03, P = 0.006), as well as during daytime (0.14 ± 0.03 vs 0.12 ± 0.03, P = 0.04). Circadian variations and sex differences were observed in QT dynamics. The latter may explain the greater susceptibility of women to torsades de pointes during treatment with drugs that prolong repolarization.     

Menadione-Induced Oxidative Stress in Bovine Heart Microvascular Endothelial Cellsa

Objective: Oxidative stress from increased production of reactive oxygen species or decreased efficiency of inhibitory and scavenger systems may contribute to vascular injury. In this study, we developed an in vitro model of vascular injury by menadione-induced oxidative stress in bovine heart microvascular endothelial cells. Methods: Oxidative stress was induced by exposure to menadione. Superoxide, hydrogen peroxide and hydroxyl radical formation was measured by superoxide dismutase-inhibitable cytochrome c reduction, the dichlorofluorescin technique and the salicylate method, respectively. Electron paramagnetic-spin resonance spectroscopy employing 5–5′-dimethyl-1-pyrroline-N-oxide for superoxide trapping was used. Endothelial cell cytotoxicity was assessed by lactate dehydrogenase release. Results: Superoxide and hydroxyl radical were produced in a time- and concentration-dependent fashion. Fluorescence in the presence of dichlorofluorescin confirmed hydrogen peroxide formation. Endothelial cell cytotoxicity became evident after 5 h of menadione treatment at concentrations of 100 μM. 3-Aminobenzamide, a poly(ADP-ribose)polymerase inhibitor, and dimethylthiourea, a hydrogen peroxide and hydroxyl radical scavenger, decreased menadione cytotoxicity, whereas deferoxamine, an inhibitor of hydroxyl radical formation, did not. Conclusions: The results suggest that menadione toxicity is mediated by poly(ADP-ribose)polymerase activation via hydrogen peroxide formation and that menadione-treated bovine heart microvessel endothelial cells provide a suitable in vitro model to study oxidative stress in endothelial cells.     

Conformational investigation of α,β-dehydropeptides VII*. Conformation of Ac-Pro-ΔAla-NHCH3 and Ac-Pro-(E)-ΔAbu-NHCH3: comparison with (Z)-substituted α,β-dehydropeptides†

The crystal structure and solution conformation of Ac-Pro-ΔAla-NHCH₃ and the solution conformation of Ac-Pro-(E)-ΔAbu-NHCH₃ were investigated by X-ray diffraction method and NMR, FTIR and CD spectroscopies. Ac-Pro-ΔAla-NHCH, adopts an extended-coil conformation in the crystalline state, with all-trans peptide bonds and the ΔAla residue being in a C₅ form, φ₁=– 71.4(4), ψ₁=– 16.8(4), φ₂=– 178.4(3) and ψ₂= 172.4(3)°. In inert solvents the peptide also assumes the C₅ conformation, but a γ-turn on the Pro residue cannot be ruled out. In these solvents Ac-Pro-(E)- ΔAbu-NHCH₃ accommodates a βII-turn, but a minor conformer with a nearly planar disposition of the CO—NH and C=C bonds (φ₂～0°) is also present. Previous spectroscopic studies of the (Z)-substituted dehydropeptides Ac-Pro-(Z)- ΔAbu-NHCH, and Ac-Pro-ΔVal-NHCH₃ reveal that both peptides prefer a βII-turn in solution. Comparison of conformations in the family of four Ac-Pro-ΔXaa-NHCH₃ peptides let us formulate the following order of their tendency to adopt a β-turn in solution: (Z)- ΔAbu > (E)- δAbu > ΔVal; ΔAla does not. None of the folded structures formed by the four compounds is stable in strongly solvating media. © Munksgaard 1996.     

Effects of Cimetidine on Sinus Node Function and Atrioventricular Conduction in Man

Electrophysiological effects of H2-receptor blockade 200 mg cimetidine IV on sinus node (SN) function and atrioventricular (AV) conduction were evaluated. Tests were performed in 21 people in basal state (group I), and in 14 people (group II) after autonomic blockade (AB) (propranolol 0.2 mg/kg, and atropine 0.04 mg/kg). We analyzed sinus cycle length (SCL), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), and secondary pause (SP) as the longest sinus pause after incremental overdrive pacing, sinoatrial conduction time (Strauss method) (SACT), Wenckebach point (WP), and blood pressure (BP). In group I, cimetidine prolonged SCL (717 ± 98 vs 860 ± 138 msec P < 0.001), SNRT (1161 ± 153 vs 1263 ± 163 msec P < 0.002), SP (943 ± 183 vs 1072 ± 187 msec P < 0.001), SACT (121 ± 20 msec vs 149 ± 21 msec P < 0.002), and lowered rate at which AV nodal Wenckebach point were observed (169 ± 24 vs 160 ± 26 beats/min P < 0.02). The drug did not produce significant change of the CSNRT (439 ± 121 vs 402 ± 107 msec. In group II, after AB cimetidine prolonged SCL (643 ± 79 vs 656 ± 86 msec P < 0.05), SP (686 ± 114 vs 717 ± 109 msec P < 0.05) and lowered WP (170 ± 19 vs 166 ± 19 beats/min P < 0.02) significantly. The effects of cimetidine, after AB on SNRT (894 ± 180 vs 920 ± 164 msec, CSNRT (243 ± 99 vs 255 ± 85 msec), SACT (85 ± 20 msec vs 90 ± 22 msec) were not significant. We conclude that H2-receptor blockade decreases SN automatically, prolongs SACT and AV conduction in man. The study suggests that histamine takes part in regulation of electrophysiological properties of the human heart in vivo.     

Effects of Cardiac Resynchronization Therapy on Heart Rate Turbulence

Background: Cardiac resynchronization therapy (CRT) improves the clinical status of patients with heart failure (HF), though its effects on heart rate turbulence (HRT) are unknown.
Methods: We measured HRT indices in 58 recipients of CRT systems (mean age = 56 ± 9 years, 41 men) in New York Heart Association HF functional class III–IV, and with a left ventricular (LV) ejection fraction ≤35%. At 6 months of follow-up, 42 patients were responders and 13 nonresponders to CRT, and three patients died suddenly. The HRT indices turbulence onset (TO%) and turbulence slope (TS ms/RR interval) were calculated from digital 24-hour electrocardiogram before and after 6 months of CRT. TO ≥ 0% and TS ≤ 2.5 ms/RR interval were considered abnormal.
Results: Mean TO in the entire population was 0.4 ± 1.5 before CRT, and decreased to −0.8 ± 7.0 during the 6 months of CRT (ns). TS increased significantly from 2.0 ± 1.7 at baseline, to 3.9 ± 3.1 (P < 0.05), and a significantly lower proportion of patients had abnormal HRT indices at 6 months. In contrast to the significant increase observed in responders, not significant change in TS was observed among the nonresponders.
Conclusions: During 6 months of CRT, improvements in HRT indices and a decrease in the proportion of patients with abnormal HRT were observed. CRT may have beneficial effects on baroreflex sensitivity.     

The Effect of Dideoxycytidine on Lymphocyte Subpopulations in Nonhuman Primates

In the present study, 2',3'-dideoxycytidine (ddC), which hasantiretroviral activity, was given chronically to uninfectednonhuman primates to determine whether it produces adverse immunologicalor hematological effects. Nine healthy adult male rhesus monkeyswere divided into three groups and given the following dosesof ddC in a gelatin vehicle: group A, 0.06, 6.0, 3.0, and 1.5mg/kg; group B, 0.6 mg/kg; group C, 0 mg/kg. Blood samples werecollected for hematologic analysis and flow cytometric analysesof lymphocyte subpopulations. Chronic ddC exposure did not causesignificant changes in the number of red blood cells, monocytes,or reticulocytes. The number of white blood cells and neutrophilsincreased and these changes were observed only in group A animalsat the 1.5 mg/kg dose. The most significant alterations observedwere decreases in the number of T helper cells (CD4) and B cells(CD20). CD4⁺ and CD20⁺ lymphocytes exhibited dose-related shiftsthat were reversible over time and after drug withdrawal. Theresults indicate that ddC has few hematologic effects but itdoes have profound but transient effects on the number of cellsin lymphocyte subpopulations in normal primates.     

Formation of optically pure N-acyl-N,N′-dicyclohexylurea in N,N′-dicyclohexylcarbodiimide-mediated peptide synthesis

N-acylurea, a side product in peptide synthesis from DCC, preserves its chiral integrity although peptides formed simultaneously in the same reaction are racemized to a large extent. This observation is inconsistent with the generally accepted opinion that racemization-prone O-acylisourea is a common intermediate for both peptides and N-acylurea. Chiral purity of N-acylureas and peptides was determined by HPLC using chiral stationary phases. An efficient method of synthesis of chirally pure N-acylureas is also presented.