Electrode-Heart Interface: Definition of the Ideal Electrode

Dans la stimulation à deux chambres, pour garder aux stimulateurs leurs avantages de petite taille, de volume réduit et de longue durée, il est nécessaire de diminuer les seuils de stimulation. Ceci peut être accompli par ľoptimisation de ľinterface électrode-coeur. Des nouvelles électrodes pourraient réquire les pertes de polarisation; de même, des nouveaux matériaux pourraient être envisagés. Les résultats de ces données doivent être rapportés à stimulation chronique.
In dual-chamber pacing in order to maintain the advantages of small pulse generator size and volume, and increased longevity, it becomes necessary to reduce pulse generator output. This may be accomplished by optimizing the electrode-heart interface. New electrode designs may reduce polarization losses; perhaps even newer materials should be considered. The results of accumulated data must be applicable to long-term pacing.     

Basal Exit Site of Clinical Ventricular Tachycardia is an Independent Predictor of Antitachycardia Pacing Failure in Implantable Cardioverter‐Defibrillators Recipients

Background: Little is known about predictors of antitachycardia pacing (ATP) failure in implantable cardioverter defibrillator (ICD) recipients. Distance between the stimulation site and the ventricular tachycardia (VT) site of origin may critically affect ATP effectiveness. We hypothesized that ATP may be less effective in ICD patients who had basal VT than in those who had apical VT. Methods: We reviewed data from 52 patients with sustained monomorphic VT and left ventricular disease referred for ICD implantation. ATP was delivered exclusively at the right ventricular apex. The clinical VTs site of origin (basal, midventricular, or apical) was determined in each patient, using 12‐lead electrocardiogram. VTs episodes treated with ATP during the 1‐year follow‐up were studied. ATP success rate (%), defined as the ratio between the number of successful ATP sequences and the number of delivered ATP sequences, was determined in each patient. Results: VT exit site was apical in 19 patients (36%), basal in 18 patients (35%), and midventricular in 15 patients (29%). In those 52 patients, 1,393 ATP sequences, delivered to treat 761 VT episodes, were analyzed. ATP success rate was found to be associated with the VT site of origin (median [interquartile range]): basal (33%[11–67]), midventricular (50%[37–100]), apical (100%[41–100]) (P = 0.027). Multivariate analysis identified basal VT site of origin as an independent predictor of ATP failure (P = 0.023). Conclusion: ATP is less effective in ICD patients who had basal VT than in those who had apical VT before ICD implantation. (PACE 2012; 35:1209–1216)     

Cardiac Surgery in Patients with Human Immunodeficiency Virus Infection: Indications and Results

Ten patients with human immunodeficiency virus (HIV) infections underwent cardiac surgery using cardiopulmonary bypass. All were in Centers for Disease Control (CDC) group II. The cardiac involvement was either urgent or severely symptomatic in all cases. One patient died due to acquired immunodeficiency syndrome (AIDS) unrelated cause. No complications were encountered in this series. Eight of the nine survivors were available for follow-up. Three of these eight patients progressed to AIDS (CDC group IV) and subsequently died. Five patients are alive and in CDC group II. Prognosis of the HIV infection and the natural history of the cardiac disease are the two main elements to be considered whenever cardiac surgery is required.     

Synthesis,biological activity and conformational analysis of cyclic GRF analogs

A novel cyclic GRF analog, cyclo(Asp⁸-Lys¹²)-[Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂, i.e. cyclo^8.12[Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂, was synthesized by the solid phase procedure and found to retain significant biological activity. Solid phase cyclization of Asp⁸ to Lys¹² proceeded rapidly (～2h) using the BOP reagent. Substitution of Ala¹² with d -Ala² and/or NH₂-terminal replacement (desNH₂-Tyr¹ or N-MeTyr¹) in the cyclo^8.12[Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂ system resulted in highly potent analogs that were also active in vivo. Conformational analysis (circular dichroism and molecular dynamics calculations based on NOE-derived distance constraints) demonstrated that cyclo^8.12[Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂ contains a long α-helical segment even in aqueous solution. A series of cyclo^8.12 stereoisomers containing d -Asp⁸ and/or d -Lys¹² were prepared and also found to be highly potent and to retain significant α-helical conformation. The high biological activity of cyclo^8.12[N-MeTyr¹,d -Ala²,Asp⁸,Ala¹⁵]-GRF(1-29)-NH₂ may be explained on the basis of retention of a preferred bioactive conformation.     

Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in athletes. Blood sampling and doping control

1 The pharmacokinetics of recombinant human erythropoietin (rHuEpo) were initially determined in two healthy volunteers after a single subcutaneous dose (50  u  kg⁻¹). Twenty subjects then received repeated subcutaneous administrations of high dose (200  u  kg⁻¹) rHuEpo and 10 subjects received placebo. An immunoradiometric assay was used to measure the concentrations of erythropoietin (Epo) in serum and urine.
2 Serum Epo concentration-time profiles were best described by a one-compartment open model with zero-order input. The mean elimination half-life (±s.d.) was 42.0±34.2  h. Clearance, uncorrected for bioavailability, was 0.05±0.01  l  h⁻¹  kg^{& minus;1}. Erythropoietin concentrations returned to normal values in serum and urine, 7 and 4 days after the last administration, respectively.
3 The recombinant hormone was well tolerated. Significant changes in reticulocytes and red blood cells, haemoglobin concentrations and haematocrit were observed after administration of rHuEpo. In the control group, these parameters remained unchanged.
4 The change in reticulocytes was used as an index of the therapeutic effect of rHuEpo. The concentration-effect relationship was best described by an exponential model.
5 These data show the limitations of the measurement of Epo concentrations in blood and urine samples, collected in athletes during competition, for antidoping control. Epo doping can be detected only during or within 4 to 7 days of ending, a course of rHuEpo.     

Repetitive BOP coupling (REBOP) in solid phase peptide synthesis

The coupling reagent (benzotriazol-1-yloxy)tris-(dimethylamino)phosphonium (BOP) hexafluorophosphate was tested in the synthesis of luliberin (LH-RH) with inexpensive classically protected Boc-amino acids, in slight excess, and benzhydryl amino resin, without any other additive. The good solubility of this reagent and its by-products is of particular interest for automated peptide synthesis. [D-H-S¹]LH-RH was also synthesized and compared with LH-RH by proton nuclear magnetic resonance spectroscopy. As shown by the biological tests and the high performance liquid chromatography study, unprotected pyroClu and Boc-His can be used without any significant racemization but Boc-His(Boc) was found to be preferable since it gave no detectable racemization and no by-products. The difficult isolation of the minority D-derivative from the crude preparation of LH-RH was resolved by a recycling procedure in reversed phase HPLC.     

Case Report: Mycotic Aneurysm of Thoracic Aorta as a Cause of Haemoptysis Role of Dynamic CT Scanning

Haemoptysis can be difficult to diagnose. A case is reported where haemoptysis resulting from a false mycotic aneurysm consequent upon a lung abscess was diagnosed prior to surgery by C.T. scanning. The place of C.T. scanning in the diagnosis of paramediastinal masses is briefly reviewed and the need for bolus injection of contrast medium during dynamic C.T. scanning is stressed.     

Diagnosis of Atrial Fibrillation Using Electrograms from Chronic Leads: Evaluation of Computer Algorithms

This study compares the performance of three detection algorithms for the recognition of atrial fibrillation in chronic pacing leads. Multiple serial recordings were obtained of wideband and filtered electrograms from chronic atrial and ventricular leads in dogs for a period up to 55 days following implantation. Each dog was recorded in sinus rhythm and induced atrial fibrillation. Four days were chosen for processing: The day of implantation and a day in the first, second or third, and fifth weeks. Three signal processing methods were assessed for performance in detection of atrial fibrillation: software recognition of rate with automatic threshold control, amplitude distribution, and frequency spectral analysis. A software trigger for rate determination was adjusted to thresholds of 10, 20, and 30% of maximum baseline-to-peak amplitude. At 10%, a rate boundary anywhere between 420 and 560 beats per minute (bpm) perfectly separated atrial fibrillation from sinus rhythm even though atrial electrograms were contaminated with large QRS deflections and double-sensing was present. At 20% and 30%, a rate boundary around 300 bpm could be used, but sensitivity and specificity were reduced to 90%. In amplitude distribution analysis, a percent of time within a baseline window provided perfect separation of atrial fibrillation from sinus rhythm. In all cases, the signal was within this window less than 43% of the time in atrial fibrillation, and more than 43% in sinus rhythm. In spectral analysis, frequency bands were examined for power content. In the 6 to 30 Hz band atrial fibrillation contained the greater power. Choosing 58% of total power as a discriminant, sensitivity and specificity of atrial fibrillation detection were 100% and 95% respectively.     

Early released lipid-soluble cardiodepressant factor and elevated oestrogenic substances in human septic shock

A cardiodepressant factor (CDF) able to decrease contractile activity of cultured rat heart cells was determined to be located in the lipid-soluble fraction of sera from men in septic shock. This heat-stable CDF has a molecular weight under 1000. Repeated fractionations of sera gave evidence of an oestrone-like chromatographic behaviour. Oestrone, oestradiol and cortisol were immunologically quantified in two groups (recovery and death) of men in septic shock. All of them were elevated in sera from patients with shock. Highest levels of oestrone 4330 pmol 1(-1), (SEM +/- 851, n = 15), oestradiol 1030 pmol 1(-1), (SEM +/- 220, n = 15) and cortisol 1096 pmol 1(-1), (SEM +/- 94, n = 15), were found in patients who failed to recover from shock. However, oestrone levels were the most striking, especially in the male. This study gives evidence for a polarity relationship between the CDF and oestrone, but natural oestrone does not appear to be a direct CDF. Moreover, this study shows that radioimmunoassay of oestrone could be an important index evaluating the severeness of septic shock.     

Presence of Activated Macrophages in a Murine Model of Early Embryo Loss

PROBLEM : Even though our knowledge of the phenomenon at play at the fetoplacental interface has greatly advanced during the past years, a complete understanding of the reasons why the developing embryo is not rejected by maternal immune effector cells remains largely unknown. METHODS : We have used immunohistochemistry with the macrophage-specific markers F4/80 and MHC II to study the relationship between decidual infiltration and resorption in murine models of embryo loss between days 6 and 10 of gestation. RESULTS : Analysis of day 8 CBA/J × DBA/2 pregnancies has revealed 2 distinct populations of embryos. The majority (69.4%) expressed low levels of F4/80⁺ cells, but a minority (30.6%) expressed much higher level of the macrophage marker. In CBA/J × BALB/c, most embryos (91.7%) expressed low numbers of F4/80⁺ cells. As earlier experiments established that products of activated macrophages (TNF-α and nitric oxide) were implicated in embryo loss in this model, the activation status of the F4/80⁺ macrophages was assessed through the cell surface expression of MHC II. Again, a similar association was established: 30.6% of the CBA/J × DBA/2 embryos were infiltrated by significantly more MHC II⁺ cells than the control CBA/J × BALB/c mating. Finally, when coordinate expression of F4/80, MHC II and CD11b was assessed, it was found that an embryo significantly infiltrated by cells bearing one of the 3 markers was also heavily infiltrated by cells bearing the 2 other markers. CONCLUSIONS : This study has shown that the augmented infiltration of the deciduum with maternal macrophages is an early event which precedes spontaneous abortion of the early embryo.