Sudden Death Caused by Heart Block in a Patient with Multiple Myeloma and Cardiac Amyloidosis

A patient with multiple myeloma and amyloidosis was admitted to hospital following successful cardiopulmonary resuscitation at home. No disturbances in heart rhythm were seen during the first 48 hours of continuous telemetric ECG recording. The patient died from ventricular asystole due to complete atrioventricular block, while he was on a 24-hour Holter monitoring the fifth night in hospital. Patients with known cardiac amyloidosis and syncope should undergo long-term ECG recordings, preferably by telemetry. Repeated registrations may be necessary to discover disturbances in heart rhythm.     

Biologically active analogues of arginine vasopressin containing conformationally restricted dipeptide fragments

In this study we described the synthesis and pharmacological properties of five new analogues of arginine vasopressin (AVP). Four of these analogues contained ethylene-bridged dipeptide Phe-Phe in positions 2 and 3; one had two N-Me-Phe residues. All new peptides were tested for vasopressor and antidiuretic activities. We also estimated the uterotonic activities of these compounds in vitro. Three analogues were highly potent V₁-antagonists. One of them, namely [Cpa¹,(Phe-Phe)^2,3,Val⁴]AVP, which seemed to not interact with either V₂ and oxytocic receptors, was outstandingly selective. It is interesting that the high antipressor potency of our second peptide, [(N-Me-Phe)^2,3]AVP, was achieved without modification of position 1. Our results open new possibilities for the design of very potent and selective V₁-antagonists of AVP.     

Heart Rate Variability: Its Association with Hemodynamic Function of the Left Ventricle in Patients with Coronary Heart Disease

Patients with heart failure secondary to coronary heart disease (CHD) are characterized by an imbalance of the autonomic nervous system, which can be assessed by analysis of the heart rate variability (HRV). However it is still unclear whether all patients with CHD reveal suppression of HRV and if it is related to hemodynamic function and contractile disturbances of the left ventricle. To answer these questions data from 105 consecutive patients were analyzed and compared with 17 healthy subjects. All study participants underwent 24-hour ambulatory ECG recordings with calculation of HRV parameters and angiographic examination after collection of clinical data and other noninvasive evaluations. Time- (SDRR, SDANN, SD, pNN50) and frequency- (LF, HF) domain parameters of HRV were assessed. All ventriculographic and hemodynamic measurements were used in the analysis. Highly significant correlations were found between all HRV parameters, and left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (P < 0.001). Patients with LVEF < 40% were characterized by significantly lower values of HRV and impairment or lack (LVEF < 20%) of diurnal variation of frequency-domain measurements of HRV. Patients with segmental akinesis or dyskinesis also had lower values of HRV. The group with dyskinesis was characterized by significantly lower diurnal rhythms of LF and HF, independent of LVEF.     

Synthesis and biological evaluation of human preproenkephalin (100-111) and its analogs*

The dodecapeptide sequence, Tyr-Gly-Gly-Phe-Met-Lys-Arg-Tyr-Gly-Gly-Phe-Met (BI), which is totally conserved in the primary structures of human, bovine, rat, and toad preproenkephalins, has been synthesized by the solid-phase method. Coupling reactions were achieved by using symmetrical anhydrides of tert.-butyloxycarbonylamino acids preformed with N-tert.-butyl,N′-methylcarbodiimide. 6-Arg and 7-Lys analogs have also been obtained. The peptides show opiate activity in both GPI and MVD assay, and possess antinociceptive properties as estimated by the hot-plate test in mice when applied intracisternally.     

Triple-Site Versus Standard Cardiac Resynchronization Therapy Study (TRUST CRT): Clinical Rationale, Design, and Implementation

Background: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure (HF), lowered LV ejection fraction, and wide QRS. However, many patients (≤40%) do not respond to this form of pacing. TRUST CRT is a prospective, single-center, randomized, single-blind, parallel, and controlled study that has been designed to treat patients with moderate to severe HF (NYHA III-IV), QRS ≥120 ms, sinus rhythm, LV dysfunction (EF ≤ 35%), and signs of mechanical dyssynchrony.
Objective: The primary objective will evaluate the 6-month's combined endpoint of alive status, freedom from hospitalization for HF or heart transplantation, relative ≥10% increase in LV ejection fraction, ≥10% in peak oxygen consumption, and ≥10% in 6-minute walking distance.
Methods: Patients with HF receiving optimal pharmacotherapy, with LV dysfunction, mechanical dyssynchrony, wide QRS and sinus rhythm will be randomized in a 1: 1 fashion to standard or triple-site CRT-D. Patients will be followed for 1 week, 1, 3, and 6 months during a blind phase, then every 6 months until study completion. One hundred patients will be enrolled by the study center.
Conclusions: TRUST CRT is a randomized, clinical trial in CRT candidates to evaluate the effectiveness of triple-site pacing versus standard resynchronization in patients with HF.     

Peptide synthesis on chitin

The use of chitin as a support for solid-phase peptide synthesis is described and illustrated by synthesis of four peptides, varying in length from 10 to 29 residues. Syntheses were performed in a continuous-flow peptide synthesizer, using Fmoc chemistry. A cleavable linker, p-[(R,S)-α-[1-(9H-fluoren-9-y1)-methoxyformamido]-2,4-dimethoxybenzyl]-phenoxyacetic acid, was attached to chitosan at the desired substitution level, and the complex acetylated to yield a linker substituted chitin. The effects of temperature, solvents and degree of linker substitution on the syntheses were studied. Acyl carrier peptide (ACP) synthesis studies indicated that temperature was the single most important parameter. Increasing the temperature of the synthesis from 20 to 55 °C resulted in an enormous improvement of this synthesis, with about 90% of the crude product being the correct peptide. Denaturing solvents, such as DMSO, could be used without significant effect on the flow properties of the support. The synthesis of one peptide was mainly improved by lowering the degree of substitution from 0.3 to 0.1 mmol/g, suggesting peptide aggregation was a problem in this case. The results of three syntheses on chitin were comparable with those obtained with a commonly used commercial support. This work shows that, under appropriate conditions, chitin can be utilized directly as a support for peptide synthesis. © Munksgaard 1996.