Biomedical subjects

D Varon

Publications and source records attributed to D Varon.

115 records · Page 7Linked to original sources

PubMedDate not supplied

The role of catecholamines on intercellular coupling, myocardial cell synchronization and self ventricular defibrillation.

Ventricular fibrillation (VF) is one of the most life threatening events. Although in humans VF is generally sustained (SVF) requiring artificial defibrillation, in various mammals and in some cases in humans VF terminates by itself, reverting spontaneously into sinus rhythm. Since VF is one of the main causes of sudden death, one of the important clinical problems today is if and how we can transform the fatal SVF into a self limited transient one (TVF). From electrophysiological studies carried out on anaesthetized open chest animals, we have found that TVF requires a high degree of intercellular coupling and synchronization. Cardiac myocytes are electrically coupled with adjacent cells. The intercellular coupling is a focus of low electrical resistance which allows rapid transmission of electrical impulses between cells. Any decrease in intercellular coupling decreases the ability of the heart for self defibrillation. The cell-to-cell coupling decreases with age, ischemia, VF and variations in physiological conditions probably due to an increase in intercellular resistance (Ri), widening in the internexal gaps, decrease in electrotonic space constant (lambda) etc. All of these factors are known to be affected by intracellular concentration of free Ca++ ([Ca++]). On the basis of studies carried out on various mammals at different ages, we hypothesized that the ability of the heart to defibrillate depends on the cardiac catecholamine level [CA], during VF. This hypothesis is supported by the facts, known from the literature, that increase in [CA] decreases intracellular free Ca++ concentration, decreases Ri and increases lambda.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

A self-protecting servo-model for explanation of the mechanism involved in spontaneous ventricular defibrillation.

Ventricular fibrillation (VF) is the most life-threatening arrhythmia. It has been suggested that VF in humans is always sustained. Recent publications indicated that VF can be either sustained (SVF) or transient (TVF), reverting spontaneously into sinus rhythm. In previous studies we have hypothesized that TVF requires, during VF, a high cardiac catecholamine level ([CA]). Since during VF sympathetic activity is enhanced, the question arises of why VF is sustained in the majority of cases. Looking on the living body as a self-protecting servo-mechanism, we propose a servo-model that on the one hand describes the mechanism involved in TVF and on the other proposes a therapeutic procedure which can help the heart in its effort to transform VF into TVF. Our model has been examined by various experimental studies. The results obtained strongly support our hypothesis.

Catecholamines↗

PubMedDate not supplied

The defibrillating effect of catecholamine reuptake inhibitors.

In previous studies we hypothesized that spontaneous termination of ventricular fibrillation (TVF) requires a high cardiac catecholamine level ([CA]) during VF. During VF, sympathetic activity is enhanced but in the majority of cases [CA] does not reach the level required for self-defibrillation, most likely due to their relatively high reuptake by sympathetic nerve terminals. One possibility of obtaining TVF is by elevation of the [CA] during VF, either by catecholamine intracoronary injection or by treatment with compounds that inhibit catecholamine reuptake. To examine this assumption, we studied the effect of VF on 3 closely related compounds: talopram, talsupram and citalopram, with norepinephrine uptake inhibition (IC50NE) of 2.9, 0.79 and 8800 and dopamine (DA) uptake inhibition (IC50DA) of 44000, 9300 and 41000, respectively, as well as 2 enantiomers of a cis-1-piperazino-3-phenylindan derivative (Lu20-037 and Lu20-036) with IC50NE of 2.5 and 910 and IC50DA of 2.3 and 1700, respectively. The results support our hypothesis relating the defibrillating effect of a compound to its IC50NE, while its inhibitory effect on DA uptake seems to conteract the NE effect.

Animals↗

PubMedDate not supplied

Ethmozine and ethacizine--new antiarrhythmic drugs with defibrillating properties.

Ventricular fibrillation (VF) is a life-threatening arrhythmia that leads to death unless electrical defibrillation is applied in time. Recent publications indicate that VF can be either sustained (SVF), requiring electrical defibrillation, or transient (TVF), reverting spontaneously into sinus rhythm. Since VF cannot be totally prevented by drugs, a new antiarrhythmic therapeutic approach has been proposed: drug-induced enhancement of the ability of the heart to defibrillate by itself. In this study we examined the defibrillating potency of two antiarrhythmic phenothiazines, ethmozine (ETM) and ethacizine (ETA), as well as their effects on catecholamine uptake and on the electrophysiological properties of the myocardial cell membrane. The antiarrhythmic-defibrillatory activity was examined in cats; the inhibitory effect on [3H]-norepinephrine (NE) uptake was examined in rat brain synaptosomes, and the electrophysiological membrane effects were examined by microelectrode recordings in perfused strips of heart ventricle from guinea-pigs. The results indicate that: 1. ETA exhibits similar but stronger antiarrhythmic-defibrillating and NE reuptake inhibitory effects than ETM; 2. ETA at 10-6 M decreases ventricular conduction time and increases Vmax while ETM at this concentration does not change them; 3. The defibrillating ability of the drugs can be related to their inhibitory potency on NE reuptake. We suggest that the risk of sympathomimetic arrhythmogenicity is prevented by the previously described, membrane stabilizing Class 1 antiarrhythmic properties of these drugs.

Action Potentials↗

PubMedDate not supplied

Prevalence of a CCR5 gene 32-bp deletion in an Israeli cohort of HIV-1-infected and uninfected hemophilia patients.

OBJECTIVE: The recently discovered connection of chemokines and their receptors to HIV pathogenesis, and the description of the 32-bp deletion in the CCR5 gene (delta 32 CCR5), led to heightened excitement and numerous reports regarding their role in HIV transmission and disease progression. The populations in most of these reports, except for one, consisted of homosexual men. Our objective was to investigate the significance of delta 32 CCR5 in hemophilia patients in Israel. STUDY DESIGN/METHODS: We have determined by polymerase chain reaction (PCR) the prevalence of delta 32 CCR5 in 34 HIV-seropositive Israeli patients with hemophilia A and compared them with a control group of 42 HIV-seronegative hemophilia patients. RESULTS: Thirteen heterozygotes were identified among the 76 hemophilia patients tested (allelic frequency, 8.5%), 5 (14.7%) among the HIV-seropositive patients, and 8 (19%) among the noninfected. CONCLUSIONS: No protective advantage to delta 32 CCR5 heterozygosity was seen as far as infection with HIV is concerned. However, a trend of a slower progression to AIDS in delta 32 CCR5 heterozygotes compared with wild-type homozygotes may be apparent, although no absolute correlation could be made.

Cohort Studies↗

PubMedDate not supplied

Carcinocythemia. Report of two cases, one simulating a Burkitt lymphoma.

Carcinocythemia is a rare complication of metastatic carcinoma, characterized by the presence of carcinoma cells in the peripheral blood, which may mimic acute leukemia. Two cases are reported in which the patients developed carcinocythemia several years after being treated for carcinoma of the breast. Cytologic examination of peripheral blood smears in both cases showed the presence of numerous large abnormal cells; in one case the cells simulated those of a Burkitt lymphoma. Cytochemical and/or immunologic marker studies ruled out a hematopoietic origin of the malignant cells in both cases and confirmed a diagnosis of carcinocythemia. The rapidly fatal outcome observed in these two cases was in accordance with the poor prognosis usually encountered with this rare phenomenon.

Adenocarcinoma↗

PubMedDate not supplied

Effects of various drugs on denervation changes in rat muscles.

The effects of drugs, known to affect lysosomal enzyme activities on denervated gastrocnemius muscles of rats were studied. The drugs used were: amiodarone, chloroquine, cortisone, streptomycin and trypan blue. The parameters investigated included changes in fibrillations in electromyographs, morphometric evaluations of muscle atrophy and replacement, and light and electron microscopic analysis of morphological changes and of histochemical acid phosphatase activity. All drug treatments reduced the intensity and frequency of fibrillations. Acid phosphatase spillage was best inhibited by trypan blue. Progressive muscle fiber atrophy with massive aggregation of mitochondria at the cell periphery occurred in denervated fibers. Atrophy was expressed both in loss of muscle weight and in reduction of average muscle fiber diameter. Administration of all the drugs resulted in slowing down of muscle weight loss, particularly 30 days after denervation. All drugs induced slowing down of the loss in average fiber diameter on day 3 after denervation, while on day 10 only cortisone and amiodarone still exerted this effect. A similar transitory slowing of denervation changes was observed in estimations of replacement of muscle by collagen and adipose tissue. Only the effect of trypan blue and amiodarone persisted on day 10. The results indicate that drugs known to inhibit lysosomal enzyme activity may slow down the denervation-derived muscle atrophy to a certain extent, but the effects are transitory.

Acid Phosphatase↗