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Biomedical subjects

M Manoach

Publications and source records attributed to M Manoach.

At least 19 recordsLinked to original sources
PubMed1992

Ventricular defibrillating properties of catecholamine uptake inhibitors.

Ventricular fibrillation (VF) is a fatal event in humans unless electrical defibrillation is applied within minutes. Recent publications describe spontaneous termination of VF in various animals and even in humans. Certain drugs can transfer a fatal, sustained VF (SVF) into a self-terminating, transient VF (TVF). Based on results obtained in animals of various species and ages, we have suggested that the occurrence of TVF requires a high cardiac catecholamine level at the time of VF. According to our hypothesis, drugs which decrease catecholamine reuptake by the sympathetic nerve terminals will increase the ability of the heart ventricles to defibrillate spontaneously. In the present study, we examined the effects of desipramine, maprotiline, mianserin, iprindole, cocaine and amphetamine on the type of VF in cats exhibiting SVF prior to the treatment. The results show that the ability of these compounds to transfer SVF to TVF is closely related to their potency to inhibit catecholamine reuptake. The establishment of the catecholamine related mechanisms of TVF may lead to the development of a new class of antiarrhythmic-defibrillatory drugs.

Amphetamine↗
PubMed1992

Pulse transmission and impedance characteristics of a non-uniform circulatory model.

In recent years, the technique of non-uniform transmission lines has been utilized in the synthesis of lines feeding antennae from transmitters, thereby maintaining matching over a wide band of frequencies and with varying load. For this reason, an electrical model based on that technique stems from the resemblance between the two systems: in both the feeding medium is non-uniform, and it is necessary to maintain a good response over a wide range of frequencies. Our non-uniform transmission line model of the arterial system, introduced in an earlier publication, supplies comprehensive answers to many questions dealing with the research into this system. Whereas in our earlier model the ohmic resistance R was considered small and not considered in the calculations, it is included in the present study. We have calculated the variation of the input impedance with the frequency and distance from the source, the effect of occluded main branches, augmentation of the pressure wave, the relationship between body size and heart rate and the matching of impedances at large bifurcations. We found that our calculated results agree very well with the quantitative results measured by other investigators in the field.

Blood Circulation↗
PubMed1991

A correlation between the structure of myocardial cells and prolonged Q-T interval in young rats.

In the present study, we examined the electrocardiogram and the structure of myocardial cells in young rats at different postnatal ages. The offspring of rats were sacrificed on different postnatal days following electrocardiographical recordings, and sections of their hearts were examined microscopically. In a number of newborns, we observed definite prolongation of the Q-T interval in the electrocardiogram on the first day of life. Normal shortening of the Q-T interval with age was demonstrated in the majority of the offspring while, in some of them, the Q-T interval remained prolonged. In the "affected" offspring, which exhibit a typical pattern of Q-T prolongation with clear ST segment, definite retardation of histological differentiation of the myocardium was found at various ages. In these cases, there were large numbers of "myoblasts" scattered between normal myocytes in different parts of the ventricular walls and septum. These myoblasts were rarely identified in newborns and offspring with a normal Q-T interval. Our results clearly show a correlation between the ratio of persistence of undifferentiated myoblasts at any age and the typical prolonged Q-T pattern in the electrocardiogram (r = 0.9). Due to the possible clinical significance, the hearts of patients with prolonged Q-T syndrome should be examined so as to reach for abnormal differentiation of the myocytes.

Animals↗
PubMed1988

A new group of defibrillatory drugs in the classification of antiarrhythmic agents.

Ventricular antiarrhythmic therapy is aimed traditionally at preventing arrhythmias and ventricular fibrillation. Recently, a new approach has been introduced, where drug therapy facilitates the ability of the heart for spontaneous defibrillation. The chemical features and the electrophysiologic properties are discussed below. The introduction of this new group of defibrillating antiarrhythmic drugs implies the extension of the common classification of antiarrhythmic drugs.

Animals↗
PubMed1988

Magnesium fluxes in ventricular fibrillation and defibrillation in untreated and dibenzepine HC1 pretreated cats.

Serum magnesium concentration (S-Mg) was estimated in 12 anesthetized cats before and after central thoracotomy, during an electrically induced ventricular fibrillation (VF) and after defibrillation (DEF), and again, in the same experimental animals, after the administration of 3 mg/kg of dibenzepine HC1--a tricyclic antidepressant reported to facilitate spontaneous DEF--as well as during a subsequently induced VF and after the spontaneous DEF which followed. In the first part of the experiment, the surgery and the induction of VF caused no significant change of mean serum magnesium concentration (S-Mg) or serum calcium concentration (S-Ca), whereas the DEF was accompanied by Mg efflux (a significant increase of mean S-Mg from 0.824 mmol/l, SD 0.182, n = 12 to 0.991 mmol/l, SD 0.182, n = 12; P less than 0.05). In the second part of the experiment, following the administration of dibenzepine HCl there was Mg influx (a lowering of mean S-Mg to 0.891 mmol/l, SD 0.160, n = 12; P less than 0.05). During VF in the pretreated cats, S-Mg remained unchanged, while S-Ca decreased significantly (P less than 0.05), followed by a rebound Ca++ efflux (a systematic rise of S-Ca) as the animals defibrilated spontaneously. Concomitantly, there was Mg efflux (a systematic rise of S-MG), the mean S-Mg rising from 0.879 mmol/l, SD 0.143, n = 9 to 1.083 mmol/l, SD 0.257, n = 7, ie to virtually the same value as that obtained after electrically induced DEF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Teratogenic effect of D-amphetamine sulphate: histodifferentiation and electrocardiogram pattern of mouse embryonic heart.

Pregnant albino mice (ICR random-bred strain) received daily injections of 50 or 100 mg/kg body weight of D-amphetamine sulphate between days 9 and 11 of gestation. Parallel control animals were injected with saline solution. Treated mice were sacrificed on day 15 or 19 of gestation. The embryos were examined for gross malformations and direct embryonic ECG recordings were made; they were weighed, and their hearts were carefully dissected. Microscopic sections of the heart were stained with hematoxylin and eosin. It was found that high doses of D-amphetamine raised the incidence of mortality in the treated pregnant mice up to 40%. The resorption rate in the survivors was high (up to 58%) following the high dose of the drug. Up to 15% of the embryos from the treated groups showed gross malformations, including skeletal and eye malformations and exencephaly. The electrocardiogram (ECG) recordings in most 19-day-old embryos from both treated groups showed a pattern with prolonged Q-T interval (PQT), similar to that of control embryos in the intermediate developmental stages (days 14-16 of gestation). The ECG of control embryos (from day 17 on) resembled that of prenatal fetuses. Microscopically, the hearts of treated embryos showed a large number of undifferentiated cardiac myoblasts. It can be inferred that high doses of D-amphetamine affect embryonic development generally and delay the histodifferentiation of the myocardium, resulting in incomplete maturation of the cardiac muscles, thus leading to the immature ECG pattern, with PQT intervals.

Abnormalities, Drug-Induced↗
PubMed1987

Reduction of infarct size following acute coronary occlusion by augmenting collateral blood supply induced by infusion of tricyclic antidepressants.

Previously, it has been shown that following occlusion of the left anterior descending artery (LAD) in cats, i.v. administration of tricyclic antidepressants (TCAD) significantly decreases the incidence of ventricular fibrillation (VF), which terminates spontaneously upon appearance. Furthermore, this treatment significantly decreases the size of the unperfused ventricular muscle (ischemic myocardium) from 44%-84% (mean 61%) to 17%-56% (mean 34%). This latter effect was demonstrated by using color demarcation of the perfused myocardium with the injection of a dye into the left atrium after 2 h of LAD occlusion in both control and treated cats. It was assumed that reduction of the unperfused area was due to an increase of collateral blood supply to the ischemic area. Although the beneficial effect of TCAD on the collateral blood supply has been clearly demonstrated in cats randomly assigned to two groups, the present study was designed to investigate the changes in the size of the ischemic area in the same animal by using two different dyes. Both dyes were injected into the left auricle after the LAD occlusion: The first was injected before the TCAD treatment and the second after the treatment. Two days after fixation in 4% formaldehyde, the hearts were sliced into three or four transverse sections. Examination of the sections indicated that there were three types of myocardial markings: (a) totally unperfused myocardium; (b) an area perfused by both colors; (c) an area perfused only by the second dye, indicating an increased collateral blood supply, the effectiveness of which was increased by the TCAD treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The effect of tricyclic antidepressants on ventricular fibrillation and collateral blood supply following acute coronary occlusion.

In previous studies, we showed that dibenzepin HCl (D) and other tricyclic antidepressants (TCAD), given either before or during occlusion of the left anterior descending artery (LAD), decreased the incidence of ventricular fibrillation (VF) following occlusion and reperfusion. Moreover, once VF develops in treated animals, it changes into a transient type, reverting spontaneously to a sinus rhythm. In the treated cats, retrograde perfusion of the occluded coronary artery was observed, most likely as a result of increased collateral blood flow. This latter effect is the subject of the present study. The LAD was occluded at its origin in 43 cats, 28 of which were treated either with D or with 5-iminodibenzyl HCl; the remaining 15 were untreated controls. Two hours after the occlusion, methylene blue was injected into the left atrium to determine color demarcation between the perfused and unperfused myocardium, and the cat was then killed. After fixing for 2 or 3 days in 4% formaldehyde, the hearts were sectioned transversely. The results showed that in the 15 control cats, the blood-supplied (blue) area ranged between 16% and 56% of the left ventricular muscle (mean 39%), while in the 28 treated cats the blue area was between 44% and 83% (mean 66%). These results clearly indicate the beneficial effect of TCAD on the blood supply of the occluded area and can explain, in part, the ability of these drugs to prevent VF even if infused after the coronary occlusion, and their protective effect against VF following reperfusion. No other antiarrhythmic drugs have been shown to possess this latter action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Ventricular self-defibrillation in mammals: age and drug dependence.

Ventricular fibrillation (VF) was electrically induced in cats, rabbits, guinea pigs and rats. In young animals of all species and also in old rats short transient VF (TVF) was followed by spontaneous reversion to normal sinus rhythm. Old cats, rabbits and guinea pigs had episodes of sustained VF (SVF) which did not terminate spontaneously; artificial electro-defibrillation was required. Dibenzepin converted the sustained response of old animals to a transient one. Verapamil antagonized the effect of dibenzepin in old animals and also changed the TVF in young animals to SVF. The effect of calcie age of the animal is an important factor in determining whether the fibrillatory red to an alteration in the properties of the cell membrane.

Aging↗