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Biomedical subjects

R Levi

Publications and source records attributed to R Levi.

192 records · Page 11Linked to original sources

The heart as a target organ in systemic allergic reactions: comparison of cardiac analphylaxis in vivo and in vitro.

The purpose of this investigation was to define and quantitatively evaluate cardiac anaphylaxis in vivo. Guinea pigs, passively sensitized with graded amounts of rabbit antipenicilloyl antibody, were anesthetized, ventilated, and challenged intravenously with a constant amount of antigen (anaphylaxis in vivo). In other experiments, guinea pig hearts were excised, perfused in a Langendorff apparatus, and challenged (analphylaxis in vitro). During in vivo anaphylaxis, sinus rate increased 10-30 beats/min, conduction arrhythmias occurred in 15 of 22 experiments, and ventricular fibrillation was seen in 8 of 22 experiments. Tachycardia and arrhythmias began approximately 20 seconds after antigen administration and were accompanied, but not preceded, by respiratory and pressor changes. During in vitro anaphylaxis, sinus rate increased 70-110 beats/min, coronary flow rate decreased 2-22%, conduction arrhythmias occurred in 21 of 31 experiments, and ventricular ectopic activity was seen in 13 of 31 experiments. Tachycardia and arrhythmias began approximately 15 seconds after antigen administration. Sinus tachycardia, atrioventricular conduction block, increased ventricular automaticity, and histamine release were characteristic features of cardiac anaphylaxis in vivo and in vitro. Both in vivo and in vitro, the intensity of the cardiac reaction depended on the amount of antibody used in passive sensitization. Our results clearly indicate that the heart reacts as a target organ in systemic anaphylaxis of the guinea pig.

Anaphylaxis↗

Cardiac histamine-ouabain interaction: potentiation by ouabain of the arrhythmogenic effects of histamine.

Cardiac effects of histamine include stimulation of sinus rate and ventricular contractile force, impairment of atrioventricular conduction and increase in ventricular automaticity. Atrioventricular block and increase in ventricular automaticity are common features of digitalis toxicity. The purpose of the present investigation was to study the influence of low concentrations of ouabain on the cardiac effects of immunologically released and administered histamine. Hearts excised from guinea pigs passively sensitized to penicillin antigens responded to antigen with sinus tachycardia, atrioventricular conduction block, increase in ventricular automaticity, decrease in coronary flow rate and histamine release. During anaphylaxis in the presence of ouabain, 10-9 and 3 times 10-9 M, the duration of conduction arrhythmia and the incidence of ventricular automaticity were greatly increased. Dose-response studies for the cardiac effects of exogenous histamine were conducted in vitro in the presence of ouabain 10-9 and 3 times 10-9 M. Ouabain, in a concentration-dependent fashion, potentiated histamine-induced prolongation of the P-R interval, but not the increases in sinus rate and in ventricular contractile force. Oution block and idioventricular also greatly increased the incidence of histamine-induced atrioventricular conduction block and idioventricular rhythms. Our results clearly identify a histamine-Ouabain interaction leading to severe disruption of atrioventricular conduction and to increased ventricular automaticity.

Animals↗

Anaphylaxis in the guinea-pig isolated heart: selective inhibition by burimamide of the positive inotropic and chronotropic effects of released histamine.

1. Anaphylaxis was induced in the isolated heart of the guinea-pig in the presence of burimamide at concentrations of 4 x 10(-5)M and 2.7 x 10(-4)M.2. Burimamide did not affect the immunological release of histamine; however, it selectively antagonized the positive inotropic and chronotropic effects of released histamine. The antagonism of the positive chronotropic effect was concentration-dependent.3. Neither the negative dromotropic effect nor the decrease in coronary flow rate occurring during anaphylaxis were inhibited by burimamide.4. The results are in agreement with the double histamine receptor theory and suggest that, in the heart of the guinea-pig, H(2)-receptors are involved in the positive inotropic and chronotropic effects of released histamine, and H(1)-receptors in the negative dromotropic effect.

Anaphylaxis↗

Inotropic effects of histamine in human myocardium: differentiation between positive and negative components.

Histamine is known to enhance the contractility of the human myocardium in vitro. We have observed that when the H2-receptor antagonist cimetidine (or ranitidine) blocks the positive inotropic effect of histamine in spontaneously beating pectinate muscles isolated from human right atrial appendage, a negative inotropic effect is unmasked. This decrease in contractility is independent of changes in rate, as it occurs in preparations paced at constant rate, is mimicked by the H1-receptor agonist 2-(2-thiazolyl)-ethylamine (ThEA) and is abolished by the H1-antagonist pyrilamine. Thus, the negative inotropic effect of histamine appears to be mediated by H1-receptors. Our data indicate that the inotropic response of the human myocardium to histamine consists of two opposing components: an increase in contraction, mediated by H2-receptors, and a decrease in contraction, mediated by H1-receptors. Given the widespread use of H2-blockers and the multitude of clinical conditions in which histamine is released, there may well be circumstances in which an H1-response predominates. This could result in a decrease in myocardial contractility.

Cimetidine↗

Antagonism of the cardiac effects of leukotriene C4 by compound SKF 88046: dissociation of effects on contractility and coronary flow.

In the present study, we evaluated the properties of an imidodisulfamide derivative, compound SKF 88046, as an antagonist of the cardiac effects of leukotrienes (LTs). LTC4 (0.1-100 ng) caused dose-related decreases in the contractile force and coronary flow rate of the isolated guinea pig heart. SKF 88046 and the prototypic anti-SRS (anti-slow reacting substance) compound FPL 55712 (4.8 X 10(-7) M) were equieffective in antagonizing the LTC4-induced decrease in coronary flow. On the other hand, SKF 88046 was more potent than FPL 55712 in antagonizing the negative inotropic effect of LTC4. Our findings demonstrate that SKF 88046 is an effective antagonist of the coronary constricting and myocardial depressant effects of LTC4, but that SKF 88046 preferentially antagonizes the negative inotropic effect of LTC4. This favors the hypothesis formulated by others that LT effects may be mediated by multiple receptors.

Animals↗