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Biomedical subjects

R Levi

Publications and source records attributed to R Levi.

At least 181 records · Page 10Linked to original sources
PubMed1980

Cardiac anaphylaxis: SRS-A potentiates and extends the effects of released histamine.

Immunologic immediate hypersensitivity reactions of the heart are characterized by tachycardia and arrhythmias caused by the release of endogenous cardiac histamine. The contribution of SRS-A to anaphylactic cardiac dysfunction was indirectly assessed by the use of the selective SRS-A receptor antagonist FPL 55712. In the presence of FPL 55712 the concentration-response curves for the chronotropic and arrhythmogenic effects of endogenous cardiac histamine were progressively shifted to the right as a function of the concentration of FPL 55712. Moreover, the duration of the positive chronotropic effect of endogenous cardiac histamine was shortened by FPL 55712. On the other hand, FPL 55712 failed to reduce the chronotropic and arrhythmogenic effects of exogenous histamine. Partially purified histamine-free SRS-A opbtained from rat peritoneum potentiated and greatly prolonged the positive chronotropic effect of exogenous histamine. Potentiation and prolongation were both blocked by FPL 55712. Thus, our results suggest that SRS-A sensitized the heart to the tachyarrhythmic effects of histamine.

Anaphylaxis↗
PubMed1980

Inhibition of thromboxane A2 biosynthesis in human platelets by burimamide.

1 Burimamide selectively inhibited the formation of thromboxane A2 from prostaglandin endoperoxides by human platelet microsomes in a dose-dependent manner (IC50 = 2.5 x 10(-5) M). Burimamide was found to be equipotent to imidazole as a thromboxane synthetase inhibitor. 2 Metiamide, cimetidine and a series of compounds either bearing a structural or pharmacological relationship to histamine caused little or no inhibition of thromboxane A2 biosynthesis by human platelet microsomes. 3 Burimamide (5 x 10(-4) to 2.3 x 10(-3) M) did not inhibit either the cyclo-oxygenase or the prostacyclin synthetase of sheep seminal vesicles or the prostacyclin synthetase of dog aortic microsomes. 4 Burimamide (2.5 x 10(-5) to 1.2 x 10(-4) M) inhibited sodium arachidonate-induced human platelet aggregation; the degree of inhibition was dependent upon the concentration of arachidonic acid used to aggregate the platelets.

Blood Platelets↗
PubMed1980

The cardiac pharmacology of tiotidine (LCL 125, 211): a new histamine H2-receptor antagonist.

The cardiac pharmacology of tiotidine, a potent and specific antagonist of H2-receptors, was studied in isolated Langendorff-perfused guinea-pig hearts. At a concentration of 2.5 x 10(-6) M, tiotidine caused a slight prolongation of the P-R interval, but had no effect on rate, contractility or coronary function. Tiotidine competitively antagonized the positive chronotropic action of histamine with an apparent dissociation constant of 3.0 x 10(-8) M (2.3 x 10(-8)-3.8 x 10(-8) M). Tiotidine abolished H2-mediated increases in contractile force leaving H2-mediated negative inotropic responses unopposed. The actions of histamine at the A-V node, manifested by lengthening of the P-R interval and A-V block, were attenuated by 2.5 x 10(-7) M tiotidine; nevertheless, higher concentrations of the antagonist did not produce additional inhibition of the negative dromotropic response. As a function of concentration, tiotidine reduced the incidence and duration of histamine-induced idioventricular arrhythmias. Based on its high affinity and specificity for the H2-receptor and relative lack of cardio-depressant effects, tiotidine appears to be a useful new drug for investigating the role of histamine in cardiac function and dysfunction.

Animals↗
PubMed1980

The cardiac effects of prostaglandins and their modification by the prostaglandin antagonist N-0164.

The cardiac actions of a number of prostaglandins and their modification by the prostaglandin antagonist sodium p-benzyl-4-[1-oxo-2-(4-chlorobenzyl)-3-phenyl propyl]phenyl phosphonate (N-0164) was studied in the isolated guinea-pig heart. Arachidonic acid, prostaglandin (PG)E2 (0.01--1 micrograms) and prostacyclin (0.01--10 micrograms), administered by bolus injection, caused dose-dependent increases in coronary flow rate, whereas PGD2, PGF2 alpha and the stable PG enderoperoxide analog U46619 (0.01--100 micrograms) caused dose-dependent decreases in coronary flow rate. Over the dose range studied, PGE2, arachidonic acid, prostacyclin and PGF2 alpha increased the sinus rate and PGD2 decreased the sinus rate, whereas U46619 had no consistent effect. Arachidonic acid, PGF2 alpha, PGD2 and U46619 produced a decrease in ventricular contractile force, whereas PGE2 had no effect and prostacyclin produced a modest increase in ventricular contractile force. N-0164 (10 ng and 100 ng/ml) selectively antagonized the coronary vasoconstrictor effects of PGD2 and PGF2 alpha. N-0164, at higher concentrations (1 micrograms/ml), antagonized the coronary vasodilator actions of PGE2; however, it did not modify the coronary vasodilator action of prostacyclin. N-0164 (10--100 ng/ml) also antagonized as a function of its concentration sinus rate changes produced by either PGD2 or PGF2 alpha, whereas at higher concentrations (1 microgram/ml), rather than antagonizing it potentiated sinus rate increases produced by either PGE2 or prostacyclin. These results suggest that the cardiac actions of prostaglandins are complex and are not readily elucidated by the use of the prostaglandin antagonist, N-0164.

Animals↗
PubMed1979

Acceleration of idioventricular rhythms by histamine in guinea pig heart: mediation by H2 receptors.

To evaluate the ability of histamine to induce ventricular arrhythmias, we studied the effects of histamine on ventricular rhythmicity in the isolated guinea pig heart with complete atrioventricular conduction block. As a function of dose (0.1-30 microgram), histamine enhanced the idioventricular rate by increasing the rate of firing of the original pacemaker and also by causing the sudden appearance of faster idioventricular rhythms that coincided with changes in pacemaker site. Anaphylaxis in the isolated guinea pig heart with complete atrioventricular conduction block caused histamine release and acceleration of idioventricular rate. The effects of histamine on idioventricular rhythmicity were not attenuated by the histamine H1 receptor antagonist chlorpheniramine, but were antagonized by the H2 receptor antagonist cimetidine. Moreover, the selective H2 agonist 4-methylhistamine (4MeH) accelerated the idioventricular rate, whereas 2-(2-thiazolyl) ethylamine (ThEA), at doses selective for H1 receptor activation, did not. The effects of histamine on idioventricular rhythmicity were not modified by the beta-adrenergic blocker pindolol. The mechanism by which histamine increases idioventricular rate probably involves two components: (1) an enhancement in automaticity of the original pacemaker, and (2) the induction of faster rhythms via reentry and/or afterdepolarizations. Whatever the mechanism, both components of the ventricular chronotropic action of histamine appear to involve exclusively histamine receptors of the H2 type. Thus, our results suggest that H2 receptor antagonists may have a role as specific antiarrhythmic agents in the treatment of cardiac dysfunctions caused by histamine release.

Anaphylaxis↗
PubMed1979

Induction of IgE antibodies to antigen isolated from tobacco leaves and from cigarette smoke condensate.

Neonatal California White rabbits were sensitized with a glycoprotein purified from cured Virginia Bright tobacco leaves. Their serums, but not serums from normal rabbits, were demonstrated by passive cutaneous anaphylaxis technique to contain heat-labile, homocytophilic antibodies to this antigen and to similar material purified from cigarette smoke condensate. Serums containing IgE antibodies to tobacco antigen would not be demonstrated to contain hemagglutinating antibodies to this antigen. These experiments demonstrate that antigen capable of triggering specific IgE-mediated release of inflammatory mediators is present in cigarette smoke. It can be hypothesized that IgE-mediated responses to antigen in cigarette smoke are causally related to the development of vascular injury and of myocardial arrhythmia in hypersensitive smokers.

Animals↗
PubMed1979

Frequency of HLA-B8 in Israeli children with celiac disease.

The frequency of HLA-B8 in 18 Israeli children with celiac disease was examined and compared with that in 27 nonceliac children hospitalized at the time of the study. The diagnosis of celiac disease was made on the basis of an intestinal biopsy and a positive response to the lymphocyte inhibition factor (LIF) test, as well as a good response to withdrawal of gluten from the diet. HLA-B8 was found in 10 of the 18 celiac patients (56%). Of the 27 nonceliac children, three (11%) had HLA-B8. The LIF-positive celiac group had an HLA-B8 frequency five times greater than that in the nonceliac group, confirming our previous finding that the LIF test is a good diagnostic criterion for celiac disease. The combination of an intestinal biopsy, the LIF test and the presence of HLA-B8 could be a useful triad for diagnosis of celiac disease.

Celiac Disease↗
PubMed1978

IgE-mediated cardiac hypersensitivity reactions. An experimental model.

To investigate the involvement of the heart in acute allergic reactions in a system immunologically analogous to that of humans, a model of cardiac anaphylaxis mediated by IgE antibodies was developed in the guinea pig. Hearts obtained from guinea pigs, passively sensitized with homologous antidinitrophenyl IgE antibodies, were perfused and challenged in vitro with antigen. Challenge resulted in sinus and ventricular tachycardia, atrioventricular conduction block and substantial histamine release. The results demonstrate that IgE antibodies can sensitize the heart and that the severity of cardiac dysfunction, which follows challenge with specific antigen, directly correlates with the magnitude of histamine released. Since myocardial ischemia and similar arrhythmias occur during immediate hypersensitivity reactions in humans, this experimental model will be helpful in the investigation of cardiac involvement in acute allergic reactions.

Anaphylaxis↗
PubMed1978

Histamine-induced negative inotropism: mediation by H1-receptors.

Histamine is known to enhance left ventricular contractility in the guinea-pig heart by interacting with H2-receptors. We have observed that when the H2-receptor antagonists metiamide and cimetidine (3 X 10(-6) and 10(-5) M) block the positive inotropic effect of histamine, a negative inotropic effect is unmasked. This negative inotropic effect is independent of changes in rate or coronary flow, is mimicked by the selective histamine H1-receptor agonists, pyridylethylamine and thiazolylethylamine (0.3--30 microgram) and is abolished by the H1-receptor antagonist chlorpheniramine (10(-7) and 10(-6) M). Thus, the negative inotropic effect of histamine appears to be mediated by H1-receptors. Our results demonstrate that the inotropic response to histamine consists of two opposing components: an increase in contraction, mediated by H2-receptors, and a decrease in contraction, mediated by H1-receptors.

Animals↗
PubMed1977

Separation of primary and secondary cardiovascular events in systemic anaphylaxis.

The purpose of this investigation was to differentiate primary cardiac participation in systemic anaphylaxis from a cardiac reaction secondary to respiratory distress. Hemocyaninsensitized guinea pigs were anesthetized with sodium pentobarbital and artifically ventilated. The chest was opened and the left ventricle cannulated. The electrocardiogram, bronchial resistance, arterial blood pressure, and left ventricular pressure and its first derivative were recorded. Following intravenous administration of antigen, the sinus rate increased by about 50-60 beats/min, left ventricular dP/dt increased by a factor of 3, and mean arterial pressure doubled. Conduction disturbances occurred in all of the experiments and ventricular fibrillation in four of six. These changes were concomitant with a 4-fold rise in bronchial resistance. To separate the cardiac and respiratory components, antigen was administered directly into the left ventricle to expose the heart to antigen before the lungs. The intracardiac challenge resulted in increases in sinus rate and left ventricular and arterial pressure quantitatively similar to changes recorded from guinea pigs after the intravenous challenge. However, all these changes preceded the rise in bronchial resistance by 60 seconds. Arrhythmias occurred as frequently as with the intravenous challenge. Our findings show that by use of an appropriate route for administration of antigen, cardiovascular and respiratory components of systemic anaphylaxis can be separated. Our data also indicate that anaphylactic cardiovascular changes can be dissociated temporally into two sets of events: an initial primary cardiac reaction caused by intracardiac release of histamine and a subsequent cardiovascular reaction secondary to systemic release of mediator.

Airway Resistance↗
PubMed1976

Cardiac histamine receptors.

Current evidence pertinent to the identification of cardiac histamine receptors in the guinea pig is reviewed. Pharmacological characterization has been aided by the use of selective agonists and antagonists for both types of histamine receptors. It appears that both H1 and H2 receptors mediate the cardiac effects of histamine. Histamine H2 receptors mediate the positive chronotropic and ventricular inotropic effects. H1 receptors mediate the negative dromotropic effect of histamine and possibly the atrial inotropic effect. Histamine-induced arrhythmias involve H1 receptors (arrhythmias of conduction) or H2 receptors (arrhythmias of automaticity), or both. The receptors mediating the histamine-induced increase in coronary flow are not as clearly defined: both H1 and H2 receptors might be implicated.

Animals↗
PubMed1975

Pharmacological characterization of cardiac histamine receptors: sensitivity to H1-and H2-receptor agonists and antagonists.

In the isolated guinea pig heart, histamine H1-receptor antagonists inhibit the histamine-induced negative dromotropic effect, but not the positive inotropic and chronotropic effects (Levi and Kuye, 1974, European J. Pharmacol. 27, 330). Burimamide, the H2-receptor antagonist, inhibits the positive chronotropic effect of histamine (Black et al., 1972, Nature 236, 385). In this study, the hypothesis that H1- and H2-receptors selectively mediate the various cardiac effects of histamine was tested: (a) by investigating the inhibition of cardiac histamine effects by burimamide; (b) by studying the cardiac effects of 2-methylhistamine (an H1-agonist) and 4-methylhistamine (an H2-agonist). Burimamide, as a function of concentration, inhibited the positive inotropic and chronotropic effects of histamine, whereas it attenuated the negative dromotropic effect of histamine at the higher concentration only. 4-Methylhistamine caused dose-dependent positive inotropic and chronotropic but not negative dromotropic effects; conversely, with 2-methylhistamine the negative dromotropic effect prevailed. Sinus tachycardia and slowing of atrioventricular conduction were also obtained in the guinea pig in vivo by the i.v. administration of histamine. Burimamide selectively antagonized the positive chronotropic effect, whereas promethazine (an H1-antagonist) selectively inhibited the negative dromotropic effect. These results substantiate the hypothesis that H2-receptors mediate the histamine-induced increase in rate and contractility, whereas H1-receptors mediate the slowing of atrioventricular conduction.

Animals↗
PubMed1975

The influence of metiamide on ouabain cardiotoxicity.

The effect of metiamide on the cardiotoxicity produced by ouabain was studied in pentobarbital-anesthetized cats. The onset of ouabain-induced ventricular tachycardia and fibrillation was significantly delayed in cats treated with metiamide as compared with cats that did not receive metiamide. Although the mechanism by which metiamide inhibits ouabain toxicity is speculative, the data suggest that histamine H2-receptor blocking agents may be useful as anti-arrhythmic drugs in digitalis cardiotoxicity.

Animals↗
PubMed1975

Selective impairment of atrioventricular conduction by 2-(2-pyridyl)-ethylamine and 2-(2-thiazolyl)-ethylamine, two histamine H1-receptor agonists.

To further characterize the receptor mediating histamine-induced impairment of atrioventricular conduction, the effects of two selective histamine H1-receptor agonists, 2-(2-pyridyl)-ethylamine (PEA) and 2-(2-thiazolyl)-ethylamine (ThEA), were investigated using the isolated guinea pig heart. These effects were compared with those of histamine and other selective agonists. PEA and ThEA produced a weak stimulation of cardiac rate and contractility; however, they produced a marked prolongation of atrioventricular conduction. The orders of relative potencies observed substantiate the hypothesis that H2-receptors mediate the positive inotropic and chronotropic effects and H1-receptors mediate the negative dromotropic effect of histamine.

Animals↗