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A Riedel

Publications and source records attributed to A Riedel.

58 records · Page 4Linked to original sources

Effect of BN 52256 and other mediator antagonists on ouabain-induced cardiac arrhythmia in a model of anaphylaxis in guinea-pigs.

Different mediators released by anaphylaxis seem to be involved in different pathophysiological conditions, including cardiac arrhythmia. Histamine, 5-HT and platelet-activating factor (PAF) could participate in the enhanced arrhythmogenicity during anaphylaxis in guinea-pigs. The threshold dose of ouabain-induced arrhythmia is decreased in actively sensitized guinea-pigs by i.p. administration of ovalbumin. The purpose of the present paper was to investigate the effect of different mediator antagonists. Antagonists of PAF (WEB 2170), histamine (clemastine) and 5-HT (cyproheptadine) in doses of 5.0 mg/kg, 5.0 mg/kg and 0.5 mg/kg, respectively, can increase the threshold dose of ouabain-induced arrhythmias signalling an antiarrhythmic effect. A combination of WEB 2170 and clemastine, each of them in inactive doses (2.0 mg/kg and 1.0 mg/kg, respectively) showed a statistically significant antiarrhythmic effect. A combination of the same dose of WEB 2170 and cyproheptadine (0.1 mg/kg) under the same conditions induced an antiarrhythmic effect, too. BN 52256 is a new antiallergic drug synthesized on the basis of a novel concept of combining inhibitory activity against various inflammatory mediators in one molecule. BN 52256 in doses of 20-80 micrograms/kg exhibited a statistically significant antiarrhythmic effect. BN 52256 needed a 12.5-125 fold lower dose to induce the same antiarrhythmic effect compared to the antagonists of PAF, histamine or 5-HT investigated in this study. Depending on the pathophysiological conditions, different mediators seem to be involved in the occurrence of cardiac arrhythmia. A complex inhibition of these mediators could induce a more specific influence on such kinds of cardiac arrhythmias.

Anaphylaxis↗

The trapidil derivative AR 12456 protects against serum hyperlipidemia in guinea pigs.

The administration of the trapidil derivative AR 12465 (5 mg/kg body weight) intraperitoneally to hypercholesterolemic guinea pigs caused a stronger reduction in serum total cholesterol (TC) than trapidil (20 mg/kg, i.p.) or a vehicle injection (saline with 5% ethanol i.p.). The stronger reduction of TC is caused by a lower level in the sum of all beta-migrating lipoproteins and an enhanced level of high-density lipoprotein. The levels of free and esterified cholesterol were not changed in kidney and left cardiac ventricle, but significantly enhanced (P less than 0.05) in the liver of all groups fed a cholesterol-rich diet. The elevation in liver cholesterol was higher in the group treated with AR 12456 than in the group treated with trapidil or with vehicle. The treatment with AR 12456 diminished the ratio TXB2/6-keto-PGF1 alpha for the capacity of aorta to form these prostanoids. In conclusion, our data show that AR 12456 has a strong antilipidemic action in guinea pigs fed a cholesterol-rich diet.

3',5'-Cyclic-AMP Phosphodiesterases↗

Antagonists of PAF and histamine inhibit ouabain-induced cardiac arrhythmias in sensitized guinea-pigs.

Platelet-activating factor (PAF) seems to be involved in different pathophysiological conditions, including cardiac arrhythmia. The arrhythmogenic potency of PAF has been shown experimentally by different methods. PAF antagonists inhibit the PAF-induced enhanced arrhythmogenicity. The present paper demonstrates that the threshold dose of ouabain-induced arrhythmia is decreased in sensitized guinea-pigs. Antagonists of PAF (BN 52021, WEB 2086, WEB 2170) and histamine antagonist clemastine can increase the threshold dose of ouabain-induced arrhythmia. A combination of WEB 2170 and clemastine, each of the drug is a low dose which is without effect when applying one of them only, shows a highly significant antiarrhythmic effect in this method. The threshold dose of ouabain necessary to induce ventricular flutter was increased from 89 micrograms/kg to 129 micrograms/kg and the threshold dose of ventricular fibrillation was enhanced from 101 micrograms/kg to 137 micrograms/kg. In dependence on the pathophysiological conditions, different mediators seem to be involved in the occurrence of cardiac arrhythmia. Therapeutically influencing these mediators could be a real chance to optimise the treatment of such kind of cardiac arrhythmias.

Anaphylaxis↗

Local effects of PAF in guinea-pig inner ear.

The effect of PAF-containing artificial perilymph at 10(-7) and 10(-8) M on the endocochlear potential (EP) was investigated in guinea-pigs. The inner ear was perfused and the EP recorded at the same time. The characteristic decline of the EP which is highly sensitive to all stimuli could be prevented by pretreating the animals with either ginkgolide B (BN 52,021) or BM 13,177 (Sulotraban). Less effective in preventing the EP decline was Daltroban (BM 13,505). The results are discussed with respect to an involvement of PAF in cochlear physiology and in the regulation of ion transport, respectively.

Animals↗