Effects of R 56865 and phenytoin on mechanical, biochemical, and morphologic changes during ouabain intoxication in isolated perfused rabbit heart
| Autor: | Thoné F, Vandeplassche L, Thies Peters, Frankow C, Tegtmeier F, Wilhelm D |
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| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment chemistry.chemical_element Digitalis Blood Pressure Oxidative phosphorylation Calcium In Vitro Techniques Creatine Ouabain Mitochondria Heart Ventricular Function Left chemistry.chemical_compound Adenosine Triphosphate Oxygen Consumption Piperidines Internal medicine medicine Animals Benzothiazoles Phosphorylation Antidote Chromatography High Pressure Liquid Pharmacology biology Myocardium Heart biology.organism_classification Calcium Channel Blockers Myocardial Contraction Thiazoles Endocrinology Ion homeostasis chemistry Phenytoin Toxicity Lactates Rabbits Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Journal of cardiovascular pharmacology. 20(3) |
| ISSN: | 0160-2446 |
| Popis: | The Na+/Ca2+ overload inhibitor R 56865 (N-[1-[4-(4-fluorophenoxy)-butyl]-4-piperidinyl)-N-methyl-2- benzothiazolamine) has been reported to prevent or attenuate ischemia- as well as ouabain-induced cellular sodium and calcium load. We investigated the potency of this compound in preventing mechanical, biochemical, and ultrastructural consequences of ouabain (OUA) intoxication in isolated rabbit heart. The protective effect of the digitalis antidote phenytoin (PHT) on the consequences of ouabain intoxication was examined for comparison. In isolated perfused rabbit heart, OUA (0.4 microM) caused an increase in left ventricular end-diastolic pressure (LVEDP) that was accompanied by depletion of high-energy phosphates (80% less than in control), accumulation of tissue lactate (12-fold) and damage of contractile elements and mitochondria. Accumulation of lactate was associated with a decrease in oxygen consumption by the isolated perfused heart. R 56865 (1.0 microM) and phenytoin (60 microM) prevented increase in LVEDP, breakdown of the energy-rich phosphates creatine phosphate (CrP) and ATP, accumulation of lactate, and morphologic changes induced by OUA. The above-mentioned toxic effects of OUA are interpreted as consequences of mitochondrial failure finally leading to breakdown of the oxidative phosphorylation. Thus, we conclude that the protective action of both compounds, R56865 and PHT, may be attributed to prevention or attenuation of mitochondrial failure due to OUA-induced disturbance of ion homeostasis. |
| Databáze: | OpenAIRE |
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