Biomaterial Database

In vivo assessment of the inotropic and toxic effects of oxidized ouabain. 1993

M Arad, and A Shotan, and M Heller, and B Rabinowitz, and G Uretzki

Heart Institute, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Israel.

Oxidized ouabain, a product of the oxidative cleavage of the rhamnose ring in ouabain has been found to have a higher inotropic toxic ratio in cultured cardiac myocytes. The purpose of our study was to evaluate the efficacy and toxicity of oxidized ouabain in comparison with ouabain in intact animals. Drugs were infused to healthy cats; the positive inotropic effect, and the time-course of development of arrhythmia were followed and recorded until death. Oxidized ouabain was associated with a higher increase in arterial blood pressure, a mean increase of 41 +/- 19% as compared with 21 +/- 8% in the ouabain group (p < 0.10). There were no significant differences in maximal increases of dP/dt or dP/dt/P (65 +/- 29%, 28 +/- 10% for oxidized ouabain and 49 +/- 16%, 27 +/- 11% for ouabain, respectively). The mean doses causing persistent arrhythmia (toxic dose) were 93 +/- 23 micrograms/kg of oxidized ouabain vs 39 +/- 14 micrograms/kg of ouabain. Lethal arrhythmias were produced by 215 +/- 46 micrograms/kg of oxidized ouabain and 62 +/- 16 micrograms/kg of ouabain. The ratio of toxic to lethal doses was 0.62 +/- 0.11 for ouabain vs 0.45 +/- 0.09 for oxidized ouabain (p < 0.05), but the inotropic to toxic dose ratios were not different. We conclude that oxidized ouabain acts similarly to the known cardiac glycosides in doses which produce inotropic effects in cats, has a lower potency as compared to ouabain, and appears to have a more benign course of intoxication.

UI	MeSH Term	Description	Entries
D009200	Myocardial Contraction	Contractile activity of the MYOCARDIUM.	Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D010042	Ouabain	A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.	Acocantherin,G-Strophanthin,Acolongifloroside K,G Strophanthin
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D001794	Blood Pressure	PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.	Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002415	Cats	The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)	Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006339	Heart Rate	The number of times the HEART VENTRICLES contract per unit of time, usually per minute.	Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001145	Arrhythmias, Cardiac	Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.	Arrhythmia,Arrythmia,Cardiac Arrhythmia,Cardiac Arrhythmias,Cardiac Dysrhythmia,Arrhythmia, Cardiac,Dysrhythmia, Cardiac