RESUMO
The pathophysiology and histopathology caused by feeding rabbits a diet containing 2% cholesterol is described. Cholesterol deposition was seen in almost all organs after 15 weeks on the diet. Lesions were seen as early as 7 weeks in the aorta and pulmonary vessels and by 11 weeks in the small intramyocardial arteries and arterioles. Evidence of myocardial ischemia could be elicited by stressing the heart by electrical pacing at rapid rates or by administration of pharmacological agents which increased oxygen consumption (isoproterenol) or decreased oxygen supply (ergonovine). Susceptibility to such stress was increased by isovolumic hemodilution which decreased the oxygen-carrying capacity of the blood. Myocardial fibrosis and infarction were evident by 15 weeks on the diet and cardiac reserve was depleted by 25 weeks as evidenced by the presence of ascites in all animals examined. The preliminary results reported here suggest that further evaluation of the atherosclerotic rabbit as a cardiac toxicity model is warranted.
Assuntos
Arteriosclerose/fisiopatologia , Animais , Arteriosclerose/complicações , Arteriosclerose/patologia , Estimulação Cardíaca Artificial , Sistema Cardiovascular/patologia , Colesterol na Dieta , Doença das Coronárias/etiologia , Eletrocardiografia , Frequência Cardíaca/efeitos dos fármacos , Isoproterenol/farmacologia , Rim/patologia , Fígado/patologia , Masculino , Coelhos , Fatores de TempoAssuntos
Antagonistas Adrenérgicos beta/toxicidade , Propanolaminas/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Carcinógenos , Cricetinae , Cães , Feminino , Teste de Tolerância a Glucose , Haplorrinos , Macaca mulatta , Masculino , Mesocricetus , Camundongos , Gravidez , Coelhos , Ratos , Reprodução/efeitos dos fármacos , Especificidade da Espécie , Teratogênicos , Fatores de TempoRESUMO
In acute and subacute toxicological studies, amphotericin B methyl ester was shown to be much less toxic than the parent antibiotic. As a single intravenous dose in mice, the methyl ester was approximately 20 times less toxic than amphotericin B. Also, the acute toxicity of the methyl ester in mice was not enhanced by the presence of chemically induced hepatic or renal damage or by the concurrent administration of amphotericin B or flucytosine. In a 1-month intraperitoneal study in rats, the methyl ester was about one-fourth as nephrotoxic as amphotericin B. In a 1-month intravenous study in dogs, the methyl ester was about one-eighth as nephrotoxic and one-fourth to one-half as hepatotoxic as the parent compound. In addition, the methyl ester, unlike amphotericin B, produced minimal renal effects, which did not increase in severity with increasing dosage. Based on the results of these studies, it is concluded that amphotericin B methyl ester has the potential for an improved therapeutic ratio in the treatment of systemic mycoses.
