RESUMO
The experiments on Wistar rats and chinchilla rabbits showed that EDIHYP (5 mg/kg intravenously) completely prevented cardiac fibrillation and mortality in rats with calcium-chloride-induced arrhythmias, (CaCl2-200 mg/kg intravenously). Administration of atropine (0.1 mg/kg, if administered subcutaneously, 30 minutes before the acute experiment) exerts no influence on the drug's antiarrhythmic activity but eliminates its cholinergic component--salivation and lacrimation. When administered in the same dose EDIHYP to a great extent prevents oubaine (strophanthin)-induced arrhythmias in rabbits but fails to influence aconitine-induced arrhythmias. This suggests that EDIHYP's ability of direct or indirect blockade of slow Ca-channels underlies the mechanism of its antiarrhythmic action.
Assuntos
Arritmias Cardíacas/tratamento farmacológico , Dimetilidrazinas/uso terapêutico , Modelos Animais de Doenças , Propionatos/uso terapêutico , Animais , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Cloreto de Cálcio , Avaliação Pré-Clínica de Medicamentos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Coelhos , Ratos , Ratos Endogâmicos , EstrofantinasRESUMO
The effects of carnitine and its structural analogue 3-(2,2,2-trimethylhydrazine) propionate (THP) were studied in rats with experimental myocardial infarction caused by occlusion of the left descending branch of the coronary artery. After one day in the group of untreated animals the relative lethality was 40.3 +/- 10.5%, the size of the infarction zone was 29.8 +/- 2.0%. Carnitine and THP decreased on the average twice the parameters as well as lactate level in the myocardium. THP prevented a reduction of ATP and AMP levels by 35 and 37%, respectively, and a decrease of adenine nucleotide pool by 30%. In this case carnitine was ineffective. It is suggested that inhibition of beta-oxidation of fatty acids by THP is energetically more beneficial for the myocardium during regional ischemia than substitution therapy with carnitine.
Assuntos
Fármacos Cardiovasculares/uso terapêutico , Carnitina/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Metabolismo Energético/efeitos dos fármacos , Coração/efeitos dos fármacos , Metilidrazinas/uso terapêutico , Animais , Fármacos Cardiovasculares/farmacologia , Carnitina/farmacologia , Doença das Coronárias/metabolismo , Doença das Coronárias/mortalidade , Avaliação Pré-Clínica de Medicamentos , Masculino , Metilidrazinas/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/mortalidade , Miocárdio/metabolismo , RatosRESUMO
The action of membranotropic preparations--mildronat and phosphaden on the course of a severe burn process of the cornea with changes in lysosomal membranes revealed in pathogenesis has been studied in 80 rabbits. As a marking lysosomal enzyme, acid phosphatase was used. Besides this, peculiarities of the clinical course of the burn process have been studied, when treated by common methods and in a complex with the mentioned preparations. The results of the study have shown expressed stabilizing action of the preparations on lysosomal membranes of the cornea in early terms of the treatment, correlative relationship between results of biochemical investigations and clinical manifestations of the action of membranotropic preparations, high effectiveness of therapeutic action of mildronat as compared with phosphaden. The results obtained can serve as a foundation for the usage of the preparations in complex treatment of patients with severe chemical burns of the eye.
Assuntos
Monofosfato de Adenosina/uso terapêutico , Queimaduras Químicas/tratamento farmacológico , Queimaduras Oculares/tratamento farmacológico , Lisossomos/efeitos dos fármacos , Metilidrazinas/uso terapêutico , Doença Aguda , Animais , Queimaduras Químicas/enzimologia , Queimaduras Químicas/etiologia , Cáusticos , Córnea/efeitos dos fármacos , Córnea/enzimologia , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Queimaduras Oculares/induzido quimicamente , Queimaduras Oculares/enzimologia , Lisossomos/enzimologia , Coelhos , Fatores de TempoRESUMO
A structural analogue of gamma-butyrobetaine 3-(2,2,2-trimethylhydrazine)propionate (THP) administered orally in doses of 50 and 150 mg/kg for 10 days prevented isoproterenol-induced increase of the activity of the hepatic isoform of lactate dehydrogenase in the rat blood serum and in a dose of 150 mg/kg prevented an increase of creatine phosphokinase activity. Against a background of the course administration of THP isoproterenol failed to cause the accumulation of acyl-insoluble acylcarnitine in the myocardium. In this case a dose-dependent decrease of free carnitine concentration and accumulation of fatty acids in the myocardium were noted. The cardioprotective effect of THP manifested itself in prevention of a decrease of ATP and ADP concentrations, accumulation of AMP and a reduction of energy charge under the influence of isoproterenol. The ability of THP to decrease the intracellular concentration of free carnitine and to depress as a result carnitine-dependent oxidation of free fatty acids may underlie the anti-ischemic effect of THP.