RESUMEN
It was found that preliminary (before ischemia) administration of vitamin E in a dose of 200 mg/kg to albino rats causes the changes in energy support of the ischemic myocardium leading to prolonged maintenance of synthesis processes: energy production, cGMP concentration, unsaturation of cell membrane lipids increase. The combination of all these factors probably determines the anti-ischemic effect of vitamin E providing adequate restoration of the myocardial function in the postischemic period.
Asunto(s)
Enfermedad Coronaria/prevención & control , Metabolismo Energético/efectos de los fármacos , Corazón/efectos de los fármacos , Miocardio/metabolismo , Oxígeno/administración & dosificación , Vitamina E/uso terapéutico , Animales , Enfermedad Coronaria/metabolismo , Enfermedad Coronaria/patología , Evaluación Preclínica de Medicamentos , Técnicas In Vitro , Miocardio/patología , Perfusión , RatasAsunto(s)
Cardiomegalia/metabolismo , Enfermedad Coronaria/metabolismo , Paro Cardíaco Inducido , Potenciales de Acción , Animales , Regulación de la Temperatura Corporal , Metabolismo Energético , Masculino , Potenciales de la Membrana , Miocardio/metabolismo , Consumo de Oxígeno , Perfusión/métodos , RatasRESUMEN
An experimental study in 307 isolated rat hearts was concerned with variations in myocardial resting tension, resting membrane potential, ATP levels and myocardial heat production in conditions of cardioplegic heart arrest by an ion-balanced cardioplegic solution with and without phosphorylated metabolites (ATP, phosphocreatine, inosine-F, glucose-6-phosphate) and dephosphorylated metabolites (glucose, inosine, and inorganic phosphates). Phosphorylated metabolites, incorporated in the solution, had a marked protective effect due to the activation of substrate regulation mechanisms at different stages of ATP synthesis and facilitation of cardiomyocyte adaptation to ischemic, hypothermic and cardioplegic exposure.
Asunto(s)
Adenosina Trifosfato/farmacología , Soluciones Cardiopléjicas/farmacología , Enfermedad Coronaria/prevención & control , Paro Cardíaco Inducido , Fosfocreatina/farmacología , Animales , Sinergismo Farmacológico , Técnicas In Vitro , Masculino , RatasRESUMEN
The energy mechanisms of formation of anti-ischemic myocardial resistance have been studied by means of vitamin E, administered to rats 24 hours before modelling ischemia in a dose of 200 mg/kg, in which the antioxidant activity of the preparation is pronounced. At the stage of ischemia, myocardial energy was studied by the differential calorimetry method, in the pre- and postischemic periods on a functioning heart in a stand according to Neely. It is shown, that vitamin E in ischemic and postischemic periods enhances the power and efficiency of myocardial energy consumptions: decreases irrational energy consumptions in the initial period of ischemia (the first 15 minutes) and supports a higher level of energy production further on, increasing thus the admissible periods of myocardial ischemia from 20-25 to 30-35 minutes, maintains in the postischemic period a higher level of total useful energy consumptions and coefficients of the oxygen utilization efficiency as compared with the experiments without preliminary administration of vitamin E. It is shown, that the anti-ischemic defence of the myocardium by vitamin E is formed already in the preischemic period and conditioned by redistribution of energy consumptions and growth of the share of energy consumptions aimed at the maintenance of the initial structural-functional homeostasis of myocardial cells.
Asunto(s)
Enfermedad Coronaria/tratamiento farmacológico , Metabolismo Energético/efectos de los fármacos , Corazón/efectos de los fármacos , Miocardio/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Vitamina E/farmacología , Animales , Calcio/metabolismo , Rastreo Diferencial de Calorimetría , Permeabilidad de la Membrana Celular/efectos de los fármacos , Enfermedad Coronaria/metabolismo , Evaluación Preclínica de Medicamentos , L-Lactato Deshidrogenasa/metabolismo , Masculino , Ratas , Factores de TiempoRESUMEN
Differential calorimetry is suggested for quantitative estimation of antiischemic activity of the drugs by determining total energy losses, the critical level of energy losses and permissible times of ischemia of isolated organs. The method allows the unraveling of the mechanisms by which antiischemic resistance of cells and organs is formed with pharmacological means.
Asunto(s)
Rastreo Diferencial de Calorimetría/métodos , Calorimetría/métodos , Fármacos Cardiovasculares/análisis , Metabolismo Energético/efectos de los fármacos , Isquemia/tratamiento farmacológico , Vitamina E/análisis , Animales , Fármacos Cardiovasculares/uso terapéutico , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/metabolismo , Isquemia/metabolismo , Cinética , Masculino , Miocardio/metabolismo , Ratas , Vitamina E/uso terapéuticoRESUMEN
The kinetics of the free fatty acids accumulation in membranes of isolated mitochondria of the brain, heart and liver of rats, with their incubation in a medium containing no substrates and ATP, was studied. The intensity of the phospholipase damage, measured by the rate of free fatty acids accumulation, augments in the sequence of: the liver-heart-brain. The amassment of fatty acids in the mitochondrial membranes is shown to give place to their penetration into the inner space of the mitochondria. A relationship between the content of the intramitochondrial calcium and the concentration of free fatty acids in in the membranes, on the one hand, and the degree of passive swelling of the cardiac mitochondria, on the other, was revealed. It is suggested that the free fatty acids or their derivatives act as carriers of calcium to the mitochondrial membrane. A preliminary administration to rats of the vitamin E and sodium selenite protects the mitochondria of the heart against the phospholipase damage. These agents display a synergic action and are effective with administration of physiological doses. It is presumed that the protective action of these substances is due to the stabilization of biological membranes.