RESUMEN
The effect of the antioxidant mexidol and two new derivatives of 3-oxypyridine, namely LBK-10 and LBK-39 on the circulation of blood and metabolism of the brain in the postischemic period was studied in acute experiments on narcotized cats under conditions of autohemoperfusion of the cerebral vessels with a stable volume of blood. Therapeutic injection of mexidol and LBK in a dose of 20 mg/kg inhibited the development of the no-flow phenomenon and restored the ischemia damaged metabolism in the brain tissues. LBK-10 reduced the lactate content in the blood flowing from the brain and contributed to constriction of the cerebral vessels.
Asunto(s)
Antioxidantes/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Picolinas/uso terapéutico , Piridinas/uso terapéutico , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatología , Gatos , Circulación Cerebrovascular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Femenino , Masculino , Factores de TiempoRESUMEN
Acute experiments were conducted on rats under nembutal anesthesia to compare the efficacy of emoxipin with that of lithium oxybutyrate and picamilon in the postischemic period after preventive and therapeutic injections in various doses. Emoxipin proved to be most effective in prevention of postischemic non-restoration of the flow of blood in the brain and in preservation of the autoregulation responses of the cerebral vessels. The possible mechanisms of the effect of the drug are discussed.
Asunto(s)
Antioxidantes/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Circulación Cerebrovascular/efectos de los fármacos , Hidroxibutiratos/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Picolinas/uso terapéutico , Ácido gamma-Aminobutírico/análogos & derivados , Enfermedad Aguda , Animales , Antioxidantes/farmacología , Isquemia Encefálica/fisiopatología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Homeostasis/efectos de los fármacos , Hidroxibutiratos/farmacología , Compuestos Organometálicos/farmacología , Picolinas/farmacología , Ratas , Ácido gamma-Aminobutírico/farmacología , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
Acute experiments on nembutal anesthetized rats showed improvement of cerebral blood flow autoregulation in the postischemic period under the effect of mexidol and the new 3-hydroxypyridine (3-HOP) derivatives LBK-10 and LBK-38 administered for prophylactic and therapeutic, purposes. The role of dopaminergic activity, solubility in lipids, and other factors in the mechanism of the activity of 3-HOP derivatives is analysed.
Asunto(s)
Antioxidantes/farmacología , Isquemia Encefálica/tratamiento farmacológico , Arterias Cerebrales/efectos de los fármacos , Homeostasis/efectos de los fármacos , Picolinas/farmacología , Piridinas/farmacología , Animales , Antioxidantes/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Isquemia Encefálica/fisiopatología , Arterias Cerebrales/fisiopatología , Venas Cerebrales/efectos de los fármacos , Venas Cerebrales/fisiopatología , Circulación Cerebrovascular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Picolinas/administración & dosificación , Piridinas/administración & dosificación , RatasRESUMEN
The effect of animal cytochrome C (Ca), biotechnological cytochrome (Cb) and its hemtetradecapeptide (HTDP) on cerebral blood flow autoregulation during rapid decrease of systemic arterial pressure (SAP) was studied in acute experiments on rats. Cytochrome C preparations caused no effect on the autoregulatory responses of the cerebral vessels in animals with normal cerebral circulation. Injection of 5 mg/kg Ca and Cb and 0.8 mg/kg HTDP promoted restoration of the phenomenon of cerebral blood flow autoregulation in ischemic brain damage in change of SAP from 120 to 60 mm Hg. Prophylactic injection of 20 mg/kg Ca and Cb and 3.3 mg/kg HTDP prevented cerebral blood flow autoregulation disturbance caused by transitory brain ischemia.
Asunto(s)
Isquemia Encefálica/fisiopatología , Circulación Cerebrovascular/efectos de los fármacos , Grupo Citocromo c/farmacología , Citocromos c , Homeostasis/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Enfermedad Aguda , Animales , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/prevención & control , Grupo Citocromo c/uso terapéutico , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Hemorragia/fisiopatología , Hipotensión/fisiopatología , Fragmentos de Péptidos/uso terapéutico , Ratas , Factores de TiempoRESUMEN
In acute experiments on anesthetized cats with cerebral ischemia in conditions of autohemoperfusion of cerebral and peripheral vessels with a stable volume of blood we found that lithium oxybutirate and new GABA derivatives: LOS 1-84 and LOS 5-79 affect the cerebral blood flow and metabolism in the brain. Prophylactic intravenous injection of lithium oxybutirate did not affect the development of postischemic hyperperfusion but inhibited postischemic hyperperfusion. The compounds prevent the development of postischemic phenomena and promote the recovery of metabolism in the brain.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Circulación Cerebrovascular/efectos de los fármacos , Hidroxibutiratos/farmacología , Compuestos de Litio/farmacología , Litio/farmacología , Compuestos Organometálicos/farmacología , Ácido gamma-Aminobutírico/farmacología , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatología , Gatos , Evaluación Preclínica de Medicamentos , Femenino , Hidroxibutiratos/uso terapéutico , Litio/uso terapéutico , Compuestos de Litio/uso terapéutico , Masculino , Compuestos Organometálicos/uso terapéutico , Factores de Tiempo , Ácido gamma-Aminobutírico/análogos & derivados , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
Biotechnological cytochrome c, heme-tetradecapeptide (HTDP) and animal cytochrome c were studied for their effects on intact and brain ischemic rats. In the latter case, the compounds were administered before ischemia induction and 15 min after artery ligation. It was found that the cytochrome c preparations did not virtually affect the cerebral circulation in intact rats. In cerebral ischemia, the cytochrome C preparations increased circulation, showing their more profound effects in case of preadministration of the drugs. The dose-independent effects of HTDP may be associated with the higher transmembranous permeability and the saturation phenomenon of this compound.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Circulación Cerebrovascular/efectos de los fármacos , Grupo Citocromo c/farmacología , Animales , Isquemia Encefálica/fisiopatología , Gatos , Grupo Citocromo c/uso terapéutico , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Femenino , Masculino , Ratas , Factores de TiempoRESUMEN
The inhibitor of angiotensin-converting enzyme captopril does not change the tone of the brain vessels but decreases the blood pressure and the tone of peripheral vessels, increases the oxygen and glucose demand in the brain in intact cats. In animals with brain ischemia, captopril decreased the tone of the brain vessels and promoted normalising of metabolic and transcapillary exchange in the brain.
Asunto(s)
Captopril/farmacología , Circulación Cerebrovascular/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Capilares/efectos de los fármacos , Capilares/metabolismo , Captopril/uso terapéutico , Gatos , Evaluación Preclínica de Medicamentos , Glucosa/metabolismo , Ataque Isquémico Transitorio/tratamiento farmacológico , Ataque Isquémico Transitorio/fisiopatología , Consumo de Oxígeno/efectos de los fármacos , Resistencia Vascular/efectos de los fármacosRESUMEN
In acute experiments on anesthetized cats under blood autoperfusion of cerebral and peripheral vessels with a stable volume of blood during cerebral ischemia there was revealed the vascular and metabolic effects of dopamine on cerebral circulation. Administration of dopamine by perfusion in a dose of 100 micrograms/kg/min for 35 min after ischemia inhibited the development of postischemic hypoperfusion of the brain and also eliminated postischemic hypotension. A significant effect of dopamine on oxidative metabolism of the brain was observed.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Dopamina/uso terapéutico , Animales , Encéfalo/metabolismo , Isquemia Encefálica/fisiopatología , Gatos , Evaluación Preclínica de Medicamentos , Femenino , Glucosa/metabolismo , Concentración de Iones de Hidrógeno , Masculino , Oxígeno/sangre , Consumo de Oxígeno , Perfusión/métodos , Factores de TiempoRESUMEN
Intravenous administration of komplamin to anesthetized cats before the brain ischemia or in the early period following ischemia prevents the development of the postischemic phenomenon of the cerebral blood flow nonrecovery and beneficially influences the cerebral metabolism: restores oxygen and glucose consumption by the brain, decreases pyruvic acid level in the arterial and venous blood, attenuates the phenomenon of acidosis. Nikoshpan improves the blood supply to the brain, restores oxygen and glucose consumption by the brain in the postischemic period only if administered before the brain ischemia.
Asunto(s)
Encéfalo/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Ataque Isquémico Transitorio/tratamiento farmacológico , Niacina/uso terapéutico , Ácidos Nicotínicos/uso terapéutico , Papaverina/análogos & derivados , Teofilina/análogos & derivados , Vasodilatadores/uso terapéutico , Niacinato de Xantinol/uso terapéutico , Animales , Encéfalo/metabolismo , Gatos , Combinación de Medicamentos/uso terapéutico , Evaluación Preclínica de Medicamentos , Femenino , Miembro Posterior/irrigación sanguínea , Isquemia/tratamiento farmacológico , Isquemia/fisiopatología , Ataque Isquémico Transitorio/fisiopatología , Masculino , Papaverina/uso terapéutico , Factores de TiempoRESUMEN
In acute experiments on anesthetized cats with total ischemia of the brain (15-minute arrest of blood autoperfusion of the cerebral vessels by a stable blood volume) it was shown that euphylline and no-shpa administered before ischemia or in the early period after ischemia inhibit or prevent the development of the postischemic phenomenon of non-recovery of the cerebral blood flow. The two drugs contributed to survival of albino rats following the brain ischemia produced by ligation of both carotid arteries.
Asunto(s)
Aminofilina/uso terapéutico , Circulación Cerebrovascular/efectos de los fármacos , Ataque Isquémico Transitorio/tratamiento farmacológico , Papaverina/análogos & derivados , Parasimpatolíticos/uso terapéutico , Resistencia Vascular/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Gatos , Evaluación Preclínica de Medicamentos , Femenino , Ataque Isquémico Transitorio/mortalidad , Ataque Isquémico Transitorio/fisiopatología , Masculino , Papaverina/uso terapéutico , RatasRESUMEN
The application of longitudinal gravitational overloads in white rats in craniocaudal and caudo-cranial directions modelled on a centrifuge is suggested for the screening of bioactive agents. The time and value of the overload are selected in such a way, as to kill 50% of animals in the control experiments. The same overload is given to animals that have previously received the tested agents. The difference in the survival rate of these animals and the control ones serves as the indicator of activity of the new compounds. This method reflects mainly the functional stability of the system of cerebral circulation.