almitrine--raubasine-drug-combination and Disease-Models--Animal

Topics: Almitrine; Animals; Brain Ischemia; Cats; Cerebral Arteries; Disease Models, Animal; Dogs; Drug Combinations; Gerbillinae; Humans; Piperazines; Rabbits; Rats; Yohimbine

The effects of ischaemia on nervous tissue and cerebral capillary vessel ultrastructure and their prevention by Duxil were studied in rabbits. Ischaemia induced by bilateral occlusion of the carotid arteries induced minor changes in the endothelium of some capillary vessels: irregularities in the luminal surface with subsequent increase in the number of caveolae, increase in the number and size of membrane microvillosities and bullae, and retraction of the nuclei. Ischaemia acted mainly on astrocyte processes and perikarion which became shollen with altered mitochondria and complete absence of glycogen. The neurons remained normal but seemed to contain slightly more lysosomes. After administration of Duxil 10 min before ischaemia was induced, there were no endothelial changes; the astrocytes were less swollen and above all, their glycogen content was preserved; there seemed to be less lysosomes in the neurons. The effects of Duxil on cell oxygenation and oxidative metabolism may account for its protective action on endothelial, glial and neural cells.

Topics: Acute Disease; Almitrine; Animals; Brain Ischemia; Disease Models, Animal; Drug Combinations; Microscopy, Electron; Piperazines; Rabbits; Telencephalon; Time Factors; Yohimbine

Duxil is a combination of almitrine and raubasine. Almitrine produces an increase of PaO2 in arterial blood, and this beneficial effect on hypoxemia is potentiated by that of raubasine on microcirculation. Pharmacological studies of Duxil in healthy animals and experimental models have demonstrated that the drug increases arterial oxygen supply, improves tissue oxygenation and is capable of correcting vascular and metabolic disorders due to hypoxia. After administration of Duxil to animals whose brain has been severely deprived of oxygen by experimental anoxia or ischaemia, the oxygen supply is sufficient for the brain cells to take up their preferential substrate (glucose) and to use it through the most energy-producing aerobic pathway. Thus, the energy stores (ATP or glycogen) of these cells are spared and above all, their structural integrity is preserved. Their functional activity may be maintained, and this would justify the use of Duxil in mental and behavioural disorders of cerebral senescence and cerebro-vascular diseases related to hypoxia.

Topics: Aging; Almitrine; Animals; Cerebrovascular Circulation; Cerebrovascular Disorders; Disease Models, Animal; Dogs; Drug Combinations; Glucose; Humans; Hypoxia, Brain; Neurons; Oxygen Consumption; Piperazines; Rabbits; Rats; Yohimbine

Unilateral ligation of the common carotid artery of gerbils results in cerebral edema and ipsilateral hemiparesia ending in death. The clinical symptoms of this experimental ischaemia can be quantified. Comparison of untreated gerbils and gerbils treated with Duxil showed that the drug reduces the neuropathological symptoms and cerebral edema induced by ischaemia and improves the vital prognosis in these animals.

Topics: Almitrine; Animals; Brain Ischemia; Disease Models, Animal; Drug Combinations; Gerbillinae; Piperazines; Time Factors; Yohimbine

The effects of ischaemia on the arterial wall were studied in fragments of common carotid artery taken downstream from the occlusion. They consisted of intracytoplasmic or intrajunctional lacunae, vacuoles, craters, detachment or disruption of cell membranes with formation of blebs or bullae, retraction of numerous nuclei, swelling of the ergastoplasm and perhaps increase in pinocytosis. The administration of Duxil, a corrector of metabolism, 10 min prior to inducing ischaemia resulted in considerable reduction of these lesions as compared to untreated animals.

Topics: Acute Disease; Almitrine; Animals; Brain Ischemia; Carotid Arteries; Disease Models, Animal; Drug Combinations; Endothelium; Microscopy, Electron; Piperazines; Rabbits; Yohimbine