[Cardiac effects of vincamine].
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Biomedical subjects
Publications and source records attributed to O Strubelt.
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Plasma concentrations and renal excretion of 14,15-dihydro-14beta-hydroxy-(3alpha,16alpha)-eburnamenine-14-carbonic acid methylester (vincamine, Vincapront) were studied in 5 healthy volunteers following the oral intake of 30 or 60 mg vincamine, respectively. After the higher dose (60 mg vincamine), the treatment was continued by the daily intake of 3 X 20 mg vincamine for 5 days. Plasma vincamine levels were determined in the morning prior to the ingestion of the first 20-mg dose and in the evening 2 h after the intake of the third 20-mg dose. Our results prove that vincamine is rapidly liberated and absorbed from the tablet formulation used, the maximum plasma levels being reached 90 min after ingestion and amounting to a mean value of 139 ng/ml after 30 mg and to a mean of 252 ng/ml after 60 mg of vincamine. There was a biphasic elimination of vincamine after both doses indicating a process of distribution influencing also the elimination phase. In the 24-h urine, unchanged vincamine amounted to 5.8% of the applied dose after 30 mg and to 7.3% after 60 mg vincamine. Vincamine did not accumulate during the daily intake of 60 mg for 6 days. Side-effects were not observed in any volunteer during the period of observation.
Caffeine given in a dose of 400 mg one hour before 1 g/kg ethanol did not influence the course of blood alcohol levels in male volunteers. Furthermore, caffeine did not improve psychomotoric skills impaired by ethanol. Two cups of coffee ingested 30 min. after ethanol (0.5 g/kg) caused a statistically significant increase of blood ethanol levels one hour afterwards (from 0.49 to 0.61%). This may be due to an accelerated absorption of ethanol caused by the ingestion of warm fluid.
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Cardiac output of rats shows seasonal variations with low values in spring and summer and high ones in autumn and winter. The stroke volume was much more implicated in these changes than the heart rate. The seasonal changes of cardiac output are probably due to changes of thyroid function.
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Blood pressure, heart rate, oxygen uptake, and blood values of PO2, PCO2, and pH were studied in unanesthetized rats for 8 hours. After a cardiotoxic dose of 20 mg/kg isoprenaline, s.c., blood pressure fell from 117 to 72 mm Hg, heart rate accelerated from 326 to 497 beats/minute, and cardiac work diminished by about 15%. Metabolic rate increased by about 80%, blood values of PO2 rose, and those of PCO2 fell somewhat, whereas blood pH dropped from 7.48 to 7.38, indicating metabolic acidosis. Propranolol (40 mg/kg, i.p.) and verapamil (50 mg/kg, i.p.), both of which almost completely prevented isoprenaline-induced cardiac necroses, inhibited the chronotropic and calorigenic actions of isoprenaline by about 50%. While propranolol inhibited the depressor effect of isoprenaline completely, verapamil enhanced it: blood pressure fell to 46 mm Hg. Isoprenaline-induced fall of blood pH was not prevented by either propranolol or verapamil. Decrease of blood pH and cardionecrotisation were enhanced when isoprenaline was given together with 4.8 g/kg ethanol, p.o. In conclusion, hemodynamic actions of isoprenaline, especially hypotension, seem to be nonessential for the production of cardiac necroses. Strong acidification can aggravate the cardiotoxicity of isoprenaline.
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