Effects of drugs on the cerebral circulation of the dog in relation to the cerebral oxygen consumption.
Drug effects were studied on the cerebral circulation by measuring the sagittal sinus outflow in the anaesthetized dog following the method of Michenfelder and by monitoring cerebral oxygen consumption. Systemic aortic pressure, heart rate and spinal fluid pressure were also studied. Since dilatation of cerebral vessels was observed in nearly all the preparations after inhalation of CO2, it was thought that gross extracerebral contamination was virtually eliminated in this preparation. A close correlation was observed between the oxygen consumption of the brain as a whole and the sagittal sinus outflow (r = 0.93, P less than 0.001); therefore it became feasible to differentiate the direct effects of drugs on cerebral blood vessels from indirect ones attributable to changes in the cerebral oxidative metabolism. Sodium pentobarbitone (5 mg kg-1, i.v.), reduced the cerebral venous outflow and caused a decrease in the oxygen consumption. Pentylenetetrazol (30 mg kg-1 i.v.) and bemegride (5 mg kg-1 i.v.) produced an increase in the blood flow and a corresponding increase in the cerebral oxygen consumption. Thus, it was concluded these substances had no direct effects on the cerebral blood vessels. Acetazolamide (10 mg kg-1, i.v.), a carbonic anhydrase inhibitor, produced a marked and sustained vasodilatation after a latent period of 0.5-1 min. There was no increase in the cerebral oxygen consumption. A similar pattern was seen after CO2 had been inhaled. Methylergometrine and dihydroergotamine (20 micrograms kg-1 i.v.) induced a prolonged vasoconstriction of the cerebral vascular bed without any changes in the oxygen consumption of the brain. Therefore this method can discriminate between indirect or direct effects of drugs on cerebral vascular outflow.
D000086:Acetazolamide / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001534:Bemegride / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002245:Carbon Dioxide / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004285:Dogs; D004876:Ergot Alkaloids / Q000494:pharmacology; D005260:Female; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D010424:Pentobarbital / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology
D004876:Ergot Alkaloids; D002245:Carbon Dioxide; D001534:Bemegride; D005996:Nitroglycerin; D010424:Pentobarbital; D000241:Adenosine; D000086:Acetazolamide; D010433:Pentylenetetrazole