Delayed treatment with nimodipine improves cerebral blood flow after complete cerebral ischemia in the dog.
Ten minutes of complete cerebral ischemia was produced in 18 dogs by temporary ligation of the aorta and venae cavae. Dogs were randomly assigned to one of three groups. A bolus dose of 10 micrograms kg-1 nimodipine, a dihydropyridine calcium entry blocker, followed by a constant infusion of 1 microgram kg-1 min-1 was given at 15, 30, or 60 min post ischemia. Cerebral blood flow and metabolism were measured for 2 h postischemia. Delayed treatment with nimodipine ameliorated or reversed the cerebral hypoperfusion that routinely occurs after complete ischemia. In the groups treated at 15 and 30 min, CBF remained above 60 ml min-1 100 g-1. In the group treated at 60 min, there was a progressive decline in CBF to 37 ml min-1 100 g-1. Following treatment with nimodipine, CBF immediately increased and was maintained above 50 ml min-1 100 g-1 for the remainder of the study. Once treatment with nimodipine was begun, CBF was approximately double that of an untreated group. Changes in CBF reflected changes in cerebrovascular resistance. Nimodipine had no effect on cerebral metabolism. Since the postischemic hypoperfusion state is believed to contribute to the ultimate neurologic damage following complete ischemia, treatment with nimodipine, even if delayed up to 60 min, may improve the outcome.
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001769:Blood; D001783:Blood Flow Velocity; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002121:Calcium Channel Blockers; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation; D004285:Dogs; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D009539:Nicotinic Acids / Q000627:therapeutic use*; D009553:Nimodipine; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D014655:Vascular Resistance
D000227:Adenine Nucleotides; D002121:Calcium Channel Blockers; D007773:Lactates; D009539:Nicotinic Acids; D011773:Pyruvates; D002245:Carbon Dioxide; D019344:Lactic Acid; D009553:Nimodipine; D019289:Pyruvic Acid; D005947:Glucose