The effects of aprotinin on outcome from cerebral ischemia in the rat.
The administration of aprotinin has been associated with a reduction in cardiac surgery-related stroke. Intrinsic neuroprotective properties of this drug have not been evaluated in laboratory outcome models of cerebral ischemia. The purpose of this study was to determine whether aprotinin exhibits neuroprotective effects against either global or focal cerebral ischemia in the rat. Fasted rats were administered aprotinin (30,000 or 60,000 KIU/kg) or vehicle (0.9% NaCl) IV before global ischemia (10 min bilateral carotid occlusion with mean arterial pressure 30 mm Hg) or focal ischemia (75 min of transient middle cerebral artery occlusion [MCAO]). Five days after global ischemia, the percentage of dead hippocampal CA1 neurons (mean +/- SD) was similar among the groups (small-dose aprotinin: 49+/-31, n = 15; large-dose aprotinin: 55+/-31, n = 13; vehicle: 47+/-31, n = 16; P = 0.74). After 7 days' recovery from MCAO, no difference among the groups was observed for either neurologic score (P = 0.99) or cerebral infarct volume (small-dose aprotinin: 136+/-80 mm3, n = 23; large-dose aprotinin: 132+/-101 mm3, n = 11; vehicle: 121+/-81 mm3, n = 21; P = 0.87).


CONCLUSIONS
Aprotinin offers no neuroprotection against either global or focal cerebral ischemia in the rat when administered as a single preischemic bolus.
Grocott
H P
HP
Neuroanesthesia Research Laboratory, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA. h.grocott@duke.edu
Sheng
H
H
Miura
Y
Y
Sarraf-Yazdi
S
S
Mackensen
G B
GB
Pearlstein
R D
RD
Warner
D S
DS
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000188:drug therapy; D016923:Cell Death / Q000187:drug effects; D002544:Cerebral Infarction / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D015842:Serine Proteinase Inhibitors; D007611:Aprotinin