The effects of aprotinin on outcome from cerebral ischemia in the rat

The administration of aprotinin has been associated with a reduction in car diac surgery-related stroke. Intrinsic neuroprotective properties of this d rug have not been evaluated in laboratory outcome models of cerebral ischem ia. The purpose of this study was to determine whether aprotinin exhibits n europrotective 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 o f transient middle cerebral artery occlusion [MCAO]). Five days after globa l ischemia, the percentage of dead hippocampal CA1 neurons (mean +/- so) wa s 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). A fter 7 days' recovery from MCAO, no difference among the groups was observe d for either neurologic score (P = 0.99) or cerebral infarct volume (small- dose aprotinin: 136 +/- 80 mm(3), n = 23; large-dose aprotinin: 132 +/- 101 mm(3), n = 11; vehicle: 121 +/- 81 mm(3), n = 21; P = 0.87). Implications: Aprotinin offers no neuroprotection against either global or focal cerebra l ischemia in the rat when administered as a single preischemic bolus.