Multifaceted therapy after global brain ischemia in monkeys.

Abstract

The pathophysiology of postischemic encephalopathy is complex, and includes tissue acidosis, edema, hypoperfusion, membrane dysfunction, impaired energy production, and possibly hypermetabolism. We tested the hypothesis that this multifactorial clinical problem must be approached with multifaceted therapy, with specific treatment aimed at each of the above postischemic changes. Eighteen minutes of complete global brain ischemia was produced with a higher pressure neck cuff in pigtailed monkeys. Control treatment postischemia (n = 9): 1) Normotension (MAP greater than or equal to 80 mmHg) restored within 2 min postischemia, 2) controlled ventilation for 24 hours with PaCO2 = 25 mmHg, 3) normothermia, and 4) phenytoin seizure prophylaxis from 20 hours postischemia. Experimental treatment (n = 10): Control treatment plus the following modifications: 1) Hemodilution to hematocrit 25% at 1-4 min postischemia, 2) brief hypertension (MAP 130 mmHg for 5 min) after accomplished hemodilution, 3) hypothermia for 6 hours, 4) pentobarbital 30 mg/kg i.v., 5) dexamethasone 4 mg/kg i.v. Outcome was evaluated at 96 hours postischemia by overall performance categories (OPC) (OPC I = normal, OPC V = brain death), neurologic deficit (ND) scores (100% ND = brain death, 0% ND = normal), and histologic damage scores of the brains. Results: Brain death developed in 1/9 control and 0/10 treated animals. The number of awake monkeys (OPC I and II) at 96 hours postischemia was significantly higher in the treated group (7/10) than in the control group (2/9) (p = 0.05). The median ND scores for the two groups were 16 and 35% respectively (p greater than 0.05). The results strongly suggest that postischemic treatment may be beneficial and that a multifaceted therapeutic approach is worth pursuing.