Cerebral metabolic changes during treatment of subacute cerebral infarction by alpha and beta adrenergic blockade with phenoxybenzamine and propranolol.

Cerebral Metabolic Changes During Treatment of Subacute Cerebral Infarction by Alpha and Beta A drenergic Blockade With Phenoxybenzamine and Propranolol • Cerebral hemispheric blood flow (HBF) and metabolism were measured in 30 patients with acute and subacute cerebral infarction before and after intracarotid infusion of the alpha adrenergic blocking agent phenoxybenzamine (PBZ) or the beta adrenergic blocker propranolol (PPL) dissolved in saline. Following intracarotid injection of 7 ng per kilogram per minute PBZ, HBF showed no change but cerebral hemispheric oxygen consumption (HMIO2) and carbon dioxide production (HMICO2) decreased. Glucose consumption (HMIG1) was unchanged but the glucose to oxygen utilization ratio (HG:O) increased. Intracarotid injection of 1.45 ^g per kilogram per minute PPL caused reduction of HBF, HMIO2, HMICO2, HMIG1 and HG:O. After PBZ infusion, mean systemic arterial blood pressure (MABP) decreased slightly, intracranial venous pressure (ICVP) and CSF pressure (CSFP) increased, and central venous pressure (CVP) remained unchanged. PPL infusion had no effect on intracranial dynamics. Possible mechanisms whereby PBZ and PPL influence cerebral metabolism and function were discussed. Inhibition of uncoupling of oxidative phosphorylation appeared to be the most likely explanation for the improvement in brain function and metabolic change associated with each of the drugs. These data support the concept that catecholamines released into brain tissue are a possible cause of uncoupled oxidative phosphorylation. Presently available evidence suggests that adrenergic blocking agents warrant clinical evaluation in the treatment of acute cerebral ischemia, infarction, hemorrhage, and anoxia. Additional