Post-ischemic hypermetabolism in cat brain.

Delayed postischemic brain hypoperfusion and hypermetabolism are likely detrimental factors to neurologic recovery after transient global brain ischemia and may be mediated by catecholamines acting via adrenergic receptors. We evaluated the effects of alpha and beta receptor blockade on cerebral blood flow (CBF) and metabolism after 16 min transient global brain ischemia. Ischemia was induced by arterial hypotension and a high pressure neck tourniquet in 13 anesthetized cats. Six cats were untreated, 4 received propranolol 1 mg/kg, IV and 3 a combination of propranolol and phentolamine, one mg/kg injected one min before recirculation. Total CBF was measured by continuous monitoring of cerebral venous 133Xe clearance after bolus intra-arterial injection. Arterial and cerebral venous oxygen, glucose and lactate were measured. Cerebral cortex glucose and lactate were measured 3 hours post-ischemia after in situ freezing with liquid N2. The cerebral cortex of 3 cats anesthetized, but not subjected to ischemia, was similarly frozen and analyzed for glucose and lactate. Total CBF was relatively constant for up to 3 h post-ischemia in all groups, but significant changes in fast and slow-flow rates and compartment sizes were observed. In untreated cats, the normal 60/40 percent relative weight of the fast and slow-flow compartments was reversed to 30/70 percent by 1 hr post-ischemia. Propranolol attenuated the size of the fast-flow compartment in the first 30 min post-ischemia which was partially restored by phentolamine. Brain oxygen consumption increased 2 to 3-fold by 1 h post-ischemia in all groups. Propranolol compromised CBF and impaired glucose and lactate oxidation which was partly reversed by phentolamine. We concluded that within the first 30 min post-ischemia, beta, and to a lesser extent, alpha receptors predominate in the modulation of cerebrovascular tone. By 1 h post-ischemia, however, adrenergic modulation of cerebrovascular tone is lost. Delayed post-ischemic hypermetabolism unlike stress-induced, but like hypoxia-induced hypermetabolism is only partially affected by beta blockade. Propranolol apparently compromises brain oxygen consumption secondary to a reduction in brain O2 supply while phentolamine improves perfusion and oxygen consumption.