Resuscitation of central nervous system (CNS) following cardiac arrest is an area of increasing pathophysiological and clinical interest. No coherent post-arrest treatment protocol can be developed without clearer understanding of the pathophysiological mechanisms which underlie such CNS damage. The role of impaired cerebral reperfusion ("no-reflow") remains controversial. In our model system (12 minutes total cerebral ischemia (TCI) in dogs, microsphere technique for measuring regional cerebral blood flow (RCBF)), post-TCI cerebral hyperemia is followed by 50% reduction in RCBF, despite no change in perfusion pressure or pCO2. Seventy to 85% of this decreased CBF in dogs is related to an increase in cerebral vascular resistance. We have also documented a strikingly similar pattern of RCBF changes after TCI in monkeys. Studies are underway exploring the pathophysiological basis of impaired reperfusion. The role of prostaglandins is being evaluated with both a cyclo-oxygenase inhibitor and a relatively specific thromboxane synthetase inhibitor. The role of calcium-influx mediated cerebral vasospasm is being studied using calcium ionophore antagonists. Additional studies with alpha adrinergic blocks, hemodilution and chronic studies quantifying neurologic outcome in post-TCI animals treated with barbiturate coma plus the pharmacological agents noted above will be pursued in the future.