A research program in cerebral ischemia was initiated by our laboratory to determine optimal strategies for cerebroprotection. Four studies relating to cerebroprotection using nuclear magnetic resonance spectroscopy in a sheep model of hypothermic cardiopulmonary bypass are summarized. These showed, first, that low-flow bypass, with a flow as low as 10 mL.kg-1 x min-1, maintained normal cerebral metabolism; second, that hypothermia increases the high-energy phosphate content and the intracellular pH of the brain; third, that hyperglycemia causes a profound intracellular acidosis; and, finally, that barbiturates prevent the normal increase in high-energy phosphates associated with hypothermia.