Objective: To test the hypothesis that adenosine 3',5'-cyclic monophosphate (cAMP) or dibutyl-cAMP (a more lipid-soluble, less rapidly metabolized analog of cAMP) would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow during the reperfusion period.
Design: Randomized, controlled, prospective study.
Setting: University research laboratory.
Subjects: Twenty-five male beagle dogs.
Interventions: Nine control dogs received saline (20-mL/kg bolus and 0.01 mL/kg/min) intravenously, beginning 25 mins before 12 mins of cerebral global ischemia (by aortic occlusion). The dogs in the experimental groups received either cAMP (40 mg/kg 25 mins before ischemia and 0.2 mg/kg/min throughout reperfusion, n = 7), or dibutyl-cAMP (6 mg/kg 25 mins before ischemia and 3 mg/kg at 60, 90, and 120 mins of reperfusion, n = 9).
Measurements and main results: Total and regional cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potentials were measured during 180 mins of reperfusion. Pretreatment with dibutyl-cAMP resulted in increased postischemic hyperemia at 30 mins of reperfusion (e.g., whole brain: control 40 +/- 6; cAMP 56 +/- 9; dibutyl-cAMP 67 +/- 10 mL/min/100 g [mean +/- SEM, p < .05 control vs. dibutyl-cAMP group]) but no difference in total cerebral blood flow or oxygen consumption during later points of reperfusion. All groups demonstrated rapid ablation of the amplitude of somatosensory evoked potentials during ischemia, with no difference between the groups. At 180 mins of reperfusion, somatosensory evoked potentials recovered to 28 +/- 4% of the preischemic baseline value in dogs treated with saline, whereas the somatosensory evoked potentials recovered to 58 +/- 4% of preischemic baseline value in the cAMP-pretreated group (p < .05), and to 70 +/- 6% of preischemic baseline value in dogs treated with dibutyl-cAMP (p < .05).
Conclusions: cAMP and dibutyl-cAMP improve recovery of cerebral electrical function after complete transient global cerebral ischemia. Although hyperemia was more prolonged in cAMP- and dibutyl-cAMP-treated dogs, there was no difference between groups in degree of postischemic delayed hypoperfusion. Therefore, we believe that the mechanism for cerebral protection afforded by cAMP and dibutyl-cAMP is not related to cerebral circulatory effects.