Effects of pentoxifylline on cerebral blood flow, metabolism, and evoked response after total cerebral ischemia in dogs

Abstract

Objective: To test the hypothesis that pentoxifylline improves recovery of cerebral electrical activity and metabolic function after a transient cerebral global ischemia by improving cerebral blood flow during the reperfusion period.

Design: Randomized, controlled, prospective study.

Setting: University research laboratory.

Subjects: Forty male beagle dogs.

Interventions: Six control dogs received pentoxifylline (40 mg/kg bolus followed by infusion at 0.2 mg/kg/hr) without ischemia. Thirteen dogs received Ringer's lactate solution with 12 mins of cerebral global ischemia (by aortic occlusion). Nine dogs received pentoxifylline before ischemic insult. Six dogs received pentoxifylline on reperfusion, and six dogs received pentoxifylline 30 mins after reperfusion.

Measurements and main results: Total and regional cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potentials were measured during 180 mins of reperfusion. Pentoxifylline did not affect cerebral blood flow, oxygen consumption, or somatosensory evoked potentials without ischemia. Pretreatment with pentoxifylline resulted in attenuated postischemic hyperemia at 10 mins of reperfusion (94 +/- 15 vs. 133 +/- 11 [SEM] mL/min/100 g; p < .05), but there was no difference in total cerebral blood flow or oxygen consumption during later points of reperfusion. Pentoxifylline treatment during reperfusion resulted in no recovery of cerebral blood flow or oxygen consumption. All ischemic groups demonstrated a rapid ablation of somatosensory evoked potential amplitude and there were no differences in the decrement of the amplitude on ischemia. At 180 mins of reperfusion, somatosensory evoked potentials recovered to the following percentages of the baseline control values: 28 +/- 4% in dogs treated with Ringer's lactate solution; 58 +/- 4% in the pentoxifylline pretreated group (p < .05); 40 +/- 5% in dogs receiving pentoxifylline at reperfusion (p > .05); and 53 +/- 8% in dogs receiving pentoxifylline at 30 mins of reperfusion (p < .05).

Conclusions: Pentoxifylline treatment improves recovery of cerebral electrical function after complete transient cerebral global ischemia by a mechanism that does not involve improvement in cerebral blood flow or global oxygen consumption.