The effect of FR167653 on cerebral ischemia-reperfusion injury after retrograde cerebral perfusion in a canine model

Abstract

Retrograde cerebral perfusion (RCP) has recently been reported to be useful for the repair of aortic arch aneurysms. However, there is a possibility that RCP supplies a limited amount of blood to the brain [1] and ischemia-reperfusion injury may occur after RCP. FR167653 (FR) is characterized as a potent suppressant of interleukin-1β and tumor necrosis factor-α. We investigated the role of FR in preventing cerebral ischemia-reperfusion injury after RCP in a canine model. A total of 12 mongrel dogs was divided into two groups: in the FR group (n = 6), FR167653 (1 mg/kg/hour) was continuously administered during the period of RCP and rewarming; in the control group (n = 6), a physiological saline solution was administered at the same dosage as the FR167653 during the same period. Following hypothermia (20°C) using cardiopulmonary bypass and circulatory arrest, RCP was performed by infusing oxygenated blood via the bilateral internal maxillary veins for 60 minutes at a perfusion pressure of 25 mmHg. The cerebral blood flow (CBF), cerebral metabolic rate for glucose (CMRGlu) and oxygen (CMRO2), and excretion of carbon dioxide (ExCO2) were measured. These results were expressed as the percentage of change from baseline values established immediately after anesthesia. CBF was significantly (p < 0.05) higher in the FR group than in the control group at 40 (159 ± 25% and 82 ± 21%, respectively) and 60 minutes (177 ± 30% and 83 ± 14%, respectively) after RCP. The lactate/pyruvate ratio of blood returned from the brain tissues was significantly (p < 0.05) lower in the FR group than in the control group at 40 and 60 minutes after RCP. CMRGlu was significantly (p < 0.05) higher in the FR group than in the control group 60 minutes after RCP. There was no significant difference in CMRO2 and ExCO2 between the two groups. It is concluded that FR167653 appears to be effective in protecting the brain from ischemia-reperfusion injury after RCP.