Experimental cardiopulmonary cerebral resuscitation : with special reference to cerebral eicosanoid production and free radical scavengers

Abstract: Reperfusion injury after restoration of spontaneous circulation (ROSC) is often considered one of the predominant factors in determining neurological outcome in cardiac arrest. Therefore one of the main targets of experimental and clinical studies has been to mitigate this reperfusion injury. Accumulated knowledge indicates that oxidative stress is perhaps the foremost cause of this reperfusion injury, and hence, free radical scavengers have been tried anticipating mitigation of the effects of ischaemia and reperfusion injury. In this series of experimental porcine studies of cardiac arrest and cardiopulmonary resuscitation (CPR), we aimed to find evidence for increased concentrations of indicators of oxidative stress and inflammation during reperfusion, to mitigate the reperfusion injury by free radiacal scavengers and alkaline buffers, and to improve 24 h neurological outcome by combining effective interventions. The results showed that the isoprostane 8-iso-PGF2alpha, an oxidative indicator, and the prostaglandin 15-keto-dihydro-PGF2alpha, an inflammatory indicator, are significantly increased in the jugular bulb plasma during reperfusion. We confirmed that S-PBN mitigated oxidative stress, as the concentration of 8-iso-PGF2alpha was lower and cerebral vascular autoregulation was better preserved during the early period of reperfusion after ROSC. Combining PBN with cerebral blood flow-promoting interventions, we found that 24 h after ROSC the neurological outcome determined by neurological deficit score (NDS) was significantly improved as compared with two control groups. The concentration of 8-iso-PGF2alpha and hypoxanthine in jugular bulb plasma were correlated to the 24 hy neurological outcome. Alkaline buffer administration during CPR could promote cerebral reperfusion and mitigate cerebral acidosis during the reperfusion period. In summary, reperfusion after ROSC induced oxidative and inflammatory reactions. The eicosanoids, 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha determined in jugular bulb plasma can be used as biomarkers of cerebral oxidative and inflammatory reactions, and for evaluating the effectiveness of interventions. The free radical scavengers PBN and S-PBN could mitigate oxidative stress and promote distribution of cerebral cortical blood flow (CCBF). Combineing measures to promote cerebral blood flow and free radical scavenger PBN significantly improved neurological outcome 24 h after ROSC. Administration of alkaline buffers mitigates cerebral acidosis and promotes CCBF in the reperfusion phase after ROSC.