The Effect Of Recombinant Human Erythropoietin On Postresuscitation Cerebral Oxygenation And Ultrastructure In Rats

ObjectiveThe object of this study is to evaluate the prospective functionofrecombinant human erythropoietion(rhEPO) during cardiopulmonary resuscitation (CPR) for postres-uscitation cerebral injury by observing the changes of cerebral extraction of oxygen (CEO₂) and cerebral ultrastructure.Material and methodsSeventy-five male Wistar rats (200g～300g) were fasted overnight except for free access to water.All animals were randomly divided into three groups:control group (C) ,adnephrin group(AD) and erythropoietin group(E).Every group animal contains 25 rats and every group was divided three little group at the point of post-resuscitation 1 h,2h,3h,respechtivly 9,8, 8 ra ts. All animals were anesthetized by abdominal injection of Chloral Hydrate andintubated aftertracheolomy.Tidal volume was adjusted by s-ustainning P_aCO₂ 35-45 and breathing frequent- cy(n=36 beat /min).Left carotid artery and right jugular vein were cannulated to monitor ECG,BT,HR and MAP.The rat cardic arrest model was founded by occluding tracheal intubation and cutting off breathing m-achine.The standard of cardic arrest was HR=0 and MAP<10mmHg. Befor resuscitation for 24 and 16 hours, erythropoietin (EPO 3000iu/Kg) was injected into abdominal cavity ,and EPO(30iu/kg) was injected into vein at 10 mins before asphyxia. After 7 m-ins cardiac arrest resuscitati- on was achieved remotely by a slow,intra-aortic infusion oxagented blood (withdrawn from the same rat before asphysia) along with a resuscita- tion composition containing heparin (500u/kg) , sodium bicarbonate (1mEq/kg) ,a-dnephrin (100u/kg) through the resuscitation channel .The success of resuscitation w-as regular autonomic heart beat and MAP>60mmHg.Rats in sham group were not subjected to asphyxia and cardiac arrest. The animals were collected arterial and jugular v-enous blood for blood gas analysis,then were killed on the point1h, 2h, and 3h after RO SC in AD group and E group to collect sample.The corresponding data from C group was assigned to 15 mins after surgical preparation .Blood gases were measured in arterial and jugular venous blood.CEO₂ was calculated from blood-gas data. The right side brain skin quality was taken and fixed with 2.5% glutaral and then ultrastructure changes in cerebral cortex were examined under electron microscopy.Stasistical analysis was performed with the use of the SPSS11.0 program. Analysis of variance(ANOVA) was ysed to compare between-group means and within-group means,Student-Newan _keuls(SNK), multiple comparisons were made to derermine differences between time points within groups or between groups at a given time . All datas are reported as mean±SD and p<0.05 was considered significantly.ResultsFor baseline mean arterial pressure (MAP) and heart rate (HR) value , there was no significant difference among three groups.MAP and HR was significantly higher b-oth in AD and E group ascompared to C group after ROSC(p <0.05),and after 2 hours, the value of three group inclined consistently.there was no obvious difference between AD and E group (p >0.05). Hb and Hct was no obviously difference (p >0.05).From blood gases,we can see S_jv02 and C_jv02 in AD group and E group was lower than C group ,and the value in E group was lower than AD group, (p <0.05).The comparence of CEO₂ and C_a-jO₂in three groups: CEO₂ and C_a-jO₂ was significantly higher both in AD and E group ascompared to C group at every durance,and the value in E group was higer than the AD' (p <0.05).The changes of cerebral ultrasructure : cerebral structure was normal in C group. Ky- toplasmwater thesaurismosis of nerve cell,oligodendrocyte and gitter cell could be obviously seen in AD group,as well the integrity of cell membrane was broken.Vacuol-ar degeneration in plastiosome ,nervous process was more critical than in E group.Vas-cular endothelial cell(VEC)was damaged and congestion in micrangium could also be observed significantly. On the opposition,these changes in E groups relieved obviously.ConclusionRecombinant human erythropoietin can not only relieve the injury of cerebral ultrastructure ,but also increase cerebral extraction rate of oxygen,and improve cerebral oxygenation in post-resuscitation rats.