Effect Of High-dose Epinephrine On Postresuscitation Cerebral Injury And Oxygenation In Rats

ObjectiveThe object of this study is to evaluate the effect of high-dose epinephrine given during cardiopulmonary resuscitation ( CPR) on postresuscitation cerebral injure and oxygenation by observing the changes of carotid artery flow( Flow) and arteriovenous difference of oxygen content ( C(a_j-)02) and cerebral extractionof oxygen ( CE02) ,as well as the superoxide dismutase(SOD) activity and malon-dialdehyde ( MDA) content of cerebral tissue in a rat model of asphyxia! cardiac arrest.Material and methodsSeventy -five male Wistar rats (200 -280g) were fasted overnight except for free access to water. The animals were randomly divided into three groups. All animals were anesthetized by abdominal injection of Chloral Hydrate and in-tubated after tracheotomy. Both femoral artery were cannulated. Carotid artery and vein were freed. ECG, MAP, HR, Flow and temperature were continuously monitored and recorded. Cardiac arrest was induced by asphyxiation. After 10minutes downflow,resuscitation was achieved remotely by a slow,intra - aortic infusion oxygenated blood (withdrawn from the same rat before asphyxia) along with a resuscitation cocktail containing heparin, sodium bicarbonate, and standard-dose epinephrine(S group)/or high-dose epinephrine(H group) through the resuscitation channel. The animals in C group were not subjectd to blood withdrawn , asphyxia and cardiac arrest. The animals were collected arterial and jugular venous blood for blood gas analysis, then were killed on the point SOminutes, 60minutes and 120minutes after ROSC in S group and H group and the corre-spending data from C group was assigned to 15 minutes after surgical preparation.Blood gases were measured in arterial and jugular venous blood. C(a_j)O2 and CEO2 was calculated from blood-gas data. SOD and MDA in cerebral tissue were determined.Stasistical analysis was performed with the use of the SPSS program. Analysis of variance (ANOVA) was used to compare between-group means and within - group means, Student-Newan-Keuls ( SNK ) multiple comparisons were made to determine differences between time points within groups or between groups at a given time. The rate of ROSC was compared with x2 test. All data are reported as mean SD. A P value of < 0.05 was considered significant.ResultsThere were no difference in the rates of initial restoration of spontaneous circulation (ROSC) between H group (90%) and S group (75%) (P > 0. 05). Baseline hemodynamic measurements did not differ significantly among three groups. Mean artrial pressure(MAP) was significantly higher both in S and H group ascompared to C group at the 5 - min after ROSC( P <0. 01) ,and MAP in H group was higher than that of S group respectively ( P <0. 01). After then MAP in both groups were reduced rapidly. There were no difference among three groups after the 60 - min of observation. Heart rates ( HR) in S group and H group were significantly magnified after ROSC(P <0.01) ,and the changes in H group were much more.The interval from beginning of resuscitation to ROSC in H group was si -gnificantly shorter than that in S group (P <0.01).Flow in H group and S group were transiently increased, and then decreased rapidly and lower than that in C group respectively (P <0.01) ,but Flow was no difference between H group and S group. C(a_j) 02 and CE02 were lower in H group than that in S group (P <0.05). Meanwhile SOD activity in cerebal tissue were decreased and MDA contents increased significantly after resuscitation compared with C group ( P < 0. 01) , SOD and MDA in H group were lower orhigher than that in S group (P <0.05).ConclusionCompared with standard - dose epinephrine, high-dose epinephrine not only decreased cerebral extraction of oxygen but also decreased SOD activity and increased MDA contents in cerebral tissue when administered during CPR in rats.