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大剂量肾上腺素对大鼠心肺复苏后脑组织损伤及氧合功能的影响

Effect of High-dose Epinephrine on Postresuscitation Cerebral Injury and Oxygenation in Rats

【作者】 于铁英

【导师】 孟凌新;

【作者基本信息】 中国医科大学 , 麻醉学, 2004, 硕士

【摘要】 目的 采用窒息致心跳停止大鼠心肺复苏模型,通过观察在心肺复苏时应用大剂量肾上腺素和标准剂量肾上腺素复苏后颈动脉血流量(Flow)、颈动-静脉血氧含量差(C(a-j)O2)、脑氧摄取率(CEO2)、脑组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量的变化,以评价大剂量肾上腺素对复苏后脑组织损伤及氧合功能的影响。 方法 75只雄性Wistar大鼠,体重200-280g。术前禁食12小时,自由饮水。动物随机分为3组,对照组(C组)、大剂量肾上腺素组(H组)、标准剂量肾上腺素组(S组),每组25只。腹腔注射10%水合氯醛300mg/kg麻醉,气管切开插管,小动物呼吸机辅助呼吸,游离右侧颈静脉,游离左侧颈动脉,连续监测颈动脉血流,双侧股动脉置管,监测心电图、体温、心率、平均动脉压。采用窒息致心跳骤停,心跳停止10分钟后,经主动脉注入由窒息前采集的氧合动脉血与肝素、碳酸氢钠和标准剂量肾上腺素(S组)/或大剂量肾上腺素(H组)的混合液制成的复苏合剂。C组不予采血、窒息、复苏,动脉置管后15min后,H组、S组在自主循环恢复后30min、60min、120min时点采集标本及动、静脉血气。各时点为9、8、8只。 检测动、静脉血气分析指标,并计算颈动-静脉血氧含量差(C(a-j)O2)、脑氧摄取率(CEO2)。检测脑组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量。 实验结果采用SPSS V11.0专业统计软件进行统计分析,数据以均数±标准差((?)±s)表示。不同时点组内、组间均数比较采用单因素方差分析,均数间的两两比较采用q检验,初期复苏率两组间比较采用x2检验,P<0.05认为统计学差异显著。结果 H组初期复苏率为90%,S组初期复苏率为75%。两组初期复苏率在统计学上无明显差异。H组、S组大鼠ROsC后MAP迅速上升在smin左右达峰值均明显高于C组(P<0.01),且H组较S组更明显(P<0.01)。之后MAP迅速下降两组明显低于C组(P<0.01)。在ROSClh以后三组MAP无显著差异。H组、S组大鼠在ROSC后HR迅速上升,并维持在较高水平,与C组比较差异显著(p<0.01),H组较S组更明显(p<0.01)。 H组、S组复苏开始到ROSC的时间分别为:H组(0.64士0.22)而n;s组(1 .88士0.31)血n,两组存在明显差异(P<0.01)。 S组、H组在ROSC后Row一过性升高,在5而n时较C组明显升高(P<0.05),之后两组凡ow迅速减低,并维持在较低的水平,均明显低于C组(p<0.01),两组无差别。S组、H组各时点C(。一jz 02、CE02均高于C组(p<0.01),H组的C(:一j)02、CEoZ低于S组(p<0·05)。脑组织各时点SoD活性两组均低于C组(P<0.05),且随时间延长进行性减低。两组MDA含量则随时间进行性增加,均高于C组(P<0.01)。在ROSC后60而n及120而nH组SOD活性低于S组(P<0.05),而MDA含量高于S组(P<0.05)。结论 与标准剂量肾上腺素比较,应用大剂量肾上腺素复苏后脑组织氧摄取率低,脑组织功能不良;且应用大剂量肾上腺素复苏后脑组织超氧化物歧化酶活性较低,丙二醛含量较高,氧自由基损伤更加严重,不利于神经功能恢复。

【Abstract】 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.

  • 【分类号】R605.974
  • 【下载频次】142
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