亚低温联合米伐西醇及U50488H对家兔心肺复苏后早期心功能影响的实验研究
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摘要
目的：最初心肺复苏成功后院内死亡的首要原因是复苏后心功能不全,本实验观察亚低温联合米伐西醇及U50488H对家兔心肺复苏后早期心功能的影响,明确三者联用能否减轻复苏后心肌损伤,改善复苏后心脏功能。方法：通过体外致颤法建立家兔心肺复苏模型,32只成年健康家兔随机分为四组,常温复苏组(A组)、亚低温复苏组(B组)、米伐西醇联合U50488H组(C组)、亚低温联合米伐西醇及U50488H组(D组)。A、B组CPR期间给予标准剂量的肾上腺素(30ug/kg),C、D组静脉注射米伐西醇及U50488H(50ug/kg；1.5mg/kg)。B、D组在自主循环恢复后开始诱导亚低温。亚低温诱导方法通过家兔耳缘静脉以1.0m1·kg-1·min-1速度泵入4℃生理盐水,并配合体表降温,15分钟内达到目标温度(32-34℃)。动态监测左室舒张末压(LVEDP).左室内压上升和下降最大速率(peak±dp/dt)及血清H-FABP浓度变化,至复苏后4h处死动物,免疫组化法观察心肌细胞ICAM-1表达情况。结果：(1)与A组比较,B、C组LVEDP及peak±dp/dt值在复苏成功后120min、180min及240min差异有统计学意义(P<0.05)；与B、C组比较,D组LVEDP及peak±dp/dt值在复苏成功后60min、120min、180min、240min差异有统计学意义(P<0.05)。(2)于复苏后60min,四组家兔H-FABP值浓度均达最高,B、C两组在120min、180min、240minH-FABP浓度明显低于A组(P<0.05),D组在120min、180min、240minH-FABP浓度明显低于B、C组(P<0.05)。(3)四组家兔心肌细胞ICAM-1表达显示：A组可见大量的ICAM-1阳性细胞,B、C组较A组少,D组可见极少量的ICAM-1阳性细胞；与A组比较,B、C组复苏后ICAM-1蛋白表达差异有统计学意义(P<0.05),与B、C组比较,D组复苏后ICAM-1蛋白表达差异有统计学意义(P<0.05)。结论：亚低温联合米伐西醇及U50488H可以改善心肺复苏后血流动力学指标,减少复苏后早期H-FABP的释放,降低心肌细胞ICAM-1的表达,减轻炎症反应和心肌损害,改善复苏后心功能不全。
Objective:Postresuscitation myocardial dysfunction contributes to the high fatality rate following successful resuscitation. The purpose of this animal research to investigate the effect of mild hypothermia combined mivazerol and U50488H on cardiac function at early stage of postresuscitation in rabbits, and to explore if they can reduce the myocardial damage and improve cardiac dysfunction after resuscitation. Methods:Ventricular fibrillation(VF) was induced by the external electricity, After setting up rabbit model of cardiopulmonary resuscitation,32rabbits were randomly divided into four groups. group A:normothermic resuscitation group,in which animals were performed standard CPR after cardiac arrest, administration of the standard doses of epinephrine (30ug/kg) during CPR; group B:mild hypothermia resuscitation group, in which animals were cooled to32-34℃after successful ROSC; group C:mivazerol combined U50488H group, administration of mivazerol(50ug/kg) and U50488H(1.5mg/kg) during CPR. group D:mild hypothermia combined mivazerol and U50488H group, administration of mivazerol(50ug/kg) and U50488H(1.5mg/kg) during CPR, and animals were cooled to32-34℃after successful ROSC. The left ventricular end-diastolic pressure(LVEDP),left ventricular pressure rise and fall rate(peak±dp/dt), serum concentrations of H-FABP were observed, In addition, animals were sacrificed on4hours after resuscitation, The ICAM-1expression on myocardial cells were detected by immunohistochemical methods. Results:(1) compared with group A,The LVEDP and peak±dp/dt of group B and C were singnificant derefences on120min,180min and240min after ROSC(P<0.05); compared with group B and C, The LVEDP and peak±dp/dt of group D were singnificant derefences on60min,120min,180min,and240min after ROSC(P<0.05).(2) serum concentrations of H-FABP reached the highest value on recovery after60min in each group..compared with group A, B, C, In group D,The serum concentrations of H-FABP singnificantlly decreased on120min,180min.and240min after ROSC(P<0.05);(3) expression of ICAM-1in four groups shows:a large number of ICAM-1positive cells can be seen in group A. compared with group A. ICAM-1positive cells in group B and C were less than group A.A very small amount of ICAM-1positive cells can be seen in group D; Compared with group A expression of ICAM-1was Significantly different in group B and C after resuscitation(P＜0.05), Compared with group B and C, expression of ICAM-1was Significantly different in group D after resuscitation (P<0.05). Conclusions:Mild hypothermia combined mivazerol and U50488H can improve Postresuscitation hemodynamics indexes and reduce serum concentrations of H-FABP at early stage of postresuscitafion, and reduce expression of ICAM-1in myocardial cells,. so that they can reduce myocardial damage and inflammation,and improve cardiac dysfunction after resuscitation.
Objective:Postresuscitation myocardial dysfunction contributes to the high fatality rate following successful resuscitation. The purpose of this animal research to investigate the effect of mild hypothermia combined mivazerol and U50488H on cardiac function at early stage of postresuscitation in rabbits, and to explore if they can reduce the myocardial damage and improve cardiac dysfunction after resuscitation. Methods:Ventricular fibrillation(VF) was induced by the external electricity, After setting up rabbit model of cardiopulmonary resuscitation,32rabbits were randomly divided into four groups. group A:normothermic resuscitation group,in which animals were performed standard CPR after cardiac arrest, administration of the standard doses of epinephrine (30ug/kg) during CPR; group B:mild hypothermia resuscitation group, in which animals were cooled to32-34℃after successful ROSC; group C:mivazerol combined U50488H group, administration of mivazerol(50ug/kg) and U50488H(1.5mg/kg) during CPR. group D:mild hypothermia combined mivazerol and U50488H group, administration of mivazerol(50ug/kg) and U50488H(1.5mg/kg) during CPR, and animals were cooled to32-34℃after successful ROSC. The left ventricular end-diastolic pressure(LVEDP),left ventricular pressure rise and fall rate(peak±dp/dt), serum concentrations of H-FABP were observed, In addition, animals were sacrificed on4hours after resuscitation, The ICAM-1expression on myocardial cells were detected by immunohistochemical methods. Results:(1) compared with group A,The LVEDP and peak±dp/dt of group B and C were singnificant derefences on120min,180min and240min after ROSC(P<0.05); compared with group B and C, The LVEDP and peak±dp/dt of group D were singnificant derefences on60min,120min,180min,and240min after ROSC(P<0.05).(2) serum concentrations of H-FABP reached the highest value on recovery after60min in each group..compared with group A, B, C, In group D,The serum concentrations of H-FABP singnificantlly decreased on120min,180min.and240min after ROSC(P<0.05);(3) expression of ICAM-1in four groups shows:a large number of ICAM-1positive cells can be seen in group A. compared with group A. ICAM-1positive cells in group B and C were less than group A.A very small amount of ICAM-1positive cells can be seen in group D; Compared with group A expression of ICAM-1was Significantly different in group B and C after resuscitation(P＜0.05), Compared with group B and C, expression of ICAM-1was Significantly different in group D after resuscitation (P<0.05). Conclusions:Mild hypothermia combined mivazerol and U50488H can improve Postresuscitation hemodynamics indexes and reduce serum concentrations of H-FABP at early stage of postresuscitafion, and reduce expression of ICAM-1in myocardial cells,. so that they can reduce myocardial damage and inflammation,and improve cardiac dysfunction after resuscitation.
引文
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