氨茶碱在心脏停搏中的疗效研究
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摘要
第一部分：目的 比较氨茶碱和肾上腺素两种药物在窒息致大鼠心脏停搏模型中的疗效。方法 采用呼气末夹闭气管8min的窒息致大鼠心脏停搏模型。36只大鼠随机分为安慰剂对照组，肾上腺组和氨茶碱组行心肺复苏，并分别给予生理盐水、0.02mg／Kg肾上腺素和10mg／Kg氨茶碱。结果 心电活动恢复率氨茶碱组为58.3％(7／12)，与肾上腺素组相近(41.7％，5／12；P=0.684)；心电活动开始恢复时间氨茶碱组为(9±23)s，明显快于肾上腺素组[(90±42)s，P=0.021]。自主循环恢复率肾上腺素组有50％(6／12)，与氨茶碱组相近(41.7％，5／12；P=1.000)。肾上腺素组复苏后1-5min平均血压为(30.3±10.2)mmHg，高于氨茶碱组[(15.0±2.4)mmHg，P=0.043；复苏6-10min肾上腺素组平均血压为(23.3±2.3)mmHg，与氨茶碱组相近[(22.7±2.2)mmHg，P=0.677]。肾上腺素组和氨茶碱组1h存活率均为16.7％(2／12)，高于对照组0％(0／12，P=0.478)。尸检肾上腺素组心脏硬度记分(2.5±0.5)明显高于对照组(1.6±0.4，P=0.007)，与氨茶碱组(2.0±0.5)比较差异接近显著(P=0.068)。结论 氨茶碱对心电活动和自主循环的恢复有明显改善作用，且与肾上腺素疗效相近。氨茶碱对心电活动的恢复起效快于肾上腺素，心脏硬度记分也低于肾上腺素。
第二部分：目的 探讨氨茶碱和肾上腺素合用在窒息致大鼠心脏停搏中的疗效是否优于单纯使用肾上腺素或氨茶碱。方法 采用呼气末夹闭气管8min的大鼠窒息致心脏停搏模型。36只大鼠随机分为氨茶碱和肾上腺素合用组，肾上腺组和氨茶碱组行心肺复苏，分别给予0.02mg／Kg肾上腺
氨茶碱在心脏停搏中的疗效研究
摘丝
素和IOmg/Kg氨茶碱、O.02mg/Kg肾仁腺素和10mg/Kg氨茶碱。结果心
电活动恢复率3组无显著性差异(尸=0.400)。心电活动j干始恢复时一间合用
组为(43士34)S，氨茶碱组为(39士23)S，两组显著快于肾上腺素组(90
士42)s，(尸一0.022和尸一0.011)。自主循环恢复率3组无显著性差异
(P二0.717)。自主循环恢复大鼠的平均血压合用组为(55.5士17.3)mmHg，
显著高于肾上腺素组[(26.7士7.8) mmHg，尸一0.000]和氨茶碱组[( 15.0土
2.4)mmHg，P=O.000]。lh存活率三组显著性差异(p=0.346)。结论氨茶
碱和肾上腺素合用对自主循环血压的恢复优于单纯使用肾上腺素或氨茶
碱。
第三部分:目的探讨氨茶碱和肾上腺素联合应用在心脏停搏患者中
的疗效是否优于单纯使用肾上腺素。方法24例心跳骤停患者给予氨茶碱
和肾上腺素联合用药，30例心跳骤停患者单用肾上腺素作为对照组。结
果心电活动恢复率合用组79.2%(19/24)，高于肾上腺素组533%(16/30)，
差异接近显著(尸二0.082)。自主循环恢复率合用组50.0%(12/24)，高于
肾上腺素组(400%，12/30)，但差异不显著(P=0.462)。合用组lh、3h、
6h的生存率分别为87.5%、542%和37.5%，显著高于肾上腺素组(lh:
56.7%;3h:20%;6h:13.3%)，(P<0.05)。结论心脏停搏患者在使用
肾上腺素基础上合用氨茶碱有助于心电活动的恢复和短期存活率的提高
Part I: Objective To compare the efficacy of aminophylline vs. epinephrine in treatment of a rat model of asphyxial cardiac arrest. Methods Asphyxial cardiac arrest was induced by clamp the endotracheal tube. After 8 min of cardiac arrest, a bolus dose of either 10mg/kg aminophylline (n=T2), 0.02mg/kg epinephrine (n=12), or 0.3ml saline (n=12) was administered in a randomized manner. Results There were 7 rats (58.3%) return cardiac electrical activity in aminophylline group, which was no statistically difference with epinephrine group (41.7%, 5/12; P=0.684). Initiation time of resuscitation in aminophylline group was (39 23) s, which was significant quicker than epinephrine group [(90 + 42) s, P=0.021)]. There were 5 (41.7%) rats return of spontaneous circulation in aminophylline group and 6 rats (50%) in epinephrine group (P=0.000). The mean arterial pressure in 1-5 min after drug administration was (30.3 10.2) mmHg in epinephrine group, which was significantly higher than aminophylline group [(15.0 + 2.4
) mmHg, P=0.043]. The mean arterial pressure in 6-10 min was (23.3 2.3) mmHg in epinephrine group, which was no statistically difference with aminophylline group [(22.7 + 2.2) mmHg, P=0.677]. The Ih survival rate in aminophylline and epinephrine group was 16.7%, which was higher than placebo group (0%,
P=0.478). At autopsy the cardiac consistency score in epinephrine group was 2.5 0.5, which was higher than those in placebo group (1.6 + 0.4, P=0.007) and aminophylline group (2.0 0.5, P=0.068). Conclusion These results suggest that aminophylline could improve the cardiac electrical activity and spontaneous circulation in the rat model of asphyxial cardiac arrest, which was no significant difference with epinephrine. Initiation time to return cardiac electrical activity after aminophylline injection was significant quicker than epinephrine and the cardiac consistency score with aminophylline administration was less than epinephrine.
Part II: Objective To compare the efficacy of aminophylline vs. epinephrine vs. the combination of aminophylline with epinephrine in a rat model of asphyxial cardiac arrest. Methods Asphyxial cardiac arrest was induced by clamp the endotracheal tube. After 8 min of cardiac arrest, a bolus dose of either lOmg/kg aminophylline (n=12), 0.02mg/kg epinephrine (n=12). or a combination of lOmg/kg aminophylline with 0.02mg/kg epinephrine (n=12) was administered in a randomized manner. Results The rates of cardiac electrical activity restoration were not statistically different between 3 groups (P=0.400). Initiation time of resuscitation was (43 34) s in aminophylline -epinephrine group and (39 23) s in aminophylline group. Either group was significantly earlier than that in epinephrine group (90 42) s (aminophylline -epinephrine vs. epinephrine, P=0.022; aminophylline vs. epinephrine, P=0.011). The rate of spontaneous circulation recovery was not statistically different between 3 groups (P=0.7\7). The mean arterial pressure in those achieving recovery of spontaneous circulation was (55.5 17.3) mmHg in aminophylline-epinephrine group, which was significantly higher than that in
epinephrine group [(26.7 7.8)mmHg, P=0.000] and aminophylline group [(15.0 2.4)mmHg, P=0.000]. Ih survival rate were not statistically different between 3 groups (P=0.346). Conclusion These results suggest that the combination of aminophylline with epinephrine can improve the recovery of blood pressure in the rat model of asphyxial cardiac arrest.
Part III : Objective To determine whether aminophylline with epinephrine has more beneficial effect than only epinephrine on the victims of cardiac arrest. Methods In a retrospective study on cardiac arrest, 24 patients received epinephrine and aminophylline and 30 patients received only epinephrine. Results There were 19 (79.2%) cases return cardiac electrical activity in epinephrine-aminophylline group and 16 (53.3%) cases in epinephrine group. The difference was marginally significant (.P=0.082). There were 12 cases (50.0%) return of spontaneous circulation in ep
第二部分：目的 探讨氨茶碱和肾上腺素合用在窒息致大鼠心脏停搏中的疗效是否优于单纯使用肾上腺素或氨茶碱。方法 采用呼气末夹闭气管8min的大鼠窒息致心脏停搏模型。36只大鼠随机分为氨茶碱和肾上腺素合用组，肾上腺组和氨茶碱组行心肺复苏，分别给予0.02mg／Kg肾上腺
氨茶碱在心脏停搏中的疗效研究
摘丝
素和IOmg/Kg氨茶碱、O.02mg/Kg肾仁腺素和10mg/Kg氨茶碱。结果心
电活动恢复率3组无显著性差异(尸=0.400)。心电活动j干始恢复时一间合用
组为(43士34)S，氨茶碱组为(39士23)S，两组显著快于肾上腺素组(90
士42)s，(尸一0.022和尸一0.011)。自主循环恢复率3组无显著性差异
(P二0.717)。自主循环恢复大鼠的平均血压合用组为(55.5士17.3)mmHg，
显著高于肾上腺素组[(26.7士7.8) mmHg，尸一0.000]和氨茶碱组[( 15.0土
2.4)mmHg，P=O.000]。lh存活率三组显著性差异(p=0.346)。结论氨茶
碱和肾上腺素合用对自主循环血压的恢复优于单纯使用肾上腺素或氨茶
碱。
第三部分:目的探讨氨茶碱和肾上腺素联合应用在心脏停搏患者中
的疗效是否优于单纯使用肾上腺素。方法24例心跳骤停患者给予氨茶碱
和肾上腺素联合用药，30例心跳骤停患者单用肾上腺素作为对照组。结
果心电活动恢复率合用组79.2%(19/24)，高于肾上腺素组533%(16/30)，
差异接近显著(尸二0.082)。自主循环恢复率合用组50.0%(12/24)，高于
肾上腺素组(400%，12/30)，但差异不显著(P=0.462)。合用组lh、3h、
6h的生存率分别为87.5%、542%和37.5%，显著高于肾上腺素组(lh:
56.7%;3h:20%;6h:13.3%)，(P<0.05)。结论心脏停搏患者在使用
肾上腺素基础上合用氨茶碱有助于心电活动的恢复和短期存活率的提高
Part I: Objective To compare the efficacy of aminophylline vs. epinephrine in treatment of a rat model of asphyxial cardiac arrest. Methods Asphyxial cardiac arrest was induced by clamp the endotracheal tube. After 8 min of cardiac arrest, a bolus dose of either 10mg/kg aminophylline (n=T2), 0.02mg/kg epinephrine (n=12), or 0.3ml saline (n=12) was administered in a randomized manner. Results There were 7 rats (58.3%) return cardiac electrical activity in aminophylline group, which was no statistically difference with epinephrine group (41.7%, 5/12; P=0.684). Initiation time of resuscitation in aminophylline group was (39 23) s, which was significant quicker than epinephrine group [(90 + 42) s, P=0.021)]. There were 5 (41.7%) rats return of spontaneous circulation in aminophylline group and 6 rats (50%) in epinephrine group (P=0.000). The mean arterial pressure in 1-5 min after drug administration was (30.3 10.2) mmHg in epinephrine group, which was significantly higher than aminophylline group [(15.0 + 2.4
) mmHg, P=0.043]. The mean arterial pressure in 6-10 min was (23.3 2.3) mmHg in epinephrine group, which was no statistically difference with aminophylline group [(22.7 + 2.2) mmHg, P=0.677]. The Ih survival rate in aminophylline and epinephrine group was 16.7%, which was higher than placebo group (0%,
P=0.478). At autopsy the cardiac consistency score in epinephrine group was 2.5 0.5, which was higher than those in placebo group (1.6 + 0.4, P=0.007) and aminophylline group (2.0 0.5, P=0.068). Conclusion These results suggest that aminophylline could improve the cardiac electrical activity and spontaneous circulation in the rat model of asphyxial cardiac arrest, which was no significant difference with epinephrine. Initiation time to return cardiac electrical activity after aminophylline injection was significant quicker than epinephrine and the cardiac consistency score with aminophylline administration was less than epinephrine.
Part II: Objective To compare the efficacy of aminophylline vs. epinephrine vs. the combination of aminophylline with epinephrine in a rat model of asphyxial cardiac arrest. Methods Asphyxial cardiac arrest was induced by clamp the endotracheal tube. After 8 min of cardiac arrest, a bolus dose of either lOmg/kg aminophylline (n=12), 0.02mg/kg epinephrine (n=12). or a combination of lOmg/kg aminophylline with 0.02mg/kg epinephrine (n=12) was administered in a randomized manner. Results The rates of cardiac electrical activity restoration were not statistically different between 3 groups (P=0.400). Initiation time of resuscitation was (43 34) s in aminophylline -epinephrine group and (39 23) s in aminophylline group. Either group was significantly earlier than that in epinephrine group (90 42) s (aminophylline -epinephrine vs. epinephrine, P=0.022; aminophylline vs. epinephrine, P=0.011). The rate of spontaneous circulation recovery was not statistically different between 3 groups (P=0.7\7). The mean arterial pressure in those achieving recovery of spontaneous circulation was (55.5 17.3) mmHg in aminophylline-epinephrine group, which was significantly higher than that in
epinephrine group [(26.7 7.8)mmHg, P=0.000] and aminophylline group [(15.0 2.4)mmHg, P=0.000]. Ih survival rate were not statistically different between 3 groups (P=0.346). Conclusion These results suggest that the combination of aminophylline with epinephrine can improve the recovery of blood pressure in the rat model of asphyxial cardiac arrest.
Part III : Objective To determine whether aminophylline with epinephrine has more beneficial effect than only epinephrine on the victims of cardiac arrest. Methods In a retrospective study on cardiac arrest, 24 patients received epinephrine and aminophylline and 30 patients received only epinephrine. Results There were 19 (79.2%) cases return cardiac electrical activity in epinephrine-aminophylline group and 16 (53.3%) cases in epinephrine group. The difference was marginally significant (.P=0.082). There were 12 cases (50.0%) return of spontaneous circulation in ep
引文
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2. Mader TJ, Smithline H, Gibson R Aminophylline in undifferentiated out-of-hospital asystolic cardiac arrest. Resuscitation, 1999, 41: 39-45.
3. Reding JS. Influence of peripheral vascular tone on cardiac resuscitation. Anesthesia and Analgesia, 1965, 44: 746-752.
4. Planta I, Well MH, Planta M, et al. Cardiopulmonary resuscitation in the rat. J Appl Physiol, 1988, 65:2641-2647.
5. Otto CW. Mechanism of action of epinephrine in resuscitation from asphyxia arrest. Crit Care Med, 1981: 321-325.
6. Kette F. Epidemiology and survival rate of out-of-hospital cardiac arrest in north-east Italy: the F.A.C.S.study. Friuli Venezia Gillia Cardiac Arrest Cooperative Study. Resuscitation, 1998, 36:153-159.
7. Ornato J, Peberdy M. The mystery of bradyasystole during cardiac arrest. Ann Emerg Med, 1996, 27:576-587.
8. American Heart Association Emergency Cardiac Care Committee. American Heart Association guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiac care (ECC). J Am Med Assoc, 1992, 268: 2171-2302.
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10. Belardinelli L, Giles W, West A. Ionic mechanisms of adenosine actions in pacemaker cells from rabbit heart. J physiol (Lond), 1988, 405: 615-633.
11. Lerman B, Belardinelli L. Cardiac electrophysiology of adenosine: basic and clinical
concepts. Circulation, 1991,83: 1499-1509.
12. Olsson R, Pearson J. Cardiovascular purinoceptors. Physiol Rev, 1990, 70: 761-765.
13. Lerman B, Engelstein E. Metabolic determinants of defibrillation: role of adenosine. Circ, 1995, 91: 838-844.
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17. Belardinelli L, Linder J, Berne R, The cardiac effects of adenosine. Prog Cardiovasc Dis, 1989, 32: 73-97.
18. Viskin S, Belhassen B, Averbuch M, et al. Aminophylline for bradyasystolic cardiac arrest refractory to atropine and epinephrine. Ann Intern Med, 1993, 118: 279-281.
19. Mader TJ, Gibson P. Adenosine receptor antagonism in refractory asystolic cardiac arrest: results of a human pilot study. Resuscitation, 1997, 35: 35-37.
20. Perouansky M, Shamir M, Hershkowitz E, et al. Successful resuscitation using aminophylline in refractory cardiac arrest with asystole. Resuscitation,1998, 38:39-41.
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39．马勇，孟庆义，钱远宇，等．氨茶碱和肾上腺素合用在心脏停搏患者中的疗效．中国急救医学，2003，23(4)：232-233．
2. Mader TJ, Smithline H, Gibson R Aminophylline in undifferentiated out-of-hospital asystolic cardiac arrest. Resuscitation, 1999, 41: 39-45.
3. Reding JS. Influence of peripheral vascular tone on cardiac resuscitation. Anesthesia and Analgesia, 1965, 44: 746-752.
4. Planta I, Well MH, Planta M, et al. Cardiopulmonary resuscitation in the rat. J Appl Physiol, 1988, 65:2641-2647.
5. Otto CW. Mechanism of action of epinephrine in resuscitation from asphyxia arrest. Crit Care Med, 1981: 321-325.
6. Kette F. Epidemiology and survival rate of out-of-hospital cardiac arrest in north-east Italy: the F.A.C.S.study. Friuli Venezia Gillia Cardiac Arrest Cooperative Study. Resuscitation, 1998, 36:153-159.
7. Ornato J, Peberdy M. The mystery of bradyasystole during cardiac arrest. Ann Emerg Med, 1996, 27:576-587.
8. American Heart Association Emergency Cardiac Care Committee. American Heart Association guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiac care (ECC). J Am Med Assoc, 1992, 268: 2171-2302.
9. Ornato J, Carveth W, Windle J. Pacemaker insertion for prehospital bradyasystolic cardiac arrest. Ann Emerg Med, 1984, 13: 101-103.
10. Belardinelli L, Giles W, West A. Ionic mechanisms of adenosine actions in pacemaker cells from rabbit heart. J physiol (Lond), 1988, 405: 615-633.
11. Lerman B, Belardinelli L. Cardiac electrophysiology of adenosine: basic and clinical
concepts. Circulation, 1991,83: 1499-1509.
12. Olsson R, Pearson J. Cardiovascular purinoceptors. Physiol Rev, 1990, 70: 761-765.
13. Lerman B, Engelstein E. Metabolic determinants of defibrillation: role of adenosine. Circ, 1995, 91: 838-844.
14．孙继文，徐江，袁芳，等．心肌缺氧时慢速心律失常腺苷假说的验证及意义．中华内科杂志，1996，35(4)：242-245．
15．张伟丽，吕国蔚．腺苷对小鼠急性重复缺氧耐受性的影响．基础医学与临床，1996，16(2)：69-72．
16. Bertolet B, Belardinelli L, Avasarala K, et al. Differential antagonism of cardiac actions of adenosine by theophylline. Cardiovasc Res, 1996, 32: 839-845.
17. Belardinelli L, Linder J, Berne R, The cardiac effects of adenosine. Prog Cardiovasc Dis, 1989, 32: 73-97.
18. Viskin S, Belhassen B, Averbuch M, et al. Aminophylline for bradyasystolic cardiac arrest refractory to atropine and epinephrine. Ann Intern Med, 1993, 118: 279-281.
19. Mader TJ, Gibson P. Adenosine receptor antagonism in refractory asystolic cardiac arrest: results of a human pilot study. Resuscitation, 1997, 35: 35-37.
20. Perouansky M, Shamir M, Hershkowitz E, et al. Successful resuscitation using aminophylline in refractory cardiac arrest with asystole. Resuscitation,1998, 38:39-41.
21. Mader TJ, Bertolet B, Ornato JP, et al. Aminophylline in treatment of atropine-resistant bradeasystole. Resuscitation, 2000, 47:105-112.
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