摘要
大剂量肾上腺素（H-Epi）与异丙肾上腺素（Iso）联用可提高冠心病心脏性猝死心肺复苏的自主循环恢复（ROSC）率，缩短ROSC时间，延长ROSC持续时间[1、2]，但两药联用时对心肺复苏的血动学影响未见报道。本组比较了H-Epi与H-Epi+Iso对冠状动脉结扎心脏骤停犬复苏疗效及其对血液动力学影响。
材料与方法：实验动物与分组：东北杂种犬24条，体重14-22公斤，分为三组，每组8条。I组：对照组，常规剂量肾上腺素（Epi），0.02mg/kg/次静脉注射；II组：大剂量肾上腺素组（H-Epi）0.2mg/kg/次静脉注射；III组：大剂量肾上腺素+异丙肾上腺素组（H-Epi+Iso）0.2mg+0.02mg/kg/次静脉注射；急性心肌梗塞及其后心室纤颤的动物模型的制作：实验犬用5%戊巴比妥钠30mg/kg静脉麻醉，背位固定，描记体表II导联心电图，气管切开插管，常规正压人工呼吸，右颈及右股动脉切开，分别行动脉及左心室插管，以多导生理记录仪（RM-6000），测定瞬时动脉血压及左室压力，左侧股静脉插管建立静脉通路。开胸，暴露心脏，切开心包，距左前降支（LAD）起始部0.5cm穿线冠脉结扎，心梗20分钟后，未出现心室纤颤（Vf）者，人工刺激心室造成Vf动物模型，分组用药并以10-20J电量心外膜电击复律，如失败，重复各组用药+电击，每条犬诱发Vf 2-3次。观察指标：1）冠脉结扎前、后体表II导联及心外膜表面心电图（ECG），观察冠脉结扎至出现Vf时间，复律后自主循环持续时间及心电图表现；2）测定左室收缩末压（LVSP），左室舒张末压（LVEDP），左室内压最大变化速率（±dp/dtmax）与
平均动脉压（MAP）；3）从Vf到复律用药剂量与转复机率。所有数据以±S表示，组间对比采用t检验及方差分析进行统计对比。
结果：三组冠脉结扎后Vf出现时间无差异（P>0.05）；H-Epi+Iso组转复机率、自主循环持续时间明显优于H-Epi组。复律后H-Epi+Iso组室性心律失常未见明显增多，H-Epi与H-Epi+Iso两组出现的窦性心动过缓及III°AVB例均在加用异丙肾上腺素后恢复正常窦性心律。冠脉结扎后、Vf出现前三组LVEDP增高，心室率增快，±dp/dtmax及MAP降低，但未见统计学差异。心室颤动转复后三组比较对LVSP影响没有显著差异（P>0.05），但H-Epi+Iso与H-Epi组较Epi组明显降低LVEDP，增加-dp/dtmax（P<0.05），这种改变H-Epi+Iso组比H-Epi组更明显（P均<0.05）。室颤转复后，H-Epi组较Epi组提高平均主动脉压，H-Epi+Iso组平均主动脉压及心率几乎无变化。
结论：冠心病性猝死，多源于室性心动过速，心室纤颤，心肺复苏除采用电击复律外，合理用药至关重要，肾上腺素是心肺复苏（CPR）首选药物，但对其用药量仍是临床讨论的焦点，异丙基肾上腺素因其主要具有β-受体兴奋作用，只提倡选择性与肾上腺素联合应用。本研究通过实验犬冠脉结扎后心室纤颤模型，使用常规量肾上腺素（Epi）、大剂量肾上腺素（H-Epi）与大剂量肾上腺素+异丙基肾上腺素（H-Epi+Iso）三组对心脏复律作用对比，提示：H-Epi组Vf转复机率、ROSC持续时间均明显高于Epi组（70.0%vs58.5%，39.25±63.6 min vs 27.8±20.7min，P均<0.05），与晚近的大多数临床观察一致。Epi剂量基本相同情况下，H-Epi+Iso组的Vf转复率高于H-Epi组（80.95% vs 70.0% P<0.05），
ROSC持续时间亦明显延长（59.83±105.9min vs 39.25±63.6min）。在室颤转复后心电图出现的III°房室传导阻滞（III°AVB）及窦性心动过缓在加用异丙肾上腺素后恢复正常窦性心律，未见室性心律失常增多（见表2）。平均动脉压未见明显下降，其机制可能在于（1）异丙基肾上腺素的β1受体兴奋作用，可使心脏起搏点兴奋性增强，加速房室传导，增快心率，从而提高心肌收缩力，增加心搏血量，改善心脏起搏点下移与传导功能障碍。（2）β2受体兴奋可扩张周围血管，舒张肾及冠状动脉，降低血管总外周阻力，可以拮抗大剂量肾上腺素心肺复苏后出现的高肾上腺素性高血压、保护心肌，减少重要器官如脑、肺、肾及肠道的损伤，有助于大剂量肾上腺素的心肺复苏。
H-Epi+Iso可明显降低LVEDP，增加-dp/dtmax，不影响平均主动脉压及心室率。可见异丙基肾上腺素增快心率，增加心肌收缩力的β效应可能有助于增加心搏量，减少周围血管阻力，从而降低LVEDP、增加-dp/dtmax，抵消其增加心肌耗O2量的作用，改善心脏血液动力学，增加室颤转复机率。在心脏性猝死，尤其冠心病所致心肌损伤时，应考虑提倡大剂量肾上腺素与异丙肾上腺素联用于心肺复苏治疗。
The use of isoproterenol as an adjuvant to high-dose epinephrine in asystolic patients may increase the likelihood of return of spontaneous circulation (ROSC), shorten the time interval from administration of isoproterenol to ROSC, and prolong the time from ROSC to death. But the effects of combined isoproterenol and epinephrine on hemodynamics in cardiopulmonary resuscitation (CPR) is not reported, so we contrast the curative effect of H-Epi and H-Epi+Iso on the resuscitation of dogs’ sudden heart arrest made by coronary artery ligation and the effect on hemodynamics.
Materials and methods: twenty-four northeast hybrid dogs, weight 14~22 kg, were randomized into three groups. group I: control group, treated with routine-dose epinephrine (Epi) 0.02mg/kg every time by intravenous injection; group II: treated with high-dose epinephrine (H-Epi) 0.2mg/kg every time, iv; group III: treated with Epi 0.2mg/kg and Iso 0.02mg/kg every time intravenous injected, which is called H-Epi+Iso group. The animal model of acute myocardial infarction and thereafter ventricular fibrillation (Vf) was made. Epinephrine and isoproterenol were used according to the grouping and electric conversion was used. If conversion was defeated we repeated intravenous drug and electric conversion, every dog had 2 to 3 times of Vf. We observe the following items: 1) Observe the II lead and epicardium electrocardiogram (ECG), detect the time from
coronary ligation to the emerge of Vf and the time of ROSC persisting, and observe the ROSC’s ECG manifest; 2) Detect LVSP, LVEDP, ±dp/dt max, MAP; 3) Detect the dose of drug that was used to make conversion emerged and the odds of conversion.
Results: There was no significant difference between the three groups as the time of Vf emerging concerned (P>0.05). The conversion odds and the ROSC persisting time of the H-Epi+Iso group were significantly superior to those of H-Epi group. The ventricular arrhythmia of H-Epi+Iso group was not increased significantly after conversion. The sinus bradycardia and III°AVB, emerged in H-Epi group and H-Epi+Iso group, were converted to sinus rhythm after Iso was used. We detected that LVEDP increased, ventricular rate increased, ±dp/dtmax and MAP decreased in all the three groups, and there was no significant difference between the three groups as the above concerned. After Vf conversed there was no significant difference between the three groups as the effect of conversion on LVSP concerned, but LVEDP increased significantly and ±dp/dtmax increased significantly in H-Epi group and H-Epi+Iso group contrasted to Epi group (P<0.05), and the above change was more significant in H-Epi+Iso group (P<0.05). After Vf conversed the MAP of H-Epi group was higher than that of Epi group, the MAP and heart rate of H-Epi+Iso group hardly changed.
Conclusion: The sudden heart death of coronary heart disease
patients is usually coming from ventricular tachycardia and Vf, the combined treatment of electric conversion and drugs is very important to CPR. Epinephrine is preferred in the course of CPR, but the dose of Epi is still a discussion focus to clinic. Iso is advocated to be use only as combined with Epi, because it is a stimulant of β–receptor. In this research we made animal model of Vf after coronary ligation, and used routine dose of Epi, high dose of Epi and high dose of Epi combined with Iso in three groups. The result manifested that the odds of conversion and the time of ROSC persisting of H-Epi group is superior to those of Epi group (70.0%vs58.5%, 39.25±63.6 min vs 27.8±20.7min, P<0.05), which is accord with the latest clinical report. When the dose of Epi is equal, the odds of conversion of H-Epi+Iso group is increased contrasted to H-Epi group (80.95% vs 70.0% P<0.05) and the ROSC persisting time of H-Epi+Iso group is prolonged contrasted to H-Epi group (59.83±105.9 min vs 39.25±63.6min). The sinus bradycardia and III°AVB emerged after conversion, but were converted to normal sinus rhythm after the use of Iso, without ventricular tach
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