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Esmolol for cardioprotection during resuscitation with adrenaline in an ischaemic porcine cardiac arrest model
Intensive Care Medicine Experimental Pub Date : 2019-12-01 , DOI: 10.1186/s40635-019-0279-5
Hilde Karlsen 1, 2 , Harald Arne Bergan 3 , Per Steinar Halvorsen 2, 4 , Kjetil Sunde 3, 4 , Eirik Qvigstad 5 , Geir Øystein Andersen 5 , Jan Frederik Bugge 3 , Theresa Mariero Olasveengen 3, 6
Affiliation  

BackgroundThe effectiveness of adrenaline during resuscitation continues to be debated despite being recommended in international guidelines. There is evidence that the β-adrenergic receptor (AR) effects of adrenaline are harmful due to increased myocardial oxygen consumption, post-defibrillation ventricular arrhythmias and increased severity of post-arrest myocardial dysfunction. Esmolol may counteract these unfavourable β-AR effects and thus preserve post-arrest myocardial function. We evaluated whether a single dose of esmolol administered prior to adrenaline preserves post-arrest cardiac output among successfully resuscitated animals in a novel, ischaemic cardiac arrest porcine model.MethodsMyocardial infarction was induced in 20 anaesthetized pigs by inflating a percutaneous coronary intervention (PCI) balloon in the circumflex artery 15 min prior to induction of ventricular fibrillation. After 10 min of untreated VF, resuscitation with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated and the animals were randomized to receive an injection of either 1 mg/kg esmolol or 9 mg/ml NaCl, prior to adrenaline. Investigators were blinded to allocation. Successful defibrillation was followed by a 1-h high-flow VA-ECMO before weaning and an additional 1-h stabilization period. The PCI-balloon was deflated 40 min after inflation. Cardiac function pre- and post-arrest (including cardiac output) was assessed by magnetic resonance imaging (MRI) and invasive pressure measurements. Myocardial injury was estimated with MRI, triphenyl tetrazolium chloride (TTC) staining and serum concentrations of cardiac troponin T.ResultsOnly seven esmolol and five placebo-treated pigs were successfully resuscitated and available for post-arrest measurements (p = 0.7). MRI revealed severe but similar reductions in post-arrest cardiac function with cardiac output 3.5 (3.3, 3.7) and 3.3 (3.2, 3.9) l/min for esmolol and control (placebo) groups, respectively (p = 0.7). The control group had larger left ventricular end-systolic and end-diastolic ventricular volumes compared to the esmolol group (75 (65, 100) vs. 62 (53, 70) ml, p = 0.03 and 103 (86, 124) vs. 87 (72, 91) ml, p = 0.03 for control and esmolol groups, respectively). There were no other significant differences in MRI characteristics, myocardial infarct size or other haemodynamic measurements between the two groups.ConclusionsWe observed similar post-arrest cardiac output with and without a single dose of esmolol prior to adrenaline administration during low-flow VA-ECMO in an ischaemic cardiac arrest pig model.

中文翻译:

艾司洛尔对缺血性猪心脏骤停模型中肾上腺素复苏期间的心脏保护作用

背景尽管国际指南中推荐肾上腺素在复苏期间的有效性仍存在争议。有证据表明,肾上腺素的 β-肾上腺素能受体 (AR) 效应是有害的,因为它会增加心肌耗氧量、除颤后室性心律失常和心跳骤停后心肌功能障碍的严重程度。艾司洛尔可以抵消这些不利的 β-AR 效应,从而保护心脏骤停后的心肌功能。我们评估了在新的缺血性心脏骤停猪模型中成功复苏的动物中,在肾上腺素之前给予单剂量的艾司洛尔是否能保持心脏骤停后的心输出量。方法 在诱发心室颤动前 15 分钟,通过在回旋支动脉中充气经皮冠状动脉介入治疗 (PCI) 球囊,在 20 只麻醉猪中诱发心肌梗塞。在未治疗的 VF 10 分钟后,开始使用静脉-动脉体外膜肺氧合 (VA-ECMO) 进行复苏,动物随机接受注射 1 mg/kg 艾司洛尔或 9 mg/ml NaCl,然后再注射肾上腺素。调查人员对分配不知情。成功除颤后,在脱机前进行 1 小时高流量 VA-ECMO 和额外的 1 小时稳定期。PCI 气球在充气 40 分钟后放气。通过磁共振成像 (MRI) 和有创压力测量评估心脏骤停前后的心脏功能(包括心输出量)。心肌损伤通过 MRI、三苯基氯化四唑 (TTC) 染色和心肌肌钙蛋白 T 的血清浓度进行评估。结果只有 7 只艾司洛尔和 5 只安慰剂治疗的猪成功复苏并可用于逮捕后测量(p = 0.7)。MRI 显示,艾司洛尔组和对照组(安慰剂)组的心输出量分别为 3.5 (3.3, 3.7) 和 3.3 (3.2, 3.9) l/min(p = 0.7)。与艾司洛尔组相比,对照组具有更大的左心室收缩末期和舒张末期心室容积(75 (65, 100) vs. 62 (53, 70) ml,p = 0.03 和 103 (86, 124) vs. 87 (72, 91) ml,对照组和艾司洛尔组分别为 p = 0.03)。MRI 特征没有其他显着差异,
更新日期:2019-12-01
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