Department of Emergency Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing, China.
PLoS One. 2013 Dec 18;8(12):e82677. doi: 10.1371/journal.pone.0082677. eCollection 2013.
Recent experimental and clinical studies have indicated that the β-adrenergic effect of epinephrine significantly increases the severity of post resuscitation myocardial dysfunction. The aim of the study was to investigate whether the short-acting β₁-selective adrenergic blocking agent, esmolol, would attenuate post resuscitation myocardial dysfunction in a porcine model of cardiac arrest.
After 8 min of untreated ventricular fibrillation and 2 min of basic life support, 24 pigs were randomized to three groups (n = 8 per group), which received central venous injection of either epinephrine combined with esmolol (EE group), epinephrine (EP group), or saline (SA group). Hemodynamic status and blood samples were obtained at 0, 30, 60, 120, 240 and 360 min after return of spontaneous circulation (ROSC). Surviving pigs were euthanatized at 24 h after ROSC, and the hearts were removed for analysis by electron microscopy, Western blotting, quantitative real-time polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Compared with the EP and SA groups, EE group had a better outcome in hemodynamic function, (improved dp/dt maxima and minima and cardiac output) (P<0.05), and improved oxygen metabolism (oxygen delivery and oxygen consumption) (P<0.05), which suggesting that EE can protect myocardial tissue from injury and improve post-resuscitation myocardial dysfunction. The protective effect of EE also correlated with reducing cardiomyocyte apoptosis, evidenced by reducing TUNEL-positive cells, increasing anti-apoptotic Bcl-2/Bax ratio and suppression of caspase-3 activity in myocardium.
Esmolol, a short-acting β₁-selective adrenergic blocking agent, given during CPR has significant effects on attenuating post resuscitation myocardial dysfunction. The current study provides a potential pharmacologic target for post resuscitation myocardial dysfunction.
最近的实验和临床研究表明,肾上腺素的β-肾上腺素能作用显著增加复苏后心肌功能障碍的严重程度。本研究旨在探讨短效β₁-选择性肾上腺素能阻滞剂艾司洛尔是否会减轻心脏骤停猪模型的复苏后心肌功能障碍。
在未经治疗的心室颤动 8 分钟和基本生命支持 2 分钟后,24 头猪随机分为三组(每组 8 头),分别接受静脉内注射肾上腺素联合艾司洛尔(EE 组)、肾上腺素(EP 组)或生理盐水(SA 组)。在自主循环恢复(ROSC)后 0、30、60、120、240 和 360 分钟时获取血流动力学状态和血液样本。存活的猪在 ROSC 后 24 小时安乐死,并取出心脏进行电镜、Western 印迹、实时定量聚合酶链反应和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记(TUNEL)检测分析。与 EP 组和 SA 组相比,EE 组的血流动力学功能(改善 dp/dt 最大值和最小值以及心输出量)(P<0.05)和氧代谢(氧输送和氧消耗)(P<0.05)更好,表明 EE 可保护心肌组织免受损伤并改善复苏后心肌功能障碍。EE 的保护作用还与减少心肌细胞凋亡有关,证据是 TUNEL 阳性细胞减少,抗凋亡 Bcl-2/Bax 比值增加,以及心肌中 caspase-3 活性抑制。
在 CPR 期间给予艾司洛尔,一种短效β₁-选择性肾上腺素能阻滞剂,对减轻复苏后心肌功能障碍有显著作用。本研究为复苏后心肌功能障碍提供了一个潜在的药物靶点。