实验性脓毒症小鼠的心率控制：伊伐布雷定和β受体阻滞剂的比较

本文由“罂粟花”授权转载

背景与目的

心动过速是脓毒症的特征表现之一。然而，心率加快不仅减少了心室充盈，而且增加了心肌耗氧量。β受体阻滞剂和伊伐布雷定（窦房结If通道的选择性抑制剂）均能控制窦性心动过速，但后者无负性肌力作用。本研究旨在评价伊伐布雷定与β受体阻滞剂（阿替洛尔）用于小鼠腹膜炎时的血流动力学效应。

方  法

雄性C57BL6小鼠诱发腹膜炎（盲肠结扎和穿刺）后2h，腹腔注射伊伐布雷定（3μg/g）、阿替洛尔（3μg/g）或安慰剂。使用有创(左心室置管)和无创(经胸超声心动图)监测来评估术后20h的血流动力学变化，包括心率、血压、左心室收缩和舒张功能(n=10只小鼠/组)。并评估三组小鼠间另一亚组(n=20只小鼠/组)术后30和60h的总死亡率。描述性数据以中位数(25%至75%)表示。

结 果  

清醒动物的经胸超声心动图评估发现，与安慰剂（601次/min[547~612]）相比，伊伐布雷定（447次/min[430~496]）和阿替洛尔（482次/min[412~505]）可减慢脓毒症引起的心动过速（P<0.001；P=0.004）。不同于伊伐布雷定，与服用安慰剂的脓毒症小鼠相比，阿替洛尔降低了心输出量、收缩压和左心室收缩功能(通过射血分数、最大左心室压力升高和前壁应变率进行评估)。与安慰剂组（5/20，25%；P=0.224）相比，伊伐布雷定（6/20，30%）或阿替洛尔（7/20，35%）用于脓毒症小鼠60h后的存活率并无差异。

结 论

伊伐布雷定或阿替洛尔控制心率的效果相似，但前者可维持血压、心输出量和左心室收缩功能。

原始文献来源及摘要

Bedet A,  Voiriot G,  Ternacle J,  et al. Heart Rate Control during Experimental Sepsis in Mice: Comparison of Ivabradine and β-Blockers.[J]. Anesthesiology, 2020, 132: 321-329.

Abstract

Background: Tachycardia is a hallmark of sepsis. An elevated heart rate could impair ventricular filling and increase myocardial oxygen demand. β-Blockers and ivabradine (a selective inhibitor of If channels in the sinoatrial node) are both able to control sinus tachycardia, with the latter drug being devoid of negative inotropic effect. This work aimed at assessing the hemodynamic effects of ivabradine as compared with a β-blocker (atenolol) during murine peritonitis.

Methods: Ivabradine (3 μg/g), atenolol (3 μg/g), or placebo was administered intraperitoneally 2 h after induction of peritonitis (cecal ligation and puncture) in male C57BL6 mice. The authors used invasive (left ventricular catheterization) and noninvasive (transthoracic echocardiography) monitoring to assess hemodynamics 20 h after surgery, including heart rate, blood pressure, left ventricular systolic, and diastolic function (n = 10 mice/group). The authors also assessed overall mortality 30 and 60 h after surgery in a distinct subset of animals (n = 20 mice/group). Descriptive data are presented as median (25th to 75th percentile).

Results: As compared with placebo (601 beats/min [547 to 612]), ivabradine (447 beats/min [430 to 496]) and atenolol (482 beats/min [412 to 505]) blunted sepsis-induced tachycardia assessed by transthoracic echocardiography in awake animals (P < 0.001 and P = 0.004, respectively). Unlike ivabradine, atenolol reduced cardiac output, systolic blood pressure, and left ventricular systolic function (as assessed by ejection fraction, maximal left ventricular pressure rise, and anterior wall strain rate) as compared with septic mice receiving placebo. There was no difference in survival 60 h after sepsis induction with ivabradine (6 of 20, 30%) or atenolol (7 of 20, 35%), as compared with placebo (5 of 20, 25%; P = 0.224).

Conclusions: Heart rate control could be similarly achieved by ivabradine or atenolol, with preservation of blood pressure, cardiac output, and left ventricular systolic function with the former drug.

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