Bakkehaug J P, Naesheim T, Torgersen Engstad E, Kildal A B, Myrmel T, How O-J
Cardiovascular Research Group, Institute of Medical Biology, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
Institute of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.
Acta Physiol (Oxf). 2016 Oct;218(2):78-88. doi: 10.1111/apha.12704. Epub 2016 May 24.
Compensatory tachycardia can potentially be deleterious in acute heart failure. In this study, we tested a therapeutic strategy of combined inotropic support (dobutamine) and selective heart rate (HR) reduction through administration of ivabradine.
In an open-chest pig model (n = 12) with left ventricular (LV) post-ischaemia dysfunction, cardiac function was assessed by LV pressure catheter and sonometric crystals. Coronary flow and blood samples from the coronary sinus were used to measure myocardial oxygen consumption (MVO2 ). LV energetics was assessed by comparing MVO2 with cardiac work at a wide range of workloads.
In the post-ischaemia heart, dobutamine (5 μg kg(-1) min(-1) ) increased cardiac output (CO) by increasing HR from 102 ± 21 to 131 ± 16 bpm (beats per min; P < 0.05). Adding ivabradine (0.5 mg kg(-1) ) slowed HR back to 100 ± 9 bpm and increased stroke volume from 30 ± 5 to 36 ± 5 mL (P < 0.05) by prolonging diastolic filling time and increasing end-diastolic dimensions. Adding ivabradine had no adverse effects on CO, mean arterial pressure and cardiac efficiency. Similar findings on efficiency and LV function were also seen using an ex vivo working mouse heart protocol.
A combined infusion of dobutamine and ivabradine had a neutral effect on post-ischaemia LV efficiency and increased left ventricular output without an increase in HR.
代偿性心动过速在急性心力衰竭中可能具有潜在危害。在本研究中，我们测试了一种联合使用正性肌力支持药物（多巴酚丁胺）和通过静脉注射伊伐布雷定选择性降低心率（HR）的治疗策略。
在一个具有左心室（LV）缺血后功能障碍的开胸猪模型（n = 12）中，通过左心室压力导管和超声晶体评估心脏功能。使用冠状动脉血流和来自冠状窦的血样来测量心肌耗氧量（MVO2）。通过在广泛的工作负荷范围内比较MVO2与心脏作功来评估左心室能量学。
在缺血后心脏中，多巴酚丁胺（5 μg kg⁻¹ min⁻¹）通过将心率从102 ± 21次/分钟增加到131 ± 16次/分钟（每分钟心跳数；P < 0.05）来增加心输出量（CO）。添加伊伐布雷定（0.5 mg kg⁻¹）使心率减慢至100 ± 9次/分钟，并通过延长舒张期充盈时间和增加舒张末期尺寸使每搏输出量从30 ± 5 mL增加到36 ± 5 mL（P < 0.05）。添加伊伐布雷定对CO、平均动脉压和心脏效率没有不良影响。使用离体工作小鼠心脏实验方案也观察到了关于效率和左心室功能的类似结果。
多巴酚丁胺和伊伐布雷定联合输注对缺血后左心室效率具有中性作用，并增加左心室输出量而不增加心率。
