Sidi A, Muehlschlegel J D, Kirby D S, Lobato E B
Department of Anesthesiology, University of Florida, College of Medicine, Gainesville, FL, USA.
Br J Anaesth. 2006 Dec;97(6):799-807. doi: 10.1093/bja/ael276. Epub 2006 Oct 11.
This study examines the effects of phosphodiesterase type III (PDEIII) inhibition vs beta stimulation on global function of the left ventricle (LV) and systemic haemodynamics in a porcine model of acute coronary stenosis with beta blockade.
A total of 18 adult swine were anaesthetized. Micromanometer-tipped catheters were placed in the ascending aorta and LV. Two pairs of ultrasonic dimension transducers were placed in the subendocardium on the short axis proximal to a left anterior descending (LAD) artery occluder and the long axis of the LV. Before ischaemia, i.v. esmolol was infused to decrease baseline heart rate (HR) by approximately 25%, and all animals received an esmolol infusion (150 microg kg(-1) min(-1)). Ischaemia was produced by reducing the flow in the LAD artery by approximately 80%, from 17(4) to 3(2) ml min(-1). Animals were randomized to receive (after esmolol) one of the following: no drug, sham only (Group 1, n=6), control (C); 50 microg kg(-1) i.v. milrinone (Group 2, n=6) followed by 0.375 microg kg(-1) min(-1) (M); or incremental doses of dobutamine (Group 3, n=6) every 10 min (5, 10 and 20 microg kg(-1) min(-1)) (D). Left ventricular function data obtained included HR, arterial and LV pressures, cardiac output (CO), Emax and dP/dT. Measurements were taken during five time periods: before ischaemia (at baseline, after esmolol) and every 10 min during ischaemia (at 10, 20 and 30 min).
The effects of beta blockade and ischaemia had a significant impact on contractility (Emax) in Group M and myocardial performance (left ventricular end-diastolic pressure, LVEDP) in all groups. Left ventricular function (Emax, CO, LVEDP and SVR) was better preserved when milrinone was added in Group M. A moderate dose of dobutamine (10 microg kg(-1) min(-1)) increased CO. Only the high dose (20 microg kg(-1) min(-1)) improved contractility (Emax), but at the expense of increased SVR. Also, LVEDP with either dose of dobutamine remained high and unchanged.
From our limited findings, it would appear that there may, theoretically, be some benefit for using milrinone in preference to other inotropic drugs in the presence of beta blockade. Milrinone administration should be considered in patients with acute ischaemic LV dysfunction and preexisting beta blockade before using other inotropic drugs such as beta stimulants.
本研究在急性冠状动脉狭窄合并β受体阻滞剂的猪模型中，考察磷酸二酯酶Ⅲ型（PDEIII）抑制与β受体激动对左心室（LV）整体功能和全身血流动力学的影响。
共18只成年猪麻醉后，将微测压导管置于升主动脉和左心室内。两对超声尺寸换能器分别置于左前降支（LAD）动脉闭塞器近端短轴的心内膜下和左心室长轴处。缺血前，静脉输注艾司洛尔使基础心率（HR）降低约25%，所有动物均接受艾司洛尔输注（150μg·kg⁻¹·min⁻¹）。通过将LAD动脉血流从17（4）ml·min⁻¹减少至3（2）ml·min⁻¹，即减少约80%来制造缺血。动物随机分组（在艾司洛尔之后）接受以下处理之一：不使用药物，仅做假手术（第1组，n = 6），为对照组（C）；静脉注射米力农50μg·kg⁻¹（第2组，n = 6），随后以0.375μg·kg⁻¹·min⁻¹持续输注（M）；或每10分钟递增剂量的多巴酚丁胺（第3组，n = 6）（5、10和20μg·kg⁻¹·min⁻¹）（D）。获取的左心室功能数据包括HR、动脉压和左心室压力、心输出量（CO）、Emax和dP/dT。在五个时间段进行测量：缺血前（基线时、艾司洛尔后）以及缺血期间每10分钟（10、20和30分钟时）。
β受体阻滞剂和缺血对M组的收缩性（Emax）以及所有组的心肌性能（左心室舒张末期压力，LVEDP）均有显著影响。M组添加米力农时，左心室功能（Emax、CO、LVEDP和SVR）得到更好的保留。中等剂量的多巴酚丁胺（10μg·kg⁻¹·min⁻¹）可增加CO。只有高剂量（20μg·kg⁻¹·min⁻¹）可改善收缩性（Emax），但代价是SVR增加。而且，两种剂量多巴酚丁胺下的LVEDP均保持在较高水平且无变化。
基于我们有限的研究结果，理论上在存在β受体阻滞剂的情况下，使用米力农可能比其他正性肌力药物更具优势。在使用其他正性肌力药物如β受体激动剂之前，对于急性缺血性左心室功能障碍且已存在β受体阻滞剂的患者，应考虑使用米力农。
