Pagel P S, Hettrick D A, Warltier D C
Medical College of Wisconsin MEB, Milwaukee 53226, USA.
Basic Res Cardiol. 1996 Jul-Aug;91(4):296-307. doi: 10.1007/BF00789302.
We examined and compared the effects of levosimendan, a new myofilament calcium sensitizer with phosphodiesterase inhibiting activity, pimobendan, and milrinone on left ventricular-arterial coupling and mechanical efficiency in 21 experiments performed in open-chest, barbiturate-anesthetized dogs instrumented for measurement of aortic and left ventricular (LV) pressure (micromanometer-tipped catheter), +dP/dt, and LV volume (conductance catheter). Myocardial contractility was assessed with the end-systolic pressure-volume relation (Ees) and preload recruitable stroke work (Msw) generated from a series of differentially loaded LV pressure-volume diagrams. LV-arterial coupling and mechanical efficiency were determined by the ratio of Ees to effective arterial elastance (Ea; the ratio of end-systolic arterial pressure to stroke volume) and the ratio of stroke work (SW) to pressure-volume area (PVA), respectively. Levosimendan (0.75, 1.5, and 3.0 micrograms.kg-1.min-1) significantly (p < 0.05) increased heart rate, +dP/dt, and ejection fraction (EF) and decreased mean arterial pressure (MAP), pressure-work index (PWI; an estimate of myocardial-oxygen consumption), and LV systolic and end-diastolic pressures (LVSP and LVEDP) and volumes (EDV and ESV). Levosimendan-induced augmentation of myocardial contractility (Ees, Msw and +dP/dt) and reductions in LV afterload (Ea) caused increases in the Ees/Ea ratio (0.61 +/- 0.10 during control to 3.3 +/- 0.7 during the high dose) consistent with enhancement of LV-arterial coupling. Levosimendan increased SW/PVA (0.48 +/- 0.05 during control to 0.84 +/- 0.04 during the high dose), indicating this drug improves the transfer of myocardial potential energy to external work. Levosimendan also increased the ratio of SW to PWI (109 +/- 18 during control to 255 +/- 50 mmHg.min.100g during the high dose), suggesting that myocardial metabolic efficiency was improved as well. Like levosimendan, pimobendan and milrinone (10, 20, and 40 and 1.0, 2.0, and 4.0 micrograms.kg-1.min-1, respectively) increased HR, +dP/dt, EF, Ees, and Msw and decreased MAP, LVSP, LVEDP, EDV, ESV, and Ea. In contrast to levosimendan, neither agent reduced PWI. Pimobendan and milrinone caused dose-related increases in Ees/Ea, SW/PVA, and SW/PWI. The results indicate that levosimendan, pimobendan, and milrinone augment myocardial contractility, produce venous and arteriolar vasodilation, and enhance LV-arterial coupling and mechanical efficiency in open-chest, barbiturate-anesthetized dogs.
我们在21个实验中，对左西孟旦（一种具有磷酸二酯酶抑制活性的新型肌丝钙敏化剂）、匹莫苯丹和米力农对开胸、巴比妥类麻醉犬左心室-动脉耦合及机械效率的影响进行了研究和比较。这些犬均安装了用于测量主动脉和左心室（LV）压力（微测压导管尖端）、+dP/dt以及LV容积（电导导管）的仪器。通过一系列不同负荷的LV压力-容积图得出的收缩末期压力-容积关系（Ees）和预负荷可募集搏功（Msw）来评估心肌收缩力。LV-动脉耦合和机械效率分别通过Ees与有效动脉弹性（Ea；收缩末期动脉压力与搏出量之比）的比值以及搏功（SW）与压力-容积面积（PVA）的比值来确定。左西孟旦（0.75、1.5和3.0微克·kg-1·min-1）显著（p < 0.05）增加心率、+dP/dt和射血分数（EF），并降低平均动脉压（MAP）、压力-功指数（PWI；心肌氧消耗的估计值）以及LV收缩压和舒张压（LVSP和LVEDP）和容积（EDV和ESV）。左西孟旦引起的心肌收缩力增强（Ees、Msw和 +dP/dt）以及LV后负荷降低（Ea）导致Ees/Ea比值增加（对照期间为0.61±0.10，高剂量期间为3.3±0.7），这与LV-动脉耦合增强一致。左西孟旦增加了SW/PVA（对照期间为0.48±0.05，高剂量期间为0.84±0.04），表明该药改善了心肌势能向外部功的转化。左西孟旦还增加了SW与PWI的比值（对照期间为109±18，高剂量期间为255±50 mmHg·min·100g），提示心肌代谢效率也得到了改善。与左西孟旦一样，匹莫苯丹和米力农（分别为10、20和40以及1.0、2.0和4.0微克·kg-1·min-1）增加HR、+dP/dt、EF、Ees和Msw，并降低MAP、LVSP、LVEDP、EDV、ESV和Ea。与左西孟旦不同，这两种药物均未降低PWI。匹莫苯丹和米力农引起Ees/Ea、SW/PVA和SW/PWI与剂量相关的增加。结果表明，左西孟旦、匹莫苯丹和米力农可增强心肌收缩力，引起静脉和小动脉血管舒张，并增强开胸、巴比妥类麻醉犬的LV-动脉耦合及机械效率。
