Ek L, Björkman J A, Carlsson E, Johansson B
Acta Med Scand Suppl. 1982;659:39-52. doi: 10.1111/j.0954-6820.1982.tb00835.x.
Experiments were performed on 5 resting conscious dogs supplied with an electromagnetic flow probe on the ascending aorta and a chronic aortic catheter for pressure recording. The animals were used repeatedly in four different types of experiment involving i.v. administration of 1. saline (controls), 2. prenalterol 45 nmol/kg (approximately 10 micrograms/kg) followed by an additional dose of 135 nmol/kg 20 min later, 3. ouabain 50 nmol/kg (approximately 30 micrograms/kg) and 4. a combination of protocols 2. and 3. Ouabain and the low dose of prenalterol exerted clear-cut positive inotropic effects as reflected in increased stroke volume and max dF/dt without significant changes in heart rate or arterial pressure. The PQ interval increased with ouabain but decreased with prenalterol. The higher dose of prenalterol caused a further rise in max dF/dt, a further shortening of the PQ time, increased heart rate and reduction in systemic vascular resistance. Higher doses of ouabain could not be given due to side-effects (vomiting). The combined treatment with ouabain and prenalterol showed their inotropic responses to be additive. Arrhythmias did not occur in any of the animals at the applied dose levels of the drugs. The experiments show that prenalterol through its beta 1-adrenoceptor stimulating action exerts a positive inotropic effect which surpasses that of emetic doses of ouabain. The inotropic response at moderate doses occurs without a change in heart rate. This fact and the apparent lack of influence of prenalterol on vascular alpha- and beta 2-adrenoceptors make the substance potentially useful clinically as an inotropic agent in cardiac failure, particularly in view of its relatively long duration of action.
对5只清醒的静息犬进行实验,在升主动脉上安装电磁流量探头,并插入一根慢性主动脉导管用于记录压力。这些动物在四种不同类型的实验中被重复使用,实验包括静脉注射:1. 生理盐水(对照组);2. 普瑞特罗45 nmol/kg(约10微克/千克),20分钟后再追加剂量135 nmol/kg;3. 哇巴因50 nmol/kg(约30微克/千克);4. 方案2和3的联合应用。哇巴因和低剂量的普瑞特罗产生了明显的正性肌力作用,表现为每搏量增加和最大dF/dt增加,而心率或动脉压无显著变化。哇巴因使PQ间期延长,而普瑞特罗使其缩短。较高剂量的普瑞特罗导致最大dF/dt进一步升高、PQ时间进一步缩短、心率增加以及全身血管阻力降低。由于副作用(呕吐),无法给予更高剂量的哇巴因。哇巴因和普瑞特罗联合治疗显示其正性肌力反应具有相加性。在所应用的药物剂量水平下,任何动物均未发生心律失常。实验表明,普瑞特罗通过其β1 - 肾上腺素能受体刺激作用发挥正性肌力作用,其作用超过催吐剂量的哇巴因。中等剂量时的正性肌力反应在心率无变化的情况下发生。这一事实以及普瑞特罗对血管α和β2 - 肾上腺素能受体明显缺乏影响,使得该物质在临床上有可能作为心力衰竭的正性肌力药物,特别是考虑到其相对较长的作用持续时间。