Lyhne Mads D, Dragsbaek Simone J, Hansen Jacob V, Schultz Jacob G, Andersen Asger, Nielsen-Kudsk Jens Erik
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Pulm Circ. 2021 Jun 14;11(3):20458940211022977. doi: 10.1177/20458940211022977. eCollection 2021 Jul-Sep.
Acute pulmonary embolism is a frequent condition in emergency medicine and potentially fatal. Cause of death is right ventricular failure due to increased right ventricular afterload from both pulmonary vascular obstruction and vasoconstriction. Inodilators are interesting drugs of choice as they may improve right ventricular function and lower its afterload. We aimed to investigate the cardiovascular effects of three clinically relevant inodilators: levosimendan, milrinone, and dobutamine in acute pulmonary embolism. We conducted a randomized, blinded, animal study using 18 female pigs. Animals received large autologous pulmonary embolism until doubling of baseline mean pulmonary arterial pressure and were randomized to increasing doses of each inodilator. Effects were evaluated with bi-ventricular pressure-volume loop recordings, right heart catheterization, and blood gas analyses. Induction of pulmonary embolism increased right ventricular afterload and pulmonary pressure ( < 0.05) causing right ventricular dysfunction. Levosimendan and milrinone showed beneficial hemodynamic profiles by lowering right ventricular pressures and volume ( < 0.001) and improved right ventricular function and cardiac output ( < 0.05) without increasing right ventricular mechanical work. Dobutamine increased right ventricular pressure and function ( < 0.01) but at a cost of increased mechanical work at the highest doses, showing an adverse hemodynamic profile. In a porcine model of acute pulmonary embolism, levosimendan and milrinone reduced right ventricular afterload and improved right ventricular function, whereas dobutamine at higher doses increased right ventricular afterload and right ventricular mechanical work. The study motivates clinical testing of inodilators in patients with acute pulmonary embolism and right ventricular dysfunction.
急性肺栓塞是急诊医学中常见的病症，且具有潜在致命性。死亡原因是肺血管阻塞和血管收缩导致右心室后负荷增加，进而引起右心室衰竭。血管扩张剂是备受关注的选择药物，因为它们可能改善右心室功能并降低其后负荷。我们旨在研究三种临床常用血管扩张剂：左西孟旦、米力农和多巴酚丁胺对急性肺栓塞的心血管影响。我们使用18只雌性猪进行了一项随机、双盲动物研究。动物接受大量自体肺栓塞，直至基线平均肺动脉压翻倍，然后随机接受每种血管扩张剂的递增剂量。通过双心室压力 - 容积环记录、右心导管检查和血气分析评估效果。肺栓塞的诱导增加了右心室后负荷和肺动脉压力（<0.05），导致右心室功能障碍。左西孟旦和米力农通过降低右心室压力和容积（<0.001）显示出有益的血流动力学特征，并改善了右心室功能和心输出量（<0.05），而未增加右心室机械功。多巴酚丁胺增加了右心室压力和功能（<0.01），但在最高剂量时以增加机械功为代价，显示出不良的血流动力学特征。在急性肺栓塞的猪模型中，左西孟旦和米力农降低了右心室后负荷并改善了右心室功能，而高剂量的多巴酚丁胺增加了右心室后负荷和右心室机械功。该研究促使对急性肺栓塞和右心室功能障碍患者进行血管扩张剂的临床试验。
