Montalescot G, Drobinski G, Meurin P, Maclouf J, Sotirov I, Philippe F, Choussat R, Morin E, Thomas D
Service de Cardiologie, Centre Hospitalier Universitaire, Pitié-Salpétrière, INSERM U348, Lariboisière, France.
Am J Cardiol. 1998 Sep 15;82(6):749-55. doi: 10.1016/s0002-9149(98)00439-1.
Long-term administration of prostacyclin (PGI2) improves the hemodynamic state, symptoms, and survival in patients with primary pulmonary hypertension, but it increases mortality in patients with heart failure despite obvious hemodynamic benefits when it is given acutely. We evaluated the mechanisms of action of PGI2 in patients with heart failure and secondary pulmonary hypertension. Nineteen patients with end-stage heart failure and pulmonary hypertension, all candidates for heart transplantation, underwent right- and left sided cardiac catheterization with micromanometer-tipped catheters and were tested for PGI2 at incremental doses. PGI2 infusion significantly improved pulmonary hemodynamics with a 47% reduction in pulmonary vascular resistance (p=0.0003) and a doubling of pulmonary artery compliance (p <0.0001), reflecting improvement in pulmonary vascular tone. The dose of PGI2 necessary to reach this hemodynamic effect correlated significantly to the baseline severity of pulmonary artery compliance (r=0.54, p=0.01). Furthermore, PGI2 produced a significant positive inotropic effect (contractile element maximum velocity increased from 1.10+/-0.09 to 1.33+/-0.13 circ/s, p <0.009). The hemodynamic effects of PGI2 infusion were independent of the plasma and urinary levels of endogen prostaglandins. Thus, PGI2 at therapeutic doses exerts a positive inotropic effect in patients with heart failure, which may explain the increased mortality rate observed with the long-term use of PGI2 in this type of patient. The spectacular acute benefits on right ventricular afterload, however, may be useful in unstable patients with heart failure and secondary pulmonary hypertension or in transplanted patients with acute right ventricular failure of the donor heart.
长期应用前列环素（PGI2）可改善原发性肺动脉高压患者的血流动力学状态、症状并提高生存率，但在心力衰竭患者中，尽管急性应用时具有明显的血流动力学益处，却会增加死亡率。我们评估了PGI2在心力衰竭合并继发性肺动脉高压患者中的作用机制。19例终末期心力衰竭合并肺动脉高压且均为心脏移植候选者的患者，采用带微测压头导管进行左右心导管检查，并接受递增剂量的PGI2检测。PGI2输注显著改善了肺血流动力学，肺血管阻力降低47%（p = 0.0003），肺动脉顺应性增加一倍（p < 0.0001），反映出肺血管张力得到改善。达到这种血流动力学效应所需的PGI2剂量与肺动脉顺应性的基线严重程度显著相关（r = 0.54，p = 0.01）。此外，PGI2产生了显著的正性肌力作用（收缩成分最大速度从1.10±0.09增加至1.33±0.13周/秒，p < 0.009）。PGI2输注的血流动力学效应与内源性前列腺素的血浆和尿液水平无关。因此，治疗剂量的PGI2对心力衰竭患者具有正性肌力作用，这可能解释了在这类患者中长期使用PGI2观察到的死亡率增加的现象。然而，PGI2对右心室后负荷的显著急性益处，可能对心力衰竭合并继发性肺动脉高压的不稳定患者或供体心脏急性右心室衰竭的移植患者有用。
