Inbar S, Schrader B J, Kaufmann E, Vestal R E, Rich S
Department of Medicine, University of Illinois, Chicago 60612.
J Am Coll Cardiol. 1993 Feb;21(2):413-8. doi: 10.1016/0735-1097(93)90683-r.
The purpose of this study was to evaluate the effects of vasodilator combination therapy in patients with primary pulmonary hypertension.
Calcium channel blockers and adenosine have each been shown to be effective in reducing pulmonary artery pressure and pulmonary vascular resistance in patients with primary pulmonary hypertension. However, the effects of combining these vasodilators have not been studied.
To test the combination, 12 patients were placed on oral nifedipine and 3 on diltiazem therapy, using a dose titrated to maximal effect (mean nifedipine dose 103 +/- 24 mg, mean diltiazem dose 300 +/- 49 mg). Patients were then given maintenance doses of the calcium channel blocker at half the cumulative loading dose at 6-h intervals. One hour after the maintenance dose of calcium blocker, all patients received an infusion of adenosine, starting with 50 micrograms/kg per min and increasing by 50 micrograms/kg per min at 2-min intervals to a maximally tolerated dose (180 +/- 63 micrograms/kg per min).
Ten patients responded to calcium channel blockers (defined as a > or = 20% decrease in pulmonary vascular resistance), with a 16% decrease in mean pulmonary artery pressure (p = 0.057), a 39% decrease in pulmonary vascular resistance (p = 0.002) and a 24% increase in stroke volume (p = 0.007). Five patients were nonresponders, with no significant changes in pulmonary artery pressure, pulmonary vascular resistance, cardiac index or stroke volume. In the calcium channel blocker responders, the combination of adenosine and calcium blocker reduced pulmonary vascular resistance by 49%, increased stroke volume by 33% and decreased mean pulmonary artery pressure by 14% compared with drug-free baseline values. In nonresponders, combination therapy resulted in nonsignificant changes in pulmonary artery pressure and pulmonary vascular resistance.
Adenosine has the ability to further decrease pulmonary artery pressure and pulmonary vascular resistance in patients with primary pulmonary hypertension who respond to calcium channel blockers. Those who fail to respond to these agents have little added effect from adenosine.
本研究旨在评估血管扩张剂联合治疗对原发性肺动脉高压患者的疗效。
钙通道阻滞剂和腺苷已被证明各自对降低原发性肺动脉高压患者的肺动脉压和肺血管阻力有效。然而，联合使用这些血管扩张剂的效果尚未得到研究。
为测试联合用药，12例患者接受口服硝苯地平治疗，3例接受地尔硫䓬治疗，剂量滴定至最大效应（硝苯地平平均剂量103±24mg，地尔硫䓬平均剂量300±49mg）。然后患者每6小时接受一次钙通道阻滞剂维持剂量，为累积负荷剂量的一半。在钙通道阻滞剂维持剂量给药1小时后，所有患者接受腺苷输注，起始剂量为50微克/千克每分钟，每隔2分钟增加50微克/千克每分钟，直至最大耐受剂量（180±63微克/千克每分钟）。
10例患者对钙通道阻滞剂有反应（定义为肺血管阻力降低≥20%），平均肺动脉压降低16%（p=0.057），肺血管阻力降低39%（p=0.002），每搏量增加24%（p=0.007）。5例患者无反应，肺动脉压、肺血管阻力、心脏指数或每搏量无显著变化。在对钙通道阻滞剂有反应的患者中，与无药物基线值相比，腺苷与钙通道阻滞剂联合使用使肺血管阻力降低49%，每搏量增加33%，平均肺动脉压降低14%。在无反应者中，联合治疗导致肺动脉压和肺血管阻力无显著变化。
腺苷能够进一步降低对钙通道阻滞剂有反应的原发性肺动脉高压患者的肺动脉压和肺血管阻力。对这些药物无反应的患者，腺苷几乎没有额外效果。
