Prielipp R C, Rosenthal M H, Pearl R G
Department of Anesthesia, Stanford University Medical Center, California.
Anesth Analg. 1988 Aug;67(8):722-9.
Patients with pulmonary hypertension challenge the anesthesiologist with complex alterations of hemodynamic function. To study the effects of multiple therapeutic interventions, a stable model of pulmonary hypertension in sheep was developed using continuous infusion of the vasoconstrictor U46619, a thromboxane A2-mimetic. The pulmonary and systemic effects of four pulmonary vasodilators (prostaglandin E1, isoproterenol, prostacyclin, and nifedipine) were compared at doses producing equivalent reduction in systemic blood pressure. Although all four drugs decreased pulmonary artery pressure and resistance, distinct differences in drug hemodynamic profiles were found. Prostaglandin E1 and isoproterenol demonstrated the greatest pulmonary specificity, increased cardiac output significantly, and decreased pulmonary vascular resistance. Prostaglandin E1 produced the largest decrease in pulmonary artery pressure (from 31 +/- 1 to 22 +/- 2 mm Hg). Isoproterenol markedly increased heart rate (from 119 +/- 6 to 182 +/- 10 beats/min) and resulted in significant dysrhythmias that necessitated limiting infusion of this drug; isoproterenol did not affect stroke volume. Prostacyclin demonstrated intermediate pulmonary specificity and produced the largest increase in cardiac output (from 1.7 +/- 0.2 to 3.1 +/- 0.3 L/min). Nifedipine exhibited the least pulmonary specificity and was the least effective agent in decreasing pulmonary artery pressure. In this model different pulmonary vasodilators exerted different hemodynamic effects, suggesting that appropriate drug selection for treatment of pulmonary hypertension should depend on baseline heart rate and rhythm, pulmonary artery pressure, systemic artery pressure, arterial oxygenation, and cardiac output.
肺动脉高压患者给麻醉医生带来了血流动力学功能复杂改变的挑战。为研究多种治疗干预措施的效果，通过持续输注血管收缩剂U46619（一种血栓素A2类似物）建立了绵羊肺动脉高压稳定模型。比较了四种肺血管扩张剂（前列腺素E1、异丙肾上腺素、前列环素和硝苯地平）在使体循环血压同等降低剂量时的肺和全身效应。尽管所有四种药物均降低了肺动脉压力和阻力，但发现药物血流动力学特征存在明显差异。前列腺素E1和异丙肾上腺素表现出最大的肺特异性，显著增加心输出量，并降低肺血管阻力。前列腺素E1使肺动脉压力下降幅度最大（从31±1降至22±2 mmHg）。异丙肾上腺素显著增加心率（从119±6增至182±10次/分钟），并导致明显的心律失常，因此需要限制该药物的输注；异丙肾上腺素不影响每搏输出量。前列环素表现出中等程度的肺特异性，使心输出量增加幅度最大（从1.7±0.2增至3.1±0.3 L/分钟）。硝苯地平表现出最小的肺特异性，是降低肺动脉压力最无效的药物。在该模型中，不同的肺血管扩张剂产生不同的血流动力学效应，这表明治疗肺动脉高压时合适的药物选择应取决于基线心率和节律、肺动脉压力、体动脉压力、动脉氧合和心输出量。
