Drummond W H, Williams B J, Webb I B
Pediatr Pharmacol (New York). 1984;4(2):59-72.
We used chronically instrumented, unanesthetized lambs to study the circulatory response to tolazoline and prostacyclin. During normoxia, tolazoline given in ten incremental doses from .01 to 6 mg/kg increased heart rate beginning at 1.1 mg/kg, cardiac output, and PVR/SVR. Systemic vascular resistance (SVR) fell, and pulmonary vascular resistance (PVR) did not change. Tolazoline given during hypoxemia, when basal PVR and heart rate were increased, caused SVR to fall at both 3.3 and 6.6 mg/kg doses, while PVR fell only at 6.6 mg/kg. During hypoxemia, even .01 mg/kg of tolazoline caused tachycardia, but cardiac output rose insignificantly, due to high variability. Prostacyclin given during normoxia caused SVR to fall without change in PVR. A significantly greater fall in SVR occurred when 6.6 micrograms/kg of PGI2 was the first dose given than when the same dose was given later in an incremental titration. Thus, neither drug is a selective pulmonary vasodilator in unanesthetized lambs. Dosing protocol may be important in determining the overall circulatory response to a given drug dose.
我们使用长期植入仪器且未麻醉的羔羊来研究对妥拉唑啉和前列环素的循环反应。在常氧状态下，以0.01至6mg/kg的十个递增剂量给予妥拉唑啉，从1.1mg/kg开始心率增加，心输出量以及肺血管阻力/体循环血管阻力（PVR/SVR）增加。体循环血管阻力（SVR）下降，而肺血管阻力（PVR）未改变。在低氧血症期间给予妥拉唑啉，此时基础PVR和心率增加，在3.3和6.6mg/kg剂量时导致SVR下降，而PVR仅在6.6mg/kg时下降。在低氧血症期间，即使0.01mg/kg的妥拉唑啉也会引起心动过速，但由于变异性高，心输出量无明显增加。在常氧状态下给予前列环素导致SVR下降而PVR无变化。当给予6.6微克/千克的前列环素（PGI2）作为首剂时，SVR的下降幅度明显大于在递增滴定中稍后给予相同剂量时。因此，在未麻醉的羔羊中，这两种药物都不是选择性肺血管扩张剂。给药方案在确定对给定药物剂量的整体循环反应中可能很重要。
