Feltes T F, Fike C D, Hansen T N
Pediatr Pharmacol (New York). 1986;5(4):261-71.
The purpose of this study was to test the hypothesis that nifedipine when given with dopamine will lower pulmonary vascular resistance in hypoxic lambs without altering systemic vascular resistance. We studied six unanesthetized lambs (ranging in age from 13 to 35 days) as they breathed air or on a separate day as they breathed 10% O2 and 3% CO2 in nitrogen. First, we infused dopamine at progressively higher rates (10, 20, 40, 80, and 160 micrograms/kg/min) while measuring mean aortic, pulmonary arterial, and left atrial pressures and heart rate continuously and cardiac output and arterial blood gas tensions at frequent intervals. Then, while maintaining the dopamine infusion at 160 micrograms/kg/min, we infused boluses of nifedipine intravenously (10 micrograms/kg) every 5 min until a cumulative dose of 50 micrograms/kg had been administered. In both groups of lambs, cardiac output increased with increasing rates of dopamine infusion (baseline to maximum dopamine: 260 +/- 20 ml/kg/min to 420 +/- 60 ml/kg/min for normoxic lambs and 400 +/- 50 ml/kg/min to 560 +/- 80 ml/kg/min for hypoxic lambs). While systemic vascular resistance and pulmonary vascular resistance did not change significantly in either group during dopamine infusion, the ratio of pulmonary vascular resistance to systemic vascular resistance increased at low rates of infusion and decreased at high rates. The peak in this ratio occurred at a rate of infusion of 20-40 micrograms/kg/min in normoxic lambs and 40-80 micrograms/kg/min in hypoxic lambs. Infusion of nifedipine did not affect cardiac output in normoxic lambs but decreased it significantly in hypoxic lambs. Nifedipine infusion did not affect pulmonary vascular resistance in the normoxic lambs and increased pulmonary vascular resistance in the hypoxic lambs. We conclude that nifedipine, even when given with high doses of dopamine, is not a specific pulmonary vasodilator.
硝苯地平与多巴胺合用时,可降低低氧血症羔羊的肺血管阻力,而不改变体循环血管阻力。我们研究了6只未麻醉的羔羊(年龄在13至35天之间),它们分别在呼吸空气时,或在另一天呼吸含10%氧气和3%二氧化碳的氮气时进行实验。首先,我们以逐渐升高的速率(10、20、40、80和160微克/千克/分钟)输注多巴胺,同时连续测量平均主动脉压、肺动脉压和左心房压以及心率,并定期测量心输出量和动脉血气张力。然后,在将多巴胺输注速率维持在160微克/千克/分钟的同时,我们每隔5分钟静脉推注一次硝苯地平(10微克/千克),直至累积剂量达到50微克/千克。在两组羔羊中,心输出量均随着多巴胺输注速率的增加而增加(正常氧合羔羊从基线到最大多巴胺剂量:260±20毫升/千克/分钟至420±60毫升/千克/分钟,低氧血症羔羊从400±50毫升/千克/分钟至560±80毫升/千克/分钟)。在多巴胺输注期间,两组的体循环血管阻力和肺血管阻力均无显著变化,但在低输注速率时肺血管阻力与体循环血管阻力的比值升高,在高输注速率时降低。该比值的峰值在正常氧合羔羊中出现在输注速率为20 - 40微克/千克/分钟时,在低氧血症羔羊中出现在输注速率为40 - 80微克/千克/分钟时。输注硝苯地平对正常氧合羔羊的心输出量无影响,但在低氧血症羔羊中使其显著降低。输注硝苯地平对正常氧合羔羊的肺血管阻力无影响,而在低氧血症羔羊中使其升高。我们得出结论,即使与高剂量多巴胺合用,硝苯地平也不是一种特异性肺血管扩张剂。