Matot I, Neely C F
Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia, USA.
Crit Care Med. 1995 Nov;23(11):1851-7. doi: 10.1097/00003246-199511000-00011.
To determine the direct effect of nicardipine on the pulmonary vascular bed of the intact-chest, spontaneously breathing cat, and to compare its effectiveness as a pulmonary vasodilator with the effectiveness of isoproterenol, nitroglycerin, and sodium nitroprusside.
Prospective, controlled animal study. Each animal received all drugs in random order.
Animal laboratory at a university.
Experiments were performed in vivo in ten intact-chest, spontaneously breathing cats with controlled pulmonary blood flow and constant left atrial pressure, during conditions of increased pulmonary vascular tone.
Five animals received intralobar injections of nicardipine (0.1 to 100 micrograms), nitroglycerin (0.1 to 10 micrograms), sodium nitroprusside (0.1 to 100 micrograms), and isoproterenol (0.01 to 1 microgram). Injections were made only when lobar arterial pressure had returned to baseline value. In another five animals, nicardipine, nitroglycerin, and sodium nitroprusside were administered intravenously as a continuous drug infusion in incremental doses titrated to produce a 20% reduction in mean systemic arterial pressure. Each dose was infused until lobar and systemic arterial pressures stabilized. A minimum, 30-min interval was allowed between the infusions of these drugs.
When pulmonary vascular tone was increased with a thromboxane A2 mimetic (analog), U46619 (a stable prostaglandin endoperoxide analog), intralobar injections of nicardipine caused dose-related decreases in lobar arterial pressure without affecting left atrial pressure. When compared with the other vasodilator agents, the order of potency was isoproterenol >> nitroglycerin > nicardipine = sodium nitroprusside. Isoproterenol reduced mean systemic arterial pressure 10 to 100 times greater than nitroglycerin, nicardipine, or sodium nitroprusside. However, there were no significant differences between the latter three drugs in producing a decrease in mean systemic arterial pressure. When infused intravenously, nitroglycerin caused the largest amount of pulmonary vasodilation for a given amount of systemic vasodilation. There were no significant differences between the pulmonary vasodilator responses of nicardipine and sodium nitroprusside.
In this feline model of increased pulmonary vascular resistance, nicardipine exerts a direct vasodilator effect in vivo on the pulmonary vascular bed. Nicardipine, nitroglycerin, and sodium nitroprusside caused similar decreases in systemic arterial pressure. However, the pulmonary vasodilator effect was greater with nitroglycerin, which suggests that nitroglycerin is more vasoselective for the pulmonary vascular bed than nicardipine or sodium nitroprusside.
确定尼卡地平对开胸、自主呼吸猫的肺血管床的直接作用，并将其作为肺血管扩张剂的有效性与异丙肾上腺素、硝酸甘油和硝普钠的有效性进行比较。
前瞻性对照动物研究。每只动物按随机顺序接受所有药物。
一所大学的动物实验室。
在肺血管张力增加的情况下，对10只开胸、自主呼吸、肺血流量受控且左心房压力恒定的猫进行体内实验。
5只动物接受叶内注射尼卡地平（0.1至100微克）、硝酸甘油（0.1至10微克）、硝普钠（0.1至100微克）和异丙肾上腺素（0.01至1微克）。仅在叶动脉压恢复到基线值时进行注射。在另外5只动物中，尼卡地平、硝酸甘油和硝普钠以递增剂量静脉持续输注，滴定至平均体动脉压降低20%。每个剂量持续输注直至叶动脉压和体动脉压稳定。这些药物输注之间至少间隔30分钟。
当用血栓素A2模拟物（类似物）U46619（一种稳定的前列腺素内过氧化物类似物）增加肺血管张力时，叶内注射尼卡地平导致叶动脉压呈剂量相关下降，而不影响左心房压力。与其他血管扩张剂相比，效力顺序为异丙肾上腺素>>硝酸甘油>尼卡地平=硝普钠。异丙肾上腺素降低平均体动脉压的幅度比硝酸甘油、尼卡地平或硝普钠大10至100倍。然而，后三种药物在降低平均体动脉压方面没有显著差异。静脉输注时，对于给定的体循环血管扩张量，硝酸甘油引起的肺血管扩张量最大。尼卡地平与硝普钠的肺血管扩张反应无显著差异。
在这种肺血管阻力增加的猫模型中，尼卡地平在体内对肺血管床发挥直接血管扩张作用。尼卡地平、硝酸甘油和硝普钠导致体动脉压有类似程度的下降。然而，硝酸甘油的肺血管扩张作用更强，这表明硝酸甘油对肺血管床的血管选择性比尼卡地平或硝普钠更高。
