Sturniolo R, Altavilla D, Berlinghieri M C, Squadrito F, Caputi A P
Institutes of Pharmacology, Faculty of Medicine, University of Messina, Italy.
Circ Shock. 1988;24(1):43-53.
Splanchnic artery occlusion (SAO) shock made by clamping splanchnic arteries for 45 min was performed in female rats infused for 30 min with vehicle, nimodipine, and verapamil before, during, or after SAO. Survival time, macrophage phagocytosis and killing, and white cell count were evaluated in conscious rats. Shocked animals pretreated with vehicle exhibited 24.6 +/- 0.9% phagocytic activity, 5.1 +/- 0.7% killing activity, and survived 177 +/- 1.7 min. Leukopenia was also present. Sham animals survived more than 300 min, and showed the following values: phagocytosis = 52.8 +/- 0.6%, killing = 18.8 +/- 0.6%. Pretreatment with nimodipine (1 microgram/kg/min x 30 min, intravenously [IV]) before SAO significantly prolonged survival time (274 +/- 4.7 min) and improved phagocytosis (38.1 +/- 0.6%) and killing (16.1 +/- 1.1%), but did not change leukopenia. Lower doses of nimodipine (0.25 and 0.5 microgram/kg/min x 30 min, IV), and all the doses of verapamil (100 and 200 micrograms/kg/min x 30 min, IV), when infused before SAO, were ineffective. Neither nimodipine nor verapamil, when infused for 30 min either during or immediately after SAO, were able to influence survival, macrophage functions, or white cell count. Moreover, nimodipine (5, 10, and 25 microM), when added "in vitro" to macrophages collected from SAO-shocked rats, significantly enhanced their phagocytic activity, while verapamil (100 and 200 microM) did not change it. Finally, in anaesthetized rats nimodipine pretreatment had a beneficial effect on the cardiovascular changes occurring during SAO shock. These data suggest that nimodipine has a beneficial effect in SAO-shocked rats only when given before SAO.
在雌性大鼠中，通过夹闭内脏动脉45分钟制造内脏动脉闭塞（SAO）休克模型。在SAO之前、期间或之后，分别给大鼠静脉输注30分钟的溶媒、尼莫地平或维拉帕米。对清醒大鼠评估生存时间、巨噬细胞吞噬和杀伤能力以及白细胞计数。接受溶媒预处理的休克动物表现出24.6±0.9%的吞噬活性、5.1±0.7%的杀伤活性，存活177±1.7分钟。同时存在白细胞减少。假手术动物存活超过300分钟，表现出以下数值：吞噬作用=52.8±0.6%，杀伤作用=18.8±0.6%。SAO之前静脉注射尼莫地平（1微克/千克/分钟×30分钟）显著延长了生存时间（274±4.7分钟），并改善了吞噬作用（38.1±0.6%）和杀伤作用（16.1±1.1%），但未改变白细胞减少情况。SAO之前静脉输注较低剂量的尼莫地平（0.25和0.5微克/千克/分钟×30分钟）以及所有剂量的维拉帕米（100和200微克/千克/分钟×30分钟）均无效。在SAO期间或之后立即静脉输注30分钟，尼莫地平和维拉帕米均无法影响生存、巨噬细胞功能或白细胞计数。此外，当将尼莫地平（5、10和25微摩尔）“体外”添加到SAO休克大鼠采集的巨噬细胞中时，显著增强了它们的吞噬活性，而维拉帕米（100和200微摩尔）则没有改变。最后，在麻醉大鼠中，尼莫地平预处理对SAO休克期间发生的心血管变化具有有益作用。这些数据表明，尼莫地平仅在SAO之前给予时，对SAO休克大鼠具有有益作用。
