Neumann F J, Ott I, Richardt G, Zimmermann R, Tillmanns H, Kübler W, Rauch B
I. Medizinische Klinik, Technische Universität, München, Germany.
J Cardiovasc Pharmacol. 1992;20 Suppl 7:S21-5.
The purpose of the study was to investigate whether gallopamil interferes with neutrophil activation. In vitro, gallopamil caused a dose-dependent reduction in phorbol myristate acetate-stimulated superoxide anion production by neutrophils as measured by the superoxide dismutase inhibited reduction of cytochrome C [concentration of 50% inhibition (IC50) = 9.5 x 10(-6) mol/L]. Furthermore, gallopamil reduced the platelet-activating factor-induced loss of neutrophil deformation, which was assessed by filtrometry (IC50 = 4.3 x 10(-6) mol/L). The effect of gallopamil was assessed in 24 patients during elective balloon angioplasty. Gallopamil (0.4 mg) or placebo (double-blind conditions) was administered by intracoronary application during the 10-min interval between the first two balloon inflations. In the placebo group, blood samples obtained simultaneously from the coronary sinus and from the femoral artery revealed an increase in the proportion of activated neutrophils in the coronary sinus blood after the second balloon inflation [nitro blue tetrazolium (NBT) score, NBT test: 15 +/- 9% relative coronary sinus and arterial blood difference, p < 0.05]; these changes in NBT score were similar to those after the first balloon inflation. In the gallopamil-treated group, however, significant arterial and coronary sinus blood differences in NBT scores were not found after the second balloon inflation. Gallopamil may, thus, attenuate the local neutrophil activation during balloon angioplasty.
本研究的目的是调查加洛帕米是否会干扰中性粒细胞的激活。在体外，加洛帕米可导致中性粒细胞经佛波酯肉豆蔻酸酯刺激产生超氧阴离子的量呈剂量依赖性减少，这是通过超氧化物歧化酶抑制的细胞色素C还原法测量的[半数抑制浓度（IC50）=9.5×10⁻⁶mol/L]。此外，加洛帕米减少了血小板活化因子诱导的中性粒细胞变形能力丧失，这是通过滤过法评估的（IC50=4.3×10⁻⁶mol/L）。在24例择期球囊血管成形术患者中评估了加洛帕米的作用。在头两次球囊充盈之间的10分钟间隔内，通过冠状动脉内给药给予加洛帕米（0.4mg）或安慰剂（双盲条件）。在安慰剂组中，在第二次球囊充盈后，同时从冠状窦和股动脉采集的血样显示冠状窦血中活化中性粒细胞的比例增加[硝基蓝四氮唑（NBT）评分，NBT试验：相对冠状窦和动脉血差异为15±9%，p<0.05]；这些NBT评分的变化与第一次球囊充盈后的变化相似。然而，在加洛帕米治疗组中，第二次球囊充盈后未发现NBT评分在动脉血和冠状窦血之间有显著差异。因此，加洛帕米可能会减轻球囊血管成形术期间局部中性粒细胞的激活。
