Böhm C, Haustein K O
Clinical Pharmacology Erfurt, Friedrich-Schiller-Universität Jena, Germany.
Int J Clin Pharmacol Ther. 1998 Jul;36(7):398-402.
The effect of organic nitrates on microcirculation was first studied in 1964 and with regard to glyceroltrinitrate (GTN) an "internal hemodilution" (i.e. a fluid shift from the extravascular fluid to the intravascular compartment) was observed. Therefore, we found it of interest to study the effects of the long-acting PETN on parameters of hemorrheology.
The effects of single doses of 25, 50, and 80 mg PETN, 0.4 mg GTN, and of placebo were investigated on the capillary erythrocyte velocity (CEV; Capiflow), the tissue oxygen tension (tcpO2), the deformability of red blood cells, the plasma viscosity and of the fibrin content of the plasma in a single-blind, randomized study over 12 h in 12 healthy female and male volunteers. The CEV and the tcpO2 were measured in the nailfold of the fourth finger and on the skin of its end phalanx, respectively. Statistical analysis was performed by analysis of variance, the calculation of epsilon (Greenhouse-Geisser), and the multiple t test.
After administration of 50 or 80 mg PETN the CEV decreased by 30% over a period of 2 or 4 h (p = 0.02 or 0.002). A decrease by 11% was measured 1 and 2 h after administration of GTN (p = 0.034). Under the same PETN doses tcpO2 increased from 1.41 to 1.78 mm mercury (p = 0.002). The deformability of red blood cells was slightly increased after 50 and 80 mg PETN under share rates of 60 Pa from 55.5 to 58.0% 8 and 12 h after intake. The plasma viscosity was decreased after intake of 50 mg PETN 4 to 8 h (1.36 vs. 1.34 Pa x s, p = 0.023) and after intake of 80 mg 2 to 12 h post dose (1.36 vs. 1.33 Pa x s, p = 0.015). The systolic or diastolic blood pressure decreased, but was not significant.
The PETN-induced decrease in CEV can be explained with the pre- and afterload decreasing properties of the nitrates. The increase in tcpO2 and erythrocyte deformability and the decrease in viscosity are additional advantageous effects on the microcirculation. If the results are transferred from the nailfold of the finger to the myocardium, the benefit of nitrates could not only be seen in the decrease in preload due to their vasodilating properties, but also in improving the parameters of microcirculation. The internal hemodilution and the slightly enhanced deformability might provide an additional supply of myocardial capillaries in case of myocardial ischemia.
1964年首次研究了有机硝酸盐对微循环的影响，关于硝酸甘油（GTN），观察到了“内源性血液稀释”（即液体从血管外液转移到血管内间隙）。因此，我们发现研究长效戊四硝酯（PETN）对血液流变学参数的影响很有意义。
在一项单盲、随机研究中，对12名健康女性和男性志愿者进行了12小时的观察，研究了单剂量25、50和80毫克PETN、0.4毫克GTN以及安慰剂对毛细血管红细胞速度（CEV；Capiflow）、组织氧分压（tcpO2）、红细胞变形性、血浆粘度和血浆纤维蛋白含量的影响。CEV和tcpO2分别在右手无名指甲襞和末节指皮肤处测量。采用方差分析、ε计算（Greenhouse-Geisser）和多重t检验进行统计分析。
服用50或80毫克PETN后，CEV在2或4小时内下降了30%（p = 0.02或0.002）。服用GTN后1小时和2小时测量到下降了11%（p = 0.034）。在相同的PETN剂量下，tcpO2从1.41毫米汞柱增加到1.78毫米汞柱（p = 0.002）。服用50和80毫克PETN后，红细胞变形性在摄入后8小时和12小时，在60 Pa的切变率下略有增加，从55.5%增加到58.0%。服用50毫克PETN后4至8小时（1.36对比1.34 Pa·s，p = 0.023）和服用80毫克PETN后给药后2至12小时（1.36对比1.33 Pa·s，p = 0.015）血浆粘度降低。收缩压或舒张压下降，但不显著。
PETN引起的CEV降低可以用硝酸盐的前负荷和后负荷降低特性来解释。tcpO2升高、红细胞变形性增加和粘度降低是对微循环的额外有利影响。如果将结果从手指甲襞转移到心肌，硝酸盐的益处不仅可以在其血管舒张特性导致的前负荷降低中看到，还可以在改善微循环参数中看到。内源性血液稀释和轻微增强的变形性可能在心肌缺血时为心肌毛细血管提供额外的血液供应。
