Ceyhan B B, Celikel T
Marmara University School of Medicine, Department of Pulmonary Medicine, Altunizade-Istanbul, Turkey.
Int J Clin Pharmacol Ther. 2000 Sep;38(9):446-51. doi: 10.5414/cpp38446.
Recent studies have shown that inhaled standard heparin exhibits protection towards various bronchoconstrictor stimuli in asthma including methacholine. Low molecular weight heparins (LMWH) (4000-5000 daltons) have higher bioavailability than standard heparins (12,000-16,000 daltons). It is possible that the anti-asthmatic activity of heparin may be molecular weight-dependent. The purpose of the present investigation was to study the effect of LMWH on methacholine-induced bronchoconstriction and to compare the effect of LMWH with that of standard heparin.
Fifteen subjects (7 male, 8 female, mean age: 33 +/- 13 years, range: 20-65) with mild asthma were studied.
Methacholine bronchial provocation tests were performed in a single-blind, crossover, randomized order and repeated 45 minutes after placebo or aerosolized standard heparin (1.000 U/kg) or aerosolized LMWH (Enoksaparin, Clexane, 0.8 mg/kg).
There was no significant difference in baseline FEV1 values between study days. The standard heparin and enoksaparin inhibited bronchoconstriction induced by methacholine. The geometric mean log PD20 values after placebo, standard heparin, and enoksaparin were 0.24 +/- 0.57 (1.74) mg/ml, 0.79 +/- 0.59 (6.17 mg/ml), 0.76 +/- 0.57 (5.75 mg/ml), respectively (p < 0.0009). Three subjects in standard heparin group and two subjects in enoksaparin group showed increased hyperreactivity, the others showed decreased bronchial hyperreactivity. The degree of protection offered by standard heparin and enoksaparin did not show any statistical difference.
These data suggest that both inhaled LMWH and inhaled standard heparin play inhibitory roles in methacholine-induced bronchoconstriction.
近期研究表明，吸入标准肝素对哮喘患者的多种支气管收缩刺激（包括乙酰甲胆碱）具有保护作用。低分子量肝素（LMWH，4000 - 5000道尔顿）比标准肝素（12000 - 16000道尔顿）具有更高的生物利用度。肝素的抗哮喘活性可能与分子量有关。本研究的目的是探讨低分子量肝素对乙酰甲胆碱诱导的支气管收缩的影响，并将其与标准肝素的作用进行比较。
对15名轻度哮喘患者（7名男性，8名女性，平均年龄：33±13岁，范围：20 - 65岁）进行了研究。
采用单盲、交叉、随机顺序进行乙酰甲胆碱支气管激发试验，并在给予安慰剂、雾化标准肝素（1000 U/kg）或雾化低分子量肝素（依诺肝素，克赛，0.8 mg/kg）45分钟后重复进行。
各研究日之间的基线第一秒用力呼气容积（FEV1）值无显著差异。标准肝素和依诺肝素均能抑制乙酰甲胆碱诱导的支气管收缩。安慰剂、标准肝素和依诺肝素后的几何平均对数PD20值分别为0.24±0.57（1.74）mg/ml、0.79±0.59（6.17 mg/ml）、0.76±0.57（5.75 mg/ml）（p < 0.0009）。标准肝素组有3名受试者、依诺肝素组有2名受试者出现高反应性增加，其他受试者支气管高反应性降低。标准肝素和依诺肝素提供的保护程度无统计学差异。
这些数据表明，吸入低分子量肝素和吸入标准肝素在乙酰甲胆碱诱导的支气管收缩中均起抑制作用。
