Lunell N O, Fredholm B, Hjemdahl P, Lewander R, Nisell H, Nylund L, Persson B, Sarby B, Wager J
Acta Med Scand Suppl. 1982;665:143-7. doi: 10.1111/j.0954-6820.1982.tb00424.x.
Labetalol was given to women with hypertension of pregnancy in their last trimester to study its acute effect on circulation and metabolism. Seven women were given 50 mg labetalol i v. There was a significant decrease of blood pressure from a mean of 143/101 +/- 4/2 (SEM) to 127/88 +/- 5/2 mm Hg. Maternal heart rate fell significantly from 77 +/- 5 to 68 +/- 3 beats per min. These changes persisted during a three-hour observation period. The hypotensive response was accompanied by a significant increase in plasma noradrenaline from 1.54 +/- 0.16 to 2.37 +/- 0.41 nmol/l, suggesting sympathetic activation. Plasma cyclic AMP, which is increased by beta 2-adrenoceptor stimulation, was significantly elevated after labetalol. This supports the hypothesis of partial beta-agonist activity of labetalol. Lipid metabolism, as judged from measurements of plasma FFA, glycerol and 3-hydroxybuturic acid, showed little change. The acute effect of labetalol on uteroplacental blood flow was determined in eight women with pregnancy hypertension using a gammacamera on line with a computer. 0.5 mCi indium-113m was given i v before and 30 min after labetalol was administered i v in a dose of 1 mg per kg body weight. After the injections of indium-113m, serial scintigrams were recorded during 10 s periods for 240 s. By computerized summation of the scintigrams, an image was obtained in which the placenta could be outlined for time-activity analysis of the isotope accumulation curve. From this curve a uteroplacental blood flow index could be calculated. Labetalol induced a significant drop of mean arterial blood pressure from 114 +/- mm Hg to 100 +/- 3 mm Hg after 30 min in this group of women. However, the uteroplacental blood flow index did not change. As we have earlier shown with this technique that uteroplacental blood flow can be severely impaired in hypertension of pregnancy, the finding of substained uteroplacental blood flow simultaneously with a decrease in blood pressure should be of clinical importance. Taken together with other studies of clinical effects, these results indicate that labetalol is useful in the treatment of hypertension of pregnancy.
给妊娠晚期的妊娠高血压妇女服用拉贝洛尔,以研究其对循环和代谢的急性影响。7名妇女静脉注射50毫克拉贝洛尔。血压从平均143/101±4/2(标准误)显著降至127/88±5/2毫米汞柱。孕妇心率从每分钟77±5次显著降至68±3次。这些变化在三小时的观察期内持续存在。降压反应伴随着血浆去甲肾上腺素从1.54±0.16纳摩尔/升显著增加至2.37±0.41纳摩尔/升,提示交感神经激活。拉贝洛尔给药后,因β2 -肾上腺素能受体刺激而增加的血浆环磷酸腺苷显著升高。这支持了拉贝洛尔具有部分β激动剂活性的假说。从血浆游离脂肪酸、甘油和3 -羟基丁酸的测量结果判断,脂质代谢几乎没有变化。使用与计算机联机的γ相机,对8名妊娠高血压妇女测定拉贝洛尔对子宫胎盘血流的急性影响。在静脉注射每公斤体重1毫克拉贝洛尔前及注射后30分钟静脉注射0.5毫居里铟 - 113m。注射铟 - 113m后,在240秒内每10秒记录一次连续闪烁图。通过对闪烁图进行计算机化求和,获得一幅可勾勒出胎盘轮廓的图像,用于对同位素积聚曲线进行时间 - 活性分析。根据该曲线可计算子宫胎盘血流指数。在这组妇女中,拉贝洛尔在30分钟后使平均动脉血压从114±毫米汞柱显著降至100±3毫米汞柱。然而,子宫胎盘血流指数没有变化。正如我们此前用该技术所表明的,妊娠高血压时子宫胎盘血流可能严重受损,在血压下降的同时子宫胎盘血流持续存在这一发现应具有临床重要性。结合其他临床疗效研究,这些结果表明拉贝洛尔可用于治疗妊娠高血压。