Deflandre J, Pirotte J, el Allaf D, Carlier J
Biomed Pharmacother. 1986;40(4):154-7.
Using two balloon-tipped flotation catheters introduced through the jugular vein, systemic and hepatic hemodynamic measurements were made in nine cirrhotic patients before and 15, 30, 45 and 60 minutes after intravenous injection of 1.5 mg/kg of sotalol. At 30 minutes, the occluded sus-hepatic pressure fell from 23.6 +/- 6.4 mm Hg to 16.7 +/- 5.7 mm Hg (P less than 0.025); the sus-hepatic pressure gradient decreased from 16.2 +/- 3.8 mm Hg to 8.1 +/- 2.7 mm Hg (P less than 0.0005) whereas cardiac output failed to show any significant change (6.8 +/- 2.4 l/minute prior to drug versus 5.7 +/- 2.1 l/minute). These results suggest that sotalol, a non selective beta-adrenoceptor blocking drug with weaker negative inotropic effects than propranolol is effective in lowering portal pressure. The decrease of the sus-hepatic pressure gradient induced by the dose we used (50.2 +/- 20.0%) is statistically greater than that observed by Westaby et al. with intravenous propranolol (31.0 +/- 8.2%). The absence of hepatic metabolism of the drug which is excreted untransformed by the kidney should facilitate the selection of the optimal oral dose. The rather long half-life should also allow administration of one single daily dose which improves patients' compliance. The long term oral efficacy remains to be demonstrated in further studies, but in view of the advantages that sotalol possesses over propranolol, these studies are deemed justified.
使用两根经颈静脉插入的带球囊漂浮导管,对9例肝硬化患者在静脉注射1.5mg/kg索他洛尔之前以及注射后15、30、45和60分钟进行全身和肝脏血流动力学测量。30分钟时,闭塞的肝下静脉压从23.6±6.4mmHg降至16.7±5.7mmHg(P<0.025);肝下静脉压梯度从16.2±3.8mmHg降至8.1±2.7mmHg(P<0.0005),而心输出量未显示任何显著变化(用药前为6.8±2.4升/分钟,用药后为5.7±2.1升/分钟)。这些结果表明,索他洛尔作为一种非选择性β肾上腺素能受体阻滞剂,其负性肌力作用比普萘洛尔弱,能有效降低门静脉压力。我们所用剂量引起的肝下静脉压梯度下降(50.2±20.0%)在统计学上大于Westaby等人静脉注射普萘洛尔时观察到的下降(31.0±8.2%)。该药物不经肝脏代谢,以原形经肾脏排泄,这应有助于选择最佳口服剂量。较长的半衰期也应允许每日单次给药,从而提高患者的依从性。索他洛尔的长期口服疗效有待进一步研究证实,但鉴于索他洛尔相对于普萘洛尔具有的优势,这些研究被认为是合理的。