Hansen P B, Buch J, Rasmussen O O, Waldorff S, Steiness E
Br J Clin Pharmacol. 1984 Dec;18(6):817-22. doi: 10.1111/j.1365-2125.1984.tb02550.x.
Short term effect of digoxin on left ventricular performance was studied in six healthy volunteers before and during atenolol or nifedipine administration. Left ventricular function was evaluated by systolic time intervals and echocardiography. No changes in left ventricular end diastolic or systolic dimensions occurred throughout the study, indicating unchanged ventricular pre- and afterload. Thus, changes in the systolic time intervals must be attributed to changes in cardiac contractility. Changes in the pre-ejection period index (PEPI) obtained from the systolic time intervals were used as a measure of digoxin-induced inotropism. A concentration-response relationship between plasma digoxin level and changes in PEPI was revealed when digoxin was given alone. Atenolol did not influence the digoxin-induced inotropism at a given serum digoxin level. During nifedipine administration no inotropic effect of digoxin could be demonstrated. Thus, it is concluded that nifedipine attenuates digoxin-induced inotropism, while atenolol seems without this effect. These results are in accordance with previous experiments and reflect the different pharmacological sites of action of beta-adrenoceptor antagonists and calcium channel blocking agents. Plasma digoxin concentration, renal digoxin clearance and creatinine clearance did not change during atenolol or nifedipine.
在6名健康志愿者中,研究了地高辛在服用阿替洛尔或硝苯地平之前及期间对左心室功能的短期影响。通过收缩期时间间期和超声心动图评估左心室功能。在整个研究过程中,左心室舒张末期或收缩期内径均未发生变化,表明心室前负荷和后负荷未改变。因此,收缩期时间间期的变化必定归因于心脏收缩力的改变。从收缩期时间间期得出的射血前期指数(PEPI)变化被用作地高辛诱导的心肌收缩力的指标。单独给予地高辛时,血浆地高辛水平与PEPI变化之间呈现浓度 - 反应关系。在给定的血清地高辛水平下,阿替洛尔不影响地高辛诱导的心肌收缩力。在服用硝苯地平期间,未显示地高辛有正性肌力作用。因此,得出结论:硝苯地平减弱地高辛诱导的心肌收缩力,而阿替洛尔似乎无此作用。这些结果与先前的实验一致,反映了β - 肾上腺素能受体拮抗剂和钙通道阻滞剂不同的药理学作用部位。在服用阿替洛尔或硝苯地平期间,血浆地高辛浓度、肾脏地高辛清除率和肌酐清除率均未改变。