Warner N J, Barnard J T, Leahey E B, Hougen T J, Bigger J T, Smith T W
Circ Res. 1984 Apr;54(4):453-60. doi: 10.1161/01.res.54.4.453.
To study the relationship of the serum digoxin concentration to the digoxin effect on monovalent cation transport during the quinidine-digoxin interaction, we used radiolabeled rubidium to measure monovalent cation active transport in myocardial biopsy samples from dogs. In a preliminary study, we showed that quinidine did not affect rubidium uptake by myocardial samples from intact dogs. Then, we studied four groups, each consisting of 13 dogs, which received either saline, low dose digoxin, high dose digoxin, or low dose digoxin plus quinidine treatment. In these groups of dogs, the following steady state serum digoxin concentrations were achieved: saline-treated, 0 ng/ml; low dose digoxin, 1.2 +/- 0.2 ng/ml (mean +/- SD); high dose digoxin, 2.4 +/- 0.4 ng/ml; and low-dose digoxin plus quinidine treated, 2.3 +/- 1.1 ng/ml. Compared to control values, rubidium uptake was decreased by 17% in dogs treated with low dose digoxin (P less than 0.05) and by 38% in dogs treated with high dose digoxin (P less than 0.01 vs. saline-treated, P less than 0.01 vs. low dose digoxin). Although low dose digoxin plus quinidine-treated dogs had the same mean serum digoxin concentration as the high dose digoxin-treated dogs, rubidium uptake in low dose digoxin plus quinidine-treated dogs was decreased by only 17% compared to control (P less than 0.05 vs. saline-treated, (P less than 0.01 vs. high dose digoxin). During the quinidine-digoxin interaction in the intact dog, the reduction in myocardial rubidium uptake is less than expected from the increase in serum digoxin concentration.
为研究在奎尼丁 - 地高辛相互作用期间血清地高辛浓度与地高辛对单价阳离子转运作用的关系,我们使用放射性标记的铷来测量犬心肌活检样本中的单价阳离子主动转运。在一项初步研究中,我们表明奎尼丁不影响来自完整犬的心肌样本对铷的摄取。然后,我们研究了四组,每组由13只犬组成,分别接受生理盐水、低剂量地高辛、高剂量地高辛或低剂量地高辛加奎尼丁治疗。在这些犬组中,达到了以下稳态血清地高辛浓度:生理盐水治疗组,0 ng/ml;低剂量地高辛组,1.2±0.2 ng/ml(均值±标准差);高剂量地高辛组,2.4±0.4 ng/ml;低剂量地高辛加奎尼丁治疗组,2.3±1.1 ng/ml。与对照值相比,低剂量地高辛治疗的犬的铷摄取减少了17%(P<0.05),高剂量地高辛治疗的犬的铷摄取减少了38%(与生理盐水治疗组相比P<0.01,与低剂量地高辛治疗组相比P<0.01)。尽管低剂量地高辛加奎尼丁治疗的犬的平均血清地高辛浓度与高剂量地高辛治疗的犬相同,但低剂量地高辛加奎尼丁治疗的犬的铷摄取与对照相比仅减少了17%(与生理盐水治疗组相比P<0.05,与高剂量地高辛治疗组相比P<0.01)。在完整犬体内奎尼丁 - 地高辛相互作用期间,心肌铷摄取的减少低于血清地高辛浓度升高所预期的减少量。