INHIBITION OF MYOCARDIAL MONO-VALENT CATION ACTIVE-TRANSPORT BY SUB-TOXIC DOSES OF OUABAIN IN DOG
INHIBITION OF MYOCARDIAL MONO-VALENT CATION ACTIVE-TRANSPORT BY SUB-TOXIC DOSES OF OUABAIN IN DOG
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DOI：
10.1161/01.res.42.6.856
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发表时间：
1978-01-01
影响因子：
20.1
通讯作者：
SMITH, TW
中科院分区：
文献类型：
--
作者：
HOUGEN, TJ;SMITH, TW
本文观察了持续亚毒性剂量哇巴因对开胸犬左室心肌一价阳离子主动转运和收缩力的影响。使用一系列活检技术，获得全层左心室心肌样品之前和1和2小时后，哇巴因输液，根据负荷剂量和输液时间表证明产生稳定的血浆和左心室心肌哇巴因浓度。在这些活检样本中，在体外测量了哇巴因对K类似物86 Rb+的可吸收性，并与哇巴因给药前活检中的转运活性和仅接受溶媒的犬活检中的值进行了比较。左心室最大dP/dt [压力随时间的变化]比基线值增加了29 ±。3 = %（SEM）和46 . ±.在哇巴因处理的狗中，在1小时和2小时的活组织检查时间，86 Rb+的主动转运分别显著减少21 ± 9%。6%，1小时和33 ±。2 h时为5%。连续ECG监测未显示任何心律失常。仅接受溶剂的对照犬的收缩性和单价阳离子转运值不变。在另一组犬中，首次明确显示持续哇巴因诱导的正性肌力作用时（30 min），显示了对活性86 Rb+转运的显著抑制。相反，去甲肾上腺素的剂量足以产生可比的dP/dt增加30-120分钟，没有改变积极的86 Rb+运输。足以诱导正性肌力作用的亚毒性剂量的哇巴因明显与心脏糖苷敏感物种中心肌单价阳离子主动转运的显著减少相关。尽管基于这些数据无法建立因果关系，但研究结果与心脏糖苷诱导的肌力与抑制心肌NaK-ATP酶介导的单价阳离子转运相关的假设一致。
The effects of sustained subtoxic doses of ouabain on left ventricular myocardial monovalent cation active transport and contractility in open-chest dogs were studied. Using a serial biopsy technique, full-thickness left ventricular myocardial samples were obtained prior to and 1 and 2 h after ouabain infusion, according to a loading dose and infusion schedule demonstrated to produce stable plasma and left ventricular myocardial ouabain concentrations. Ouabain-inhibitable uptake of the K analogue 86Rb+ was measured in vitro in these biopsy samples and compared with transport activity in biopsies taken prior to ouabain administration and values in biopsies from dogs receiving vehicle alone. Left ventricular maximum dP/dt [change of pressure with time] increased above baseline values by 29 .+-. 3 = % (SEM) and 46 .+-. 9% in ouabain-treated dogs at the 1- and 2-h biopsy times, respectively, and active transport of 86Rb+ was significantly reduced by 21 .+-. 6% at 1 h and 33 .+-. 5% at 2 h. Continuous ECG monitoring did not show any arrhythmias. Control dogs receiving vehicle alone had unchanged values for contractility and monovalent cation transport. In another group of dogs, significant inhibition of active 86Rb+ transport was demonstrated at the time a sustained ouabain-induced positive inotropic effect was first clearly demonstrable (30 min). In contrast, norepinephrine in doses sufficient to produce comparable increases in dP/dt for 30-120 min did not change active 86Rb+ transport. Subtoxic doses of ouabain sufficient to induce a positive inotropic effect apparently are associated with significant reduction of myocardial monovalent cation active transport in a cardiac glycoside-sensitive species. Although a causal relationship cannot be established on the basis of these data, the findings are consistent with the hypothesis that cardiac glycoside-induced inotropy is related to inhibition of myocardial NaK-ATPase-mediated monovalent cation transport.