The antiarrhythmic effects of the nucleoside transporter inhibitor, R75231, in anaesthetized pigs
The antiarrhythmic effects of the nucleoside transporter inhibitor, R75231, in anaesthetized pigs
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核苷转运蛋白抑制剂 R75231 对麻醉猪的抗心律失常作用
DOI：
10.1111/j.1476-5381.1993.tb13612.x
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发表时间：
1993
影响因子：
7.3
通讯作者：
H. Belle
中科院分区：
文献类型：
--
作者：
C. Wainwright;J. Parratt;H. Belle
1观察了嘌呤核苷转运抑制剂R75231对麻醉猪缺血性心律失常的影响。2在闭胸猪（n = 4）中，R75231对平均动脉血压产生中度剂量依赖性降低（在25、50和100 μg kg−1时分别从97 ± 4 mmHg降至95 ± 4、90 ± 1和83 ± 2 mmHg），并使腺苷静脉推注剂量的血压剂量反应曲线向左发生剂量相关偏移。在离体红细胞悬液中评估的R75231对腺苷摄取的抑制程度在25、50和100 μg kg−1剂量下分别为43 ± 5%、64 ± 13和114 ± 15%。3开胸猪，静脉注射R75231（50 μg kg−1; n = 6和100 μg kg−1; n = 10）诱导收缩压和舒张压的剂量相关性降低，这比闭胸猪更明显（50和100 μg kg−1时的平均压力分别为86 ± 4至70 ± 2 mmHg和88 ± 6至60 ± 6 mmHg），而不影响心率或心肌收缩力。这些猪的冠状动脉闭塞导致继发性血压降低。在对照组（n = 10）中未观察到这一点。较低剂量的R75231未发挥任何抗心律失常作用，而较高剂量显著降低了室颤的发生率，从对照猪的80%降至30%。两种剂量均未改变室性心动过速的发生率（50和100 μg kg−1分别为33%和40%，对照组为30%），也未对室性异位搏动总数产生任何影响（85 ± 47和130 ± 31 vs对照组110 ± 19）。100 μg kg−1剂量的R75231也可减弱缺血诱导的QRS间期缩短，但两种剂量均未改变闭塞后观察到的ST段压低。4这些结果表明，核苷转运抑制剂R75231在离体完全抑制腺苷摄取的剂量下，在严重心肌缺血模型中发挥抗心肌缺血作用。然而，尽管该药物在闭胸动物中的血液动力学影响极小，但不能排除R75231在开胸猪中诱导的血压降低是该药物抗肿瘤作用的可能贡献机制。
1 The effect of R75231, an inhibitor of purine nucleoside transport, were examined on ischaemic arrhythmias in anaesthetized pigs. 2 In closed chest pigs (n = 4), R75231 exerted a moderate dose‐dependent decrease in mean arterial blood pressure (from 97 ± 4 mmHg to 95 ± 4, 90 ± 1 and 83 ± 2 mmHg at 25, 50 and 100 μg kg−1 respectively) and produced a dose‐related shift to the left of the blood pressure dose‐response curve to intravenous bolus doses of adenosine. The degree of inhibition of adenosine uptake by R75231, assessed ex vivo in erythrocyte suspensions, was 43 ± 5%, 64 ± 13 and 114 ± 15% at doses of 25, 50 and 100 μg kg−1 respectively. 3 In open chest pigs, intravenous injection of R75231 (50 μg kg−1; n = 6 and 100 μg kg−1; n = 10) induced a dose‐related decrease in both systolic and diastolic arterial blood pressure which was more marked than in closed‐chest pigs (mean pressure 86 ± 4 to 70 ± 2 mmHg and 88 ± 6 to 60 ± 6 mmHg with 50 and 100 μg kg−1 respectively), without affecting heart rate or myocardial contractility. Coronary artery occlusion in these pigs caused a secondary decrease in blood pressure. This was not observed in controls (n = 10). The lower dose of R75231 did not exert any antifibrillatory effects, whereas the higher dose significantly reduced the incidence of ventricular fibrillation, from 80% in control pigs to 30%. Neither dose modified the incidence of ventricular tachycardia (33% and 40% with 50 and 100 μg kg−1 respectively, compared to 30% in controls) or had any effect on the total number of ventricular ectopic beats (85 ± 47 and 130 ± 31 vs 110 ± 19 in controls). R75231, at a dose of 100 μg kg−1, also attenuated the ischaemia‐induced shortening of QRS‐interval, but neither dose modified the ST‐segment depression seen following occlusion. 4 These results show that the nucleoside transport inhibitor, R75231, exerts an antifibrillatory effect in a model of severe myocardial ischaemia in a dose which completely inhibits adenosine uptake ex vivo. However, while this agent has minimal haemodynamic effects in closed chest animals, the reduction in blood pressure induced by R75231 in open‐chest pigs cannot be excluded as a possible contributory mechanism of the antiarrhythmic effects of this drug.
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影响因子：
3.6
作者：
Paul,S;Feoktistov,I;Hollister,AS;Robertson,D;Biaggioni,I
通讯作者：
Biaggioni,I
增加细胞内腺苷可改善心肌恢复。
DOI：
--
发表时间：
1990
期刊：
The Journal of thoracic and cardiovascular surgery
影响因子：
--
作者：
Bolling,SF;Bies,LE;Bove,EL;Gallagher,KP
通讯作者：
Gallagher,KP
影响因子：
15.9
作者：
CRONSTEIN, BN;DAGUMA, L;WILLIAMS, M
通讯作者：
WILLIAMS, M
影响因子：
37.8
作者：
OLAFSSON, B;FORMAN, MB;VIRMANI, R
通讯作者：
VIRMANI, R