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Anesth Analg. 1959 Nov-Dec;38:478-84.
2
Action of local anesthetics on coupling systems in muscle.局部麻醉药对肌肉中偶联系统的作用。
J Pharmacol Exp Ther. 1967 Aug;157(2):388-405.
3
The accumulation of organic bases by the human platelet.人体血小板对有机碱的蓄积
J Pharmacol Exp Ther. 1967 Jan;155(1):112-6.
4
Factors controlling the washout of the interstitial space of the isolated, perfused rat heart.控制离体灌注大鼠心脏间质空间洗脱的因素。
J Physiol. 1968 Jun;196(3):747-59. doi: 10.1113/jphysiol.1968.sp008534.
5
A comparison of the accumulation and release of 3H-ouabain and 3H-digitoxin by guinea-pig heart muscle.豚鼠心肌对3H-哇巴因和3H-地高辛的摄取与释放比较。
Br J Pharmacol Chemother. 1968 Mar;32(3):598-608. doi: 10.1111/j.1476-5381.1968.tb00460.x.
6
On the mode of action of local anesthetics.论局部麻醉药的作用方式。
Annu Rev Pharmacol. 1966;6:405-30. doi: 10.1146/annurev.pa.06.040166.002201.

普鲁卡因在离体心脏中的摄取、结合与药理作用之间的关系。

Relationship between the uptake, binding and pharmacological action of procaine in the isolated heart.

作者信息

Boullin D J, Sullivan T J

出版信息

Br J Pharmacol. 1969 Feb;35(2):322-31. doi: 10.1111/j.1476-5381.1969.tb07991.x.

DOI:10.1111/j.1476-5381.1969.tb07991.x
PMID:5774045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1703246/
Abstract
  1. The uptake, efflux and pharmacological actions of procaine hydrochloride were studied on isolated hearts of female guinea-pigs. The hearts were perfused with Krebs solution containing (14)C-procaine (0.1-500 mug/ml.) by the Langendorff technique at 37 degrees C, using a constant flow pump. Hearts and cardiac effluent were assayed for procaine by liquid scintillation spectrometry.2. Accumulation of procaine did not appear to involve active transport mechanisms for the following reasons. The rate of procaine uptake was most rapid at the highest perfusion concentration (500 mug/ml.), when it was three times faster than at the lowest concentration (0.1 mug/ml.); it was not affected by lowering the temperature to 3 degrees C. The ratio of the concentration of procaine in the heart to the concentration in the perfusing fluid decreased with increasing concentration in the perfusion fluid.3. When the efflux of (14)C-procaine from hearts previously perfused with procaine-containing Krebs solution for 10 min was compared with the efflux of (14)C-inulin, the patterns of efflux of both compounds were similar, and showed at least two exponential components. At the highest concentration of procaine (500 mug/ml.) the efflux of procaine was more rapid than that of inulin.4. A relationship was found between the pharmacological action of procaine, the rate of uptake and the level of procaine in the heart. When the procaine-containing perfusion fluid was changed to a procaine-free solution, the heart rate increased rapidly, and there was a rapid decline in the levels of procaine in the hearts.5. It is concluded that guinea-pig hearts accumulate procaine by a passive diffusion process, and that the pattern and rate of efflux indicate that the drug is loosely bound. If it is permissible to extrapolate from these findings to the antiarrhythmic effect in man, the short duration of its action may be due to loose binding rather than to rapid metabolic inactivation.
摘要

  1. 研究了盐酸普鲁卡因在雌性豚鼠离体心脏中的摄取、流出及药理作用。采用Langendorff技术，在37℃下用含（14）C-普鲁卡因（0.1 - 500μg/ml）的Krebs溶液通过恒流泵灌注心脏。用液体闪烁光谱法测定心脏和心脏流出液中的普鲁卡因。

  2. 普鲁卡因的积累似乎不涉及主动转运机制，原因如下。在最高灌注浓度（500μg/ml）时，普鲁卡因摄取速率最快，比最低浓度（0.1μg/ml）时快三倍；将温度降至3℃对其无影响。心脏中普鲁卡因浓度与灌注液中浓度之比随灌注液中浓度升高而降低。

  3. 当比较先前用含普鲁卡因的Krebs溶液灌注10分钟的心脏中（14）C-普鲁卡因的流出与（14）C-菊粉的流出时，两种化合物的流出模式相似，且至少呈现两个指数成分。在最高普鲁卡因浓度（500μg/ml）时，普鲁卡因的流出比菊粉更快。

  4. 发现普鲁卡因的药理作用、摄取速率与心脏中普鲁卡因水平之间存在关联。当含普鲁卡因的灌注液换成不含普鲁卡因的溶液时，心率迅速增加，心脏中普鲁卡因水平迅速下降。

  5. 得出结论，豚鼠心脏通过被动扩散过程积累普鲁卡因，流出模式和速率表明该药物结合松散。如果可以从这些发现推断其对人类的抗心律失常作用，其作用持续时间短可能是由于结合松散而非快速代谢失活。