EFFECT OF LIDOCAINE ON CONTRACTURE, INTRACELLULAR SODIUM, AND PH IN ISCHEMIC RAT HEARTS
EFFECT OF LIDOCAINE ON CONTRACTURE, INTRACELLULAR SODIUM, AND PH IN ISCHEMIC RAT HEARTS
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DOI：
10.1152/ajpheart.1993.264.6.h1884
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发表时间：
1993-06-01
影响因子：
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通讯作者：
MALLOY, CR
中科院分区：
文献类型：
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作者：
BUTWELL, NB;RAMASAMY, R;MALLOY, CR
研究了全脑缺血时细胞内钠浓度（[Na+]i）、细胞内pH、[ATP]和挛缩之间的关系。采用Na-23核磁共振（NMR）技术，以1,4,7,10-四氮杂环十二烷-1,4,7,10-四（亚膦酸甲酯）铥（TmDOTP5-）作为顺磁移试剂，监测胞内Na。在相同条件下，用p -31核磁共振谱法监测高能磷酸盐和pH。利多卡因（130 muM）是一种IB类快速钠通道阻滞剂，已知可保护缺血心肌，可延长无搏动和有搏动心脏的挛缩时间（240次/分钟）。节律性心脏缺血10分钟后，利多卡因组[Na+]i低于未治疗组。利多卡因的加入也显著减轻了ATP的消耗以及细胞内酸中毒的发生。然而，在挛缩时，两组之间的[Na+]i或pH没有差异。有趣的是，利多卡因对缺血期间Na(i)+积累的影响主要表现在缺血前5=10 min，而对pH的影响则发生在缺血后9 min。这一发现提示Na- h交换器以外的机制可能在缺血过程早期Na(i)+的积累中起作用。
The relationships among intracellular Na concentration ([Na+]i), intracellular pH, [ATP], and contracture during global ischemia were studied in isolated, perfused rat hearts. Intracellular Na was monitored by Na-23 nuclear magnetic resonance (NMR) spectroscopy using thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonate) (TmDOTP5-) as the paramagnetic shift reagent. High-energy phosphates and pH were monitored under the same conditions using P-31-NMR spectroscopy. Lidocaine (130 muM), a class IB fast Na channel blocker known to protect ischemic myocardium, prolonged the time to contracture in both unpaced and paced hearts (240 beats/min). After 10 min of global ischemia in paced hearts, [Na+]i was lower in the lidocaine-treated group compared with untreated hearts. The addition of lidocaine also significantly attenuated the depletion of ATP as well as development of intracellular acidosis. At the time of contracture, however, there was no difference in [Na+]i or pH between the two groups. Interestingly, the effect of lidocaine on Na(i)+ accumulation during ischemia was manifested during the first 5=10 min of ischemia, while its effect on pH occurred after 9 min. This finding suggests that a mechanism other than the Na-H exchanger may play a role in the accumulation of Na(i)+ early in the course of ischemia.