Why did the NHE inhibitor clinical trials fail?
Why did the NHE inhibitor clinical trials fail?
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DOI：
10.1016/j.yjmcc.2008.09.715
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发表时间：
2009-02
影响因子：
5
通讯作者：
Allen, David G.
中科院分区：
文献类型：
--
作者：
Murphy, Elizabeth;Allen, David G.
Karmazyn [1]首先表明，Na-H交换（NHE）抑制剂阿米洛利改善了缺血后离体大鼠心脏的收缩恢复。这一结果已在一系列动物模型和各种NHE 1抑制剂中得到反复证实，并自然引发了对人类心脏缺血性损伤是否会显示类似益处的兴趣。关于质膜NHE参与缺血期间细胞内Na+（[Na+] i）升高的问题存在一些分歧[2-6]。图1说明了NHE在引起[Na+] i升高中的作用，[Na+] i升高然后通过Na-Ca交换刺激胞质Ca 2+升高。这一争论对最近的一些临床试验产生了影响。分歧的主要领域似乎是NHE是否有助于缺血期间Nai的升高。我认为，数据表明它确实如此。我建议我们通过集中讨论以下问题来讨论这一争议。
Karmazyn [1] first showed that the Na–H exchange (NHE) inhibitor amiloride improved the contractile recovery of the isolated rat heart following ischemia. This result has been repeatedly confirmed in a range of animal models and with various NHE1 inhibitors and has naturally triggered interest in whether ischemic damage to human hearts would show a similar benefit.There has been some disagreement regarding the involvement of the plasma membrane NHE in the rise in intracellular Na+([Na+] i) during ischemia [2–6]. Fig. 1 illustrates the proposed role of NHE in causing a rise in [Na+] i which then stimulates a rise in cytosolic Ca2+ via the Na–Ca exchange. This controversy has implications for a number of recent clinical trials. The main area of disagreement seems to be whether NHE contributes to the rise in Nai during ischemia. I would argue that the data suggest that it does. I propose that we discuss the controversy by focusing on the following questions.
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影响因子：
4.6
作者：
Mentzer, Robert M.;Bartels, Claus;Weisel, Richard D.
通讯作者：
Weisel, Richard D.
影响因子：
--
作者：
PIKE, MM;LUO, CS;POHOST, GM
通讯作者：
POHOST, GM
DOI：
10.1016/s0022-2828(85)80119-x
发表时间：
1985-01-01
影响因子：
5
作者：
LAZDUNSKI, M;FRELIN, C;VIGNE, P
通讯作者：
VIGNE, P
影响因子：
4.3
作者：
ten Hove, M;van Emous, JG;van Echteld, CJA
通讯作者：
van Echteld, CJA
影响因子：
--
作者：
BUTWELL, NB;RAMASAMY, R;MALLOY, CR
通讯作者：
MALLOY, CR