Allen David G, Xiao Xiao-Hui
Department of Physiology and Institute for Biomedical Research, University of Sydney F13, NSW 2006, Sydney, Australia.
Cardiovasc Res. 2003 Mar 15;57(4):934-41. doi: 10.1016/s0008-6363(02)00836-2.
The coupled exchanger theory describes one of the central mechanisms of damage in the ischemic heart. The theory proposes that anaerobic glycolysis produces lactate and protons and that the protons can leave the cardiac cell on the cardiac Na+/H+ exchanger (NHE1). The subsequent rise in [Na+]i stimulates the cardiac Na+/Ca2+ exchanger (NCX) and results in an increase in [Ca2+]i which promotes myocardial cell damage. Although the general features of this theory are widely accepted, there is dispute about some aspects, specifically whether the NHE1 remains active during ischemia or not. We review the evidence on this issue and conclude that NHE1 is substantially inhibited during ischemia. This issue is central to the design of a clinical trial of NHE1 inhibitors in the treatment of human cardiac ischemia and the existing clinical trials are considered in this light.
耦合交换器理论描述了缺血性心脏损伤的核心机制之一。该理论提出，无氧糖酵解产生乳酸和质子，质子可通过心脏钠氢交换体（NHE1）离开心肌细胞。随后细胞内[Na⁺]升高会刺激心脏钠钙交换体（NCX），导致细胞内[Ca²⁺]增加，进而促进心肌细胞损伤。尽管该理论的总体特征已被广泛接受，但在某些方面仍存在争议，特别是NHE1在缺血期间是否仍保持活性。我们回顾了关于这个问题的证据，并得出结论：缺血期间NHE1会受到显著抑制。这个问题对于设计NHE1抑制剂治疗人类心脏缺血的临床试验至关重要，并且将根据这一点来考量现有的临床试验。
