Pierce G N, Meng H
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Am J Cardiovasc Pathol. 1992;4(2):91-102.
Previous work has associated cardiac dysfunction and damage after ischemia/reperfusion with metabolic alterations in the heart or alterations in the myocardial ionic homeostasis. Unfortunately, neither mechanism on its own has been able to conclusively explain the pathology. Instead, recent data suggest that the two mechanisms may be interrelated. The low intracellular pH during ischemia (due to the accumulation of metabolic by-products) may stimulate the Na(+)-H+ exchange pathway during reperfusion to remove H+ from the cell in exchange for will lead to accelerated Ca2+ entry via Na+. The subsequent accumulation of Na+ in the cell Na(+)-Ca2+ exchange, which can ultimately result in intracellular Ca2+ overload, contractile dysfunction and damage. This hypothesis is supported by the known biochemical characteristics of the cardiac Na(+)-H+ exchanger. Pharmacological studies also support this hypothesis as a mechanism involved in ischemic/reperfusion damage. Dimethylamiloride, a blocker of Na(+)-H+ exchange, has provided significant protection against ischemic/reperfusion injury to the heart. A series of studies have indicated that the mechanism through which dimethylamiloride acts is via inhibition of the Na(+)-H+ exchange pathway. The data, therefore, are consistent with an important interaction between metabolism and ionic alterations, which includes a central role for Na(+)-H+ exchange in ischemic/reperfusion damage to the heart.
先前的研究表明，缺血/再灌注后心脏功能障碍和损伤与心脏代谢改变或心肌离子稳态改变有关。不幸的是，这两种机制单独都无法确凿地解释这种病理现象。相反，最近的数据表明这两种机制可能相互关联。缺血期间细胞内pH值降低（由于代谢副产物的积累）可能会在再灌注期间刺激Na(+)-H+交换途径，以将H+从细胞中排出，以换取Na+，这将导致Ca2+通过Na+加速进入细胞。随后细胞内Na+的积累会通过Na(+)-Ca2+交换导致细胞内Ca2+过载，最终导致收缩功能障碍和损伤。这一假设得到了心脏Na(+)-H+交换器已知生化特性的支持。药理学研究也支持这一假设，认为它是缺血/再灌注损伤的一种机制。二甲基amiloride，一种Na(+)-H+交换阻滞剂，对心脏缺血/再灌注损伤提供了显著的保护作用。一系列研究表明，二甲基amiloride发挥作用的机制是通过抑制Na(+)-H+交换途径。因此，这些数据与代谢和离子改变之间的重要相互作用是一致的，其中包括Na(+)-H+交换在心脏缺血/再灌注损伤中的核心作用。
