Hypertonic perfusion inhibits intracellular Na and Ca accumulation in hypoxic myocardium.
Hypertonic perfusion inhibits intracellular Na and Ca accumulation in hypoxic myocardium.
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DOI：
10.1152/ajpcell.2000.278.5.c953
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发表时间：
2000-05
期刊：
影响因子：
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通讯作者：
H. Ho;H. Liu;P. Cala;S. Anderson
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文献类型：
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作者：
H. Ho;H. Liu;P. Cala;S. Anderson
许多证据支持缺氧/缺血性损伤主要是由于细胞内Ca浓度（[Ca]（i））增加，这是由于1）细胞内pH（pH（i））降低，2）刺激Na/H交换增加Na摄取，从而增加细胞内Na（Na（i）），3）Na梯度降低，通过Na/Ca交换减少或逆转净Ca转运。Na/H交换器（NHE）也被高渗溶液刺激;然而，高渗介质可能抑制NHE对pH（i）变化的响应（Cala PM和马尔多纳多HM. J Gen Physiol 103：1035-1054，1994）。因此，我们测试了高渗灌注减弱酸诱导的心肌Na（i）增加，从而减少缺氧期间Ca（i）积累的假设。用100%O（2）或100%N（2）平衡的HEPES缓冲Krebs-Henseleit溶液灌注兔心脏。在缺氧或常氧酸化（NH（4）Cl洗脱）前5分钟开始高渗灌注。通过NMR测量Na（i）、[Ca]（i）、pH（i）和高能磷酸盐。对照溶液为295 mosM，通过加入NaCl或蔗糖将高渗溶液调节至305、325或345 mosM。在60分钟的缺氧（295 mosM）期间，Na（i）从22+/-1上升到100+/-10 meq/kg干重，而[Ca]（i）从347+/-11上升到1，306 +/-89 nM。在高渗低氧灌注（325 mosM）时，Na（i）和[Ca]（i）的增加分别减少65%和60%（P<0.05）。高渗灌注也使常氧酸化后的Na摄取减少了87%（P<0.05）。这些数据与以下假设一致：轻度高渗灌注减少酸诱导的Na蓄积，从而减少缺氧期间Na/Ca交换介导的Ca（i）蓄积。
Much evidence supports the view that hypoxic/ischemic injury is largely due to increased intracellular Ca concentration ([Ca](i)) resulting from 1) decreased intracellular pH (pH(i)), 2) stimulated Na/H exchange that increases Na uptake and thus intracellular Na (Na(i)), and 3) decreased Na gradient that decreases or reverses net Ca transport via Na/Ca exchange. The Na/H exchanger (NHE) is also stimulated by hypertonic solutions; however, hypertonic media may inhibit NHE's response to changes in pH(i) (Cala PM and Maldonado HM. J Gen Physiol 103: 1035-1054, 1994). Thus we tested the hypothesis that hypertonic perfusion attenuates acid-induced increases in Na(i) in myocardium and, thereby, decreases Ca(i) accumulation during hypoxia. Rabbit hearts were Langendorff perfused with HEPES-buffered Krebs-Henseleit solution equilibrated with 100% O(2) or 100% N(2). Hypertonic perfusion began 5 min before hypoxia or normoxic acidification (NH(4)Cl washout). Na(i), [Ca](i), pH(i), and high-energy phosphates were measured by NMR. Control solutions were 295 mosM, and hypertonic solutions were adjusted to 305, 325, or 345 mosM by addition of NaCl or sucrose. During 60 min of hypoxia (295 mosM), Na(i) rose from 22+/-1 to 100+/-10 meq/kg dry wt while [Ca](i) rose from 347+/-11 to 1,306+/-89 nM. During hypertonic hypoxic perfusion (325 mosM), increases in Na(i) and [Ca](i) were reduced by 65 and 60%, respectively (P<0.05). Hypertonic perfusion also diminished Na uptake after normoxic acidification by 87% (P<0.05). The data are consistent with the hypothesis that mild hypertonic perfusion diminishes acid-induced Na accumulation and, thereby, decreases Na/Ca exchange-mediated Ca(i) accumulation during hypoxia.