Hypertonic perfusion inhibits intracellular Na and Ca accumulation in hypoxic myocardium

Hung S Ho, Hong Liu, Peter M Cala, Steven E. Anderson

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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% O2 or 100% N2. Hypertonic perfusion began 5 min before hypoxia or normoxic acidification (NH4Cl 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume278
Issue number5 47-5
StatePublished - 2000

Keywords

  • Intracellular pH
  • Myocardial hypoxia
  • Nuclear magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

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