Amiloride delays the ischemia-induced rise in cytosolic free calcium

E. Murphy, M. Perlman, R. E. London, C. Steenbergen

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312 Scopus citations


An increase in cytosolic free calcium (Ca(i)) has been shown to occur early during ischemia in perfused rat, ferret, and rabbit hearts. It has been proposed that this increase in Ca(i) may occur as a result of exchange of Na(i) for Ca(o), which occurs as a result of an increase in Na(i) arising from exchange of Na(o) for H+(i). The latter exchange is stimulated by the intracellular acidification that occurs during ischemia. To test this hypothesis, we examined Ca(i), Na(i), ATP, and pH(i) during ischemia in rats in the presence and absence of 1 mM amiloride, a Na-H exchange inhibitor. Ca(i) was measured using 19F nuclear magnetic resonance (NMR) of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5F-BAPTA)-loaded rat hearts. Na(i) was measured using 23Na NMR, and the shift reagent 1, 4, 7, 10-tetraazacyclododecane-N,N',N'',N'''-tetramethylenephosphonate (Tm[DOTP]-5) was used to separate Na(i) and Na(o). ATP and pH were determined from 31P NMR measurements. During 20 minutes of ischemia, amiloride did not significantly alter the ATP decline but did significantly attenuate the rise in Na(i) and Ca(i). After 20 minutes of ischemia, time-averaged Ca(i) was 1.0±0.2 μM (mean±SEM) in amiloride-treated hearts compared with 2.3±0.9 μM in nontreated hearts. After 20 minutes of ischemia, Na(i) in the untreated heart was threefold greater than control, whereas in the amiloride-treated heart, Na(i) was not significantly different from control. These data are consistent with the involvement of Na-Ca exchange in the rise in Ca(i) during ischemia. In addition, recovery of contractile function during reperfusion after 20 minutes of ischemia was significantly better in amiloride-treated hearts (71±10%) than in nontreated hearts (24±13%). These data are consistent with the hypothesis suggesting that the elevation in Ca(i) during ischemia may contribute to postischemic contractile dysfunction.

Original languageEnglish (US)
Pages (from-to)1250-1258
Number of pages9
JournalCirculation research
Issue number5
StatePublished - 1991
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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