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. 1988 Sep;82(3):920–927. doi: 10.1172/JCI113699

Acidosis during early reperfusion prevents myocardial stunning in perfused ferret hearts.

M Kitakaze 1, M L Weisfeldt 1, E Marban 1
PMCID: PMC303603  PMID: 3417873

Abstract

Cellular calcium overload figures prominently in the pathogenesis of the contractile dysfunction observed after brief periods of ischemia (myocardial stunning). Because acidosis is known to antagonize Ca influx and the intracellular binding of Ca, we reasoned that acidosis during reperfusion might prevent Ca overload and ameliorate functional recovery. We measured developed pressure (DP) and 31P-nuclear magnetic resonance spectra in 26 isovolumic Langendorff-perfused ferret hearts. After 15 min of global ischemia, hearts were reperfused either with normal solution (2 mM [Ca]o, Hepes-buffered, pH 7.4 bubbled with 100% O2; n = 6) or with acidic solutions (pH 6.6 during 0-3 min, pH 7.0 during 4-6 min) before returning to the normal perfusate (n = 7). Ventricular function after 30 min of reperfusion was much greater in the acidic group (105 +/- 5 mmHg at 2 mM [Ca]o) than in the unmodified reperfusion group (79 +/- 7 mmHg, P less than 0.001); similar differences in DP were found over a broad range of [Ca]o (0.5-5 mM, P less than 0.001) and during maximal Ca2+ activation (P less than 0.001). Intramyocardial pH (pHi) was lower in the acidic group than in the unmodified group during early reperfusion, but not at steady state. Phosphate compounds were comparable in both groups. To clarify whether the protective effect of acidosis is due to intracellular or extracellular pH, we produced selective intracellular acidosis during early reperfusion by exposure to 10 mM NH4Cl for 6 min just before ischemia (n = 6). For the first 12 min of reperfusion with NH4Cl-free solution (pH = 7.4), pHi was decreased relative to the unmodified group. Recovery of DP was practically complete, and maximal Ca2+-activated pressure was comparable to that in a nonischemic control group (n = 5). These results indicate that transient intracellular acidosis can prevent myocardial stunning, presumably owing to a reduction of Ca influx into cells and/or competition of H+ for intracellular Ca2+ binding sites during early reperfusion.

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Selected References

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