Relative roles of Ca2+-dependent and Ca2+-independent mechanisms in hypoxic contractile dysfunction

Yukihiro Koretsune, Eduardo Marban

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Contractile function is known to be impaired during hypoxia or metabolic inhibition, but the relative importance of activator Ca2+ deficiency compared with the accumulation of depressant metabolites remains controversial. To distinguish between these possibilities, we used nuclear magnetic resonance (NMR) spectroscopy to measure the most likely mediators - intracellular [Ca2+] ([Ca2+]i), inorganic phosphate concentration ([Pi]), and pH - before and during hypoxia in perfused ferret hearts. Ca2+ transients were quantified by gated fluorine-19 NMR spectroscopy. Left ventricular developed pressure decreased to steady-state levels approximately 60% of control values after 20 minutes of hypoxic perfusion (induced by equilibrating the perfusate with 10% O2-90% N2). With hypoxia, phosphorus NMR revealed an increase in [Pi] and a mild intracellular acidosis. Both [Pi] and intracellular pH correlate well with the extent of decline of developed pressure in each heart, but multiple regression analysis points to the changes in [Pi] as the dominant influence. In contrast, [Ca2+], at end diastole was not influenced by hypoxia, whereas the peak systolic values were paradoxically increased. The ratio of Ca2+ transient amplitude in hypoxia to that in control had no correlation with percent of developed pressure. These findings indicate that contractile failure during relatively mild, steady-state hypoxia is not due to a critical failure of any of the mechanisms that regulate cytoplasmic activator Ca2+. Instead, the accumulation of Pi (and to a lesser degree, H+) mediates hypoxic contractile dysfunction.

Original languageEnglish (US)
Pages (from-to)528-535
Number of pages8
Issue number2
StatePublished - Aug 1990


  • 5F-BAPTA
  • Acidosis
  • Inorganic phosphate
  • Nuclear magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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