Mechanism of early ischemic contractile failure. Inexcitability, metabolite accumulation, or vascular collapse?

Y. Koretsune, M. C. Corretti, H. Kusuoka, E. Marban

Research output: Contribution to journalArticlepeer-review


The basis of early ischemic contractile failure was investigated in perfused ferret hearts at 27°C. Isovolumic left ventricular developed pressure fell by more than 50% within 30 seconds of the onset of total global ischemia and reached zero by 5 minutes. Monophasic action potential recordings revealed no decrease in excitability during this period. Phosphorus nuclear magnetic resonance spectra obtained at 30-second resolution showed no significant changes in inorganic phosphate or phosphocreatine during the first 30 seconds of ischemia. Intracellular pH (pH(i)) and ATP changed even more slowly; therefore, none of these metabolites could account for the rapid fall in force. To gauge the contribution of intravascular pressure, we compared ordinary aortic flow occlusion with tissue-level ischemia induced by massive coronary microembolization at the level of the precapillary arterioles. Functional depression developed significantly more slowly in the microembolized hearts, despite accumulation of inorganic phosphate and protons comparable with that in ordinary ischemia. After microembolization, the time course of functional depression reflected much more closely the concomitant inorganic phosphate and pH(i) changes. Thus, our results provide novel evidence supporting the importance of vascular collapse in the mechanism of early ischemic contractile failure.

Original languageEnglish (US)
Pages (from-to)255-262
Number of pages8
JournalCirculation research
Issue number1
StatePublished - 1991


  • Acidosis
  • Action potential
  • Erectile effect
  • Inorganic phosphate
  • Ischemia
  • Vasotropic effects

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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