Pathophysiology and Pathogenesis of Contractile Failure in Stunned Myocardium

Hideo Kusuoka, Masafumi Kitakaze, Yukihiro Koretsune, Michitoshi Inoue, Eduardo Marban

Research output: Contribution to journalArticlepeer-review

Abstract

To investigate excitation-contraction coupling in stunned myocardium, intracellular free calcium concentration ([Ca2+]i) was measured before and after ischemia in perfused hearts using gated 19F NMR and the Ca2+ indicator 5F-BAPTA. Maximal Ca2+-activated force was also measured in parallel experiments. Stunned myocardium was created by reperfusion after 15 min global ischemia at 37°C in isolated ferret hearts. In stunned myocardium, peak [Ca2+]i was paradoxically higher than that in control, but maximal Ca2+-activated pressure was lower in stunned hearts. These results indicate that contractile failure in stunned myocardium is due to a decrease in the myofilament sensitivity to Ca2+ as well as to a decrease in maximal Ca2+-activated force; failure of activator Ca2+ delivery cannot be implicated. The role of intracellular calcium overload in the pathogenesis of stunned myocardium was also investigated. Time-averaged 19F NMR measurements directly revealed the increase in [Ca2+]i during ischemia and in the early phase of reperfusion. The strategies to prevent Ca overload during reperfusion with modified reperfusate succeeded in preserving contractile function. Transient Ca overload without ischemia induced by different causes, i.e., high [Ca]0 perfusion, ventricular fibrillation or treatment with adriamycin, also produced contractile dysfunction that outlasted the interventions themselves. Thus, we propose that transient Ca overload during ischemia and early reperfusion initiates long-lasting contractile dysfunction in stunned myocardium.

Original languageEnglish (US)
Pages (from-to)878-884
Number of pages7
JournalJAPANESE CIRCULATION JOURNAL
Volume55
Issue number9
DOIs
StatePublished - Sep 1991

Keywords

  • Calcium overload
  • Excitation-contraction coupling
  • Nuclear Magnetic resonance
  • Stunned myocardium

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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