Protective effect of the protease inhibitor leupeptin against myocardial stunning

Yasushi Matsumura, Hideo Kusuoka, Michitoshi Inoue, Masatsugu Hori, Takenobu Kamada

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


To elucidate whether activation of intracellular protease causes the contractile dysfunction of postishemic reperfused heart (stunned myocardium), the effect of leupeptin, a cysteine-protease inhibitor, was evaluated in isolated guinea pig hearts. Left ventricular (LV) isovolumic pressure was measured in hearts reperfused after global ischemia (15 min, 37°C). Recovery of developed pressure during reperfusion in hearts treated with 50 μM leupeptin was significantly greater than that in untreated hearts [94.3 ± 3.2% of control, n = 11 (mean ± SEM] vs. 78.1 ± 3.1%, n = 14), and was almost identical to that in nonischemic control (93.5 ± 1.6%, n = 11). Maximal Ca2+-activated pressure, the intact-heart correlate of maximal Ca2+-activated force, was also evaluated at the end of experiments during tetani elicited by rapid pacing after exposure to ryanodine. Maximal Ca2+-activated pressure in hearts treated with leupeptin (168 ± 4.6 mm Hg) was significantly higher than in untreated stunned hearts (144.5 ± 5.7 mm Hg), but significantly lower than in nonischemic control (198.4 ± 5.5 mm Hg). These results indicate that leupeptin has a protective effect against myocardial stunning. In coupling with previous reports of transient increase in intracellular [Ca2+] during ischemia and/or reperfusion, activation of proteases by Ca2+overload is suggested to play a significant role in myocardial stunning.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalJournal of cardiovascular pharmacology
Issue number1
StatePublished - Jul 1993
Externally publishedYes


  • Calcium overload
  • Ischemia
  • Protease inhibitor
  • Reperfusion
  • Stunned myocardium

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine


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