Protective effect of the protease inhibitor leupeptin against myocardial stunning

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

Research output: Contribution to journalArticle

Abstract

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
Volume22
Issue number1
StatePublished - 1993
Externally publishedYes

Fingerprint

Myocardial Stunning
Protease Inhibitors
Pressure
Reperfusion
Peptide Hydrolases
Ischemia
Cysteine Proteinase Inhibitors
Ryanodine
leupeptin
Tetanus
Ventricular Pressure
Guinea Pigs

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Matsumura, Y., Kusuoka, H., Inoue, M., Hori, M., & Kamada, T. (1993). Protective effect of the protease inhibitor leupeptin against myocardial stunning. Journal of Cardiovascular Pharmacology, 22(1), 135-142.

Protective effect of the protease inhibitor leupeptin against myocardial stunning. / Matsumura, Yasushi; Kusuoka, Hideo; Inoue, Michitoshi; Hori, Masatsugu; Kamada, Takenobu.

In: Journal of Cardiovascular Pharmacology, Vol. 22, No. 1, 1993, p. 135-142.

Research output: Contribution to journalArticle

Matsumura, Y, Kusuoka, H, Inoue, M, Hori, M & Kamada, T 1993, 'Protective effect of the protease inhibitor leupeptin against myocardial stunning', Journal of Cardiovascular Pharmacology, vol. 22, no. 1, pp. 135-142.
Matsumura, Yasushi ; Kusuoka, Hideo ; Inoue, Michitoshi ; Hori, Masatsugu ; Kamada, Takenobu. / Protective effect of the protease inhibitor leupeptin against myocardial stunning. In: Journal of Cardiovascular Pharmacology. 1993 ; Vol. 22, No. 1. pp. 135-142.
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