Open AccessProtective Effect of the Protease Inhibitor Leupeptin Against Myocardial Stunning
Author(s) -
Yasushi Matsumura,
Hideo Kusuoka,
Michitoshi Inoue,
Masatsugu Hori,
Takenobu Kamada
Publication year - 1993
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-199307000-00021
Subject(s) - leupeptin , medicine , cardiology , ischemia , calpain , endocrinology , ryanodine receptor , protease , chemistry , calcium , biochemistry , enzyme
To elucidate whether activation of intracellular protease causes the contractile dysfunction of post-ischemic 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 degrees C). Recovery of developed pressure during reperfusion in hearts treated with 50 microM 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 Ca(2+)-activated pressure, the intact-heart correlate of maximal Ca(2+)-activated force, was also evaluated at the end of experiments during tetani elicited by rapid pacing after exposure to ryanodine. Maximal Ca(2+)-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.