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Increased cross-bridge cycling rate in stunned myocardium
Decreased Ca2+ responsiveness of the myofilaments underlies myocardial stunning. Given that cross-bridge cycling is a major determinant of myofilament behavior, we quantified cross-bridge cycling rate in stunned myocardium. After stabilization, rat hearts were subjected to 20 min of no-flow global i...
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Published in: | American journal of physiology. Heart and circulatory physiology 2006-02, Vol.59 (2), p.H886 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | Decreased Ca2+ responsiveness of the myofilaments underlies myocardial stunning. Given that cross-bridge cycling is a major determinant of myofilament behavior, we quantified cross-bridge cycling rate in stunned myocardium. After stabilization, rat hearts were subjected to 20 min of no-flow global ischemia and 30 min of reperfusion at 37 degrees C. Control hearts were perfused continuously at 37 degrees C for 60 min. Trabeculae were dissected and chemically skinned with 1% Triton X-100. The muscles were then activated with solutions of varied Ca2+ concentration ([Ca2+]). Force-[Ca2+] relations, rate of force redevelopment after release (ktr), muscle stiffness (km), and myofilament ATP consumption were determined. Maximal Ca2+-activated force (Fmax) was depressed in stunned myocardium (49 +/- 5 vs. 82 +/- 5 mN/mm2, P < 0.01). Western immunoblotting showed degradation of troponin I in stunned myocardium. The ktr at Fmax was significantly increased in stunned muscles (19.82 +/- 2.74 vs. 13.19 +/- 0.96 s-1, 22 degrees C, P < 0.01; 7.49 +/- 0.52 vs. 5.81 +/- 0.54 s-1, 10 degrees C, P < 0.05). The ratio of km measured at 100 Hz over that at 1 Hz, during Fmax, is lower in stunned muscles (8.22 +/- 1.56 vs. 12.94 +/- 0.71, P < 0.05). In comparison with km at rigor, km at Fmax is significantly lower in the stunned group (78.82 +/- 6.11 vs. 93.27 +/- 3.03%, P < 0.05). Myofilament ATP consumption at Fmax did not change in stunned muscles (5,901 +/- 952 vs. 5,596 +/- 972 pmol.microl-1.min-1, P = 0.49). These results show that cross-bridge cycling is increased in stunned myocardium. Such increases are likely the result of increased transition rate from force-generating states to non-force-generating states. Thus stunned myocardium still maintains ATP consumption in spite of lower force development, rationalizing the long-standing paradox of decreased force but unchanged oxygen consumption in the postischemic heart. [PUBLICATION ABSTRACT] |
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ISSN: | 0363-6135 1522-1539 |