Increased cross-bridge cycling rate in stunned myocardium

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Abstract

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°C. Control hearts were perfused continuously at 37°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 (F max) 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°C, P < 0.01; 7.49 ± 0.52 vs. 5.81 ± 0.54 s-1, 10°C, P < 0.05). The ratio of k m 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 F max is significantly lower in the stunned group (78.82 ± 6.11 vs. 93.27 ± 3.03%, P < 0.05). Myofilament ATP consumption at F max did not change in stunned muscles (5,901 ± 952 vs. 5,596 ± 972 pmol·μ1-1·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.

Original languageEnglish (US)
Pages (from-to)H886-H893
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume290
Issue number2
DOIs
StatePublished - Feb 1 2006

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Keywords

  • Contraction
  • Cross-bridge cycling
  • Myocardial stunning

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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