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 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 (k_tr), muscle stiffness (k_m), 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 k_tr at F_max 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 F_max, is lower in stunned muscles (8.22 ± 1.56 vs. 12.94 ± 0.71, P < 0.05). In comparison with k_m at rigor, k_m 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.