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 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 (k(tr)), muscle stiffness (k(m)), 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 k(tr) 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 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 k(m) at rigor, k(m) 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 x microl(-1) x 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.
Gao
Wei Dong
WD
Dept. of Anesthesiology and Critical Care Medicine, Johns Hopkins Univ. School of Medicine, Tower 711, 600 N. Wolfe St., Baltimore, MD 21287, USA. wgao3@jhmi.edu
Dai
Tieying
T
Nyhan
Daniel
D
D008841:Actin Cytoskeleton / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D006652:Histological Techniques; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D017682:Myocardial Stunning / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D010210:Papillary Muscles / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D019210:Troponin I / Q000378:metabolism
D019210:Troponin I; D000255:Adenosine Triphosphate; D002118:Calcium