title: Increased cross-bridge cycling rate in stunned myocardium.
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 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.
authors.affiliation: 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
authors.forename: Wei Dong
authors.initials: WD
authors.lastname: Gao
authors.forename: Tieying
authors.initials: T
authors.lastname: Dai
authors.forename: Daniel
authors.initials: D
authors.lastname: Nyhan
mesh_terms: 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
chemical_list: D019210:Troponin I; D000255:Adenosine Triphosphate; D002118:Calcium