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: Wei Dong Gao, Tieying Dai, Daniel Nyhan
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 290 Issue 2 Pg. H886-93 (Feb 2006) ISSN: 0363-6135 [Print] United States
• PMID: 16172165 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Troponin I
• Adenosine Triphosphate
• Calcium

Topics

• Actin Cytoskeleton (metabolism)
• Adenosine Triphosphate (metabolism)
• Animals
• Blotting, Western
• Calcium (metabolism)
• Histological Techniques
• In Vitro Techniques
• Male
• Myocardial Contraction
• Myocardial Stunning (physiopathology)
• Myocardium (metabolism)
• Osmolar Concentration
• Papillary Muscles (metabolism, physiopathology)
• Rats
• Rats, Inbred Strains
• Troponin I (metabolism)