Cardiac troponin I is modified in the myocardium of bypass patients.
BACKGROUND
Selective proteolysis of cardiac troponin I (cTnI) is a proposed mechanism of contractile dysfunction in stunned myocardium, and the presence of cTnI degradation products in serum may reflect the functional state of the remaining viable myocardium. However, recent swine and canine studies have not demonstrated stunning-dependent cTnI degradation.


RESULTS
To address the universality of cTnI modification, myocardial biopsy samples were obtained from coronary artery bypass patients (n=37) before and 10 minutes after removal of cross-clamp. Analysis of biopsy samples for cTnI by Western blotting revealed a spectrum of modified cTnI products in myocardium both before and after cross-clamp, including degradation products (7 products resulting from differential N- and C-terminal processing) and covalent complexes (3 products). In particular, a 22-kDa cTnI degradation product with C-terminal proteolysis was identified, which may represent an initial ischemia-dependent cTnI modification, similar to cTnI(1-193) observed in stunned rat myocardium. Although no systematic change in amount of modified cTnI was observed, subgroups of patients displayed an increase (n=10, 85+/-5% of cTnI remaining intact before cross-clamp versus 75+/-5% after) or a decrease (n=12, 67+/-5% before versus 78+/-5% after). Electron microscopy demonstrated normal ultrastructure in biopsy samples, which suggests no necrosis was present. In addition, cTnI modification products were observed in serum through a modified SDS-PAGE methodology.


CONCLUSIONS
cTnI modification, in particular proteolysis, occurs in myocardium of bypass patients and may play a key role in stunning in some bypass patients.
McDonough
J L
JL
Department of Physiology, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
Labugger
R
R
Pickett
W
W
Tse
M Y
MY
MacKenzie
S
S
Pang
S C
SC
Atar
D
D
Ropchan
G
G
Van Eyk
J E
JE
D001706:Biopsy; D015153:Blotting, Western; D003250:Constriction; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D017682:Myocardial Stunning / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019210:Troponin I / Q000032:analysis / Q000378:metabolism*
D019210:Troponin I