Cardiac troponin I is modified in the myocardium of bypass patients

Background-Selective proteolysis of cardiac tropanin I (cTnI) is a proposed mechanism of contractile dysfunction in stunned myocardium, and the presen ce of cTnI degradation products in serum may reflect the functional state o f the remaining viable myocardium. However, recent swine and canine studies have not demonstrated stunning-dependent cTnI degradation. Methods and Results-To address the universality of cTnI modification, myoca rdial 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 p roducts in myocardium both before and after cross-clamp, including degradat ion products (7 products resulting from differential N- and C-terminal proc essing) and covalent complexes (3 products). In particular, a 22-kDa cTnI d egradation product with C-terminal proteolysis was identified, which may re present an initial ischemia-dependent cTnI modification, similar to cTnT(1- 193) observed in stunned rat myocardium. Although no systematic change in a mount of modified cTnI was observed, subgroups of patients displayed an inc rease (n = 10, 85+/-5% of cTnI remaining intact before cross-clamp versus 7 5+/-5% after) or a decrease (n = 12 67+/-5% before versus 78+/-5% after). E lectron microscopy demonstrated normal ultrastructure in biopsy samples, wh ich suggests no necrosis was present. In addition, cTnI modification produc ts were observed in serum through a modified SDS-PAGE methodology. Conclusions-TnI modification, in particular proteolysis, occurs in myocardi um of bypass patients and may play a key role in stunning in some bypass pa tients.