Cardiac
troponin I (cTnI) degradation has been noted in the
stunned myocardium of rodents after
ischemia and reperfusion and is one proposed mechanism for the decreased left ventricular (LV) contractility in postischemic hearts. cTnI degradation has been best described after reperfusion of the ischemic myocardium. The effect of
ischemia, independent of reperfusion, on cTnI breakdown has not been well characterized. We tested the hypothesis that progressive cTnI degradation occurs with increasing durations of
ischemia and that this
ischemia-based degradation is, in part,
oxidant mediated. Isolated perfused rat hearts underwent global
ischemia of 15, 20, or 25 min with and without reperfusion. A second series of hearts was treated with the
antioxidants tiron (10 mM) and
N-acetylcysteine (4 mM) before 20 min of global
ischemia without reperfusion. cTnI degradation was measured using a cTnI-specific antibody and Western blot analyses. A progressive increase in cTnI degradation was seen with increasing duration of
ischemia (no reperfusion), which correlated with the return of LV developed pressure during reperfusion. The extent of cTnI degradation was increased in hearts pretreated with
antioxidants, although the qualitative degradation pattern was not altered. We conclude that a time-dependent cTnI breakdown occurs during global
ischemia that is independent of reperfusion. cTnI breakdown during
ischemia is further increased in the presence of
antioxidants, suggesting ROS generated during
ischemia may play a cTnI protective role.