Degradation of rat cardiac troponin I during ischemia independent of reperfusion.
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.
Palmer
Brian S
BS
Department of Emergency Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Klawitter
Paul F
PF
Reiser
Peter J
PJ
Angelos
Mark G
MG
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D019210:Troponin I / Q000378:metabolism*
D000975:Antioxidants; D019210:Troponin I; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D000111:Acetylcysteine