© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Stunned peri-infarct canine myocardium is characterized by degradation of troponin T, not troponin I
aDepartment of Physiology, Queen's University, Kingston, Ontario, Canada
bDepartment of Medicine, Division of Cardiology, Heart Institute, Good Samaritan Hospital, University of Southern California, Los Angeles, CA, USA
cDepartments of Emergency Medicine and Anesthesiology, University of Massachusetts Medical School, Worcester, MA 01655, USA
* Corresponding author. Department of Emergency Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. Tel.: +1-508-334-0507; fax: +1-508-856-6902. Email address: karin.przyklenk{at}umassmed.edu
Objective: Degradation of cardiac troponin I (cTnI) has been proposed to represent the underlying molecular mechanism responsible for post-ischemic contractile dysfunction of viable but ‘stunned’ myocardium. However, this concept is largely derived from models of brief, sublethal ischemia essentially devoid of necrosis, and there is speculation that defects in cTnI may be model-dependent. Accordingly, our primary aim was to evaluate the integrity of cardiac troponins—i.e., cTnI, as well as cTnT and cTnC—in viable but stunned peri-infarct tissue. In addition, we addressed the as-yet unexplored issue of whether the profound reduction of infarct size evoked by brief preconditioning ischemia (PC) was accompanied by a favorable attenuation in ischemia/reperfusion-induced degradation of cTnI, cTnT or cTnC in the remaining viable subepicardium. Methods: Anesthetized open-chest dogs received 10 min of PC ischemia or a comparable control period, followed by 1 h of sustained coronary occlusion and 3 h of reperfusion. Subepicardial biopsies from the center of the soon-to-be ischemic territory were obtained at baseline and at 30 min and 3 h post-reflow, and myofilament protein integrity (intact cTnI, cTnT and cTnC, as well as degradation bands and covalent complexes) were assessed by Western immunoblotting. In addition, in all dogs, wall thickening was measured by echocardiography, collateral blood flow was assessed during sustained occlusion by injection of radiolabeled microspheres, and infarct size was delineated by tetrazolium staining. Results: Although PC was, as expected, cardioprotective (infarct size of 2±1% of the risk region vs. 17±6% in controls; p<0.05), both control and PC groups exhibited profound and comparable contractile dysfunction following reflow (mean wall thickening reduced to 20–22% of baseline values). There was, however, no significant degradation of cTnI in the viable but stunned, peri-infarct tissue. We did observe degradation of cTnT in the stunned subepicardium, an effect that was attenuated in dogs that received antecedent PC ischemia. However, there was no correlation between post-ischemic wall thickening and the immunoreactivity of the intact cTnT band, or wall thickening and the intensity of the cTnT degradation products. Conclusions: Our results suggest cTnI degradation is not a universal determinant of post-ischemic myocardial stunning. Moreover, the dissociation between cTnT degradation and wall thickening argue against a direct ‘cause-and-effect’ relationship between proteolysis of cTnT and acute, post-ischemic contractile dysfunction of stunned peri-infarct myocardium.
KEYWORDS Peri-infarct myocardium; Troponin T; Troponin I
Time for primary review 27 days
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