© 1999 American Heart Association, Inc.
Integrative Physiology |
Absence of Troponin I Degradation or Altered Sarcoplasmic Reticulum Uptake Protein Expression After Reversible Ischemia in Swine
Presented in part at the 69th Scientific Sessions of the American Heart Association, New Orleans, La, November 10–13, 1996, and the Experimental Biology Meeting, Washington, DC, April 17–21, 1999.
From the Veterans Affairs Western New York Healthcare System (J.A.F., J.M.C.) and the Departments of Medicine (J.A.F., J.M.C.), Biochemistry (T.-C.L.), Surgery (J.F.), and Physiology and Biophysics (S.A.T., J.M.C.) at the State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY.
Correspondence to John M. Canty Jr, MD, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Biomedical Research Bldg, Room 345, 3435 Main St, Buffalo, NY 14214. E-mail canty{at}buffalo.edu
Abstract—The findings of
troponin I (TnI) proteolysis (in isolated rat hearts) and induction of
selected sarcoplasmic reticulum (SR) calcium-regulatory genes (after
repetitive total coronary occlusions in swine) have given rise
to the hypothesis that the time course of functional recovery of
stunned myocardium reflects the resynthesis of reversibly
damaged proteins. Although stunning occurs after brief total occlusions
and prolonged partial occlusions (ie, short-term hibernation), the time
course of functional recovery varies from a few hours to several days,
suggesting that the severity of protein damage or mechanisms
responsible for the dysfunction may differ. To study this, we examined
SR gene expression and TnI degradation in stunned
myocardium produced by 10-minute total left anterior
descending coronary artery (LAD) occlusions (n=4) or 1-hour
partial LAD occlusions, in which flow was reduced to 
50% of control
values for 60 minutes (n=6) in swine. One hour after reperfusion, LAD
wall thickening was severely depressed in both models despite normal
perfusion and no triphenyltetrazolium
chloride evidence of necrosis. Normal myocardium
exhibited TnI immunoreactivity at 31 kDa and a weak secondary band at
27 kDa. Irreversible injury or calpain activation in vitro produced a
marked increase in the intensity of the 27-kDa band, consistent
with TnI degradation. Stunned myocardium demonstrated no
change in the 31- or the 27-kDa band, and the percentage of the 27- to
31-kDa band remained constant after 10-minute total occlusions
(LAD, 5.9±0.9%; normal, 4.9±1.6%) and 1-hour partial
occlusions (LAD, 8.5±1.9%; normal, 7.3±1.4%) and in sham controls
(LAD, 10.9±1.5%; normal, 9.8±1.4%). Northern analysis
showed no alterations in TnI or SR gene expression, but the stress
protein HSP-70 was variably induced. Thus, stunned
myocardium occurs without TnI degradation or altered SR
gene expression, indicating that additional mechanisms are responsible
for the reversible dysfunction after single episodes of regional
ischemia in swine.
Key Words: ischemia • myocardial stunning • troponin I • sarcoplasmic reticulum • HSP-70
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