JTCS Sign the Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Torsten Doenst
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fischer-Rasokat, U.
Right arrow Articles by Doenst, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fischer-Rasokat, U.
Right arrow Articles by Doenst, T.
Related Collections
Right arrow Myocardial protection

J Thorac Cardiovasc Surg 2003;126:1806-1812
© 2003 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

Insulin-induced improvement of postischemic recovery is abolished by inhibition of protein kinase C in rat heart

Ulrich Fischer-Rasokat, BSa, Torsten Doenst, MDa,*

a Department of Cardiovascular Surgery, Albert-Ludwigs University of Freiburg, Freiburg, Germany

Received for publication January 3, 2003; revisions received June 9, 2003; accepted for publication July 17, 2003.

* Address for reprints: Torsten Doenst, MD, Department of Cardiovascular Surgery, University of Freiburg, Hugstetter Str. 55, 79106 Freiburg i. Br., Germany
doenst{at}ch11.ukl.uni-freiburg.de

OBJECTIVE: We demonstrated earlier that postischemic addition of insulin improves recovery of function in isolated rat heart by phosphatidylinositol 3-kinase. Activation of phosphatidylinositol 3-kinase before ischemia improves recovery of the heart after ischemia through protein kinase C. We tested whether protein kinase C activation is required for the positive inotropic effect of insulin during reperfusion.

METHODS: Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing [2-3H]glucose (5 mmol/L, 0.05 µCi/mL) plus oleate (0.4 mmol/L) and were subjected to 15 minutes of global ischemia followed by 35 minutes of reperfusion with or without insulin (1 mU/mL). We measured cardiac power, glucose uptake, and tissue metabolites. The protein kinase C inhibitor chelerythrine (5 µmol/L) was added either at the beginning of the experiment or together with insulin. Experiments were repeated under normoxic conditions.

RESULTS: Cardiac power before ischemia was 9.63 to 12.4 mW. Insulin improved recovery of power after ischemia (96.3% ± 10.8% versus 65.7% ± 3.79%, P < .05). This effect was abolished by chelerythrine (55.3% ± 6.49%). However, chelerythrine given at reperfusion did not block insulin's effect on recovery (101.0% ± 4.25%, P < .05). Postischemic glucose uptake was not increased by insulin (3.07 ± 0.32 before, 3.45 ± 0.34 µmol/min/gdw after ischemia, not significant) and was not affected by chelerythrine (3.01 ± 0.26 before, 3.29 ± 0.32 µmol/min/gdw after ischemia, not significant). Under normoxic conditions, chelerythrine did not influence insulin's effects on glucose uptake or power.

CONCLUSION: The results suggest that (1) insulin's effect on recovery is dependent on ischemia-induced protein kinase C activation, (2) the activity of protein kinase C during reperfusion may not be important for this effect of insulin, and (3) protein kinase C plays no role in insulin's effect on glucose uptake under normoxic or postischemic conditions.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS
Copyright © 2003 by The American Association for Thoracic Surgery.