HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Steven F. Bolling Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rohs, T. J. Articles by Bolling, S. F. Search for Related Content PubMed PubMed Citation Articles by Rohs, T. J. Articles by Bolling, S. F.

Ann Thorac Surg 1998;65:1680-1684
© 1998 The Society of Thoracic Surgeons

---

Original articles: cardiovascular

Postischemic Function and Protein Kinase C Signal Transduction

^a Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA

Accepted for publication January 31, 1998.

Address reprint requests to Dr Bolling, Section of Thoracic Surgery, The University of Michigan Hospitals, 1500 E Medical Center Dr, 2120D Taubman Center, Box 0344, Ann Arbor, MI 48109
e-mail: (sbolling{at}umich.edu)

Background. The protective effects of myocardial preconditioning may occur by way of multiple mechanisms, with G-protein-mediated protein kinase C (PKC) translocation as a final common pathway. In this study we investigate the pharmacologic induction of preconditioning, by PKC translocation, using PKC agonists/antagonists to reveal its effects on contractile function after myocardial ischemia.

Methods. Langendorff-perfused rabbit hearts received: (1) control; (2) dimethyl sulfoxide (vehicle); (3) acetylcholine (0.55 mmol/L; PKC agonist); (4) 1,2-s,n-dioctanoylglycerol (DOG; 22 mmol/L; PKC agonist); (5) chelerythrine (0.8 mmol/L; PKC antagonist); or (6) DOG–chelerythrine followed by a 2-hour ischemic period, using modified St. Thomas cardioplegia and a 45-minute reperfusion period. The period of ischemia was chosen so as to allow for improvement by appropriate agonists. To observe metabolic changes, tissue nucleotides and nucleosides were measured. Membrane and cytosolic fractions of PKC were determined by an anti-PKC antibody directed against the PKC isozyme. Lactate levels and myocardial pH were measured.

Results. The PKC agonists DOG and acetylcholine showed the greatest recovery of developed pressure (68% ± 2%, 60% ± 9%, respectively). Although pH, lactate, and nucleotide levels were similar between groups at all times, myocyte PKC translocation demonstrated 25% of PKC isoforms on cell membrane sites during baseline, which shifted to 67% ± 17% with unprotected ischemia. DOG mimicked this shift with 58% ± 12% of PKC isoforms on membranes, which was also blocked by chelerythrine to 35% ± 7%.

Conclusions. These data demonstrate that PKC translocation results in improved postischemic function, not by alteration of energetics or metabolism, and deserves further investigation.

This article has been cited by other articles:

				C. Stamm, I. Friehs, D. B. Cowan, H. Cao-Danh, S. Noria, M. Munakata, F. X. McGowan Jr., and P. J. del Nido Post-ischemic PKC inhibition impairs myocardial calcium handling and increases contractile protein calcium sensitivity Cardiovasc Res, July 1, 2001; 51(1): 108 - 121. [Abstract] [Full Text] [PDF]

				D. Belhomme, J. Peynet, M. Louzy, J.-M. Launay, M. Kitakaze, and P. Menasche Evidence for Preconditioning by Isoflurane in Coronary Artery Bypass Graft Surgery Circulation, November 9, 1999; 100(90002): II-340 - 344. [Abstract] [Full Text] [PDF]