Circulation. 2003;108:2304-2307
Published online before print November 3, 2003, doi: 10.1161/01.CIR.0000101682.24138.36
Published online before print November 3, 2003, doi: 10.1161/01.CIR.0000101682.24138.36
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(Circulation. 2003;108:2304.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
Inhibition of 
-Protein Kinase C Protects Against Reperfusion Injury of the Ischemic Heart In Vivo
From the Departments of Molecular Pharmacology (K. Inagaki, L.C., D.M.-R.), Cardiovascular Medicine (F.I., F.H.L., M.R., P.G.Y.), and Comparative Medicine (D.M.B.), Stanford University School of Medicine, Stanford, Calif; and the Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC (K. Imahashi, E.M.).
Correspondence to Daria Mochly-Rosen, Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305-5174. E-mail mochly{at}stanford.edu
Received August 8, 2003; revision received September 19, 2003; accepted September 22, 2003.
Background— Current treatment for acute myocardial infarction (AMI) focuses on reestablishing blood flow (reperfusion). Paradoxically, reperfusion itself may cause additional injury to the heart. We previously found that 
-protein kinase C (PKC) inhibition during simulated ischemia/reperfusion in isolated rat hearts is cardioprotective. We focus here on the role for PKC during reperfusion only, using an in vivo porcine model of AMI.
Methods and Results— An intracoronary application of a selective PKC inhibitor to the heart at the time of reperfusion reduced infarct size, improved cardiac function, inhibited troponin T release, and reduced apoptosis. Using 31P NMR in isolated perfused mouse hearts, we found a faster recovery of ATP levels in hearts treated with the PKC inhibitor during reperfusion only.
Conclusions— Reperfusion injury after cardiac ischemia is mediated, at least in part, by PKC activation. This study suggests that including a PKC inhibitor at reperfusion may improve the outcome for patients with AMI.
Key Words: reperfusion • cardioprotection • kinases
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