QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.062547v1 309/3/1256    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liem, D. A. Articles by Duncker, D. J. Search for Related Content PubMed PubMed Citation Articles by Liem, D. A. Articles by Duncker, D. J.

CARDIOVASCULAR

The Tyrosine Phosphatase Inhibitor Bis(Maltolato)Oxovanadium Attenuates Myocardial Reperfusion Injury by Opening ATP-Sensitive Potassium Channels

Experimental Cardiology, Thoraxcenter, Cardiovascular Research School (COEUR), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands (D.A.L., B.C.G., S.K., O.C.M., P.D.V., D.J.D.); and GHO Pharma, Maastricht, The Netherlands (C.C.G., S.K.)

Vanadate has been shown to inhibit tyrosine phosphatase, leading to an increased tyrosine phosphorylation state. The latter has been demonstrated to be involved in the signal transduction pathway of ischemic preconditioning, the most potent endogenous mechanism to limit myocardial infarct size. Furthermore, there is evidence that phosphatase inhibition may be cardioprotective when given late after the onset of ischemia, but the mechanism of protection is unknown. We tested the hypothesis that the organic vanadate compound bis(maltolato)oxovanadium (BMOV) limits myocardial infarct size by attenuating reperfusion injury and investigated the underlying mechanism. Myocardial infarction was produced in 112 anesthetized rats by a 60-min coronary artery occlusion, and infarct size was determined histochemically after 180 min of reperfusion. Intravenous infusion of BMOV in doses of 3.3, 7.5, and 15 mg/kg i.v. decreased infarct size dose-dependently from 70 ± 2% of the area at risk in vehicle-treated rats down to 41 ± 5% (P < 0.05 versus control), when administered before occlusion. Administration of the low dose just before reperfusion was ineffective, but administration of the higher doses was equally cardioprotective as compared with administration before occlusion. The cardioprotection by BMOV was abolished by the tyrosine kinase inhibitor genistein and by the ATP-sensitive potassium (K⁺_ATP) channel blocker glibenclamide but was not affected by the ganglion blocker hexamethonium. We conclude that BMOV afforded significant cardioprotection principally by limiting reperfusion injury. The mode of action appears to be by opening of cardiac K⁺_ATP channels via increased tyrosine phosphorylation.

Address correspondence to: Dirk J. Duncker, Experimental Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: d.duncker{at}erasmusmc.nl

This article has been cited by other articles:

				K. Przyklenk, M. Maynard, C. E. Darling, and P. Whittaker Aging Mouse Hearts Are Refractory to Infarct Size Reduction With Post-Conditioning J. Am. Coll. Cardiol., April 8, 2008; 51(14): 1393 - 1398. [Abstract] [Full Text] [PDF]