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This Article Full Text Full Text (PDF) All Versions of this Article: 292/3/H1551    most recent 00151.2006v1 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 ISI Web of Science 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 ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Manintveld, O. C. Articles by Duncker, D. J. Search for Related Content PubMed PubMed Citation Articles by Manintveld, O. C. Articles by Duncker, D. J.

Cardiac effects of postconditioning depend critically on the duration of index ischemia

¹Division of Experimental Cardiology, Thoraxcenter and ²Department of Biochemistry, Cardiovascular Research Institute COEUR, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

Submitted 9 February 2006 ; accepted in final form 16 November 2006

Postconditioning (POC) is known as the phenomenon whereby brief intermittent ischemia applied at the onset of reperfusion following index ischemia limits myocardial infarct size. Whereas there is evidence that the algorithm of the POC stimulus is an important determinant of the protective efficacy, the importance of the duration of index ischemia on the outcome of the effects of POC has received little attention. Pentobarbital sodium-anesthetized Wistar rats were therefore subjected to index ischemia produced by coronary artery occlusions (CAO) of varying duration (15–120 min) followed by reperfusion, without or with postconditioning produced by three cycles of 30-s reperfusion and reocclusion (3POC30). 3POC30 limited infarct size produced by 45-min CAO (CAO45) from 45 ± 3% to 31 ± 5%, and CAO60 from 60 ± 3% to 47 ± 6% (both P 0.05). In contrast, 3POC30 increased infarct size produced by CAO15 from 3 ± 1% to 19 ± 6% and CAO30 from 36 ± 6 to 48 ± 4% (both P 0.05). This deleterious effect of 3POC30 was not stimulus sensitive because postconditioning with 3POC5 and 3POC15 after CAO30 also increased infarct size. The cardioprotection by 3POC30 after CAO60 was accompanied by an increased stimulation of Akt phosphorylation at 7 min of reperfusion and a 36% lower superoxide production, measured by dihydroethidium fluorescence, after 2 h of reperfusion. Consistent with these results, cardioprotection by 3POC30 was abolished by phosphatidylinositol-3-OH-kinase inhibition, as well as nitric oxide (NO) synthase inhibition. The deleterious effect of 3POC30 after CAO15 was accompanied by an increased superoxide production with no change in Akt phosphorylation and was not affected by NO synthase inhibition. In conclusion, the effect of cardiac POC depends critically on the duration of the index ischemia and can be either beneficial or detrimental. These paradoxical effects of POC may be related to the divergent effects on Akt phosphorylation and superoxide production.

myocardial infarction; rat; reperfusion injury; reperfusion injury salvage kinase pathway; reactive oxygen species

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				O. C. Manintveld, P. D. Verdouw, and D. J. Duncker The RISK of ROCK Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2563 - H2565. [Full Text] [PDF]