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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/H1444    most recent 01279.2006v1 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 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 Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Zatta, A. J. Articles by Vinten-Johansen, J. Search for Related Content PubMed PubMed Citation Articles by Zatta, A. J. Articles by Vinten-Johansen, J.

Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation

¹Department of Cardiothoracic Surgery, Carlyle Fraser Heart Center/Crawford Long Hospital, Emory University School of Medicine, Atlanta, Georgia; and ²Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, Texas

Submitted 22 November 2006 ; accepted in final form 15 January 2008

Opioids introduced at reperfusion (R) following ischemia (I) reduce infarct size much like postconditioning, suggesting the hypothesis that postconditioning increases cardiac opioids and activates local opioid receptors. Anesthetized male rats subjected to 30 min regional I and 3 h R were postconditioned with three cycles of 10 s R and 10 s reocclusion at onset of R. Naloxone (NL), its peripherally restricted analog naloxone methiodide, -opioid receptor (DOR) antagonist naltrindole (NTI), -opioid receptor antagonist norbinaltorphimine (NorBNI), and µ-opioid receptor (MOR) antagonist H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH² (CTAP) were administered intravenously 5 min before R. The area at risk (AAR) was comparable among groups, and postconditioning reduced infarct size from 57 ± 2 to 42 ± 2% (P < 0.05). None of the antagonists alone altered infarct size. All antagonists abrogated postconditioning protection at higher doses. However, blockade of infarct sparing by postconditioning was lost, since tested doses of NL, NTI, NorBNI, and CTAP were lowered. The efficacy of NorBNI declined first at 3.4 µmol/kg, followed sequentially by NTI (1.1), NL (0.37), and CTAP (0.09), suggesting likely MOR and perhaps DOR participation. Representative small, intermediate, and large enkephalins in the AAR were quantified (fmol/mg protein; mean ± SE). I/R reduced proenkephalin (58 ± 9 vs. 33 ± 4; P < 0.05) and sum total of measured enkephalins, including proenkephalin, peptide B, methionine-enkephalin, and methionine-enkephalin-arginine-phenylalanine (139 ± 17 vs. 104 ± 7; P < 0.05) compared with shams. Postconditioning increased total enkephalins (89 ± 8 vs. 135 ± 5; P < 0.05) largely by increasing proenkephalin (33 ± 4 vs. 96 ± 7; P < 0.05). Thus the infarct-sparing effect of postconditioning appeared to involve endogenously activated MORs and possibly DORs, and preservation of enkephalin precursor synthesis in the AAR.

postconditioning; reperfusion injury; opioid receptor activation; myocardial enkephalins

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