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Postconditioning and intermittent bradykinin induced cardioprotection require cyclooxygenase activation and prostacyclin release during reperfusion

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Abstract

Postconditioning (PostC), obtained with brief intermittent cycles of ischemia alternating with reperfusion applied after the ischemic event, has been shown to reduce infarct size. Recently, we have shown that PostC triggering includes B2 receptor activation and its downstream pathway. Moreover, we showed that BK intermittent infusion induces a cardioprotection similar to PostC. The aim of this study was to investigate the involvement of cyclooxygenase-(COX)-derivated prostaglandins, such as prostacyclin (PGI2) pathway in the cardioprotective action mediated by intermittent BK infusion.

Isolated rat hearts underwent 30 min ischemia and 120 min reperfusion. Myocardial damage was evaluated using nitro-blue-tetrazolium staining. The production of metabolite of PGI2, 6-keto-PGF1α, was evaluated with EIA assay on the samples collected during reperfusion. The perfusion pressure and the left ventricular pressure were monitored. In Control hearts, the infarct size was 64% ± 4% of risk area. PostC reduced significantly the infarct size (28% ± 4% P < 0.001 Vs. Control). BK intermittent protocol to mimic PostC, attenuated infarct size (40% ± 2% P < 0.01 Vs. Control). The BK-intermittent and PostC protections were abolished with COX-inhibition. Intermittent BK and PostC enhanced the release of prostacyclin metabolite, 6-keto-PGF1α, in the late phase of reperfusion (i.e., 6-keto-PGF1α peaked 30 min after protective maneuvers). Also the stable PGI2 analogue, Iloprost, given in the early reperfusion reduced infarct size and improved post-ischemic heart function. In conclusion, protection by PostC and intermittent BK requires COX activation and PGI2 release during late reperfusion. These data suggest that COX must not be inhibited to have PostC protection. This finding should be kept present by future clinical studies on PostC.

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Acknowledgments

We thank Regione Piemonte; Compagnia di San Paolo”; the Consorzio Interuniversitario per le Ricerche Cardiovascolari (CIRC) and the Italian Ministry of University and Research (MIUR, PRIN). We Thank Dr. Giovanni Berta for insightful suggestions.

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  1. Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Regione Gonzole 10, 10043, Orbassano, TO, Italy

    Claudia Penna, Daniele Mancardi, Francesca Tullio &  Pasquale Pagliaro

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  1. Claudia Penna
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  2. Daniele Mancardi
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Correspondence to Pasquale Pagliaro.

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Returned for 1. Revision: 6 August 2007 1. Revision received: 16 November 2007

Returned for 2. Revision: 22 November 2007 2. Revision received: 23 November 2007

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Penna, C., Mancardi, D., Tullio, F. et al. Postconditioning and intermittent bradykinin induced cardioprotection require cyclooxygenase activation and prostacyclin release during reperfusion. Basic Res Cardiol 103, 368–377 (2008). https://doi.org/10.1007/s00395-007-0695-7

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  • DOI: https://doi.org/10.1007/s00395-007-0695-7

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