Abstract
The aim of this study was to assess early preconditioning protection against stunning in conscious sheep and analyze the role of ATP-dependent potassium (KATP) channels in the protective mechanism. Chronically instrumented animals were submitted to a 12 min reversible ischemia and 2 h reperfusion. Early preconditioning, consisting of six 5 min occlusion–5 min reperfusion periods, followed by 45 min normoperfusion before the prolonged ischemia protected against stunning (P < 0.01). In these experimental conditions, current agents used to analyze sarcolemmal (sKATP) and mitochondrial (mKATP) KATP channels could not clearly establish their participation in the protective mechanism. At doses that inhibit sKATP channels they were unable to block preconditioning protection against stunning (glibenclamide) or conversely, blocked preconditioning at doses that do not inhibit these channels (HMR1098). Moreover, both mKATP channel agonists (diazoxide) and antagonists (5HD) protected against stunning, a response that could be due to their effect via an alternative mitochondrial pathway.
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Acknowledgments
The authors wish to thank María Inés Besansón and Pedro Iguain for performing the anesthesia and follow-up of the animals during surgery, Marta Tealdo, and technicians: Juan Mansilla, Osvaldo Sosa, and Juan Ocampo for animal care, and Julio Martínez and Fabián Gauna for technical assistance. We also gratefully acknowledge the donation of HMR1098 by Sanofi-aventis.
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Lascano, E.C., Negroni, J.A. & del Valle, H.F. Early preconditioning protection against stunning in conscious sheep. Role of KATP channels. Mol Cell Biochem 331, 247–257 (2009). https://doi.org/10.1007/s11010-009-0166-6
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DOI: https://doi.org/10.1007/s11010-009-0166-6