Abstract
Evidence of delayed preconditioning (PC) in man is limited. Adenosine is proposed as a trigger via action on the A1 receptor in many species and the mitochondrial KATP channel is a likely end effector. We examined the ability of a brief, simulated ischemic episode on day one to provide delayed cardioprotection against lethal, simulated ischemia on day two in a human cardiac cell line with reference to the role of adenosine, the p38MAP kinase signalling pathway and mitochondrial KATP channel.
Results: PC and adenosine administered on day 1 protected against cell death on day 2 as measured by LDH release and propidium iodide (PI) exclusion: (%LDH release: PC: 12.1 ± 1.1%, ADO: 11.9 ± 2.0% vs control: 36.4 ± 1.1%, %PI positive: PC: 14.6% ± 1.4%, ADO: 17.9 ± 2.0% vs control: 34.4 ± 2.0% respectively). This protection is abolished by treatment with SB203580 prior to the protective stimulus on day 1: [PC + SB (%LDH release 28.6 ± 2.8%, %PI positive 34.7 ± 2.2%) and ADO + SB (%LDH release 25.3 ± 2.9%; %PI positive 33.7 ± 7.3%)]. Similarly 5-hydroxydecanoate abolished protection, when given immediately prior to lethal simulated ischemia on day 2: [PC + 5-HD; (%LDH release 31.9 ± 4.8%; %PI positive 29.5 ± 2.0%) and ADO + 5-HD (%LDH release 36.9 ± 4.0%; %PI positive 34.8 ± 2%)].
Conclusion: In this model delayed PC can be mimicked by adenosine and involves the p38MAP kinase pathway and the mitochondrial KATP channel.
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Received: 2 November 1999, Returned for revision: 24 November 1999, Revision received: 23 December 1999, Accepted: 20 January 2000
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Carroll, R., Yellon, D. Delayed cardioprotection in a human cardiomyocyte-derived cell line: the role of adenosine, p38MAP kinase and mitochondrial KATP . Basic Res Cardiol 95, 243–249 (2000). https://doi.org/10.1007/s003950050187
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DOI: https://doi.org/10.1007/s003950050187