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.