Delayed cardioprotection in a human cardiomyocyte-derived cell line: the role of adenosine, p38MAP kinase and mitochondrial KATP.
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%)].


CONCLUSIONS
In this model delayed PC can be mimicked by adenosine and involves the p38MAP kinase pathway and the mitochondrial KATP channel.
Carroll
R
R
The Hatter Institute, Department of Academic and Clinical Cardiology, University College Hospitals and Medical School, London, UK.
Yellon
D M
DM
D000241:Adenosine / Q000502:physiology*; D002460:Cell Line; D003652:Decanoic Acids / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006880:Hydroxy Acids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008565:Membrane Proteins / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D015221:Potassium Channels; D011725:Pyridines / Q000494:pharmacology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D003652:Decanoic Acids; D006880:Hydroxy Acids; D007093:Imidazoles; D008565:Membrane Proteins; D015221:Potassium Channels; D011725:Pyridines; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000241:Adenosine; C093642:SB 203580