Pharmacological targets revealed by myocardial postconditioning.
Postconditioning is an intervention in which controlled, brief, intermittent periods of ischaemia at the onset of reperfusion protect myocardium from the lethal consequences of reperfusion ('reperfusion injury'). Postconditioning has been demonstrated in humans with acute myocardial infarction and offers the possibility of further limiting infarct size in patients undergoing reperfusion therapy. We review current research that focuses on the molecular mechanisms of postconditioning. The molecular pathways are incompletely mapped but they probably converge on suppression of mitochondrial permeability transition pore opening during early reperfusion, an event that is thought to promote cell death at reperfusion. A number of upstream signalling pathways, activated by autacoid factors, converge on this crucial target and these offer a range of realistic possibilities for pharmacological induction of a postconditioned state.
Burley
Dwaine S
DS
Welsh School of Pharmacy, Cardiff University, UK.
Baxter
Gary F
GF
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use; D012898:Autacoids / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000628:therapy; D009292:Narcotic Antagonists; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011957:Receptors, Opioid / Q000819:agonists / Q000627:therapeutic use; D018047:Receptors, Purinergic P1 / Q000627:therapeutic use
D051017:Apoptosis Regulatory Proteins; D012898:Autacoids; D002316:Cardiotonic Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009292:Narcotic Antagonists; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011957:Receptors, Opioid; D018047:Receptors, Purinergic P1; D009320:Atrial Natriuretic Factor