Role of K+ATP channels in ischemic preconditioning and cardioprotection.
Since the phenomenon of ischemic preconditioning was first described some 15 years ago, interest in strategies aimed at reducing infarct size has increased. During the past 10 years, investigations into the mechanism of ischemic preconditioning have clearly demonstrated the cardioprotective effect of K+ATP channel opening. Thus, K+ATP channel activation has been shown to be involved in cardioprotection by a variety of stimuli, including a brief period of complete ischemia (classical ischemic preconditioning) or a partial coronary artery occlusion. In addition, ischemia in remote organs and nonischemic stimuli in the heart such as ventricular pacing, stretch, and heat stress also confer protection via K+ATP channel activation. Pharmacological agents that open K+ATP channels reduce infarct size, but K+ATP channel opening must occur prior to or early during the sustained infarct-producing coronary artery occlusion, while the degree and memory of cardioprotection are less than those produced by classical ischemic preconditioning. Although the exact mechanism by which K+ATP channel activation protects is still incompletely understood, recent studies indicate a role for the mitochondrial K+ATP channels. Before K+ATP channel opening can be employed in patients at increased risk of developing myocardial infarction (e.g., unstable angina), it is mandatory to determine whether tolerance (tachyphylaxia) occurs with repeated administration of K+ATP channel openers in a fashion similar to what occurs with ischemic preconditioning.
Duncker
D J
DJ
Thoraxcenter, Erasmus University Rotterdam, The Netherlands.
Verdouw
P D
PD
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D018882:Heat Stress Disorders; D006801:Humans; D007511:Ischemia / Q000503:physiopathology* / Q000517:prevention & control; D019157:Ischemic Preconditioning, Myocardial; D054086:KATP Channels; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D020011:Protective Agents / Q000627:therapeutic use; D013610:Tachycardia
D018528:ATP-Binding Cassette Transporters; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D020011:Protective Agents; C092520:uK-ATP-1 potassium channel