KATP channels mediate late preconditioning against infarction produced by monophosphoryl lipid A. Am J Physiol 1996 Dec;271(6 Pt 2):H2723-9
Date
12/01/1996Pubmed ID
8997336DOI
10.1152/ajpheart.1996.271.6.H2723Scopus ID
2-s2.0-0030459703 (requires institutional sign-in at Scopus site) 67 CitationsAbstract
The cardioprotective effect of myocardial preconditioning (PC) to reduce infarct size has been shown to last approximately 90 min (early PC), and then a second window of protection (SWOP or late PC) appears 24 h later. Although much work has been done to characterize early PC, little has been done to investigate potential mediators of SWOP. To that end, we have used monophosphoryl lipid A (MLA), a nontoxic endotoxin derivative, to produce SWOP and have examined the role of ATP-sensitive potassium (KATP) channels in mediating its cardioprotection. Adult mongrel dogs were given MLA (3, 10, or 35 micrograms/kg i.v.) 24 h before a 60-min left anterior descending coronary artery occlusion and 3 h of reperfusion. After reperfusion, the hearts were stained for myocardial infarction with triphenyltetrazolium. MLA produced a dose-dependent reduction in infarct size that was associated with an enhanced shortening of the monophasic action potential duration during early ischemia. To further examine the role of KATP channels, animals were treated with MLA (35 micrograms/kg) and 24 h later were administered either glibenclamide (0.3 mg/kg i.v.) or 5-hydroxydecanoate (7.5 mg/kg intracoronary over 20 min), two structurally distinct KATP-channel antagonists. Both glibenclamide and 5-hydroxydecanoate abolished the cardioprotection produced by MLA. These results demonstrate that the cardioprotective effect of late PC produced by MLA is dependent on functional KATP channels and is the first study to suggest that late PC may be the result of an increased KATP current during ischemia.
Author List
Mei DA, Elliott GT, Gross GJMESH terms used to index this publication - Major topics in bold
Action PotentialsAdenosine Triphosphate
Animals
Collateral Circulation
Coronary Circulation
Dogs
Hemodynamics
Ischemic Preconditioning, Myocardial
Lipid A
Myocardial Infarction
Myocardium
Potassium Channels
Reaction Time
