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.