Katp channels mediate late preconditioning against infarction
produced by monophosphoryl lipid a.
Mei, David A., Gary T. Elliott, and Garrett J. Gross.
Department of Pharmacology and Toxicology, Medical College of
Wisconsin, RIBI ImmunoChem Research Inc
APStracts 3:0420H, 1996.
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 hours 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 [mu]g/kg, iv) 24 hrs before a 60 min LAD occlusion and 3
hrs of reperfusion. Following reperfusion, the hearts were stained
for myocardial infarction using triphenyltetrazolium. MLA produced a
dose dependent reduction in infarct size which 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 [mu]g/kg), and 24 hours later
administered either glibenclamide (0.3 mg/kg iv) or 5
-hydroxydecanoate (5HD, 7.5 mg/kg intracoronary over 20 min), two
structurally distinct KATP channel antagonists. Both glibenclamide
and 5HD abolished the cardioprotection produced by MLA. These results
demonstrate that the cardioprotective effect of late PC produced by
MLA is dependent upon functional KATP channels and is the first study
to suggest that late PC may be the result of an increased KATP
current during ischemia.
Received 18 July 1996; accepted in final form 24 September 1996.
APS Manuscript Number H642-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996