Katp channels and memory of ischemic preconditioning in dogs:
synergism between adenosine and katp channels.
Yao, Zhenhai, Tsuneo Mizumura, David A. Mei, and Garrett J. Gross.
Department of Anesthesia, Massachusetts General Hospital, Harvard
Medical School, Boston, Massachusetts 02114, Department of
Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee,
Wisconsin 53226
APStracts 3:0330H, 1996.
Results from numerous studies have shown that there is an important
link between adenosine A1 receptors and ATP-sensitive potassium
(KATP) channels in mediating the cardioprotective effects of ischemic
preconditioning (PC). The major aim of the present study was to
determine if occupation of A1 receptors and/or opening of KATP
channels are involved in the time delay between the PC stimulus and
the prolonged ischemic insult or the "memory" of PC to reduce infarct
size. Barbital anesthetized dogs were subjected to 1 hour of left
anterior descending coronary artery (LAD) occlusion followed by 4
hours of reperfusion. Ischemic PC was elicited by 10 minutes of LAD
occlusion followed by 1 hour of reperfusion (1 hour "memory") prior
to the 1 hour occlusion period. Either adenosine (800 g/min),
bimakalim (3 g/min), a combination of two lower doses of each agent
(adenosine 400 g/min, bimakalim 0.3 g/min,), or an equivalent volume
of saline were infused into the LAD for 10 minutes followed by a 1
hour drug-free period prior to the 1 hour ischemic insult. In another
series, glibenclamide, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a
selective A1 receptor blocker, or PD 115,199 (PD), a nonselective
adenosine receptor antagonist, were administered 50 minutes after
ischemic PC, 10 minutes prior to the 1 hour occlusion period. Infarct
size (IS) was expressed as a percent of the area at risk (IS/AAR).
Preconditioning with 1 hour of reperfusion resulted in a marked
reduction in infarct size (8.1 6.5% vs 29.8 5.8% in controls).
Administration of adenosine or bimakalim followed by a 1 hour drug
-free period had no effect on infarct size, however, the simultaneous
administration of adenosine and bimakalim resulted in a marked
decrease in infarct size (11.5 2.7% ). One hour after ischemic PC,
administration of glibenclamide blocked while DPCPX or PD did not
affect the protective effect of ischemic PC. These results provide
evidence that opening of myocardial KATP channels may play an
important role in the memory of ischemic PC in the canine heart, and
also suggest that adenosine and the KATP channel may have a
synergistic interaction which is important for the memory phase of
PC.
Received 30 October 1995; accepted in final form 22 July 1996.
APS Manuscript Number H1010-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996