Channel in the rat heart: blockade of ischemic and acetylcholine
-mediated preconditioning by glybenclamide.
Qian, Yong-Zhen, Joseph E. Levasseur, Kazu-Ichi Yoshida, Rakesh C.
Kukreja.
Eric Lipman Laboratories of Molecular and Cellular Cardiology,
Division of Cardiology, Medical College of Virginia, Virginia
Commonwealth University Richmond Va 23298; and Department of
Anesthesiology, Kanagawa Dental College, Kanagawa 238, Japan
APStracts 2:0506H, 1995.
The objective of this study was to examine if the opening of KATP
channel plays an important role in ischemic preconditioning (PC) in
the rat heart. A second goal was to test the role of acetylcholine
(ACh) in mimicking PC and test if it could be blocked by KATP
antagonist. Glybenclamide, a specific antagonist of the KATP channel
was given as two doses of 0.3 mg/kg each, which was greater than one
dose used by other investigators. Six groups of rats were subjected
to ischemia and reperfusion (I/R) using these protocols: control
(I/R), 30 min of ischemia followed by 90 min reperfusion (n=6);
preconditioned - hearts given 5 min ischemia 10 min prior to I/R
(n=9); glybenclamide treatment 60 and 30 min prior to PC (n=13);
glybenclamide treatment prior to I/R (n=15); ACh infusion for 5 min
(18 g/ml) given at a rate of 0.15 ml/min followed by equilibration
for 10 min prior to I/R, n=13; glybenclamide treatment prior to ACh
infusion followed by I/R (n=11). Preconditioning reduced the
infarcted area (expressed as % area at risk) from 42.0 4.4 in control
to 8.7 6 (P<0.05, mean SE). Glybenclamide blocked the protection
conferred by PC (39.1 4.5 %, P<0.05) without having significant
effect on control non-preconditioned hearts. ACh infusion in lieu of
PC significantly although partially reduced infarct size (25.0 5.63%,
P<0.05) which was again blocked by glybenclamide (44.2 5.0 %,
p<0.05). Our data suggests that opening of KATP channel for
ischemic and ACh mediated preconditioning is also present in the rat
heart, similar to reported for other species.
Received 7 November 1994; accepted in final form 27 October 1995.
APS Manuscript Number H993-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95