The myocardial protective role of KATP channel activation and shortening of monophasic action potential duration by ischemic preconditioning in cat.
- Author:
Jong Seon PARK
1
;
Dong Gu SHIN
;
Young Jo KIM
;
Bong Sup SHIM
Author Information
1. Department of Internal Medicine, College of Medicine, Yeung Nam University.
- Publication Type:Original Article
- Keywords:
Ischemic preconditioning;
KATP channel;
Monophasic action potential
- MeSH:
Action Potentials*;
Animals;
Cats*;
Glyburide;
Infarction;
Ischemia;
Ischemic Preconditioning*;
Nicorandil;
Reperfusion
- From:Korean Journal of Medicine
1999;57(1):13-23
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: This study was designed to evaluate the role of KATP channel activation and change of monophasic action potential duration on cardioprotective effect of ischemic preconditioning in cat. METHODS: 34 cats were divided into 4 groups: control (n=10), ischemic preconditioning(n=8), glibenclamide pre-treated(n=8) and nicorandil pre-treated group(n=8). Ischemic preconditioning was done in ischemic preconditioning and glibenclamide pre-treated groups by 3 episodes of 5 min ischemia and 10 min reperfusion. All subjects underwent 40 min of ischemia and 40 min reperfusion. The KATP channel antagonist glibenclamide was given as intravenous bolus (0.5mg/kg) 10 min before ischemic precondtioning and infused (5 microgram/min) during ischemic preconditioning. Nicorandil, a KATP channel opener was injected as intravenous bolus (0.5mg/kg) before 40 min ischemic procedure. Monophasic action potential duration at 50% repolarization(MAP50) was measured in the ischemic and non-ischemic area respectively by epicardial probe throughout the experiment. The effects of ischemic preconditioning were determined by infarct size (% area at risk). RESULTS: Ischemic preconditioning or pretreatment with nicorandil prior to 40 min ischemia demonstrated a significant reduction in infarct size(26.6+/-7%, 33+/-8% infarction of the risk zone, respectively, p<0.01, p<0.05 vs. control) with respect to control(42+/-7% infarction of the risk zone). Pretreatment with glibenclamide abolished the effect of ischemic preconditioning(40+/-8% infarction of the risk zone, p=NS vs. control) Ischemic preconditioning group exhibited a significant reduction of ischemic area MAP50 duration in the ischemic area during preconditioning; at first preconditioning 123+/-9msec vs. 137+/-19msec control(p=NS), at second preconditioning 105+/-16msec vs. 140+/-19msec control(p<0.01), at third preconditioning 109+/-15msec vs. 138+/-19msec control(p<0.05). Pretreatment with glibenclamide prevented the reduction of MAP50 in the ischemic area during ischemic preconditioning. During 40 minutes ischemia, MAP50 shortening was more pronounced in the preconditioned group than in control group; at 10 min 85+/-22 msec vs. 131+/-31msec control(p<0.05), at 20 min 88+/-21msec vs. 130+/-32msec control(p<0.05), and at 30 min 103+/-24msec vs. 136+/-30msec control(p<0.05). This shortening effect was prevented by glibenclamide pretreatment. Nicorandil pretreatment pronounced the ischemic shortening of MAP50 in ischemic area and the nicorandil effect was most significant during early ischemic period; at 10 min 97+/-21msec(p<0.05 vs. control), at 20 min 104+/-32msec (p=NS vs. control), and at 30 min 134+/-28msec(p=NS vs. control). MAP50 measured in non-ischemic area was not significantly different between groups. CONCLUSION: We conclude that KATP channel activation and monophasic action potential duration shortening play a important role in myocardial protection during ischemic injury.
