Detection of endogenous acetylcholine release during brief ischemia in the rabbit ventricle: a possible trigger for ischemic preconditioning.
OBJECTIVE
To examine endogenous acetylcholine (ACh) release in the rabbit left ventricle during acute ischemia, ischemic preconditioning and electrical vagal stimulation.


METHODS
We measured myocardial interstitial ACh levels in the rabbit left ventricle using a cardiac microdialysis technique. In Protocol 1 (n=6), the left circumflex coronary artery (LCX) was occluded for 30min and reperfused for 30min. In Protocol 2 (n=5), the LCX was temporarily occluded for 5min. Ten minutes later, the LCX was occluded for 30min and reperfused for 30min. In Protocol 3 (n=5), bilateral efferent vagal nerves were stimulated at 20Hz and 40Hz (10V, 1-ms pulse duration).


RESULTS
In Protocol 1, a 30-min coronary occlusion increased the ACh level from 0.39+/-0.15 to 7.0+/-2.2nM (mean+/-SE, P<0.01). In Protocol 2, a 5-min coronary occlusion increased the ACh level from 0.33+/-0.07 to 0.75+/-0.11nM (P<0.05). The ACh level returned to 0.48+/-0.10nM during the interval. After that, a 30-min coronary occlusion increased the ACh level to 2.4+/-0.49nM (P<0.01). In Protocol 3, vagal stimulation at 20Hz and 40Hz increased the ACh level from 0.29+/-0.06 to 1.23+/-0.48 (P<0.05) and 2.44+/-1.13nM (P<0.01), respectively.


CONCLUSIONS
Acute ischemia significantly increased the ACh levels in the rabbit left ventricle, which appeared to exceed the vagal stimulation-induced ACh release. Brief ischemia as short as 5min can also increase the ACh level, suggesting that endogenous ACh release can be a trigger for ischemic preconditioning.
Kawada
Toru
T
Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, Japan. torukawa@res.ncvc.go.jp
Akiyama
Tsuyoshi
T
Shimizu
Shuji
S
Kamiya
Atsunori
A
Uemura
Kazunori
K
Li
Meihua
M
Shirai
Mikiyasu
M
Sugimachi
Masaru
M
D000109:Acetylcholine / Q000378:metabolism*; D000222:Adaptation, Physiological; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000294:innervation / Q000378:metabolism*; D017551:Microdialysis; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D011817:Rabbits; D014630:Vagus Nerve; D055536:Vagus Nerve Stimulation
D000109:Acetylcholine