Detection of endogenous acetylcholine release during brief ischemia in the rabbit ventricle: A possible trigger for ischemic preconditioning

AimsTo examine endogenous acetylcholine (ACh) release in the rabbit left ventricle during acute ischemia, ischemic preconditioning and electrical vagal stimulation.Main methodsWe 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 30 min and reperfused for 30 min. In Protocol 2 (n = 5), the LCX was temporarily occluded for 5 min. Ten minutes later, the LCX was occluded for 30 min and reperfused for 30 min. In Protocol 3 (n = 5), bilateral efferent vagal nerves were stimulated at 20 Hz and 40 Hz (10 V, 1-ms pulse duration).Key findingsIn Protocol 1, a 30-min coronary occlusion increased the ACh level from 0.39 ± 0.15 to 7.0 ± 2.2 nM (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 ± 0.11 nM (P < 0.05). The ACh level returned to 0.48 ± 0.10 nM during the interval. After that, a 30-min coronary occlusion increased the ACh level to 2.4 ± 0.49 nM (P < 0.01). In Protocol 3, vagal stimulation at 20 Hz and 40 Hz increased the ACh level from 0.29 ± 0.06 to 1.23 ± 0.48 (P < 0.05) and 2.44 ± 1.13 nM (P < 0.01), respectively.SignificanceAcute 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 5 min can also increase the ACh level, suggesting that endogenous ACh release can be a trigger for ischemic preconditioning.