Abstract 14772: Cardiac Vagal Control in Knock-in Mouse model of Dilated Cardiomyopathy
Background: It has been reported that cardiac vagal nerve activity is reduced in heart failure, but cardiac vagal nerve activity in heart failure has only been evaluated by indirect methods in mice.
Objective: To evaluate cardiac vagal nerve activity and identify the abnormality of cardiac vagal control in heart failure using a knock-in mouse model of dilated cardiomyopathy (DCM) with ΔK210 mutation in the cardiac troponin T gene.
Methods: Microdialysis technique was applied to the left ventricular myocardium of anesthetized mice and myocardial interstitial acetylcholine (ACh) levels were measured by HPLC as an index of ACh release from cardiac vagal nerve endings. The effects of electrical stimulation of left cervical vagal nerves at 5 and 10 Hz (peripheral vagal control) and alpha-2 adrenergic stimulation by intravenous medetomidine at 0.1 mg/kg (central vagal control) were examined in wild-type (WT) mice (n=7) and DCM mice (n=7).
Results: At baseline, heart rate was lower (390 ± 8 vs. 415 ± 4 bpm, P<0.05) and myocardial interstitial ACh level was higher (1.21 ± 0.17 vs. 0.73 ± 0.10 nM, P<0.05) in WT mice than in DCM mice. Vagal nerve stimulation decreased heart rate and increased myocardial interstitial ACh level in WT and DCM mice, and the responses of heart rate and myocardial interstitial ACh level (0.55 ± 0.09 vs. 0.58 ± 0.07 nM after vagotomy, 1.85 ± 0.19 vs. 1.78 ± 0.25 nM at 5Hz, 3.27 ± 0.32 vs. 3.30 ± 0.44 nM at 10 Hz) did not differ between WT and DCM mice. In contrast, intravenous medetomidine decreased heart rate and increased myocardial interstitial ACh level in both WT and DCM mice, but the responses of heart rate and myocardial interstitial ACh level (6.78 ± 1.10 vs. 3.18 ± 0.70 nM at 0-10 min after medetomidine administration, P<0.05) were larger in WT mice than in DCM mice.
Conclusion: In a mouse model of DCM, peripheral vagal control including ACh release from vagal nerve endings and heart rate control was preserved, but central vagal control through alpha-2 adrenergic receptors was impaired.
Author Disclosures: D. Zhan: None. C. Du: None. T. Akiyama: None. S. Morimoto: None. S. Shimizu: None. T. Kawada: None. M. Shirai: None. J.T. Pearson: None.
- © 2016 by American Heart Association, Inc.