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 P P 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.