Abstract
Background: Compared to sympathetic stimulation (SS), normal hearts are more sensitive to vagal stimulation induced atrial fibrillation (AF). In contrast, we have recently demonstrated that failing hearts are less sensitive to vagal stimulation induced AF and more sensitive to SS induced AF. The exact mechanism underlying this SS enhanced AF in heart failure (HF) remains to be investigated. We now hypothesize that SS can worsen ryanodine receptor dysfunction already present in HF, leading to enhanced AF vulnerability. Consequently dantrolene, by stabilizing ryanodine receptors, can decrease SS enhanced AF inducibility in HF. Methods and Results: A rat myocardial infarction (MI)-HF model was used. MI was produced in rats by coronary artery ligation. HF was confirmed in 17 rats 2 months after the surgery. These animals were randomized into control (vehicle treated, n=9) and dantrolene (10mg/kg, IP, n=8) groups. In vivo atrial electrophysiology and AF inducibility tests under SS were studied using a catheter approach in all animals 30 minutes after the respective treatments. SS was mimicked by intravenous isoproterenol (0.1ug/min) infusion. Compared with the control group, dantrolene treatment significantly reduced AF inducibility and AF duration under SS (figure). Conclusion: The ryanodine receptor stabilizer dantrolene can significantly attenuate SS enhanced AF inducibility in a rat MI-HF model, suggesting that ryanodine receptor dysfunction may play a critical role in enhancing AF inducibility under SS in HF. The ryanodine receptor stabilizer dantrolene may be a new treatment option in reducing AF in HF.
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