Failing hearts are more vulnerable to dobutamine and caffeine-induced ventricular arrhythmias: Ameliorated with dantrolene treatment

BACKGROUND Compared with normal hearts, failing hearts are more vulnerable to develop atrial fibrillation under sympathetic stimulation. It has been shown that dobutamine and caffeine challenge can induce spontaneous ventricular tachyarrhythmias in normal hearts. OBJECTIVE This study was designed to investigate whether failing hearts have increased vulnerability to dobutamine- and caffeine- induced ventricular arrhythmias, and whether dantrolene treatment provides therapeutic benefits in this condition. METHODS A myocardial infarction (MI)-heart failure (HF) rat model was used 2 months after surgery. Sham-surgery animals served as the control animals. MI-HF rats were randomized into MI-HF untreated and MI-HFdantrolene-treated groups. Dobutamine (25 mg/kg, intraperitoneal [IP]) and caffeine (50 mg/kg, IP) were administered acutely to induce ventricular arrhythmias. MI-HFdantrolene group received dantrolene (10 mg/kg, IP) 30 minutes before the arrhythmia test. Spontaneous Ca2+ sparks in isolated ventricular myocytes from control and MI-HF rats were also examined. RESULTS Dobutamine induced less inotropic response in MI-HF rats than in control rats. Dobutamine + caffeine induced ventricular tachyarrhythmias in 9 of 10 MI-HF rats, while no ventricular arrhythmia was induced in the control rats (P < .01). Dantrolene treatment significantly decreased ventricular arrhythmia inducibility (n = 2 of 10, P < .05) in MI-HF rats. In isolated ventricular myocytes, Ca2+ sparks were significantly increased in MI-HF rats, and dantrolene treatment decreased Ca2+ sparks in these animals. CONCLUSION Although dobutamine evoked less inotropic effects, failing hearts were more vulnerable to dobutamine and caffeine- induced ventricular tachyarrhythmias. Dantrolene treatment decreased Ca2+ sparks in isolated ventricular myocytes from failing hearts and ameliorated ventricular tachyarrhythmias induced by dobutamine and caffeine in MI-HF rats in vivo.