Animal model
CONSTRICTION
All animal work followed IACUC-approved protocols at the respective institutions. A pressure overload model of HF and SCD was surgically generated with ascending aortic constriction (AC) and a daily bolus of low-dose isoproterenol (2 mg/kg/day) for β-adrenergic challenge. The surgical procedure and animal model have been previously described in detail (Normal ControlHF (AC + once daily β-adrenergic challenge till end point)HF+DS (HF animals received DS therapy till endpoint)HF+DS (+/-) (HF animals received DS therapy till week 3; DS was stopped after week 3)HF+DS (-/+) (HF animals without DS therapy till week 3; DS therapy was started during week 3 and continued till endpoint)Personnel involved in data collection and analysis were blinded to the treatment and non-treatment groups. All groups received similar incisions and thus, could not be distinguished based on these interventions. Each animal was assigned a unique computer-generated numeric ID. Some data were collected in part at Johns Hopkins University and the University of Cincinnati. Only male animals were used for this study because of heterogeneity in the phenotype of female animals. The progression of HF in female guinea pigs were delayed and the incidence of VT/VF/SCD was distinct from males. Females and ovariectomized females will be the focus of a follow-up study.