LAUSR

Severe hyper-catecholaminergic states likely cause heart failure and cardiac fibrosis. While previous studies demonstrated the effects of beta-blockade in experimental models of single-catecholamine excess states, the detailed benefits of beta-blockade in more realistic models of hyper-adrenergic states are less clearly understood. In this study, we examined different therapeutic dosages and the effects of propranolol in rats with hyper-acute catecholamine-induced heart failure, and subsequent cardiopulmonary changes. Rats (n = 41) underwent a 6 h infusion of epinephrine and norepinephrine alone, with additional low-dose (1 mg/kg) or high-dose propranolol (10 mg/kg) at hour 1. Cardiac and pulmonary tissues were examined after 6 h. Catecholamine-only groups had the lowest survival rate. Higher doses of propranolol (15 mg/kg) caused similarly low survival rates and were not further analyzed. All low-dose propranolol rats survived, with a modest survival improvement in the high-dose propranolol groups. Left ventricular (LV) systolic pressure and LV end-diastolic pressure improved maximally with low-dose propranolol. Cardiac immunohistochemistry revealed an LV upregulation of FGF-23 in the catecholamine groups, and this improved in low-dose propranolol groups. These results suggest catecholamine-induced heart failure initiates early pre-fibrotic pathways through FGF-23 upregulation. Low-dose propranolol exerted cardio-preventative effects through FGF-23 downregulation and hemodynamic-parameter improvement in our model of hyper-acute catecholamine-induced heart failure.