Abstract 16046: Myofilament Phosphorylation in Experimental Diastolic Heart Failure
Introduction: Phosphorylation of cardiac myofilaments including Myosin Binding Protein-C (cMyBP-C), phospholamban (Plb), troponin I, troponin T and myosin light chains (MLC 1 and 2) regulate cardiac systolic and diastolic function. We hypothesized that myofilament phosphorylation may be reduced in a canine model of DHF. We assessed the acute impact of beta-adrenergic blockade on myofilament phosphorylation and cardiac function in vivo.
Methods: A model of DHF was produced by inducing chronic hypertension (bilateral renal wrap) in elderly dogs (n=9). Normal young adult (YN, n=5) dogs were controls. Dogs underwent hemodynamic assessment (conductance catheter) before and 15 minutes after propranolol infusion. In a separate group of dogs (n=5 DHF and n=5 YN), serial full thickness LV biopsies were harvested from the beating heart before and 15 minutes after propranolol. Myofilament phosphorylation was assessed by one- or two-dimensional SDS-PAGE using Western Blot or phospho (ProQ Diamond) and total protein (Deep Purple) stains. Conscious echocardiography and blood pressure was assessed prior to acute study.
Results: DHF dogs were characterized by LV hypertrophy, lower afterload-dependent index of contractility (EF), higher afterload-independent indices of contractility (Ees & PRSW), impaired LV relaxation (higher tau) and decreased phosphorylation of cMyBP-C but no significant differences in Plb (table) or in troponin I, troponin T, or MLC-1 or MLC-2 (not shown). Propranolol resulted in an acute decrease in phosphorylation of cMyBP-C and Plb but not of other myofilament proteins and impaired contractility with a trend towards impairment of LV relaxation (p=0.13).
Conclusion: Specific deficits in phosphorylation of cMyBP-C may be uniquely associated with DHF. Phosphorylation status of cMyBP-C and Plb are exquisitely sensitive to acute beta-adrenergic blockade in vivo and may contribute to acute effects on cardiac function.
- © 2011 by American Heart Association, Inc.