Canine Cardiac Digitalis Receptors are Preserved in Congestive Heart Failure Induced by Rapid Ventricular Pacing

Abstract

In dogs, it has been reported that acute ischemia or severe and terminal heart failure results in a selective reduction of myocardial α₃ isoform of Na, K-ATPase activity. The aim of this study was to evaluate if a similar change in the two canine digitalis receptor isoforms occurs following 4 weeks of rapid ventricular pacing-induced heart failure without profound necrosis. Heart failure was induced in dogs by rapid ventricular pacing (240 beats × min^-1). Digitalis receptors were quantitated by [³H]-ouabain binding with isolated microsomal membranes from sham-operated (n = 3) and heart failure dogs (n = 4) and by Western blot analysis using specific α₁ and α₃ polyclonal antibodies. In kinetic studies, similar dissociation rates of 19 to 22 × 10^-4 s^-1 and 1.3 to 2.4 10^-4 s^-1 corresponding to high and low affinity sites respectively, were found in sham-operated and CHF dogs. Immunoblotting showed similar abundance of α₁ isoform in the two groups; however, levels of α₃ were increased by at least 50% in pacing-induced heart failure animals. In conclusion, heart failure selectively modulates the expression of cardiac α₃ isoform in dogs.