BS33 The interplay of calcium fluxes and calcium buffering in heart failure and treatment with PDE5 inhibition
Abstract
Introduction Heart failure (HF) is marked by impaired calcium (Ca2+) handling, which compromises contractility and heightens arrhythmogenic risk. Ca2+ buffering within cardiac myocytes is essential for stabilizing intracellular Ca2+. It is underexplored in HF, especially in large-animal models. This study examines how HF alters Ca2+ buffering power and investigates the potential of phosphodiesterase inhibition in restoring Ca2+ dynamics. Methods HF was induced in adult sheep through tachypacing, and animals were divided into three groups: control, HF (n=10), and HF treated with tadalafil (20 mg daily, n=6). Ventricular cardiac myocytes were isolated, and intracellular Ca2+ was measured using Fluo-5F. Voltage clamp was achieved via a perforated patch clamp. Sarcoplasmic reticulum (SR) Ca2+ content and cellular buffering properties were measured by applying a 5 mM caffeine and 20 mM 2,3-butanedione monoxime solution. Protein levels were quantified using western blotting. All data were analysed with nested statistical models. Results HF significantly reduced Ca2+ transient amplitude compared to controls (325.2±34.6nmol/L vs. 169.0±16.8nmol/L, p=0.005), with tadalafil treatment showing no notable improvement (149.4±30.5nmol/L, p=0.96 vs. HF). Ca2+ influx via the L-type Ca2+ channel was also reduced in HF (peak current density 1.26±0.17pA/pF vs. 2.10±0.16pA/pF in controls, p=0.007), this remained impaired in the tadalafil group (1.32±0.22pA/pF, p=0.99 vs. HF). SR Ca2+ content…
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