Xanthine oxidase inhibition ameliorates cardiovascular dysfunction in dogs with pacing-induced heart failure ✰

Abstract We hypothesized that chronic xanthine oxidase inhibition (XOI) would have favorable effects on both ventricular and vascular performance in evolving heart failure (HF), thereby preserving ventricular–vascular coupling. In HF, XOI reduces oxidative stress and improves both vascular and myocardial function. Dogs were randomized to receive either allopurinol (100 mg/day p.o.) or placebo following surgical instrumentation for chronic measurement of left-ventricular pressure and dimension and during induction of HF by rapid pacing. In the placebo group ( n = 8), HF was characterized by increased LV end-diastolic pressure (LVEDP, 10.2 ± 5.5 and 29.8 ± 3.9 mmHg, before and after HF, respectively, P P P P P n = 9) profoundly attenuated both the Ea increase (from 22.3 ± 3 to 25.6 ± 4.6 mmHg/mm, P = NS) and the fall in Ees (from 11.8 ± 1.1 to 11.7 ± 1, P = NS), thereby preserving the Ees/Ea ratio (from 0.58 ± 0.1 to 0.56 ± 0.1, P