Effects of XO inhibitors in chronic heart failure


Disease or Trigger

Mode of XO Inhibition

Effects of XO Inhibition

Mouse Coronary ligation-induced HF Allopurinol Allopurinol doubled the survival and improved contractility and response to isoproterenol both in vivo and in isolated muscle; allopurinol also reduced the elevated XO activity in mice with heart failure Stull et al. (2004)
Mouse Coronary ligation-induced HF Allopurinol Allopurinol improved left ventricular contractile function, decreased ROS generation, attenuated LV cavity dilation, and reduced myocardial hypertrophy and fibrosis Engberding et al. (2004)
Mouse Transgenic model of cardiomyopathy Allopurinol Chronic treatment prevented myofibrillar protein oxidation and preserved cardiac function Duncan et al. (2005)
Mouse Acute heart failure Allopurinol, oxypurinol XO inhibitors improved ventricular function Naumova et al. (2005)
Rat Monocrotaline-induced right ventricular hypertrophy and failure model and HF-induced by coronary ligation N.A. Increase in myocardial XO levels de Jong et al. (2000)
Rat Coronary ligation-induced HF Oxypurinol Oxypurinol improved cardiac contractility and mechanoenergetic coupling in HF without affecting resting tension and intracellular Ca2+ transients Kögler et al. (2003)
Rat Coronary ligation-induced HF Allopurinol Both acute (5-day) and chronic (10-week) treatment with allopurinol improved LV hemodynamics; chronic treatment also prevented LV remodeling Mellin et al. (2005)
Rat Spontaneously hypertensive heart failure rat Oxypurinol 4-week treatment restored cardiac structure and function Minhas et al. (2006)
Dog Pacing-induced HF Allopurinol Allopurinol decreases myocardial oxygen consumption and increases mechanical efficiency in dogs with pacing-induced HF; increased myocardial XO activity or levels and subsequent increases in oxidative stress in the failing hearts Ekelund et al. (1999); Saavedra et al. (2002)
Dog Pacing-induced HR Allopurinol Allopurinol had no effects on LV contractile function or adrenergic responsiveness in normal conscious animals; in pacing-induced CHF, allopurinol improved LV systolic function at rest and during adrenergic stimulation and exercise Ukai et al. (2001)
Dog Pacing-induced HF Allopurinol Allopurinol ameliorated increases in afterload and reductions in myocardial contractility during evolving HF, thereby preserving ventricular-vascular coupling Amado et al. (2005)
Human (56 patients) CHF N.A. In patients with CHF, elevated circulating uric acid levels correlate with inflammatory markers (e.g., TNF-α and ICAM-1) Leyva et al. (1998)
Human (9 patients) Idiopathic dilated cardiomyopathy Allopurinol Intracoronary administration of allopurinol resulted in an acute improvement in myocardial efficiency by diminishing oxygen consumption in the presence of standard supportive therapy Cappola et al. (2001)
Human (19 patients) CHF Allopurinol Allopurinol improved endothelial function Doehner et al. (2002); Farquharson et al. (2002)
Human (1760 patients) CHF Allopurinol High-dose treatment with allopurinol was found to beneficially affect survival, whereas low-dose allopurinol treatment actually appeared to increase mortality Struthers et al. (2002)
Human (50 patients) CHF Allopurinol 3-month allopurinol treatment had no effect on excerise capacity but reduced B-type natriuretic peptide, a surrogate marker for prognosis in CHF Gavin and Struthers (2005)
Human (405 patients multicenter)
Failed to show significant benefits
Cardiome Pharma Corp. (Vancouver, BC, Canada)
  • HF, heart failure; N.A., not applicable; TNF-α, tumor necrosis factor-α; ICAM-1, intercellular adhesion molecule-1.