Impact of Elevated Uric Acid on Ventricular Remodeling in infarcted Rats with Experimental Hyperuricemia

Previous studies using uric acid-lowering drugs in normouricemic animals are not suitable to answer the effect of hyperuricemia on ventricular remodeling after myocardial infarction. The purpose of this study was to determine whether hyperuricemia adversely affects ventricular remodeling in infarcted rats with elevated uric acid. Male Wistar rats with extensive anterior myocardial infarction were randomly assigned into either vehicle, oxonic acid, oxonic acid + allopurinol, oxonic acid + benzbromarone, or oxonic acid + tempol for 4 weeks. Post-infarction was associated with increased oxidant release, as measured by myocardial superoxide and isoprostane levels. Hyperuricemia was associated with a further higher oxidative stress, which substantially increased left ventricular cavity and dysfunction and markedly enhanced myocardial hypertrophy and fibrosis. These changes were prevented by allopurinol. For similar levels of urate lowering, benzbromarone had no effect on ventricular remodeling. In spite of hyperuricemia, tempol attenuated ventricular remodeling. Hyperuricemia is associated with unfavorable ventricular remodeling probably through a superoxide-dependent pathway. Chronic administration of allopurinol and tempol is associated with attenuated ventricular remodeling.