Key result
In infarcted rats, hyperuricemia worsened ventricular remodeling, which was prevented by allopurinol, ABT-627, and tempol, but not by the uricosuric agent benzbromarone.
Why the study?
Does hyperuricemia worsen ventricular remodeling in infarcted rats, and can uric acid-lowering or antioxidant therapies prevent it?
RCT
randomly assigned
Does hyperuricemia worsen ventricular remodeling in infarcted rats, and can uric acid-lowering or antioxidant therapies prevent it?
Hyperuricemia exacerbates post-infarction ventricular remodeling via superoxide and endothelin-1 pathways, which can be attenuated by allopurinol or targeted pathway inhibitors but not by simple uricosuric agents.
Hyperuricemia may worsen post-MI remodeling in rats via oxidative/endothelin pathways; leaves open translation to human HF therapy.
Hyperuricemia is associated with cardiovascular disease, but it is usually considered a marker rather than a risk factor. 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 aged 8 wk were randomly assigned into either vehicle, oxonic acid, oxonic acid + allopurinol, oxonic acid + benzbromarone, oxonic acid + ABT-627, or oxonic acid + tempol for 4 wk starting 24 h after ligation. Postinfarction was associated with increased oxidant production, as measured by myocardial superoxide, isoprostane, xanthine oxidase activity, and dihydroethidium staining. Compared with normouricemic infarcted rats, hyperuricemic infarcted rats had a significant increase of superoxide production (1.7×) and endothelin-1 protein (1.2×) and mRNA (1.4×) expression, which was associated with increased left ventricular dysfunction and enhanced myocardial hypertrophy and fibrosis. These changes were all prevented by treatment with allopurinol. For similar levels of urate lowering, the uricosuric agent benzbromarone had no effect on ventricular remodeling. In spite of equivalent hyperuricemia, the ability of both ABT-627 and tempol to attenuate ventricular remodeling suggested involvement of endothelin-1 and redox pathways. Hyperuricemia is associated with unfavorable ventricular remodeling probably through a superoxide and endothelin-1-dependent pathway. Uric acid lowering without inhibition of superoxide and endothelin-1 may not have an effect on remodeling. Chronic administration of allopurinol, ABT-627, and tempol is associated with attenuated ventricular remodeling.
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Chen et al. (2011) conducted an RCT in Myocardial infarction with experimental hyperuricemia. Allopurinol, benzbromarone, ABT-627, or tempol (with oxonic acid) vs. Vehicle was evaluated on Ventricular remodeling (superoxide production, endothelin-1 expression, left ventricular dysfunction, hypertrophy, and fibrosis). In infarcted rats, hyperuricemia worsened ventricular remodeling, which was prevented by allopurinol, ABT-627, and tempol, but not by the uricosuric agent benzbromarone.
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