Delayed treatment effects of xanthine oxidase inhibition on systolic overload-induced left ventricular hypertrophy and dysfunction.
The nonpurine selective xanthine oxidase (XO) inhibitor febuxostat attenuates development of left ventricular (LV) hypertrophy and dysfunction in mice when treatment is initiated within 1 hour of transverse aortic constriction (TAC). This study investigated whether a 7-day delay of treatment with the XO inhibitors febuxostat or allopurinol would reverse TAC-induced changes after onset of heart failure (HF). Neither treatment significantly affected TAC-induced LV hypertrophy; only febuxostat caused a modest improvement in LV function ( approximately 10% increase in LV ejection fraction). However, the purine analog allopurinol tended to increase mortality compared with vehicle or febuxostat in HF mice.
Xu
X
X
Cardiovascular Division, Department of Medicine, University of Minnesota, The Center of Vascular Biology, Minneapolis, Minnesota 55455, USA.
Zhao
L
L
Hu
X
X
Zhang
P
P
Wessale
J
J
Bache
R
R
Chen
Y
Y
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D003251:Constriction, Pathologic / Q000150:complications; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D000069465:Febuxostat; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013844:Thiazoles / Q000627:therapeutic use*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D013844:Thiazoles; D000069465:Febuxostat; D000493:Allopurinol; D014969:Xanthine Oxidase