Xanthine oxidase inhibition improves left ventricular dysfunction in dilated cardiomyopathic hamsters.
BACKGROUND
Oxidative stress is implicated in cardiac remodeling and failure. We tested whether xanthine oxidase (XO) inhibition could decrease myocardial oxidative stress and attenuate left ventricular (LV) remodeling and dysfunction in the TO-2 hamster model of dilated cardiomyopathy.


RESULTS
TO-2 hamsters were randomized to treatment with the XO inhibitor, allopurinol, or vehicle from 6 to 12 weeks of age. F1B hamsters served as controls. TO-2 hamsters treated with vehicle progressively developed severe LV systolic dysfunction and dilation between 6 and 12 weeks. Marked cardiac fibrosis was apparent in these hamsters at 12 weeks in comparison with F1B controls. The ratio of reduced to oxidized glutathione (GSH/GSSG) was decreased and malondialdehyde levels were increased in the hearts of vehicle-treated TO-2 hamsters. Treatment with allopurinol from 6 to 12 weeks attenuated LV dysfunction and dilation as well as myocardial fibrosis and the upregulation of a fetal-type cardiac gene. Allopurinol also inhibited both the decrease in GSH/GSSG ratio and the increase in malondialdehyde levels in the heart.


CONCLUSIONS
These results indicate that chronic XO inhibition with allopurinol attenuates LV remodeling and dysfunction as well as myocardial oxidative stress in this model of heart failure. Allopurinol may prove beneficial for the treatment of heart failure.
Hayashi
Keiko
K
Department of Pathophysiology Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Kimata
Hirotaka
H
Obata
Koji
K
Matsushita
Aya
A
Fukata
Ayako
A
Hashimoto
Katsunori
K
Noda
Akiko
A
Iwase
Mitsunori
M
Koike
Yasuo
Y
Yokota
Mitsuhiro
M
Nagata
Kohzo
K
D000493:Allopurinol / Q000008:administration & dosage*; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006224:Cricetinae; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D012333:RNA, Messenger; D000493:Allopurinol; D014969:Xanthine Oxidase