Allopurinol attenuates left ventricular remodeling and dysfunction after experimental myocardial infarction: a new action for an old drug?
BACKGROUND
Accumulating evidence suggests a critical role for increased reactive oxygen species (ROS) production in left ventricular (LV) remodeling and dysfunction after myocardial infarction (MI). Increased expression of xanthine oxidase (XO), a major source of ROS, has recently been demonstrated in experimental and clinical heart failure; however, a potential role for LV remodeling processes remains unclear. We therefore studied the effect of long-term treatment with allopurinol, a potent XO inhibitor, on myocardial ROS production and LV remodeling and dysfunction after MI.


RESULTS
Mice with extensive anterior MI (n=105) were randomized to treatment with either vehicle or allopurinol (20 mg x kg(-1) x d(-1) by gavage) for 4 weeks starting on day 1 after surgery. Infarct size was similar among the groups. XO expression and activity were markedly increased in the remote myocardium of mice after MI, as determined by electron spin resonance spectroscopy. Myocardial ROS production was increased after MI but markedly reduced after allopurinol treatment. Importantly, allopurinol treatment substantially attenuated LV cavity dilatation and dysfunction after MI, as assessed by echocardiography, and markedly reduced myocardial hypertrophy and interstitial fibrosis.


CONCLUSIONS
The present study reveals a novel beneficial effect of treatment with allopurinol, ie, a marked attenuation of LV remodeling processes and dysfunction after experimental MI. Allopurinol treatment therefore represents a potential novel strategy to prevent LV remodeling and dysfunction after MI.
Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
Niels
N
Engberding
Stephan
S
Spiekermann
Arnd
A
Schaefer
André
A
Heineke
Antje
A
Wiencke
Maja
M
Müller
Martin
M
Fuchs
Denise
D
Hilfiker-Kleiner
Burkhard
B
Hornig
Helmut
H
Drexler
Ulf
U
Landmesser
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D004353:Drug Evaluation, Preclinical; D005355:Fibrosis; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D018384:Oxidative Stress; D011897:Random Allocation; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000517:prevention & control*; D020257:Ventricular Remodeling / Q000187:drug effects*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D017382:Reactive Oxygen Species; D013481:Superoxides; D000493:Allopurinol; D014969:Xanthine Oxidase