NSU-MD Faculty Articles

Allopurinol enhanced adenine nucleotide repletion after myocardial ischemia in the isolated rat heart

Publication Title

The Journal of clinical investigation

Publisher

American Society for Clinical Investigation

ISSN

0021-9738

Publication Date

1-1-1988

Keywords

Adenine Nucleotides, Adenosine Diphosphate, Adenosine Triphosphate, Allopurinol, Animals, Coronary Disease, Free Radicals, Hypoxanthine, Hypoxanthines, Male, Myocardial Revascularization, Myocardium, Oxygen, Rats, Rats, Inbred Strains

Abstract

Allopurinol, a competitive inhibitor of xanthine oxidase, has been shown to have a protective effect on ischemic myocardium, but its mechanism of action remains controversial. We used an isolated rat heart preparation to test the hypothesis that allopurinol could restore adenosine triphosphate (ATP) levels and improve the recovery of left ventricular function after global myocardial ischemia. Hearts were equilibrated for 30 min, subjected to 10 min of global, normothermic (37 degrees C) ischemia, and reperfused for 15, 30, and 60 min. Hearts treated with allopurinol (100 microM) exhibited greater ATP levels and improved function during reperfusion than did untreated control hearts. Hearts treated with hypoxanthine (100 microM), the substrate for xanthine oxidase, also showed increased ATP and functional recovery compared with controls. These results suggest that allopurinol may protect the globally ischemic myocardium by enhancing the salvage of hypoxanthine for reincorporation into adenine nucleotides.

DOI

10.1172/JCI113288

Volume

81

Issue

1

First Page

16

Last Page

20

Disciplines

Medicine and Health Sciences

Peer Reviewed

Find in your library

Share

COinS