Allopurinol enhances adenine nucleotide levels and improves myocardial function in isolated hypoxic rat heart

Biochemistry. Biokhimii︠a︡
Said Y KhatibF El-Migdadi

Abstract

Allopurinol, a competitive inhibitor of xanthine oxidase, was found to have a protective effect on ischemic myocardium. Its mechanism of action is still controversial. We used Langendorff isolated rat heart preparation to test the hypothesis that allopurinol could maintain a level of the adenine nucleotide pool (ATP, ADP, and AMP) that would protect and improve the functional activity of the heart during a period of hypoxia. Hearts were initially perfused for 30 min until steady state was attained. This was followed by 20 min of experimental perfusion divided into 5 min of control perfusion followed by 15 min of hypoxic perfusion with or without allopurinol in the perfusate. Hearts were quick-frozen and enzymatically analyzed for adenine nucleotides and creatine phosphate at the end of the hypoxic period. Left ventricular pressure, heart rate, and coronary flow were measured in all preparations. Allopurinol (0.1 mM) treated hearts had greater levels of ATP (12.3 +/- 0.8 vs. 9.3 +/- 0.8 micromol/g dry weight; p < 0.01). This improvement occurred in the presence as well as the absence of glucose. Total adenine nucleotides improved from 17 +/- 1 to 20.3 +/- 2.4 micromol/g dry weight (p < 0.01). This improvement also occurred in th...Continue Reading

Citations

Mar 2, 2018·Circulation Journal : Official Journal of the Japanese Circulation Society·Shogo TannoIchiro Hisatome
Aug 27, 2003·Circulation Journal : Official Journal of the Japanese Circulation Society·Yoshiharu KinugasaChiaki Shigemasa
Dec 24, 2010·Current Opinion in Rheumatology·Eswar Krishnan, Jeremy Sokolove
Sep 1, 2011·Nature Reviews. Cardiology·Bernard R Chaitman, Abhay A Laddu

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