Impairment of the post-anoxic recovery of isolated rat hearts by intravascular hypoxanthine and xanthine.
Hypoxanthine is the final product of the catabolism of ATP in the stored red cell. Upon transfusion, this purine may be uptaken by the endothelial cell and oxidized in a post-ischemic or post-anoxic environment with production of oxygen-derived free radicals. We have tested this hypothesis with a isolated perfused rat heart model monitoring the recovery of the heart function from 20 min anoxia in the presence of 0.1 mM hypoxanthine or xanthine. Addition of 0.1 mM guanine minimized the fraction of hypoxanthine to be salvaged. The presence of hypoxanthine in the vascular space impaired the recovery of the end-diastolic pressure, left ventricular developed pressure, contraction rate, and coronary perfusion pressure. We conclude that intravascular hypoxanthine is oxidized by the endothelial cell xanthine oxidase contributing to the post-anoxic reoxygenation injury. Since the injury led by equimolar xanthine was nearly half of that observed for hypoxanthine, this injury appears to be correlated to the stoichiometry of the oxygen-derived free radical generating reaction.
Tarantola
M
M
Istituto Scientifico San Raffaele, Universita' di Milano, Italy.
Motterlini
R
R
Beretta
M
M
Rovida
E
E
Samaja
M
M
D000818:Animals; D001802:Blood Substitutes / Q000633:toxicity; D005609:Free Radicals; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000633:toxicity*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D019820:Xanthine; D014970:Xanthines / Q000633:toxicity*
D001802:Blood Substitutes; D005609:Free Radicals; D007042:Hypoxanthines; D014970:Xanthines; D019820:Xanthine; D019271:Hypoxanthine; D010100:Oxygen