Oxygen radical injury and loss of high-energy compounds in anoxic and reperfused rat heart: prevention by exogenous fructose-1,6-bisphosphate.
Isolated Langendorff-perfused rat hearts after 10 minutes preperfusion, were subjected to a substrate-free anoxic perfusion (20 minutes) followed by 20 minutes reperfusion with a glucose-containing oxygen-balanced medium. Under the same perfusion conditions, the effect of exogenous 5mM fructose-1,6-bisphosphate has been investigated. The xanthine dehydrogenase to xanthine oxidase ratio, concentrations of high-energy phosphates and of TBA-reactive material (TBARS) were determined at the end of each perfusion period in both control and fructose-1,6-bisphosphate-treated hearts. Results indicate that anoxia induces the irreversible transformation of xanthine dehydrogenase into oxidase as a consequence of the sharp decrease of the myocardial energy metabolism. This finding is supported by the protective effect exerted by exogenous fructose-1,6-bisphosphate which is able to maintain the correct xanthine dehydrogenase/oxidase ratio by preventing the depletion of phosphorylated compounds during anoxia. Moreover, in control hearts, the release of lactate dehydrogenase during reperfusion, is paralleled by a 50% increase in the concentration of tissue TBARS. On the contrary, in fructose-1,6-bisphosphate-treated hearts this concentration does not significantly change after reoxygenation, while a slight but significant increase of lactate dehydrogenase activity in the perfusates is observed. On the whole these data indicate a direct contribution of oxygen-derived free radicals to the worsening of post-anoxic hearts. A hypothesis on the mechanism of action of fructose-1,6-bisphosphate in anoxic and reperfused rat heart and its possible application in the clinical therapy of myocardial infarction are presented.
Department of Experimental Medicine and Biochemical Sciences, II University of Rome Tor Vergata, Italy.
B
B
Tavazzi
L
L
Cerroni
D
D
Di Pierro
G
G
Lazzarino
M
M
Nuutinen
J W
JW
Starnes
B
B
Giardina
D000818:Animals; D004734:Energy Metabolism; D005609:Free Radicals; D005635:Fructosediphosphates / Q000494:pharmacology*; D006598:Hexosediphosphates / Q000494:pharmacology*; D000860:Hypoxia / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008297:Male; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D005609:Free Radicals; D005635:Fructosediphosphates; D006598:Hexosediphosphates; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; C029063:fructose-1,6-diphosphate; D010100:Oxygen