title: Kinetics of high-energy phosphates in allopurinol-pretreated ischaemic and post-ischaemic skeletal muscle: an in vivo magnetic resonance spectroscopy study.
abstract: Allopurinol (AP) protects skeletal muscle function against ischaemia-induced injury, but the mechanism is not yet clear. As AP acts as a competitive xanthine oxidase inhibitor, both a reduction of oxygen-derived free radicals and an enhancement of purine resynthesis (salvage pathway) might be involved. We investigated the in vivo kinetics of high-energy phosphates in skeletal muscle after AP pretreatment using 31P-magnetic resonance spectroscopy during 2 h of ischaemia and 3 h of reperfusion in rat hindlimbs. Three animals (group A) were pretreated with a total of 160 mg/kg AP i.p., 3 control animals (group B) received the same amount of 0.9% saline solution. ATP decreased to 18.6 +/- 1.3% of the pre-ischaemic value in group A and to 17.3 +/- 2.8% in group B after 2 h of ischaemia, and rose to only 47.7 +/- 1.5 and 50.5 +/- 1.8%, respectively, after 3 h of reperfusion. Phosphocreatine fell to 7.2 +/- 2.9 and 7.6 +/- 2.2% of pre-ischaemic values after 2 h of ischaemia and rose again to 36.5 +/- 12.9 and 45.4 +/- 20.4% after 3 h of reperfusion. Inorganic phosphate (Pi) increased 5-fold after 2 h of ischaemia, irrespective of the treatment. After 3 h of reperfusion, Pi was still 4 times the pre-ischaemic value. The kinetics of ATP, PCr, and Pi levels were not statistically different between the two groups. These results indicate that the ATP salvage pathway does not play an important role in AP-induced attenuation of ischaemia/reperfusion-induced muscle damage.
authors.affiliation: Department of Surgical Research, University of Basel, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Gürke
authors.forename: P
authors.initials: P
authors.lastname: Erhard
authors.forename: A
authors.initials: A
authors.lastname: Marx
authors.forename: F
authors.initials: F
authors.lastname: Harder
authors.forename: J
authors.initials: J
authors.lastname: Seelig
authors.forename: M
authors.initials: M
authors.lastname: Heberer
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control
chemical_list: D010725:Phosphocreatine; D000493:Allopurinol; D000255:Adenosine Triphosphate