Protection from reperfusion injury in the isolated rat heart by postischaemic deferoxamine and oxypurinol administration.
A Langendorff isolated rat heart preparation was used to determine the effect of oxypurinol, a xanthine oxidase inhibitor, and deferoxamine, an iron binding agent, on the extent of myocardial reperfusion injury after 60 minutes of ischaemia. Thirty rats were divided into three groups of 10, and an isolated heart preparation made from each rat. The isolated hearts were perfused for 15 minutes with a modified Krebs-Henseleit perfusate solution to permit stabilisation of the preparation. Each heart was then subjected to 60 minutes of total ischaemia at 37 degrees C followed by 60 minutes of reperfusion with either saline treated perfusate, oxypurinol treated perfusate (1.3 mmol.litre-1), or deferoxamine treated perfusate (0.61 mmol.litre-1). Reperfusion injury was assessed by the total amount of creatine phosphokinase released into the perfusate, by changes in myocardial vascular resistance, and by morphological examination. The saline treated group released significantly more creatine phosphokinase into the perfusate than either the oxypurinol treated group (p less than 0.05) or the deferoxamine treated group (p less than 0.05). The mean vascular resistance increased for all groups during the 60 minutes of reperfusion compared with that just before ischaemia but was significantly greater in the saline treated group than in the drug treated groups (p less than 0.01). Ultrastructural examination of a randomly selected heart from each group after 60 minutes of reperfusion showed pronounced attenuation of mitochondrial and endoplasmic reticulum swelling, increased maintenance of membrane integrity, and diminished separation of myofilaments in the oxypurinol treated and deferoxamine treated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
Badylak
S F
SF
Hillenbrand Biomedical Engineering Center, Purdue University, W Lafayette, IN 47907.
Simmons
A
A
Turek
J
J
Babbs
C F
CF
D000818:Animals; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology*; D003402:Creatine Kinase / Q000378:metabolism; D003676:Deferoxamine / Q000627:therapeutic use*; D006321:Heart / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000201:enzymology / Q000648:ultrastructure; D010117:Oxypurinol / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects
D011743:Pyrimidines; D003402:Creatine Kinase; D010117:Oxypurinol; D003676:Deferoxamine