Deferoxamine, an iron chelator, reduces myocardial injury and free radical generation in isolated neonatal rabbit hearts subjected to global ischaemia-reperfusion.
The protective action of deferoxamine, an iron chelator, against functional and metabolic deteriorations of ventricular muscle, induced by ischaemia-reperfusion, was investigated in Langendorff-perfused hearts of neonatal rabbits in comparison with superoxide dismutase (SOD) plus catalase. The perfused hearts were subjected to normothermic (37 degrees C) global ischaemia for 45 min following cardiac arrest with St Thomas cardioplegic solution and then reperfused with oxygenated Krebs-Henseleit solution. In control hearts, the recovery of the left ventricular developed pressure (LVDP) after 30 min reperfusion was 50.7 +/- 3.1% (mean +/- SE, n = 5) of the pre-ischaemic value. The LVDP recovery was significantly improved in the hearts treated with deferoxamine at 10-100 microM (89.4 +/- 1.4% at 30 microM, P < 0.01 vs. control). The improvement in LVDP was less prominent when treated with 30 x 10(4) U/l SOD plus 30 x 10(4) U/l catalase (67.9 +/- 2.0%, P < 0.01 vs. deferoxamine at 30 microM). CPK leakage into the coronary effluent during the initial 5 min of reperfusion was reduced to around half of the control value with 30 microM deferoxamine (P < 0.05 vs. control), while unaffected by the addition of SOD plus catalase. Free radicals in the coronary effluent were measured with electron spin resonance spectroscopy in separate experiments by using a spin-trapping agent, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). A burst of DMPO-OH signal was detected during the initial minutes of reperfusion. The intensity of DMPO-OH signal was significantly reduced by 30 microM deferoxamine to about one-third of control.(ABSTRACT TRUNCATED AT 250 WORDS)
Katoh
S
S
Department of Thoracic Surgery, School of Medicine, Nagoya University, Japan.
Toyama
J
J
Kodama
I
I
Akita
T
T
Abe
T
T
D000818:Animals; D000831:Animals, Newborn; D002374:Catalase / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
D005609:Free Radicals; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D003676:Deferoxamine