Deferoxamine reduces the reperfusion injury in isolated neonatal rabbit hearts after hypothermic preservation.
The protective action of deferoxamine, an iron chelator, against reperfusion injury following hypothermic preservation was investigated in the Langendorff-perfused hearts of neonatal rabbits. Left ventricular function and radical generation were used as parameters to evaluate functional and metabolic changes. The free radicals in coronary effluents were measured with an electron spin resonance spectroscope using a spin trapping agent, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The hearts were preserved in cold St. Thomas solution at 4 degrees C for 6 h following cardiac arrest, then reperfused with oxygenated Krebs-Henseleit solution in a control. Deferoxamine (100 microM) was added to the perfusate just prior to reperfusion in group I, and 3 min after the start of reperfusion in group II. In the control group, the left ventricular developed pressure (LVDP) after 30-min reperfusion recovered up to 43.5 +/- 3.1% (mean +/- SD, n = 5) the preischemic value. Group I showed a significant improvement in LVDP recovery after 30-min reperfusion at 57.1 +/- 3.1% (P < 0.01 vs control), but group II did not (47.5 +/- 2.3%). When a burst of DMPO-OH signals was detected during the initial 5 min of reperfusion, the signal intensity in group I was significantly reduced to about 35-40% of the control value. Group II showed a similar intensity to the control group. Thus, we conclude that deferoxamine may exert a protective action against the dysfunction of neonatal mammalian hearts induced by preservation-reperfusion through an inhibition of iron-catalyzed radical formation.
Department of Circulation, Nagoya University, Japan.
S
S
Katoh
J
J
Toyama
I
I
Kodama
K
K
Kamiya
T
T
Akita
T
T
Abe
D000818:Animals; D000831:Animals, Newborn; D003497:Cyclic N-Oxides; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000032:analysis; D007036:Hypothermia, Induced / Q000009:adverse effects*; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009926:Organ Preservation / Q000009:adverse effects*; D011817:Rabbits; D016277:Ventricular Function, Left / Q000187:drug effects*
D003497:Cyclic N-Oxides; D005609:Free Radicals; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D003676:Deferoxamine