"Chemical preconditioning" by 3-nitropropionate reduces ischemia-reperfusion injury in cardiac-arrested rat lungs.
BACKGROUND
Chemical preconditioning was defined as the induction of resistance to massive disruption of energy metabolism through prior chemical suppression of oxidative phosphorylation, by which phenomena similar to those resulting from increased ischemic tolerance as a result of ischemic preconditioning can be induced. It could be induced by the inhibitor of either mitochondrial complex I or II. We investigated whether or not chemical preconditioning by 3-nitropropionate (an inhibitor of the mitochondrial complex II) can suppress ischemia-reperfusion injury in cardiac-arrested lungs, which will be the major problem in lung transplants donated from non-heart-beating cadavers.


RESULTS
In an isolated rat lung perfusion model with fresh rat blood as perfusate, administration of 3-nitropropionate (20 mg/kg) immediately before the induction of cardiac arrest attenuated pulmonary dysfunction during reperfusion after 1 hr postmortem warm ischemia and 1 hr cold preservation. 3-Nitropropionate administration reduced the mitochondrial respiratory functions (state 3 and state 4 respiration, and the respiratory control ratio) before cardiac arrest and kept them at a lower level of activity than when decreased by ischemia alone. 3-Nitropropionate administration also reduced the ATP levels immediately after drug administration. However, 3-nitropropionate did not significantly reduce lipid peroxidation in the lung tissue and mitochondria.


CONCLUSIONS
These results demonstrated that chemical preconditioning by 3-nitropropionate administration immediately before cardiac arrest suppressed succinate-related oxidation during postmortem warm ischemia and reduced ischemia-reperfusion injury in cardiac arrested rat lungs.
Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Japan. thirata@kuhp.kyoto-u.ac.jp
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T
Hirata
T
T
Fukuse
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S
Ishikawa
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S
Hanaoka
Q
Q
Chen
T
T
Shoji
H
H
Wada
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D006323:Heart Arrest / Q000503:physiopathology*; D008054:Lipid Peroxides / Q000378:metabolism; D008168:Lung / Q000098:blood supply* / Q000737:chemistry / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000737:chemistry / Q000502:physiology; D009574:Nitro Compounds; D011422:Propionates / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D012129:Respiratory Function Tests; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
D000227:Adenine Nucleotides; D008054:Lipid Peroxides; D009574:Nitro Compounds; D011422:Propionates; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid