Effect of the free radical scavenger MCI-186 on pulmonary ischemia-reperfusion injury in dogs.
BACKGROUND
Free radical scavengers and superoxide dismutase have been found to protect against cerebral ischemic damage, and it was suggested that oxygen free radicals contribute to ischemia-reperfusion injury induced by cerebral ischemic damage. MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent scavenger and inhibitor of hydroxyl radicals and protective agent of peroxidative injury. The purpose of this study was to evaluate the effects of MCI-186 on pulmonary ischemia-reperfusion injury in a simulated transplanted lung model.


METHODS
Fourteen dogs were divided into two groups (n = 7 each). In the MCI group, MCI-186 was continuously administered at 3 mg/kg/hour intravenously (IV) from 30 minutes before reperfusion until 30 minutes after reperfusion (total administration time 1 hour). Vehicle was administered in the control group. Warm ischemia was induced for 3 hours by clamping the left pulmonary artery and veins. Simultaneously, the left stem bronchus was bisected and then anastomosed before reperfusion. The right pulmonary artery was ligated 15 minutes after reperfusion, and the right stem bronchus was then bisected.


RESULTS
The respiratory gas exchange, hemodynamic changes, wet-to-dry weight ratio (WDR) and malondialdehyde (MDA) concentration in the tissue were significantly improved (p < 0.05) in the MCI group. The histologic damage was more severe in the control group and polymorphonuclear neutrophil (PMN) infiltration was reduced in the MCI group.


CONCLUSIONS
MCI-186 has a protective effect on pulmonary ischemia-reperfusion injury through the inhibition of lipid peroxidation.
Akao
Takahiko
T
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Takeyoshi
Izumi
I
Totsuka
Osamu
O
Arakawa
Kazuhisa
K
Muraoka
Masato
M
Kobayashi
Katsumi
K
Konno
Kenjiro
K
Matsumoto
Koshi
K
Morishita
Yasuo
Y
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004285:Dogs; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D008168:Lung / Q000098:blood supply*; D016040:Lung Transplantation / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology*
D016166:Free Radical Scavengers; D000077553:Edaravone; D000983:Antipyrine