A novel hydroxyl radical scavenger, nicaraven, protects the liver from warm ischemia and reperfusion injury.
BACKGROUND
Reactive oxygen species have been considered to be involved in liver injury at the procurement, preservation, and transplantation from donors without beating hearts. A novel hydroxyl radical scavenger, nicaraven with hydrophilic and lipophilic properties, infiltrates both intracellular and extracellular spaces where it effectively scavenges reactive oxygen species. Protection by nicaraven against ischemia and reperfusion damage of the brain, heart, and kidneys has been shown. The effect of this agent on the liver remains unclear.


METHODS
Two-hour total hepatic vascular exclusion was used. Eighteen beagle dogs were randomly assigned to 2 groups: 12 animals were not treated (group I) and 6 were treated with nicaraven (group II). Nicaraven was administered intravenously (2mg/kg/min) for 60 minutes before ischemia and for 3 hours, starting 30 minutes before reperfusion.


RESULTS
Two-week survival rates were 25% in group I and 100% in group II (P <.01). Nicaraven inhibited lipid peroxidation in the liver, improved hepatic and systemic hemodynamics and energy metabolism, and suppressed liver enzyme release, endothelin-1 elevation in hepatic venous blood, histologic damage, and neutrophil infiltration into the liver.


CONCLUSIONS
Nicaraven exerted hepatic protection against warm ischemia and reperfusion injury. This may indicate nicaraven as a potential candidate to attenuate liver injury from warm ischemia and preservation in transplantation from donors without beating hearts.
Yokota
R
R
First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
Fukai
M
M
Shimamura
T
T
Suzuki
T
T
Watanabe
Y
Y
Nagashima
K
K
Kishida
A
A
Furukawa
H
H
Hayashi
T
T
Todo
S
S
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D004285:Dogs; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D007208:Indocyanine Green; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects; D016031:Liver Transplantation; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009926:Organ Preservation; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013696:Temperature
D000227:Adenine Nucleotides; D019332:Endothelin-1; D016166:Free Radical Scavengers; D009536:Niacinamide; D017665:Hydroxyl Radical; D007208:Indocyanine Green; C042625:nicaraven