The relationship of hepatic tissue oxygenation with nitric oxide metabolism in ischemic preconditioning of the liver.
Ischemic preconditioning (IPC) may increase the hepatic tolerance of ischemic injury during liver surgery and transplantation via nitric oxide (NO) formation. This study investigates the effect of IPC on hepatic tissue oxygenation and the role of NO stimulation and inhibition on the preconditioning effect in the rat liver. Study groups had 1) sham laparotomy; 2) 45-min lobar liver ischemia and 2-h reperfusion (IR); 3) IPC with 5-min ischemia and 10-min reperfusion before IR; 4) L-arginine before IR; and 5) Nw-Nitro-L-arginine methyl ester (L-NAME) + IPC before IR. Hepatic tissue oxygenation was monitored by near-infrared spectroscopy. Plasma alanine aminotransferase and plasma nitrite/nitrate were measured. Following IR there was significant decrease in oxyhemoglobin and cytochrome oxidase and an increase in deoxyhemoglobin (PA redox state, PL-arginine did not attenuate the impairment in hepatic tissue oxygenation after IR (P>0.05 vs IR). In contrast, inhibition of NO synthesis blocked the effect of IPC and further impaired tissue oxygenation (decreased cytochrome oxidase CuA redox state and increased deoxyhemoglobin, both PL-arginine and increased by NO blockade with L-NAME (Plasma ALT, all P< 0.05 vs IR). Hepatic tissue oxygenation correlated significantly with ALT and plasma nitrite/nitrate. Ischemic preconditioning significantly improved hepatic intra cellular oxygenation and reduced hepatocellular injury. NO stimulation reduced hepatocellular injury, whereas inhibition of nitric oxide synthesis blocked the effect of IPC and reduced tissue oxygenation and increased hepatocellular injury.
University Department of Surgery and Liver Transplantation Unit, Royal Free and University College Medical School, University College London, Royal Free Hospital, London, UK.
Rahul S
RS
Koti
Alexander M
AM
Seifalian
Alan G
AG
McBride
Wenxuan
W
Yang
Brian R
BR
Davidson
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003576:Electron Transport Complex IV / Q000378:metabolism; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D010100:Oxygen / Q000378:metabolism*; D010108:Oxyhemoglobins / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism
D009566:Nitrates; D009573:Nitrites; D010108:Oxyhemoglobins; D009569:Nitric Oxide; D003576:Electron Transport Complex IV; D000410:Alanine Transaminase; D010100:Oxygen