Prevention of ischemia/reperfusion injury in the rat liver by atrial natriuretic peptide.
OBJECTIVE
Atrial natriuretic peptide (ANP) protects against hypoxia/reoxygenation-induced damage of cultured hepatocytes, thus suggesting a therapeutic potential in the liver. Therefore, the effects of ANP on hepatic ischemia/reperfusion injury after warm ischemia were studied.


METHODS
Livers of male Sprague-Dawley rats subjected to 60 minutes of warm ischemia at 37 degrees C were perfused in the presence or absence of 200 and 20 nmol/L ANP.


RESULTS
Sinusoidal lactate dehydrogenase efflux increased to 2000 +/- 264 and 126 +/- 50 mU.min-1.g liver-1 after 1 minute and 60 minutes of reperfusion, but it only increased to 1240 +/- 160 and 22 +/- 16 mU.min-1.g liver-1 in the presence of 200 nmol/L ANP during the preischemic and postischemic perfusion period. The postischemic bile flow (0.67 +/- 0.18 microL.min-1.g liver-1) was significantly improved with 200 nmol/L ANP (0.92 +/- 0.05) and showed a linear correlation to biliary glutathione excretion. In contrast, 20 nmol/L ANP had no protective effects. Administration of 200 nmol/L ANP during the preischemic perfusion period alone (but not after starting reperfusion) markedly preserved postischemic liver function.


CONCLUSIONS
Continuous ANP administration or ANP pretreatment alone prevents hepatic ischemia/reperfusion injury, possibly because of influences on intracellular signal transduction processes. The correlation between bile flow and biliary glutathione excretion supports the hypothesis that biliary glutathione transport is one of the osmotic driving forces in postischemic bile formation.
Bilzer
M
M
Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany.
Witthaut
R
R
Paumgartner
G
G
Gerbes
A L
AL
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001646:Bile / Q000502:physiology; D001659:Biliary Tract / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008102:Liver Circulation; D008297:Male; D010477:Perfusion; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
D007773:Lactates; D011773:Pyruvates; D009320:Atrial Natriuretic Factor; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D019803:Glutathione Disulfide