Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation.
Ischemia/reperfusion (IR) injury in transplanted livers contributes to organ dysfunction and failure and is characterized in part by loss of NO bioavailability. Inhalation of NO is nontoxic and at high concentrations (80 ppm) inhibits IR injury in extrapulmonary tissues. In this prospective, blinded, placebo-controlled study, we evaluated the hypothesis that administration of inhaled NO (iNO; 80 ppm) to patients undergoing orthotopic liver transplantation inhibits hepatic IR injury, resulting in improved liver function. Patients were randomized to receive either placebo or iNO (n = 10 per group) during the operative period only. When results were adjusted for cold ischemia time and sex, iNO significantly decreased hospital length of stay, and evaluation of serum transaminases (alanine transaminase, aspartate aminotransferase) and coagulation times (prothrombin time, partial thromboplastin time) indicated that iNO improved the rate at which liver function was restored after transplantation. iNO did not significantly affect changes in inflammatory markers in liver tissue 1 hour after reperfusion but significantly lowered hepatocyte apoptosis. Evaluation of circulating NO metabolites indicated that the most likely candidate transducer of extrapulmonary effects of iNO was nitrite. In summary, this study supports the clinical use of iNO as an extrapulmonary therapeutic to improve organ function following transplantation.
Lang
John D
JD
Department of Anesthesiology, University of Washington School of Medicine, Seattle, Washington 98108-1597, USA. jdlang@u.washington.edu
Teng
Xinjun
X
Chumley
Phillip
P
Crawford
Jack H
JH
Isbell
T Scott
TS
Chacko
Balu K
BK
Liu
Yuliang
Y
Jhala
Nirag
N
Crowe
D Ralph
DR
Smith
Alvin B
AB
Cross
Richard C
RC
Frenette
Luc
L
Kelley
Eric E
EE
Wilhite
Diana W
DW
Hall
Cheryl R
CR
Page
Grier P
GP
Fallon
Michael B
MB
Bynon
J Steven
JS
Eckhoff
Devin E
DE
Patel
Rakesh P
RP
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D016923:Cell Death; D005260:Female; D006801:Humans; D007902:Length of Stay; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*
D017382:Reactive Oxygen Species; D009569:Nitric Oxide
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