Lang JD Jr et al. (2007) Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation. J Clin Invest 117: 2583–2591

A serious complication of liver transplantation is hepatic ischemia/reperfusion (IR) injury, which can cause poor initial function, or even non-function, of the liver graft. The cellular mechanisms underlying liver IR are extremely complex, involving several cell types and different mediators. Identifying a target for therapeutic intervention has, therefore, been difficult, but evidence from human and animal studies suggests that decreased hepatic production of nitric oxide (NO) might be important.

Clinical administration of NO to treat lung injury mediated by inflammation is generally unsuccessful, but it has revealed that inhaled NO (iNO) has various extra-pulmonary activities. Notably, it can inhibit myocardial injury in patients undergoing cardiopulmonary bypass. To investigate whether iNO has similar positive effects on liver IR, Lang et al. conducted a prospective, blinded, randomized placebo-controlled trial in patients undergoing liver transplantation. Their primary objective was to test the hypothesis that pre-emptive administration of iNO might decrease IR-induced injury via an anti-inflammatory mechanism.

Patients randomly allocated to receive iNO rather than placebo during surgery had a significantly decreased length of hospital stay and more favourable levels of serum aminotransferases and coagulation times, indicating that iNO hastened the restoration of liver function after transplantation. The authors conclude that clinical use of iNO as an extrapulmonary therapeutic can improve early function of the liver after transplantation. They also suggest that the most likely candidate transducer of extrapulmonary effects of iNO is nitrite, but further investigations are required to elucidate the mechanisms involved.