N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation

Abstract

In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P < or = 0.02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment.

Figures

Fig. 1

Absolute concentrations (ng/ml) of sP-selectin in arterial, portal venous and hepatic venous plasma 1 h after reperfusion of the liver graft. The data show the mean values ±s.e.m. of the NAC-treated (n = 9) and control patients (n = 10). The differences are not significant. □, Control group (n = 10); ▪, NAC group (n = 9).

Fig. 2

Balance values of sP-selectin (µg/min) across the intestinal organs, the liver and the total of both ( = splanchnic balance), 1 h after reperfusion of the liver graft. Mean values ±s.e.m. Positive values indicate an uptake, negative values indicate the release of sP-selectin. □, Control group (n = 10); ▪, NAC group (n = 9).