Administration of nitric oxide restores the abolished hepatic artery buffer responses in early porcine endotoxaemia

Abstract

Abstract Background Among other organs, the liver may be severely compromised by the altered haemodynamic conditions of septic shock. The hepatic artery buffer response (HABR), which is mediated mainly by adenosine 5′-triphosphate and nitric oxide as the second messenger, and is ablated during endotoxaemia, plays a central role in the autoregulation of liver perfusion. It was hypothesized that a temporarily decreased synthesis of nitric oxide during early endotoxaemia might be responsible for the dysfunction of the HABR and that administration of nitric oxide could re-establish the autoregulation of hepatic blood flow. Methods The experiment was performed in 15 juvenile Landrace pigs, which were randomly assigned to receive endotoxin (ET) 1·7 μg kg−1 min−1 (Escherichia coli) and the non-enzymatic nitric oxide donor sodium nitroprusside (SNP) 3 μg kg−1 min−1 (ET-SNP group; n = 7) or ET 1·7 μg kg−1 min−1 (E. coli) and vehicle (ET group; n = 8). ET and nitric oxide were administered into the portal vein. Study measurements (haemodynamic measurements, liver perfusion) were performed for 5 h. Results ET caused a significant decrease in liver perfusion after 5 h. Hepatic arterial flow (Qha) was reduced by 50 per cent and portal vein flow (Qpv) by 38 per cent. The additional administration of nitric oxide ameliorated liver perfusion; Qha and Qpv were not altered significantly in the ET-SNP group. The mechanical reduction of Qpv to approximately 50 per cent of baseline increased Qha in all animals before administration of ET. Flow increase in the hepatic artery due to partial Qpv occlusion (HABR) was lost in the ET group, while nitric oxide preserved a mean increase of 28 per cent in Qha (P < 0·01). At time zero the Qpv reduction decreased mean hepatic artery resistance (HAR) in both groups. Thereafter ET infusion led to a continuous loss of the response of HAR to reduction of Qpv, while nitric oxide administration kept the response of HAR at pre-ET levels throughout the experiment. At 4 and 5 h the reactivity of HAR to manipulations of Qpv had returned to baseline levels in the ET group. Conclusion Early administration of the non-enzymatic nitric oxide donor SNP during endotoxaemia is able to re-establish an autoregulatory response of the hepatic artery following reduction of hepatic blood flow.