Model assisted analysis of the hepatic arterial buffer response during ex vivo porcine liver perfusion

Objective: The hepatic arterial buffer response is a well known phenomenon in hepatic circulation, describing the response of hepatic arterial resistance to changes in portal vein flow. Several vasoactive metabolites underlying its mechanism have been proposed, however, there is currently no clear consensus. The aim of this study was to investigate the hepatic arterial buffer response of porcine livers preserved in a controlled ex vivo perfusion machine. Methods: Porcine livers were perfused on an ex vivo perfusion machine and hemodynamic experiments investigating the hepatic arterial resistance response to portal vein flow and vena cava pressure variations were conducted. A simple hemodynamic model was developed to support the interpretation of the received measurements. Further, a mechanism was proposed that explains hepatic arterial resistance changes in response to vena cava pressure as myogenic and in response to portal vein flow as a combined washout and myogenic effect. Results: A clear correlation between hepatic sinusoidal pressure levels and hepatic arterial resistance was observed where an increase of approximately 4~mmHg of hepatic sinusoidal pressure level results in doubling of the hepatic arterial resistance. This relation was considered during the analysis of the portal vein flow variations resulting in a reduced isolated effect of adenosine washout on hepatic arterial resistance. With an average buffer capacity of 27% during our experiments, the hepatic arterial buffer response shows to be unimpaired in the ex vivo scenario. Conclusion: First, washout and myogenic effects both influence the hepatic arterial buffer response and, second, hepatic sinusoidal pressure levels strongly influence the hepatic arterial resistance. Significance: These results present new findings in hemodynamics of the liver, which are fundamental for successful ex vivo liver perfusion.