Quantification of the hepatic oxygen consumption by[O-15]H2O, [O-15]CO and[O-15]O-2 PET: Relationship between tissue oxygenation and oxygen consumption

Background: The knowledge of the relationship between oxygen delivery (DO2) and oxygen consumption (VO2) of the liver is of major importance to unders tand liver dysfunction in postaggression metabolism. Using the freely diffu sible tracers [O-15] H2O and [O-15]O-2 in combination with the Positron Emi ssion Tomography (PET), it is possible to quantify the arterial (f(a)) and portal venous (f(p)) hepatic blood flow as well as the VO2 on a regional ba sis. [O-15] CO binds to hemoglobin with high affinity and, therefore, label s red blood cells. In combination with PET, [O-15]CO allows the localizatio n of larger vessels, especially the portal vein, within the field of view. This study was performed to explore the potential of [O-15] H2O, [O-15] O-2 and [O-15] CO PET in the measurement of the hepatic oxygen consumption. Methods: Liver blood now and oxygen uptake was investigated in 6 anaestheti zed pigs. The hepatic DO2 was calculated as the product of the regional f(a ) and f(p) (measured by [O-15] H2O PET) and the O-2-content of the arterial and portal venous blood. To investigate the reliability of this PET method over a wide flow range, segmental arterial flow reductions were induced by occlusions of several branches of the hepatic artery of varying size and l ocalization yielding different degrees of arterial flow impairment. The por tal venous blood flow was not mechanically impaired. Before and after arter ial occlusion, the liver tissue's oxygenation (TPO2) was measured directly using a needle electrode system (Eppendorf pO(2)-Histograph) to allow compa risons with the regional DO2 and VO2. After bolus injection of approx. 2.2 GBq [O-15] H2O, f(a) and f(p) were measured by a 10-min dynamic PET scan. T he oxygen uptake was determined after inhalation of 3 GBq [O-15] O-2. After inhaltation of 3 GBq [O-15] CO, a 10-min PET scan followed to localize the portal vein. Kinetic parameters for f(a), f(p) and oxygen uptake were esti mated from tissue, arterial and portal venous blood activity curves using a n extended one tissue compartment model to account for the dual blood suppl y. The resulting flow estimates were then compared with microspheres refere nce blood flow measurements obtained from multiple liver tissue samples (po st mortem). Results: The regional VO2 of the liver was determined as 0.048 +/- 0.03 und in occluded and 0.08 +/- 0.021 in normally perfused regions [ml O-2/(min . cm(3))] (mean +/- SD). A highly significant hyperbolic relationship was fo und between DO2 and VO2 (r(2) = 0.65; p < 0.001), reflecting the well known relation of these parameters for the liver as a whole. In hypoxic arterial ly occluded regions (TPO2 6.4 +/- 3.9 mm Hg), the mean oxygen extraction in creased to 79%, while in normally perfused regions (TPO2 23.8 +/- 6.7 mm Hg ), the O-2-extraction was found to be 40%. Conclusion: Combining [O-15] H2O, [O-15] O-2 and [O-15] CO PET allows the e stimation of the hepatic VO2 on a regional basis. For the first time, it is possible to investigate pathophysiological aspects of the oxygen consumpti on during liver failure (i.e. shock, sepsis, cirrhosis, transplant dysfunct ion) including possible pharmacological influences.