MARKERS OF CELLULAR DYSOXIA DURING ORTHOTOPIC LIVER-TRANSPLANTATION IN PIGS

Objective: To characterize global, regional, and end-organ markers of cellular dysoxia during orthotopic liver transplantation and early rep erfusion in pigs. Design: Descriptive study. Setting: University hospi tal research laboratory. Animals and interventions: 7 fasted, anesthet ized, and mechanically ventilated Yorkshire pigs underwent orthotopic liver transplantation. Oxygen consumption (VO2) and oxygen delivery (D O2) were both calculated using standard formulae. Gastric interstitial pH and the gastroarterial partial pressure of carbondioxide (PCO2) gr adient were measured with a gastric tonometer. The following were dete rmined from arterial blood samples: serum lactate to pyruvate ratio, s erum 3-hydroxybutyrate to acetoacetate ratio, plasma free fatty acids, and plasma free and total carnitine levels. Measurements and results: Data were collected 1 h after induction of anesthesia (I), at the end of the anhepatic phase (A), and 1 h after reperfusion (R). Median (ra nge) VO2 values obtained at the specified time points were: I 318 (206 -1860), A 210 (152-408), R 330 (214-424) ml/kg per min, respectively ( NS); DO2 values were: I 1828 (1382-3259), A 1219 (452-2492), R 1741 (1 345-12 071) ml/kg per min, respectively (NS). The lactate to pyruvate ratio, reflecting the redox potential of the cytosol, progressively in creased: I 22 (9-46), A 29 (16-68), R 43 (23-55) (P < 0.05). Gastric i nterstitial pH, as well as the gastroarterial PCO2 gradient values at the specified time points did not reach statistical significance. Leve ls of ketone bodies (3-hydroxybutyrate+acetoacetate) remained lower th an 0.120 mmol/l. The ketone body ratio did not significantly vary over time (NS). Plasma esterified and free carnitine concentrations and fr ee fatty acid values remained within normal limits (NS). Among these m arkers, the ketone body ratio presented the largest area under the rec eiver operating characteristic curve as a marker of postoperative mort ality, with an inflexion point at 0.9. Conclusions: In this study, ort hotopic liver transplantation was associated with significant variatio ns over time in the redox potential of the cytosol. Postoperative mort ality was, however, related to the redox state of the liver mitochondr ia. Our data suggest the occurrence of abnormal tissue oxygenation dur ing liver transplantation.