Metabolism during liver transplantation: The effect of dichloroacetate

Dichloroacetate (DCA) stimulates pyruvate dehydrogenase (PDH), accelerating recovery of the postischemic heart. Because DCA also stimulates hepatic PDH, it may facilitate graft recovery during liver transplantation (OLT). Hepatic removal and replacement during OLT produce major changes in O₂ consumption (VO₂) and return of baseline VO₂ has been used to index early graft function. We examined the effect of DCA on O₂ metabolism during OLT. Forty patients received DCA 80 mg/kg intravenously in divided doses, and 40 served as controls. Serial measurements were made for body temperature hemodynamics O₂ metabolic indices, and plasma substrate and hormonal concentrations. Oxygen delivery (DO₂I) and consumption (VO₂I) indices were calculated. Patients exhibited stable hemodynamics, with similar fluid and blood product requirements. Compared with the dissection stage, DO₂I and VO₂I were decreased during the anhepatic stage (31% and 36%, respectively) then returned to dissection stage values soon after portal vein unclamping. Temperature decreased during the anhepatic stage and returned toward dissection stage value after graft perfusion. DCA reduced lactic acidosis and NaHCO₃ use but did not alter hemodynamics or measures of O₂ metabolism or body temperature. VO₂ is decreased during the anhepatic stage largely due to loss of hepatic metabolism. Restoration of VO₂ by 30 min after portal vein unclamping reflects rapid recovery of O₂ metabolism by the graft liver, but DCA does not accelerate recovery of VO₂. DCA does not seem to facilitate early graft hepatic function as indexed by VO₂. Implications: We evaluated whether dichloroacetate, which stimulates pyruvate dehydrogenase, can accelerate recovery of graft liver hepatic function during liver transplantation, as indexed by oxygen consumption. We found that despite evidence that it activated pyruvate dehydrogenase, dichloroacetate did not affect recovery of transplanted liver function.