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The influence of combined replenishment of L-3,5,3′-triiodothyronine (T3) and vasopressin (antidiuretic hormone [ADH]) on both hepatic metabolism and systemic hemodynamics was assessed in brain-dead dogs. Arterial ketone body ratio (AKBR) was measured as a parameter of hepatic metabolism, which reflects the redox state (free nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide) of liver mitochondria. Mean arterial blood pressure (MAP) was significantly decreased from 110.4±3.8 to 44.4±1.7 mmHg, at 1 hr after completion of brain death (P<0.01). In the control group AKBR was maintained thereafter at near control value of 1.0 with a significant decrease in serum lactate concentration in spite of marked hypotension. T3 infusion at a rate of 1 μg/kg/hr elevated the AKBR but did not elevate MAP. Vasopressin infusion at a rate of 0.1 U/kg/hr sustained AKBR and elevated MAP significantly at 1 hr after administration but tended to decrease thereafter. Combined administration of T3 and ADH elevated the AKBR to about 2.0, and MAP was restored to near-normal level. Other parameters such as glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactic dehydrogenase, reflecting liver cell injury and serum creatinine, and blood urea nitrogen as renal function, were maintained within normal range. These results indicate that combined T3 and vasopressin administration has a beneficial synergistic effect on both hepatic energy metabolism and systemic hemodynamics without any detrimental influence to other conventional parameters. Therefore, it is suggested that this combined administration may contribute to the management of potential multiorgan donors.

Operative risk and stress were analyzed in 28 parent-donors whose children received partial liver transplantations at the Second Department of Surgery, Kyoto University Hospital between June 1990 and December 1991. Graft-harvesting operations were classified into three types: left lobectomy (group L, n=12), left lateral segmentectomy (group S, n=15), and right lobectomy (n=l). Since donor safety is a primary concern, great care was taken to minimize potential damage to the remaining lobes of the donor liver as well as the graft liver by avoiding stressful maneuvers such as hepatic vascular clamping during the transection of the hepatic parenchyma. In all cases the arterial ketone body ratio, which reflects the hepatic mitochondrial redox potential, was maintained at over 0.7 throughout the donor operation as well as postoperatively. There was no significant difference in the postoperative RBC, WBC, serum GOT, and total bilirubin between groups L and S, although the abnormalities exhibited by the single right lobectomy case tended to be larger and more prolonged. All cases were within the range acceptable for immediate discharge, and all donors of groups L and S were subsequently discharged within 14 days without any postoperative complications. The single right lobectomy donor was discharged on POD 17 because of transient slight icterus, which is the only postoperative complication encountered in this series thus far. The present analyses would indicate that the risk and operative stress to the donor in living-related partial liver transplantation can be minimal when the left lobe or left lateral segment of the liver is used for the graft.

Changes in the arterial ketone body ratio (AKBR [ace-toacetate/3-hydroxybutyrate]), which reflect the redox state of the liver mitochondria (NAD+/NADH), as well as those in total ketone body concentration (TKB) and blood glucose level were studied in 30 living-related liver transplantations (LRLT) performed in pediatric patients at Kyoto University Hospital from June 1990 to January 1992. AKBR increased to over 1.0 within 6 hr after reperfusion of the graft in 11 cases (37), within 12 hr in 7 (23), on POD 1 in 8 (27), and on POD 2 in the remaining 4 cases (13). TKB significantly increased while AKBR remained below 0.7 (266±40 μmol/L), but it significantly decreased in accordance with the recovery of AKBR above 1.0 (61 ±6 μmol/L). This indicates the change in the predominant energy substrate for hepatic mitochondria from fatty acid to glucose during the AKBR recovery process. In 6 cases, the AKBR transiently decreased to below 1.0 after initial recovery concomitant with the fall in blood glucose level and the increase in TKB. However, the AKBR was rapidly restored to over 1.0 again immediately after the glucose administration was increased. This suggests that glucose administration to maintain blood glucose level between 150 and 250 mg/dl is essential for the AKBR recovery above 1.0 that accompanies the normalization of graft metabolic functions, and that, along with the postoperative minimal increase in serum enzymes and favorable outcome of the transplant with no incidence of a primary nonfunctioning graft, the prompt and successful recovery of AKBR reflects the expected high viability of the graft in our LRLT cases.

Arterial blood ketone body ratio was measured after orthotopic liver transplantation in piglets. Ketone body ratio immediately decreased at the beginning of the anhepatic phase and was rapidly restored to the normal levels within 30 min after the revascularization of the allograft. Serum lactate and pyruvate levels increased in anhepatic phase and gradually decreased after revascularization. Changes in the lactate and pyruvate levels were always preceded by changes in ketone body ratio. In the case of transplantation after 12-hr-preservation of the allograft, ketone body ratio failed to maintain normal levels after transplantation, resulting in a high mortality. It is suggested that the elevation of decreased ketone body ratio is prerequisite for the normalization of the deranged metabolic state after liver transplantation, and that ketone body ratio provides an accurate means to assess the initial metabolic function of the allograft.