Preoperative fasting improves survival after 90% hepatectomy
T. P. Sarac, H. C. Sax, R. Doerr, U. Yuksel, R. Pulli and J. Caruana
Department of Surgery, University of Rochester Medical Center, NY.
OBJECTIVE: To assess whether alterations in preoperative fatty acid
oxidation and gluconeogenesis induced by fasting will affect survival and
liver regeneration following 90% hepatectomy in the rat. DESIGN: In a
randomized, controlled trial, Wistar rats (N = 157) were separated into two
groups. Rats in the first group fasted for 24 hours. Rats in the second
group were allowed to eat ad libitum until the time of operation. These
groups were further randomized to receive either 20% glucose or tap water
ad libitum postoperatively. INTERVENTIONS: Ninety percent hepatectomy;
24-hour fast; 5% glucose feeding. MAIN OUTCOME MEASURES: Survival, DNA
synthesis in the hepatic remnant along with glucokinase activity (GKA) and
glycogen content, serum ketone bodies (KB), free fatty acid (FFA), glucose,
and ad libitum glucose consumption (GC) were serially quantified. RESULTS:
Fasting rats that were offered glucose (fasted/glucose) after hepatectomy
demonstrated better survival at 48 hours than the rats that were fed before
the procedure and given glucose following hepatectomy (fed/glucose), 95% vs
52% (P < .05). The fasted/glucose group also had a greater peak rate of
DNA synthesis (550 +/- 110 vs 275 +/- 40 disintegrations per minute per
0.001 mg of DNA, P < .05). Survival was poor in both groups when only
tap water was offered to the animals after hepatectomy (31% vs 12%). In the
fasted/glucose group, GC 1 hour after hepatectomy was greater than that for
fed rats (1.3 +/- 0.175 vs 0.73 +/- 0.176 g/h, P < .05), yet GKA was
suppressed (3.4 +/- 0.42 vs 8.05 +/- 2.77 nmol/min per milligrams of
protein, P < .05). Fasting before hepatectomy and consuming glucose
after causes elevations in both FFA (1.26 +/- 0.19 vs 0.82 +/- 0.13
mol/mL., P < .05) and KB (18.96 +/- 2.82 vs 11.4 +/- 3.94 mmol/mL, P
< .05). Normal glucose was maintained in the fasted/glucose group, but
fell to 63 +/- 14 mg/dL at 8 hours after hepatectomy in the fed/glucose
group. CONCLUSIONS: Fasting before hepatectomy shifts energy utilization to
fat oxidation and gluconeogenesis, which appears to ameliorate liver
failure after hepatectomy in this severe model of hepatic resection.