Temporal relationship of hepatocellular dysfunction and ischemia in sepsis
G. W. Machiedo, T. Hurd, B. F. Rush Jr, G. Dikdan, J. McGee and T. Lysz
Surgical Service, Veterans Administration Medical Center, East Orange, NJ.
To determine whether hepatic dysfunction in sepsis results from
hypoperfusion or direct cellular injury, Sprague-Dawley rats underwent
either cecal ligation and puncture or sham operation. After either two or
six hours, effective hepatic blood flow was measured using the galactose
clearance method. Hepatocytes were isolated and intracellular sodium and
potassium and glucose production were measured. Hepatic blood flow in
septic rats decreased as early as two hours after sepsis when compared with
sham-operated rats (3.8 +/- 1.4 vs 8.7 +/- 3.1 mL/min/100 g body weight).
Intracellular sodium and potassium levels and glucose production in septic
rats were not significantly different when compared with controls at two
hours. After six hours, hepatic blood flow remained depressed and
intracellular sodium level was increased compared with sham-operated rats
(41.7 +/- 10.4 vs 31.4 +/- 5.9 mmol/L [41.7 +/- 10.4 vs 31.4 +/- 5.9
mEq/L]) and potassium decreased compared with controls (90.7 +/- 7.9 vs
111.5 +/- 6.7 mmol/L [90.7 +/- 7.9 vs 111.5 +/- 6.7 mEq/L]). Glucose
production was decreased in septic rats after six hours when compared with
controls (4.7 +/- 1.5 vs 15.4 +/- 6.4 mumol/g hepatocytes). These data
suggest that hepatic blood flow is decreased before alterations in
intracellular sodium and potassium as well as glucose production.