Effect of increased cardiac output on liver blood flow, oxygen exchange and metabolic rate during longterm endotoxin-induced shock in pigs.
We investigated hepatic blood flow, O2 exchange and metabolism in porcine endotoxic shock (Control, n = 8; Endotoxin, n = 10) with administration of hydroxyethylstarch to maintain arterial pressure (MAP)>60 mmHg. Before and 12, 18 and 24 h after starting continuous i.v. endotoxin we measured portal venous and hepatic arterial blood flow, intracapillary haemoglobin O2 saturation (Hb-O2%) of the liver surface and arterial, portal and hepatic venous lactate, pyruvate, glycerol and alanine concentrations. Glucose production rate was derived from the plasma isotope enrichment during infusion of [6,6-2H2]-glucose. Despite a sustained 50% increase in cardiac output endotoxin caused a progressive, significant fall in MAP. Liver blood flow significantly increased, but endotoxin affected neither hepatic O2 delivery and uptake nor mean intracapillary Hb-O2% and Hb-O2% frequency distributions. Endotoxin nearly doubled endogenous glucose production rate while hepatic lactate, alanine and glycerol uptake rates progressively decreased significantly. The lactate uptake rate even became negative (P<0.05 vs Control). Endotoxin caused portal and hepatic venous pH to fall significantly concomitant with significantly increased arterial, portal and hepatic venous lactate/pyruvate ratios. During endotoxic shock increased cardiac output achieved by colloid infusion maintained elevated liver blood flow and thereby macro- and microcirculatory O2 supply. Glucose production rate nearly doubled with complete dissociation of hepatic uptake of glucogenic precursors and glucose release. Despite well-preserved capillary oxygenation increased lactate/pyruvate ratios reflecting impaired cytosolic redox state suggested deranged liver energy balance, possibly due to the O2 requirements of gluconeogenesis.
Santak
B
B
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinik für Anästhesiologie, Klinikum der Universität, Ulm, Germany.
Radermacher
P
P
Adler
J
J
Iber
T
T
Rieger
K M
KM
Wachter
U
U
Vogt
J
J
Georgieff
M
M
Träger
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects*; D005943:Gluconeogenesis / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects*; D019289:Pyruvic Acid / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism*; D013552:Swine; D013997:Time Factors
D006454:Hemoglobins; D019344:Lactic Acid; D019289:Pyruvic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase