Hepatocellular function and nutrient blood flow in experimental peritonitis.
The pathophysiologic basis of organ failure and reduced oxygen consumption in peritoneal infection remains undefined. Plausible explanations include alteration of tissue nutrient blood flow and a primary cellular injury that impairs oxygen metabolism. To define this controversy, we created peritonitis in rats by cecal ligation and puncture. Controls had sham operation. Rats were sacrificed at 6 or 18 hours, liver mitochondria were isolated, and oxidative phosphorylation was studied polarographically. In additional animals indocyanine green (ICG) clearance was studied at low (5 mg/kg) or high (15 mg/kg) doses. The low-dose ICG clearance reflects total hepatic blood flow; a Lineweaver-Burk plot of clearance versus the dose permits extrapolation of clearance to an infinite dose as an indicator of cellular function. Mitochondria studied at 6 hours (n = 10) and 18 hours (n = 10) indicated no differences when compared to paired controls. ICG clearance was unchanged between peritonitis and control rats at 6 hours. However, at 18 hours peritonitis rats had a prolonged half-life of 2.49 +/- 0.31 minutes for the low-dose and 5.29 +/- 0.41 minutes for the high-dose compared to 1.65 +/- 0.07 and 4.34 +/- 0.10 minutes, respectively, for the controls. The Lineweaver-Burk plot of clearance versus dose resulted in peritonitis and control clearance rates intercepting each other at an extrapolated infinite dose. These data indicate that hepatocellular function measured by mitochondrial function and ICG clearance was unaltered. Low-dose ICG clearance indicated reduced total hepatic blood flow. The reduced oxygen consumption in peritonitis appears to have its genesis in altered nutrient blood flow.
D000818:Animals; D007208:Indocyanine Green; D008102:Liver Circulation; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D010538:Peritonitis / Q000097:blood / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains
D007208:Indocyanine Green