A novel method for determining hepatic sinusoidal oxygen permeability in the isolated perfused rat liver using [15O]O2.

Measurement of hepatic sinusoidal permeability of oxygen and other substrates may help elucidate the mechanisms responsible for impaired liver function in cirrhosis. However studies of sinusoidal oxygen permeability in normal liver and various disease states have been limited due to the considerable technical difficulties involved in the use of standard techniques. We have developed a new method for measuring sinusoidal oxygen permeability in the isolated perfused rat liver that overcomes the difficulties of previous methods by using [(15)O]O(2) and an in-line fluid monitor. This method uses data obtained from impulse response curves of radiolabelled red cells, albumin and oxygen that are fitted mathematically using the axial dispersion model to yield rate constants that describe oxygen transit through the liver. We have demonstrated the utility and reproducibility of this method by comparing multiple injections and permeability determinations in the same preparation. This approach could be used in isolated perfused organs to study oxygen permeability in a range of disease states.

The effect of oxygen supplementation on the arterial ketone body ratio in human cirrhosis.

BACKGROUND/AIMS: Data from studies in experimental models have suggested that the impairment of mitochondrial function and altered redox state that occur in cirrhosis may be due to impaired hepatic oxygenation. Since interventions that improve oxygen delivery to hepatocytes may improve mitochondrial functions, we studied the effects of oxygen supplementation on the arterial ketone body ratio (AKBR) in normal volunteers and patients with cirrhosis. METHODS: After a 2-hour fast, ketone bodies were measured in arterial blood taken from patients and controls while breathing room air and then after breathing oxygen via a face mask at 12 liters/min for 60 min. RESULTS: The AKBR was reduced in cirrhotic patients compared with controls, 0.74 +/- 0.23 and 1.51 +/- 0.4, respectively (p = 0.002). Oxygen supplementation significantly improved the AKBR in cirrhotic patients, from 0.74 +/- 0.23 to 1.04 +/- 0.28 (p = 0.001) but did not affect the AKBR in controls. CONCLUSION: These findings suggest that reduced hepatocyte oxygenation contributes to impaired hepatic mitochondrial function in cirrhosis. Strategies at increasing hepatic oxygen delivery may improve hepatic mitochondrial function in patients with chronic liver disease.

Randomized comparison of nasojejunal and nasogastric feeding in critically ill patients.

OBJECTIVE: Critically ill patients often develop large gastric residual volumes during nasogastric feeding as a result of poor gastroduodenal motility. Nasojejunal feeding may decrease the severity of this complication. The aim of this study was to determine whether nasojejunal feeding improved tolerance of enteral nutrition by reducing gastric residual volumes. DESIGN: Randomized, prospective, clinical study. SETTING: Intensive care unit of a university-affiliated hospital. PATIENTS: Seventy-three intensive care unit patients expected to require nutritional support for at least 3 days. INTERVENTIONS: Patients were randomized to receive enteral nutrition via a nasojejunal tube (placed endoscopically) (34 patients) or a nasogastric tube (39 patients). A strict protocol was followed, which included regular gastric residual volume measurement (in both groups), the use of predetermined criteria for intolerance, and an attempt at nasojejunal feeding for those nasogastrically fed patients who were intolerant of enteral nutrition. MEASUREMENTS AND MAIN RESULTS: Endoscopic placement of nasojejunal tubes was successful in 98% with no complications of insertion. Patients fed via a nasojejunal tube had 1) a reduced total gastric residual volume in both the first 24 (197 vs. 491 mL, p = .02) and 48 hrs (517 vs. 975 mL, p = .02); 2) a reduced incidence of a single gastric residual volume >150 mL (32% vs. 74%, p = .001); and 3) a trend toward a reduced incidence of intolerance of enteral nutrition (13% vs. 31%, p = .09). Only 13% of those nasogastrically fed patients who were initially intolerant of enteral nutrition remained intolerant once fed via a nasojejunal tube, and only 1.4% of all patients met criteria for commencement of parenteral nutrition. CONCLUSIONS: Enteral nutrition delivered via a nasojejunal tube is associated with a significant reduction in gastric residual volume, a strong trend toward improved tolerance of enteral nutrition, and an extremely low requirement for parenteral nutrition.