Reliable assessment of hepatic function during liver regeneration is crucial after liver surgery or liver transplantation. 99m Tcgalactosyl human serum albumin ( 99m Tc-GSA) scintigraphy, 99m Tc-mebrofenin hepatobiliary scintigraphy (HBS), the indocyanine green (ICG) clearance test, and the galactose elimination capacity (GEC) are common quantitative liver function tests. However, to our knowledge, comparative analysis between these tests has never been performed during liver regeneration. The aim of this study was therefore to compare 99m Tc-GSA scintigraphy, 99m Tc-mebrofenin HBS, the ICG clearance test, and GEC in the assessment of hepatic function during liver regeneration in rats. Methods: Rats were subjected to 70% partial hepatectomy (PHx). Liver function and functional volume were determined at predefined times after PHx and expressed as a percentage of baseline (pre-PHx) values. Results: During liver regeneration, functional liver volume measured by 99m Tc-GSA SPECT correlated strongly with conventional liver volume based on wet weight. One day after 70% PHx, conventional liver volume overestimated liver function as measured by 99m Tc-mebrofenin uptake and excretion rates, 99m Tc-GSA uptake rate, and ICG clearance. On days 5 and 7, 99m Tc-mebrofenin uptake and ICG clearance had recovered to levels similar to conventional liver volume, whereas 99m Tc-GSA uptake reflected a reduced liver function in relation to conventional liver volume and 99m Tc-mebrofenin uptake. The GEC measurements consistently overestimated liver function during regeneration. Conclusion: Volumetric assessment of the liver should be complemented by liver function-specific assays. Functional regeneration is impaired, compared with volumetric regeneration, in the early phase of liver regeneration. In later stages of liver regeneration, 99m Tc-GSA uptake underestimates hepatic regeneration in comparison to liver volume and 99m Tc-mebrofenin uptake. GEC is of less value because it is only minimally affected by 70% PHx and is influenced by factors not related to liver function. 99m Tc-mebrofenin HBS has the advantage of providing visual and quantitative information regarding both uptake and excretory liver function.

Cholestasis impairs liver regeneration following partial liver resection (PHx). Bile acid receptor farnesoid X-receptor (FXR) is a key mediator of liver regeneration. The effects of FXR agonist obeticholic acid (OCA) on liver (re)growth were therefore studied in cholestatic rats. Animals underwent sham surgery or reversible bile duct ligation (rBDL). PHx with concurrent internal biliary drainage was performed 7 days after rBDL. Animals were untreated or received OCA (10 mg/kg/day) per oral gavage from rBDL until sacrifice. After 7 days of OCA treatment, dry liver weight increased in the rBDL + OCA group, indicating OCA-mediated liver growth. Enhanced proliferation in the rBDL + OCA group prior to PHx concurred with a rise in Ki67-positive hepatocytes, elevated hepatic Ccnd1 and Cdc25b expression, and an induction of intestinal fibroblast growth factor 15 expression. Liver regrowth after PHx was initially stagnant in the rBDL + OCA group, possibly due to hepatomegaly prior to PHx. OCA increased hepatobiliary injury markers during BDL, which was accompanied by upregulation of the bile salt export pump. There were no differences in histological liver injury. In conclusion, OCA induces liver growth in cholestatic rats prior to PHx but exacerbates biliary injury during cholestasis, likely by forced pumping of bile acids into an obstructed biliary tree.

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T ransfusion-associated circulatory overload (TACO) is the largest cause of transfusion-related major morbidity and mortality. 1-3 Current understanding of TACO is that volume overload occurs, specifically ABBREVIATIONS: AKI = acute kidney injury; BALF = bronchoalveolar lavage fluid; COP = colloid osmotic pressure; CVP = central venous pressure; ECV = estimated circulating volume; KDA = ketamine-dexmedetomidine-atropine solution; LVEDP = left ventricular end-diastolic pressure; MAP = mean arterial pressure; MI = myocardial infarction; PV = pressure-volume (catheter); PCWP = pulmonary capillary wedge pressure; RL = Ringer's lactate; TACO = transfusion-associated circulatory overload; WD = pulmonary wet weight/dry weight (ratio).From the

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Volatile organic compounds in breath can reflect host and pathogen metabolism and might be used to diagnose pneumonia. We hypothesized that rats with Streptococcus pneumoniae ( SP) or Pseudomonas aeruginosa ( PA) pneumonia can be discriminated from uninfected controls by thermal desorption-gas chromatography-mass-spectrometry (TD-GC-MS) and selected ion flow tube-mass spectrometry (SIFT-MS) of exhaled breath. Male adult rats ( n = 50) received an intratracheal inoculation of 1) 200 µl saline, or 2) 1 × 107 colony-forming units of SP or 3) 1 × 107 CFU of PA. Twenty-four hours later the rats were anaesthetized, tracheotomized, and mechanically ventilated. Exhaled breath was analyzed via TD-GC-MS and SIFT-MS. Area under the receiver operating characteristic curves (AUROCCs) and correct classification rate (CCRs) were calculated after leave-one-out cross-validation of sparse partial least squares-discriminant analysis. Analysis of GC-MS data showed an AUROCC (95% confidence interval) of 0.85 (0.73–0.96) and CCR of 94.6% for infected versus noninfected animals, AUROCC of 0.98 (0.94–1) and CCR of 99.9% for SP versus PA, 0.92 (0.83–1.00), CCR of 98.1% for SP versus controls and 0.97 (0.92–1.00), and CCR of 99.9% for PA versus controls. For these comparisons the SIFT-MS data showed AUROCCs of 0.54, 0.89, 0.63, and 0.79, respectively. Exhaled breath analysis discriminated between respiratory infection and no infection but with even better accuracy between specific pathogens. Future clinical studies should not only focus on the presence of respiratory infection but also on the discrimination between specific pathogens.

Background: Septic patients are often anemic, requiring red blood cell (RBC) transfusions. However, RBC transfusions are associated with organ injury. The mechanisms of RBC-induced organ injury are unknown, but increased clearance of donor RBCs from the circulation with trapping in the organs could play a role. We hypothesized that washing of RBCs prior to transfusion may reduce clearance and trapping of donor cells and thereby reduce organ injury. Methods: Sprague-Dawley rats were inoculated intratracheally with 107 colony-forming units (CFU) of Streptococcus pneumoniae or vehicle as a control and transfused with either a washed or standard (non-washed) biotinylated RBC transfusion from syngeneic rats. Controls received saline. Blood samples were taken directly after transfusion and at 24 h to calculate the 24 h post transfusion recovery (PTR). After sacrifice, flow cytometry was used to detect donor RBCs in organs and blood. The organs were histologically scored by a pathologist and CFUs in the lung and blood were counted. Results: The 24h-PTR was similar between healthy and pneumoseptic rats after a standard transfusion. In healthy rats, a washed transfusion resulted in a higher PTR and less accumulation of donor RBCs in the organs compared with a standard transfusion. However, during pneumonia, this effect of washing was not seen. Transfusion did not further augment lung injury induced by pneumonia, but washing decreased bacterial outgrowth in the lungs associated with reduced lung injury. Conclusion: In healthy recipients, washing increased 24h-PTR of donor RBCs and decreased trapping in organs. In pneumoseptic rats, washing reduced bacterial outgrowth and lung injury, but did not improve PTR.

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