Plasma apolipoprotein AV levels in mice are positively associated with plasma triglyceride levels.

Apolipoprotein AV (apoAV) overexpression causes a decrease in plasma triglyceride (TG) levels, while deficiency of apoAV causes hypertriglyceridemia in both men and mice. However, contrary to what would be expected, plasma apoAV and TG levels in humans are positively correlated. To address this apparent paradox, we determined plasma apoAV levels in various mouse models with median TG levels ranging from 30 mg/dl in wild-type mice to 2089 mg/dl in glycosylphosphatidylinositol-anchored HDL binding protein 1-deficient mice. The data show that apoAV and TG levels are positively correlated in mice (r = +0.798, P < 0.001). In addition, we show that LPL gene transfer caused a simultaneous decrease in TG and apoAV in LPL-deficient mice. The combined data suggest that apoAV levels follow TG levels due to an intimate link between the apoAV molecule and TG-rich lipoproteins, comprising both secretion and removal of these lipoproteins. Taken together, the data suggest that higher plasma apoAV levels reflect an increased demand for plasma TG hydrolysis under normal physiological conditions.

Effect of fluid supplementation and modality on peritoneal permeability characteristics in a rat peritoneal dialysis model.

OBJECTIVE: Hemoconcentration may influence peritoneal permeability parameters in anesthetized animals without fluid supplementation. Therefore, the aim of this study was to investigate the effects of fluid supplementation on peritoneal permeability in an acute peritoneal dialysis model in anesthetized rats. DESIGN: To study the effect of fluid supplementation on peritoneal permeability characteristics, 24 anesthetized male Wistar rats were investigated in 3 groups during a 4-hour standardized peritoneal permeability analysis with a 3.86% glucose dialysis solution (SPARa). The groups included a control group with no fluid supplementation (None, n = 8), a group with continuous subcutaneous infusion of 0.9% NaCl 3 mL/hr (SC, n = 9), and a group with continuous intravenous infusion of 0.9% NaCl 3 mL/hr (IV, n = 7). Inflow, sampling, and outflow of the dialysate during the SPARa occurred via a cannula inserted intraperitoneally in the lower left quadrant of the abdomen. Blood was drawn at the end of the dwell. Baseline blood samples were obtained from six separate untreated rats. RESULTS: Plasma osmolality was significantly lower in the IV group (334+/-1.4 mOsm/kg) compared to the None group (348+/-0.7 mOsm/kg, p < 0.01), and not different from the SC group (335+/-6.4 mOsm/kg), but higher than baseline (314+/-5.3 mOsm/kg, p < 0.001). Urine production during the dwell was not different among the groups: None 10.6+/-5.3 mL; SC 8.0+/-6.0 mL; and IV 10.5+/-5.6 mL. Transcapillary ultrafiltration after 4 hours was significantly higher in the IV group (p < 0.05) compared to the other two groups. Net ultrafiltration and effective lymphatic absorption were similar in all groups. Mass transfer area coefficient of urea (MTACurea) was significantly greater in the IV group (155+/-23.2 microL/minute, p < 0.003), but not different between the None (118+/-16.2 microL/min) and SC (123+/-25.9 microL/min) groups. Correcting these for the baseline plasma concentration resulted in higher values, but the IV data remained greater than the SC and None groups (p < 0.01). The glucose absorption, albumin, and IgG clearances and the sieving of sodium were alike in all groups. CONCLUSION: It can be concluded that IV fluid supplementation is more effective in preventing dehydration than SC supplementation, and it enhanced some peritoneal permeability characteristics in anesthetized rats during a 4-hour investigation. It is therefore important to standardize fluid supplementation in experiments with anesthetized animals.

Ultrastructure of basement membranes of peritoneal capillaries in a chronic peritoneal infusion model in the rat.

BACKGROUND: Long-term peritoneal dialysis with glucose- based dialysis solutions has been associated with diabetiform alterations of peritoneal tissue. A peritoneal infusion model in the rat was developed to study the effect of chronic infusion of a glucose-based dialysis solution and an isotonic non-glucose solution on the ultrastructure of the basement membranes of peritoneal capillaries. The effect of ageing was also studied in an untreated control group. METHODS: A vascular access port (Rat-o-Port) with attached peritoneal catheter was implanted subcutaneously in the neck of nine male Wistar rats. The rats were divided randomly into three groups: the glucose group (n = 3) was infused daily for 20 weeks with 60 ml/kg body weight 3.86% glucose solution. A control group (n = 2) was infused daily for 20 weeks with 60 ml/kg body weight Ringer's lactate. The untreated control group (n = 4) was studied at the onset of the experiment and after 20 weeks. Omental tissue was obtained from each rat at the end of the experimental period for ultrastructural examination. RESULTS: Extensive lamination of basement membranes of omental capillaries was found in the glucose group. This was in contrast to the untreated control group where clear, single basement membranes were seen at the onset of the experiment and after 20 weeks. These latter findings were similar to those in the Ringer's lactate group. CONCLUSIONS: The chronic infusion model in the rat is suitable for the investigation of the effects on the ultrastructure of peritoneal capillaries of chronic exposure to dialysis fluids. The duplications of basement membranes of omental capillaries found in the glucose group show a striking resemblance to those found in long-term peritoneal dialysis patients. This suggests a role for glucose in the development of peritoneal ultrastructural alterations found in long-term peritoneal dialysis.