Prevention of catheter thrombosis increases survival, but does not modify lung injury in rats receiving long-term parenteral nutrition.

It has previously been shown that rats receiving total parenteral nutrition (TPN) or each component of TPN die within 40 days of treatment. Central catheter thrombosis and lung injury were constant findings. The aim of the present study was to examine the impact of central thrombosis on lung injury and survival in rats receiving long-term parenteral nutrition. In the first part of the study TPN was infused via the jugular vein and incidence of central venous thrombosis and rate of survival were recorded. Addition of low molecular weight heparin (LMWH) reduced central thrombosis from 6 out of 7 animals to 2 out of 7 animals (p=0.027) and increased survival from 17.1+/-4.5 days to 32.4+/-4.9 days (p=0.04). In the second part of the study four infusion groups were established. Group 1 (controls) received saline 100 mL/kg/day via the jugular vein (n=6). Group 2 received Intralipid 40 mL/kg/day via the jugular vein (n = 7). Group 3 received Intralipid 40 mL/kg/day via the portal vein (n = 7). Group 4 received Intralipid 40 mL/kg/day with added LMWH 70 U/kg/day (n = 7). Lung injury and occurrence of central thrombosis were investigated. Lung injury was assessed by measuring pulmonary arterial pressure (Ppa), clearance of serotonin by the vascular endothelium and the capillary filtration coefficient (CFC). Either infusion via the portal vein or the addition of LMWH to the infusion via the jugular vein prevented central thrombus formation, but the lung injury was not modified by this method compared with infusing Intralipid via the jugular vein without LMWH. In conclusion, central thrombus formation contributes to death in rats receiving parenteral nutrition. The mechanism of the injurious effect of central thrombosis remains unknown, but central thrombus formation seems not to increase lung injury caused by Intralipid.

Pulmonary function in rats dying from long-term parenteral nutrition.

Infusion of Vamin or Intralipid causes death in a rat model of continuous parenteral nutrition. Morphological investigations have shown vascular injury and thrombus formation in the lungs. In this study, lung function in rats was examined before death due to parenteral nutrition. The rats were fed saline intravenously (group I); 100 mL kg(-1) day(-1) (controls); a 7% amino acid-glucose solution (Vamin-Glukos) (group II); 100 mL kg(-1) day(-1), or 20% fat emulsion (Intralipid) (group III); 40 mL kg(-1) day(-1). The infusion was stopped when the condition of the rats deteriorated. In a saline-perfused, isolated lung model, pulmonary arterial pressure (Ppa), transpulmonary pressure (Ptp), endothelial function, measured as inactivation of serotonin (bioassay), and the capillary filtration coefficient (CFC) were determined. Haematological parameters were also evaluated. Constant findings in group II and III were central thrombus formation, anaemia and thrombocytopenia. Ppa increased from 0.7 (0.04) kPa in group I to 1.4 (0.1) kPa and 1.7 (0.1) kPa in groups II and III, respectively (p<0.001). Inactivation of serotonin was reduced to 36% (2) in group II and 37% (2) in group III compared with 74% (5) in group I (p<0.002). CFC increased to 25 mg min(-1) (5) (group II) and 30 mg min(-1) (6) (group III) compared with 13 mg min(-1) (2) in controls (p=0.01). The study shows that major pulmonary hypertension and severe reduction of the endothelial function are present when rats deteriorate after infusion of parenteral nutrition substrates.

Haematological disorders and lung alveolar macrophage function following total parenteral nutrition in rats.

Alterations in haematological parameters have been reported both clinically and experimentally following administration of total parenteral nutrition (TPN). Fat emulsions also affect function of the mononuclear phagocytic system. We have examined haematological parameters and pulmonary alveolar macrophages in rats fed intravenously with the individual components of TPN; a 20 % fat emulsion (Intralipid) and an amino acid solution (Vamin-Glucos), for 1, 3 and 7 days as a continuous infusion. The control groups were given saline infusion for the same periods of time. Haemoglobin, haematocrit, red blood cells, leukocytes, leukocyte superoxide anion production, leukocyte distribution, platelets and platelet aggregation were measured. Lung lavage fluid was examined for alveolar macrophage concentration and procoagulant activity of macrophages. Several of the animals in the experimental groups developed superior caval vein thrombosis. Both experimental groups developed anaemia after 7 days of infusion. Thrombocytopaenia occurred in both experimental groups after 3 and 7 days of infusion. Platelet aggregation decreased already after 1 day of infusion. We did not observe any alteration in counts, distribution in peripheral blood, or superoxide production of leukocytes. The concentration of alveolar macrophages in the lung lavage fluid increased in the experimental groups. The tissue factor activity of the alveolar macrophages increased in the group receiving Intralipid. Our observations are consistent with a granulomatous inflammation reaction.

Pulmonary hypertension and microvascular injury in rats given parenteral nutrition.

Clinical reports have suggested that parenteral nutrition may damage the lungs. We studied the pathophysiologic pulmonary changes in rats receiving a fat emulsion (Intralipid), an amino acid solution (Vamin-glucose) or saline solution. Control rats were not infused. The pulmonary arterial pressure, capillary filtration coefficient and inactivation of serotonin were determined in isolated, perfused lungs following the in vivo perfusion with the respective solutions. After 12 days of Intralipid infusion the rats showed pulmonary hypertension, increased capillary filtration coefficient and reduced inactivation of serotonin compared with control lungs. Reduction of serotonin inactivation was found after only 3 days. Vamin-glucose infusion altered only serotonin clearance. Saline infusion did not change lung function compared with controls. The study suggests that parenteral nutrition in rats may lead to severe and possibly lethal pulmonary changes.