Effects of heparin and low molecular weight heparin on lipid transport during parenteral feeding in the rat.
BACKGROUND
Treatment with heparin has been reported to interfere with lipid metabolism by release of Lipoprotein Lipase (LPL) into the circulation. The purpose of the present study was to determine the effects on LPL activity by anticoagulants in combination with total parenteral nutrition (TPN) in the rat. In an earlier investigation we could show that TPN, per se, caused a three-fold increase of triglyceride content in liver tissue, retention of lipids in the circulation and disturbed cholesterol metabolism with accumulation of cholesterol in the non High Density Lipoprotein (HDL) fraction of lipoproteins. The activity of Hepatic Lipase (HL) was decreased, while the activities of LPL in adipose tissue and heart were up-regulated.


METHODS
Effects on lipid metabolism by TPN for seven days with or without simultaneous administration of heparin or Low Molecular Weight Heparin (LMWH) were studied in 52 healthy male Sprague-Dawley rats. Combinations of Heparin or LMWH and discontinuous or continuous administration of TPN solutions (including approximately 8 g triglycerides/kg body weight daily) were investigated.


RESULTS
Addition of LMWH, but not heparin, to treatment with TPN resulted in significant up-regulation of LPL activity in the heart. Combination of heparin and continuous administration of TPN solutions was followed by modest, but significant, increases of S-Triglycerides and HDL-Triglycerides. No differences between the TPN groups were observed concerning liver steatosis, cholesterol metabolism, phospholipid metabolism or HL activity.


CONCLUSIONS
Treatment with LMWH during TPN resulted in up-regulated LPL activity in the heart, which might represent a compensatory mechanism for enzyme release from the capillary walls induced by anticoagulants. Administration of heparin, a more effective lipase-releasing agent, was not associated with increased LPL activity. Heparin treatment in combination with continuous TPN administration was followed by increased levels of triglycerides in blood and HDL particles, suggesting that treatment with heparin might have impaired the capacity for LPL up-regulation, resulting in the development of hyperlipidemia. Further investigations are necessary for evaluation of the mechanisms. Depletion of LPL activity could not be demonstrated by this study in healthy rats.
Roth
B
B
Department of Anaesthesia and Intensive Care, University of Lund, Sweden.
Ekelund
M
M
Fan
B G
BG
Ekstrom
U
U
Nilsson-Ehle
P
P
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D010289:Parenteral Nutrition, Total; D051381:Rats; D017207:Rats, Sprague-Dawley
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin; D008071:Lipoprotein Lipase