Lower plasma levels of lipoprotein lipase after infusion of low molecular weight heparin than after administration of conventional heparin indicate more rapid catabolism of the enzyme.
The functional pool of lipoprotein lipase (LPL) is anchored to heparan sulfate at the vascular endothelium. Injection of heparin releases the enzyme into the circulating blood. Animal experiments have shown that the enzyme is then extracted and degraded by the liver. Low molecular weight (LMW) heparin preparations are widely used in the clinic and are supposed to release less LPL. In this study, we infused a LMW heparin into healthy volunteers for 8 hours. The peak of LPL activity was only about 30% and the subsequent plateau of LPL activity only about 40% compared with those seen with conventional heparin. When a bolus of heparin was given after 4 hours' infusion of LMW or conventional heparin, only relatively small, and similar, amounts of LPL entered plasma. This suggests that the difference between LMW and conventional heparin lay in the ability to retain LPL in the circulating blood, not in the ability to release the lipase. Triglycerides (TGs) decreased when the heparin infusion was started, as expected from the high circulating LPL activities. After 1 to 2 hours, TG levels increased again, and after 8 hours they were about twice as high as before the heparin infusion. This indicates that the amount of LPL available for lipoprotein metabolism had become critically low in relation to TG transport rates. This study indicates that LMW heparin compared with conventional heparin causes as much or more depletion of LPL and subsequent impairment of TG clearing.
Nasstrom
Birgit
B
Division of Nephrology, Department of Internal Medicine, Umeå University, Umeå, Sweden.
Stegmayr
Bernd G
BG
Olivecrona
Gunilla
G
Olivecrona
Thomas
T
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D002784:Cholesterol / Q000097:blood; D017985:Dalteparin / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D008071:Lipoprotein Lipase / Q000097:blood*; D008099:Liver / Q000201:enzymology; D008297:Male; D014280:Triglycerides / Q000097:blood
D000925:Anticoagulants; D014280:Triglycerides; D006493:Heparin; D002784:Cholesterol; D008071:Lipoprotein Lipase; D015951:Factor Xa; D017985:Dalteparin