Continuous intravenous heparin administration in humans causes a decrease in serum lipolytic activity and accumulation of chylomicrons in circulation.
Heparin is a well-known, widely used anticoagulant drug. In addition to its anticoagulant properties, however, it also has a marked influence on fat metabolism. Postprandial lipoproteins may contribute significantly to the development of coronary heart disease. Therefore, it is important to evaluate the effects of heparin on these lipoproteins. The effect of continuous heparin administration on postprandial lipoprotein metabolism was studied in 11 patients with thromboembolic disease. Results were compared with those in a group of six patients given no heparin. Two vitamin A-fat loading tests were done: the first, 5 days before heparin was started and the second, on the fourth day of continuous heparin drip of 1000 U/h, maintaining PTT levels at twice the baseline. To study the effect of acute heparin, an additional fat loading test was done in five patients on the first day of heparin treatment. Vitamin A, specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). The concentrations of chylomicron (Sf > 1000)- and nonchylomicron (Sf < 100)-retinyl palmitate were measured for 10 h postprandially. Four days of continuous intravenous heparin administration increased the area below the chylomicron RP curve from 11091 +/- 4393 to 17684 +/- 5949 micrograms/l.h (P < 0.003). When measured on the first day of heparin treatment in five patients, the area of the chylomicron fraction was reduced from 16678 +/- 6895 to 10474 +/- 3893 micrograms/l.h (P < 0.05). Postheparin lipoprotein lipase activity was significantly lower on the fourth day of heparin, administration than before treatment: 1.8 +/- 1.1 vs. 4.1 +/- 1.3 mumol/FFA per ml per h, respectively (P < 0.0005). In the six control patients with thromboembolic disease in whom heparin therapy was not indicated, no changes in postprandial lipoprotein levels or in lipolytic activity during hospitalization were found. The study demonstrates that 4 days of heparin administration causes an accumulation of chylomicrons in the circulation, most probably as a result of a marked decrease in serum lipolytic activity.
Weintraub
M
M
Department of Internal Medicine C, Tel Aviv Medical Center, Israel.
Rassin
T
T
Eisenberg
S
S
Ringel
Y
Y
Grosskopf
I
I
Iaina
A
A
Charach
G
G
Liron
M
M
Rubinstein
A
A
D000328:Adult; D000368:Aged; D002914:Chylomicrons / Q000097:blood* / Q000187:drug effects; D005223:Fats / Q000494:pharmacology; D005260:Female; D006493:Heparin / Q000008:administration & dosage* / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D008049:Lipase / Q000097:blood; D008055:Lipids / Q000097:blood; D008066:Lipolysis / Q000187:drug effects*; D008071:Lipoprotein Lipase / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D014801:Vitamin A / Q000494:pharmacology
D002914:Chylomicrons; D005223:Fats; D008055:Lipids; D008074:Lipoproteins; D014801:Vitamin A; D006493:Heparin; D008049:Lipase; D008071:Lipoprotein Lipase