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Continuous intravenous heparin administration in humans causes a decrease in serum lipolytic activity and
M Weintraub1, T Rassin, S Eisenberg
1Department of Internal Medicine C, Tel Aviv Medical Center, Israel.
Insights
Heparin administration significantly alters fat metabolism, leading to increased chylomicrons and decreased lipolytic activity. This study reveals heparin
Area of Science:
- Biochemistry
- Pharmacology
- Cardiovascular Medicine
Background:
- Heparin is a widely used anticoagulant.
- Heparin influences fat metabolism, impacting postprandial lipoproteins.
- Postprandial lipoproteins are implicated in coronary heart disease development.
Purpose of the Study:
- To evaluate the effects of continuous heparin administration on postprandial lipoprotein metabolism.
- To assess changes in chylomicron levels and lipolytic activity during heparin treatment.
Main Methods:
- Vitamin A-fat loading tests were conducted before and during heparin administration.
- Retinyl palmitate (RP) concentrations in chylomicron and nonchylomicron fractions were measured.
- Postheparin lipoprotein lipase (LPL) activity was assessed.
Main Results:
- Four days of heparin increased the chylomicron RP curve area (P < 0.003).
- Acute heparin administration reduced the chylomicron fraction area (P < 0.05).
- Postheparin LPL activity significantly decreased after 4 days of heparin (P < 0.0005).
Conclusions:
- Continuous heparin administration for 4 days leads to chylomicron accumulation.
- This accumulation is likely due to a marked decrease in serum lipolytic activity.
- Heparin's effects on lipoprotein metabolism warrant consideration in clinical practice.
Abstract:
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.