Biphasic effects of low-molecular-weight and conventional heparins on chylomicron clearance in rats.
Chylomicrons labeled in vivo with [14C]triglycerides and [3H]retinyl esters were injected in rats at a series of times after administration of conventional unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or saline. In saline controls the clearance of both chylomicron triglycerides and retinyl esters seemed to follow exponential courses, with half-lives of about 5 and 10 minutes, respectively. Five minutes after administration of LMWH or UFH, the triglyceride clearance rates were dramatically increased and were associated with an increased appearance of the radiolabel in circulating free fatty acids (FFAs). The clearance of [3H]retinol radioactivity, ie, chylomicron particles, was also enhanced 5 minutes after heparin injection. From 75% to 90% disappeared from the circulation within the first 5 minutes. Their continued disappearance was much slower, with a slope similar to that of the saline-treated rats. Hence, it was as if a new, rapid exponent had been added to the disappearance curve that accounted for most of the particle clearance. Injection of chylomicrons 1 hour after the heparins resulted in substantially slower clearance compared with saline-treated controls of both triglyceride and retinol radioactivity in rats given a high dose of LMWH or a low dose of either heparin. Appearance of label in plasma FFAs was also decreased, suggesting that impeded lipolysis was responsible, at least in part, for the impeded chylomicron clearance. Four and 24 hours after heparin injection all studied parameters of chylomicron clearance had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medical Biochemistry and Biophysics, University of Umeå, Sweden.
O
O
Chevreuil
M
M
Hultin
P
P
Ostergaard
T
T
Olivecrona
D000818:Animals; D002914:Chylomicrons / Q000493:pharmacokinetics* / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D008066:Lipolysis; D051381:Rats; D013997:Time Factors; D014280:Triglycerides / Q000493:pharmacokinetics; D014801:Vitamin A / Q000493:pharmacokinetics
D002914:Chylomicrons; D006495:Heparin, Low-Molecular-Weight; D014280:Triglycerides; D014801:Vitamin A; D006493:Heparin