Heparin release

J5. Jaume, J. C., Mendel, C. M Frost, P. H., Greenspan, F. S and Laughton, C. W., Extremely low doses of heparin release lipase activity into plasma and can thereby cause artifactual elevations in serum free thyroxine concentration as measured by equilibrium dialysis. Thyroid 6, 79-84 (1996). 

To investigate heparin release in response to an electric current, the swollen heparin-polymer matrix was attached to a woven platinum cathode in a continuously stirred PBS solution (pH 7.4), and an electric current of 20 mA was applied. When the electric current was on, the polymer surface facing the cathode dissolved, thereby releasing heparin. The amount of heparin released was assayed by the Azure II method at pH 11 to prevent complexation of the two dissolved polymers. The release pattern of heparin showed a complete on-off profile in response to the applied electric field, as shown in Figure 23 [50],... 

Figure 23 Heparin release rate (normalized to pg/15 min per 50 mg device) from hepa-rin-polyallylamine complex matrix with the application of step function electric current in PBS (pH 7.4) solution (mean SD). (O, , A) Off state ( ) 20 mA ( ) 15 mA (A) 10 mA. (From Ref. 48.)...

A Gutowska, YH Bae, SW Kim. Heparin release from thermosensitive hydrogels. J Controlled Release 22 95-99, 1992. 

What are the experimental data underlying the first hypothesis It is common knowledge today that the covalently bound heparin (if bound to the polymer rigidly and inexorably) is usually less active than ionically attached heparin which is capable of elution. In a series of works a group of Japanese investigators, who are today probably the only supporters to this concept, has disclosed the correlation between thromboresistance of the polymer and the amount of heparin released into the bloodstream 68 71). The minimal elution rate of heparin providing sufficient thromboresistance was found to be 4 x 10s g/cm2 min. The decrease of the rate of elution resulted in a drastic decrease of thromboresistance. 

The TFPI pool bound to the endothelium has been shown to be heparin releasable in a number of studies (104,106), Venous occlusion and agents such as I-deamino-8-D-arginine vasopressin (DDAVP) that induce exocytosis of endothelial granular proteins do not cause the release of TFPI (106). Repeated heparin administration is observed to release... 

Novotny Wp Palmier MO, Wun TC, Broze GJ, Miletich JR Purification and properties of heparin releasable lipoprotein-associated inhibitor. Blood 1991 78 394-400. 

Hoppensteadt DA, Fasanella A, Fareed J, Effect of protamine on heparin releasable TFPI antigen levels in normal volunteers, Thromb Res 1995 79(3)325-330. 

Jeong M, Owen W, Staab M, et al. Does heparin release coating of the Wallstent limit thrombosis and platelet deposition Results in a porcine carotid injury model [abstr]. Circulation 1995 92 1-37. 

An, D., Pulinilkunnil, T., Qi, D., Ghosh, S., Abrahani, A., and Rodrigues, B. 2005. The metabolic switch AMPK regulates cardiac heparin-releasable lipoprotein lipase. Am J Physiol Endocrinol Metab 288(1) E246-E253. 

E2. Enholm, C., Shaw, W., Greten, H., and Brown, W. V., Purification from human plasma of a heparin-released lipase with activity against triglyceride and phopholipids. J. Biol. Chem. 250, 6756-6761 (1975). 

The mechanism by which heparinized surfaces maintain their non-thrombogenicity has been investigated by a number of experimental techniques. The evidence indicates that the absence of clotting in in vitro experiments is not caused by heparin release into the blood because normal clotting occurred in heparinized vessels to which either tissue thromboplastin or an activating surface such as kaolin was added. In addition, a number of surfaces which contained large amounts of heparin caused clotting in contacted blood. These surfaces presumably did not... 

Heparin-releasable hepatic triglyceride lipase deficiency... 

The close association of histamine and heparin release in anaphylactic shock and in peptone shock suggests that complexes of histamine and heparin are held in biological systems. Histamine binds heparin in vitro, as shown by displacement tests, by dialysis, and by paper chromatography . Dextran sulphate, polymannuronic acid sulphate, polysulphated xylan and the iV-succinyl derivative of de-W-sulphated heparin give compounds with... 

Heparin and heparinoids are absorbed in only trace amounts when given in large doses orally . EDTA increases the absorption . Subcutaneous and intramuscular injection of various depot heparin preparations have not been found very satisfactory. They fail to give satisfactory blood levels and they increase Sensitization. With subcutaneous injection, the ability of heparin to become fixed to protein becomes a factor modifying absorption. One of the basic difficulties in deciding on the value of subcutaneous or intramuscular injections of heparin is that there has been no quantitative comparison made of the blood levels of heparin administered in these two ways, to determine how much appears in the circulation in active form. It is possible that much heparin never reaches the circulation. This is to be expected when it is remembered that heparin released by mast cells does not reach the circulation. Depository forms of heparin have been replaced by the use of concentrated heparin solutions (40 gm per cent), so that volumes of 0-2 to 0-4 ml. ean be injected into subcutaneous fat tissue or intramuscularly. 

Displacement by plasma of radiolabeled thrombin and radio-labeled thrombin-antithrombin III inactive complex from a heparinized surface was measured and found to be significant for example, removing 63% of the thrombin and 90% of the complex that could not be removed by phosphate-buffered saline alone. Heparin-poly(vinyl alcohol) (PVA) gel beads with a very low heparin release rate, prepared by acetal coupling of the heparin to the PVA, adsorbed thrombin and potentiated the inactivation of thrombin by antithrombin 111, as measured by both thrombin time and chromogenic substrate assays. 

Figure 9.27 Controlled release activated by cellular infiltration and enzyme activity. Adapted from [93], The gel consists of a fibrin base with covalently bound bidomain peptides. The peptide has a domain that confers heparin binding and a domain that is susceptible to enzymatic degradation. The agent for release is a growth factor that binds with high affinity to heparin. Release is initiated by cellular invasion of the gel and local secretion of an enzyme that cleaves the peptide.

Myocardial LPL activity was estimated in post-heparin perfusate ( heparin-releasable ) and in acetone/ether-dried ground tissue powders ( residual-tissue ) by using a H-labelled triolein substrate emulsion and counting radioactivity in evolved fatty acids extracted in methanol/chloroform/heptane. ... 

Hal, physiologically active) and tissue-residual (nascent) components and compared to NEFA-perfused hearts (Fig. 3). Total (heparin-releasable -l- tissue-residual) LPL activity was significantly increased in VLDL-perfused hearts compared to hearts perfused with NEFA (1.1 mM oleate) under identical conditions perfusion with endotoxic VLDL (VLDL-LPS) increased the proportion of the enzyme present at the endothelium (i.e. heparin-releasable) whilst decreasing the amount of residual enzyme in the tissue (i.e. causing translocation of the enzyme from intracellular to endothelial site) (Fig. 3). 

Anderson, L.G., Carroll, R., Ewart, HS., Achatya, A. Severson, D.L. (1997) Am-J-Physiol, 273, E759-E767. Eatty acids reduce heparin-releasable LPL activity in cultured cardiomyocytes from rat heart. 

FIGURE 6.29 Autoregulation of heparin release from a thrombin-sensitive biore-sponsive hydrogel, (a) Thrombin formation, (b) Responsive heparin release, (c) Heparin-catalyzed thrombin inhibition, (d) No further heparin release. Source Maitz et al. [115]. Reproduced with permission of Nature Publishing Group. 

Park, Y., M.W. Pariza. Lipoxygenase Inhibitors Inhibit Heparin-Releasable Lipoprotein Lipase Activity in 3T3-L1 Adipocytes and Enhance Body Eat Reduction in Mice by Conjugated Linoleic Acid. Biochim. Biophys. Acta 1534 27—33 (2001). 

Heparin Release increases with charge ratios starting at z (Heparin)/ z (DNA) > 25 No release for z (Heparin)/ z (DNA) < 250, larger ratios not tested... 

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