Heparinized surfaces

However, in spite of the significant diversity in the quantitative evaluation of platelet adhesion, the platelets adhered onto heparinized surfaces are neither aggregated nor activated 4-78>. In other words, the intracellular contents of the adhered platelets, which may otherwise contribute to the blood clotting process, is not evolved into the bloodstream. This conclusion is verified by the results of Table 12, which indicate that the increased platelet adhesion does not result in a worse thrombo-resistance the blood clotting time at a HCP surface is an order of magnitude higher than that at the surface of the initial non-heparinized polymer. 

Attempts to develop more stable and more satisfactory heparin surfaces on various polymers. 

Heparin can be attached to a variety of surfaces by means of complex formation with quaternary ammonium salts. Depending on the method used to attach heparin, the resulting surfaces may or may not release heparin when contacted with blood plasma. The removal of heparin from surfaces by plasma protein fractions was studied and it was found that alpha-globulins removed greater amounts than any other fraction. Heparinized surfaces adsorb proteins when exposed to blood or plasma. However, with the possible exception of thrombin, there is no consistent pattern of protein adsorption which can be related to their nonthrombogenicity. 

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... 

An important factor in the interaction of foreign surfaces with blood is the rapid adsorption of plasma proteins onto such surfaces when they are exposed to blood (4). For this reason the adsorption of radioactively tagged blood components on heparinized and unheparinized surfaces was measured. Proteins were dissolved in approximate physiological concentrations in a buffered (pH 7.35) physiological saline solution and the solutions were exposed to the test surfaces for 2 hours at 37 °C. in a static system. After the exposure, the surfaces were rinsed with physiological saline and distilled water and then dried. The amount of protein on the surfaces was determined in a 27r-gas flow proportional counter (7). As shown in Table III, although both heparinized surfaces were nonthrombogenic, there is no consistent pattern of either increased or decreased adsorption of the proteins caused by the heparinization. In-... 

Table III. Ratio of Adsorption of Proteins on Heparinized Surface to Unheparinized Surface...

It has been shown that heparinized surfaces can be made which lose either no heparin or extremely small amounts of heparin upon exposure to plasma. These surfaces adsorb proteins and with the exception of thrombin, there is no consistent pattern of protein adsorption which can be related to their nonthrombogenicity. 

Heparin-like copolymers containing up to 100 units of sulfonated glucose or lactose have been prepared by polymerizing with acrylamide using arenediazonium salts with cyanate anions to form a thrombo-resistant heparinized surface. 

While a biologically active surface performs well based on the specific biological reaction, it is a highly perturbable surface tailored for the specific reaction that could, in principle, cause other biological reactions. For instance, a heparinized surface seems to increase hemolysis (breakdown of red blood cells). When the biologically active agents wear out, the surface of the treated material returns to the untreated surface, which required the surface modification to be blood compatible in the first place. 

Austen, W. G., Protein-Platelet Interaction on Heparinized Surfaces, J. Biomed. Mater. Res. (1969) 3, 69. 

Heparinized surfaces must leach heparin to be nonthrombogenic. (General corollary Immobilized antithrombogenic drugs are ineffective unless they leach into the flowing blood.)... 

Heparinized surfaces that bind antithrombin III do not need to leach heparin to be nonthrombogenic. 

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. 

These results indicate that, under partial derivatization, the chemical nature of the derivatized end group is not critical to anticoagulant activity within the limited number of derivatizing agents tested however, the degree of derivatization is critical. Furthermore, both carboxylic and hydroxyl heparin groups can be utilized in heparin surface coupling reactions. 

Although patients with pseudoexfoliation syndrome generally showed higher blood-aqueous barrier permeability than the control subjects, the patients implanted with heparin surface-modified intraocular lenses showed decreased permeability compared with the control subjects after surgery (95). Correspondingly, eyes with exfoliation syndrome exhibited a reduced incidence of posterior capsule opacification after implantation of heparin surface-modified intraocular lenses (96). 

Heparin surface modification and heparin treatments of lenses may reduce the incidence of postoperative endophthalmitis and intraocular inflammation. Significantly fewer Staphylococcus epidermidis attached to heparin surface-modified intraocular lenses and to regular poly(methyl methacrylate) intraocular leuses treated with heparin than to untreated poly(methyl methacrylate) intraocular lenses (104). When heparin was added to the medium, the numbers of Pseudomonas aeruginosa adhering to the contact lenses were significantly lower than those adhering to the control lenses (105). 

Ravalico G, Tognetto D, Baccara F. Heparin-surface-modified intraocular lens implantation in eyes with pseudoexfoliation syndrome. J Cataract Refract Surg 1994 20 543-549. 

Zetterstrom C. Incidence of posterior capsule opacification in eyes with exfoliation syndrome and heparin-surface-modified intraocular lenses. J Cataract Refract Surg 1993 19 344-347. 

Abu el-Asrar AM, Shibl AM, Tabbara KF, al-Kharashi SA. Heparin and heparin-surface-modification reduce Staphylococcus epidermidis adhesion to intraocular lenses. Int Ophthalmol 1997 21 71-74. 

Two additional application areas of surface graft copolymers include (1) the use of heparinized surfaces to reduce thrombosis in surgical implants, and (2) the use of immobilized enzymes as catalysts. 

Wettability, surface free energy, surface charge and compliance have been studied. Heparinized surfaces have exhibited considerable compatibility with blood. Typically, heparin is surface bound using cationic materials including tridodecyl methylammonium chloride, benzalkonium chloride, octadecylamine and quaternary ammonium polymers. Since polyelectrolyte complexes of heparin and chitosan have been prepared and exhibit either thrombogenic or non thrombogenic properties chitosan can be coated onto artificial polymeric supports and then reacted with heparin or with heparin-like substances... 

The catheters were inplanted for 30 min in carotid and femoral arteries. I-Fibrinogen was injected prior to implantation the radioactivity of the entire catheter and extruded thrombus was determined by y-ray spectrometry. Table I presents the data on chitosan--heparin coated polyethylene catheters. The tridodecyl methylammonium chloride-heparin surface performs poorly in comparison to the chitosan--heparin cyanoborohydride surface. 

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