P T Cahalan

Ension, Pittsburgh, Pennsylvania, United States

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Publications (31)63.9 Total impact

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    ABSTRACT: Silicone and Dacron are used in a wide spectrum of implantable and indwelling medical products. They elicit a foreign body response, which results in a chronic inflammatory environment and collagenous encapsulation of the medical device that compromises the immune system's ability to effectively fight infections at the biomaterial surface. The objective of this work is to evaluate a novel process to modify silicone and Dacron with a bioactive collagen surface coupled to a gentamicin impregnated hydrogel graft and assess the surface's cytocompatibility and infection resistance properties. Samples of silicone and polyethylene terephthalate (Dacron velour) were modified by plasma deposition and activation followed by a co-polymer acrylic acid (AA)/acrylamide (AAm) hydrogel graft and covalent immobilization of a bioactive collagen surface. The modified surfaces were characterized using FTIR, contact angle, staining, SEM, and XPS. The poly (AA-AAm) hydrogel was impregnated with gentamicin and tested for controlled release characteristics. Each modified surface was evaluated for its ability to resist infection and to promote normal healing as measured by bacterial growth inhibition (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) in both broth and agar conditions as well as using fluorescence microscopy to observe adherence of 3T3-NIH fibroblasts. The addition of the poly (AA-AAm) hydrogel with gentamicin inhibited bacterial growth and the subsequent addition of the collagen surface promoted robust fibroblast adhesion on both silicone and Dacron materials. Thorough surface characterization and in vitro bacterial and fibroblast evaluation results suggest that this novel surface bioengineering process generated a highly effective surface on silicone and Dacron with the potential to reduce infection and promote healing.
    No preview · Article · Nov 2015 · Journal of Biomaterials Applications
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    ABSTRACT: Intravenous administration of heparin and heparin-bonded extracorporeal circuits are frequently used to mitigate the deleterious effects of blood contact with synthetic materials. The work described here utilized human blood in a micro-perfusion circuit to experimentally examine the effects of intravenous and surface-bound heparin on cellular activation. Activation markers of coagulation and of the inflammatory response were examined using flow cytometry; specifically, markers of platelet, monocyte, polymorphonuclear leukocyte (PMN), and lymphocyte activation were quantified. The results indicate that surface-bound heparin reduces the inflammatory response whereas systemically administered heparin does not. This finding has important implications for blood-contacting devices, particularly within the context of recently elucidated connections between inflammation pathways and coagulation disorders. Data presented indicate that surface-bound heparin and intravenously administered heparin play distinct, but vital roles in rendering biomaterial surfaces compatible with blood.
    Full-text · Article · Feb 2013 · Perfusion
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    ABSTRACT: The blood compatibility of materials and surfaces used for medical device fabrication is a crucial factor in their function and effectiveness. Expansion of device use into more sensitive and longer term applications warrants increasingly detailed evaluations of blood compatibility that reach beyond the customary measures mandated by regulatory requirements. A panel of tests that assess both deposition on the surface and activation of circulating blood in contact with the surface has been developed. Specifically, the ability of a surface to modulate the biological response of blood is assessed by measuring: (1) dynamic thrombin generation; (2) surface-bound thrombin activity after exposure to blood; (3) activation of monocytes, polymorphonuclear leukocytes, lymphocytes, and platelets; (4) activation of complement; and (5) adherent monocytes, polymorphonuclear leukocytes, lymphocytes, and platelets on blood-contacting surfaces. The tests were used to evaluate surfaces modified with immobilized heparin (Ension's proprietary bioactive surface) and demonstrated that the modified surfaces reduced platelet activation, leukocyte activation, and complement activation in flowing human blood. Perfusion of the surfaces with human platelet-rich plasma showed that the immobilized heparin surfaces also reduce both dynamic thrombin levels in the circulating plasma and residual thrombin generated at the material surface.
    Full-text · Article · Dec 2011 · Journal of Biomaterials Applications
  • P. Wearden · G. Johnson · P. Cahalan · M. Gartner

    No preview · Article · Apr 2011 · The Journal of Heart and Lung Transplantation
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    ABSTRACT: Collagen was covalently linked to the surface of Titanium (Ti) by a surface modification process involving deposition of a thin film from hydrocarbon plasma followed by acrylic acid grafting. The composition and properties of surface-modified Ti were investigated by a number of surface sensitive techniques: XPS, ATR-IR, atomic force microscopy and AFM force-separation curves. In vitro tests were performed to check samples cytotoxicity and the behavior of osteoblast-like SaOS-2 cells. In vivo experiments involved 12 weeks implants in rabbit muscle as general biocompatibility assessment and 1-month implants in rabbit bone to evaluate the effect of surface modification on osteointegration rate. Results of XPS measurements show how surface chemistry is affected throughout each step of the surface modification process, finally leading to a complete and homogeneous collagen overlayer on top of the Ti samples. AFM data clearly display the modification of the surface topography and of the surface area of the samples as a consequence of the grafting and coupling process. AFM force-distance curves show that the interfacial structure responds by shrinking or swelling to variations of ionic force of the surrounding aqueous environment, suggesting that the aqueous interface of the biochemically modified Ti samples has enhanced degrees of freedom as compared to the inorganic surface of plain Ti. As to biological evaluations, the biochemically modified Ti samples are safe in terms of cytotoxicity and in vivo biocompatibility assessment. SaOS-2 cells growth rate is lower on collagen modified surfaces, and no significant difference is detected in terms of alkaline phosphatase production as compared to control Ti. Importantly, implants in rabbit femur show a significant increase of bone growth and bone-to-implant contact in the case of the collagen modified samples, confirming that biochemical modifications of Ti surface can enhance the rate of bone healing as compared to plain Ti.
    Preview · Article · Dec 2003 · Biomaterials
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    ABSTRACT: Heparinization of artificial surfaces has been proven to reduce the intrinsic thrombogenicity of such surfaces. The mechanism by which immobilized heparin reduces thrombogenicity is not completely understood. In the present study heparin-, alginic acid- and chondroitin-6-sulphate-coated surfaces were examined for protein adsorption, platelet adhesion and thrombin generation. The protein-binding capacity from solutions of purified proteins was significantly higher for heparin-coated surfaces when compared with alginic acid- and chondroitin sulphate-coated surfaces. Yet, when the surfaces were exposed to flowing plasma, only the heparinized surface adsorbed significant amounts of antithrombin. None of the surfaces adsorbed fibrinogen under these conditions, and as a result no platelets adhered from flowing whole blood. Our results indicate that protein adsorption and platelet adhesion from anticoagulated blood cannot be used to assess the thrombogenicity of (coated) artificial surfaces. Indeed, the thrombin generation potentials of the different surfaces varied remarkable: while non-coated surface readily produced thrombin, alginic acid- and chondroitin sulphate-coated surfaces showed a marked reduction and virtually no thrombin was generated in flowing whole blood passing by heparinized surfaces.
    Preview · Article · Jun 2003 · Biomaterials
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    ABSTRACT: The foreign body reactions to collagen-immobilized polyurethane (PU-CI) films during subcutaneous implantation in rats were characterized. The underlying concept is that collagen-immobilization will improve the tissue integration. Since the method of collagen-immobilization involves the covalent coupling of collagen to an acrylic acid (AA) based surface graft, both non-modified PU and PU-AA were used as controls. Bare PU has a flat surface, whereas both PU-AA and PU-CI displayed a slightly roughened surface. Implantation showed that PU-CI induced early after implantation a far more intense foreign body reaction than PU and PU-AA. This reaction consisted of increased presence of fibrin, granulocytes and macrophages. Roughening of the surface as with PU-AA induced only a small increase in fibrin formation and cellular migration. At day 5 the reaction to PU-CI had slowed down; giant cell formation now slowly started but was decreased compared to PU and PU-AA. At day 10 capsules around each type of material looked similar, but in contrast to PU. PU-CI films could no longer be dissected from their capsules. Only at week 3 this also occurred with PU, at which time point again similar capsules with the three materials were observed. At week 6, of the three materials PU-CI showed the thinnest capsule with most immediate adherence of connective tissue. These results show that collagen-immobilization of PU increased the early tissue reaction and therefore the tissue integration. The thin capsule observed at 6 weeks may be beneficial in e.g. infectious circumstances, when easy access for immune reactions is needed. This, and the long-term performance of PU-CI will be a matter of future investigations.
    No preview · Article · Apr 2002 · Biomaterials
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    ABSTRACT: Calcification limits the long-term durability of xenograft glutaraldehyde (GA)-crosslinked heart valves. Previously, a study in rats showed that epoxy-crosslinked heart valves reduced lymphocyte reactions to the same extent as the GA-crosslinked control and induced a similar foreign-body response and calcification reaction. The present study was aimed at reducing the occurrence of calcification of epoxy-crosslinked tissue. Two modifications were carried out and their influence on cellular reactions and the extent of calcification after 8 weeks' implantation in weanling rats was evaluated. First, epoxy-crosslinked valves were post-treated with two detergents to remove cellular elements, phospholipids and small soluble proteins, known to act as nucleation sites for calcification. The second approach was to study the effect of the impaired balance between negatively and positively charged amino acids by an additional crosslinking step with a dicarboxylic acid. The detergent treatment resulted in a washed-out appearance of especially the cusp tissue. With the dicarboxylic acid, both the cusps and the walls had a limited washed-out appearance. The wall also demonstrated some detachment of the subendothelium. After implantation, both detergent and dicarboxylic acid post-treatment histologically resulted in reduced calcification at the edges of cusps and walls. However, total amounts of calcification, measured by atomic emission spectroscopy, were not significantly reduced. Data concerning the presence of lymphocytes varied slightly, but were in the same range as the GA-crosslinked control, i.e., clearly reduced compared with a noncrosslinked control. It is concluded that both the double detergent and the dicarboxylic acid post-treatment of epoxy-crosslinked heart valve tissue do not represent a sound alternative in the fabrication of heart valve bioprostheses.
    No preview · Article · Jul 2001 · Journal of Biomedical Materials Research
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    ABSTRACT: One of the most important problems with ICD systems is infection. The aim of this study was an in vivo evaluation of the efficacy of defibrillator systems in terms of infection resistance. The polyurethane leads were coupled with heparin and loaded with the antibiotic gentamicin, while the PGs were modified to release gentamicin. Group I was comprised of 10 pigs implanted with either a standard or a modified system for 2 weeks; group II was implanted during 4 weeks. The lead was inserted into the heart wall via the jugular vein. The other end was subcutaneously tunneled to the armpit where the PG was positioned. A cocktail of Staphylococcus aureus and epidermidis was injected at the site of the PG. Evaluation was performed macroscopically, by taking bacterial swabs during explantation and by microscopic processing. The results showed that 3 out of 5 modified defibrillator-systems in group I and 1-2 out of 5 in group II were judged as noninfected, whereas all standard systems were infected. Infection rates of the remaining modified defibrillators showed variances, as found with the standards, from slight to moderate to high, to even high/severe in group II (1x standard and 1x modified). With the modified systems, this may be related to production of humoral factors by an intensified early tissue reaction, as indicated by a swelling at day 6 at the site of the PG. When infected, whether or not modified, usually only Staphylococcus aureus was present. Spreading of infection seemed to occur by inoculation via blood, for example, based on the observation that group II in general showed an increase in infected fibrotic overgrowth in the heart, while infectious problems were low in the jugular vein. It is concluded that the modification at short term shows enhanced infection resistance. An increased infection rate already at 4 weeks, however, indicates that the modification may not hold in the long run. Special attention is needed concerning the more intense early tissue reaction.
    No preview · Article · Jan 2001 · Journal of Biomedical Materials Research
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    ABSTRACT: Dermal sheep collagen was crosslinked with 1,4-butanediol diglycidyl ether (BDDGE) or modified with glycidyl isopropyl ether (PGE). The reduction in amine groups as a function of time was followed to study the overall reaction kinetics of collagen with either BDDGE or PGE. Linearization of the experimental data resulted in a reaction order of 2 with respect to the amine groups in the PGE masking reaction, whereas a reaction order of 2.5 was obtained in the BDDGE crosslinking reaction. The reaction orders were independent of the pH in the range of 8.5-10.5 and the reagent concentration (1-4 wt %). The reaction order with respect to epoxide groups was equal to 1 for both reagents. As expected, the reaction rate was favored by a higher reagent concentration and a higher solution pH. Because the BDDGE crosslinking reaction occurs via two distinct reaction steps, the content of pendant epoxide groups in the collagen matrix was determined by treating the collagen with either O-phosphoryl ethanolamine or lysine methyl ester. The increase in either phosphor or primary amine groups was related to the content of pendant groups. Crosslinking at pH 9.0 resulted in a low reaction rate but in a high crosslink efficacy, especially after prolonged reaction times. A maximum concentration of pendant epoxide groups was detected after 50 h. Reaction at pH 10.0 was faster, but a lower crosslinking efficacy was obtained. At pH 10.0, the ratio between pendant epoxide groups and crosslinks was almost equal to 1 during the course of the crosslinking reaction.
    Full-text · Article · Oct 2000 · Journal of Biomedical Materials Research
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    ABSTRACT: Calcification limits the long-term durability of xenograft glutaraldehyde-crosslinked heart valves. In this study, epoxy-crosslinked porcine aortic valve tissue was evaluated after subcutaneous implantation in weanling rats. Non-crosslinked valves and valves crosslinked with glutaraldehyde or carbodiimide functioned as control. Epoxy-crosslinked valves had somewhat lower shrinkage temperatures than the crosslinked controls, and within the series also some macroscopic and microscopic differences were obvious. After 8 weeks implantation, cusps from non-crosslinked valves were not retrieved. The matching walls were more degraded than the epoxy- and control-crosslinked walls. This was observed from the higher cellular ingrowth with fibroblasts, macrophages, and giant cells. Furthermore, non-crosslinked walls showed highest numbers of lymphocytes, which were most obvious in the capsules. Epoxy- and control-crosslinked cusps and walls induced lower reactions. Calcification, measured by von Kossa-staining and by Ca-analysis, was always observed. Crosslinked cusps calcified more than walls. Of all wall samples, the non-crosslinked walls showed the highest calcification. It is concluded that epoxy-crosslinked valve tissue induced a foreign body and calcification reaction similar to the two crosslinked controls. Therefore, epoxy-crosslinking does not represent a solution for the calcification problem of heart valve bioprostheses. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 53: 18–27, 2000
    No preview · Article · Feb 2000 · Journal of Biomedical Materials Research
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    ABSTRACT: Calcification limits the long-term durability of xenograft glutaraldehyde-crosslinked heart valves. In this study, epoxy-crosslinked porcine aortic valve tissue was evaluated after subcutaneous implantation in weanling rats. Non-crosslinked valves and valves crosslinked with glutaraldehyde or carbodiimide functioned as control. Epoxy-crosslinked valves had somewhat lower shrinkage temperatures than the crosslinked controls, and within the series also some macroscopic and microscopic differences were obvious. After 8 weeks implantation, cusps from non-crosslinked valves were not retrieved. The matching walls were more degraded than the epoxy- and control-crosslinked walls. This was observed from the higher cellular ingrowth with fibroblasts, macrophages, and giant cells. Furthermore, non-crosslinked walls showed highest numbers of lymphocytes, which were most obvious in the capsules. Epoxy- and control-crosslinked cusps and walls induced lower reactions. Calcification, measured by von Kossa-staining and by Ca-analysis, was always observed. Crosslinked cusps calcified more than walls. Of all wall samples, the non-crosslinked walls showed the highest calcification. It is concluded that epoxy-crosslinked valve tissue induced a foreign body and calcification reaction similar to the two crosslinked controls. Therefore, epoxy-crosslinking does not represent a solution for the calcification problem of heart valve bioprostheses.
    No preview · Article · Feb 2000 · Journal of Biomedical Materials Research
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    ABSTRACT: Dermal sheep collagen (DSC), which was crosslinked with 1, 4-butanediol diglycidyl ether (BD) by using four different conditions, was characterized and its biocompatibility was evaluated after subcutaneous implantation in rats. Crosslinking at pH 9.0 (BD90) or with successive epoxy and carbodiimide steps (BD45EN) resulted in a large increase in the shrinkage temperature (T(s)) in combination with a clear reduction in amines. Crosslinking at pH 4.5 (BD45) increased the T(s) of the material but hardly reduced the number of amines. Acylation (BD45HAc) showed the largest reduction in amines in combination with the lowest T(s). An evaluation of the implants showed that BD45, BD90, and BD45EN were biocompatible. A high influx of polymorphonuclear cells and macrophages was observed for BD45HAc, but this subsided at day 5. At week 6 the BD45 had completely degraded and BD45HAc was remarkably reduced in size, while BD45EN showed a clear size reduction of the outer DSC bundles; BD90 showed none of these features. This agreed with the observed degree of macrophage accumulation and giant cell formation. None of the materials calcified. For the purpose of soft tissue replacement, BD90 was defined as the material of choice because it combined biocompatibility, low cellular ingrowth, low biodegradation, and the absence of calcification with fibroblast ingrowth and new collagen formation.
    Full-text · Article · Dec 1999 · Journal of Biomedical Materials Research
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    ABSTRACT: Crosslinking of dermal sheep collagen (DSC) was accomplished using 1, 4-butanediol diglycidyl ether (BDDGE). At pH values > 8.0, epoxide groups of BDDGE will react with amine groups of collagen. The effects of BDDGE concentration, pH, time, and temperature were studied. Utilization of a 4-wt % BDDGE instead of 1-wt % resulted in a faster reaction. Whereas similar values of shrinkage temperature were obtained, fewer primary amine groups had reacted at a lower BDDGE concentration, which implies that the crosslinking reaction had a higher efficacy. An increase in pH from 8.5 to 10.5 resulted in a faster reaction but reduced crosslink efficacy. Furthermore, an increase in reaction temperature accelerated the reaction without changing the crosslink efficacy. Crosslinking under acidic conditions (pH < 6.0) evoked a reaction between epoxide groups and carboxylic acid groups of collagen. Additional studies showed that no oligomeric crosslinks could be formed. However, hydrolysis of the epoxide groups played a role in the crosslink mechanism especially under acidic reaction conditions. The macroscopic properties of these materials were dependent on the crosslinking method. Whereas a flexible and soft tissue was found if crosslinking was performed at pH < 6.0, a stiff sponge was obtained under alkaline conditions. Reaction of DSC with a monofunctional compound (glycidyl isopropyl ether) led to comparable trends in reaction rate and in similar macroscopical differences in materials as observed with BDDGE.
    Full-text · Article · Sep 1999 · Journal of Biomedical Materials Research
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    ABSTRACT: Cross-linking of dermal sheep collagen (N-DSC, T(S) = 46 degrees C, number of amine groups = 31 (n/1000)) with 1,4-butanediol diglycidyl ether (BDDGE) at pH 9.0 resulted in a material (BD90) with a high T(S)(69 degrees C), a decreased number of amine groups of 15 (n/1000) and a high resistance towards collagenase and pronase degradation. Reaction of DSC with BDDGE at pH 4.5 yielded a material (BD45) with a T(S) of 64 degrees C, hardly any reduction in amine groups and a lower stability towards enzymatic degradation as compared to BD90. The tensile strength of BD45 (9.2 MPa) was substantially improved as compared to N-DSC (2.4 MPa), whereas the elongation at break was reduced from 210 to 140%. BD90 had a tensile strength of 2.6 MPa and an elongation at break of only 93%. To improve the resistance to enzymes and to retain the favorable tensile properties, BD45 was post-treated with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) in the presence of N-hydroxysuccinimide (NHS) to give BD45EN. Additional cross-linking via the formation of amide bonds took place as indicated by the T(S) of 81 degrees C and the residual number of amine groups of 19 (n/1000). BD45EN was stable during exposure to both collagenase and pronase solutions. The tensile properties (tensile strength 7.2 MPa, elongation at break 100%) were comparable to those of BD45 and glutaraldehyde treated controls (G-DSC). Acylation of the residual amine groups of BD45 with acetic acid N-hydroxysuccinimide ester (HAc-NHS) yielded BD45HAc with a large reduction in amine groups to 10 (n/1000) and a small reduction in T(S) to 62 degrees C. The stability towards enzymatic degradation was reduced, but the tensile properties were comparable to BD45.
    Full-text · Article · Jun 1999 · Biomaterials
  • R Blezer · L Cahalan · P T Cahalan · T Lindhout
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    ABSTRACT: In the present study we used an in-vitro technique to examine initiation and propagation of blood coagulation at the surface of tantalum coronary stents exposed to flowing platelet-rich and platelet-free plasma. The time course of factor IXa production at the surface of the stent was not influenced by platelets. In spite of a significant factor IXa production, no thrombin activity was detected when the tantalum stent was exposed to platelet-free plasma; only when the stent was exposed to platelet-rich plasma was extensive thrombin production observed. These findings indicate that tantalum triggers blood coagulation, but that (adherent) platelets are essential for thrombin generation. Heparin-coated tantalum stents exposed to flowing platelet-rich plasma showed that factor IXa generation was slightly reduced compared with the bare stent. However, the heparin coating drastically delayed the onset of thrombin generation and largely reduced the steady-state production of thrombin. We found a clear relationship between the antithrombin binding capacity and the antithrombogenic potential of the heparin-coated stents. The mode of action of immobilized heparin is thought to abrogate thrombin generation by inhibiting thrombin-dependent positive feedback reactions at the surface of the coronary stent.
    No preview · Article · Aug 1998 · Blood Coagulation and Fibrinolysis
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    ABSTRACT: Tissue reactions to implantable pacemaker leads were investigated in an early infection model in rabbits. Both standard leads and surface-modified leads were used. The surface modification technique was applied to achieve controlled release of the antibiotic gentamicin. The insulating polyurethane tubing material of the leads was provided with an acrylic acid/acrylamide copolymer surface graft and then loaded with gentamicin. Implantation periods varied from day 4, to week 3 1/2, to week 10. We investigated tissue reactions in the absence of an infectious challenge and also the efficacy of surface-modified leads in preventing infection after challenge with Staphylococcus aureus was evaluated. It was demonstrated that the applied surface modification did not induce adverse effects although during early postimplantation an increase in infiltration of granulocytes and macrophages and wound fluid and fibrin deposition were observed. After bacterial challenge, standard leads were heavily infected at each explantation period, denoted by abscesses, cellular debris, and bacterial colonies. In contrast, little or no infection was observed, either macroscopically or by bacterial cultures, with the surface-modified leads. Microscopy showed little evidence of the bacterial challenge, and that primarily at day 4. It was concluded that the applied surface modification demonstrated enhanced infection resistance and thus represents a sound approach to the battle against infectious complications with biomaterials.
    No preview · Article · Aug 1998 · Journal of Biomedical Materials Research
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    ABSTRACT: In this study the intrinsic thrombogenicity of the extracorporeal circuits and the benefit of heparin-bonded circuits in an extracorporeal life support system without full systemic heparinization and with minimal interference of the so called material-independent factors was tested in four calves. In two circuits (group A) all blood-contacting surfaces were coated with end-point-attached heparin and the other two were non-coated (group B). Under standardized conditions the calves were perfused at a blood flow rate of 2 L/min. After only one bolus injection of heparin (250 IU/kg body weight) before cannulation, plasma heparin activity rapidly decreased in both groups: half life of about 55 minutes. This decrease of the heparin activity was accompanied by a fall of the activated clotting time (ACT) level to baseline values. The experiments using a heparin-coated circuit, had a runtime of more than 360 minutes, whereas the experiments using a non-coated circuit had to be terminated after a runtime of 255 minutes, because massive fibrin formation was noticed in the circuit. This formation was accompanied by a rapid increase in the line pressure, measured just before the inlet of the oxygenator. The macroscopic inspections after terminating the experiments and rinsing the circuit showed a clean circuit in group A. The fibrinopeptide A (FPA) level increased faster during perfusion with the non-coated circuit than in the heparin coated circuit. Lung histopathological examinations of the lungs of the animals in group A showed no fibrin deposition, whereas most of the blood vessels of the lung preparations of the animals in group B were partially or completely occluded with fibrin. These results suggest that heparin-bonding greatly reduces the thrombogenicity of the extracorporeal circuit, and therefore it can reduce the need for systemic heparinization in an extracorporeal life support system.
    No preview · Article · Jun 1998 · The International journal of artificial organs
  • R Blezer · G M Willems · P T Cahalan · T Lindhout
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    ABSTRACT: We have made use of a novel flow reactor to study the initiation and propagation of the ex vivo blood coagulation processes at artificial surfaces. The flow reactor consisted of a primary glass or polymer capillary that is connected to a secondary glass capillary, which inner wall was coated with a phospholipid bilayer of 25 mol% dioleoylphosphatidylserine/75 mol% dioleoylphosphatidylcholine (DOPS/DOPC). Citrated platelet free plasma and a CaCl2 solution were delivered by syringe pumps and mixed just before the entrance of the flow reactor. The outflowing plasma was assayed for factor XIa, factor IXa, factor Xa and thrombin activity. Perfusion of recalcified plasma through a bare glass capillary resulted in a transient generation of fluid phase factor XIa. In contrast, factor IXa production increased slowly to attain a stable steady-state level. We established that surface-bound factor XIa was responsible for a continuous production of factor IXa. Factor IXa-induced generation of factor Xa and thrombin was only observed when contact activated plasma was subsequently perfused through a DOPS/DOPC-coated capillary, showing that propagation of the factor IXa trigger requires a procoagulant, phosphatidylserine-containing, phospholipid membrane. The negatively charged inner surface of a heparin-coated polyurethane capillary, generated like the glass capillary significant amounts of factor XIa and factor IXa when perfused with recalcified plasma. No differences were found between unfractionated heparin and heparin devoid of anticoagulant activity. Thus, it is concluded that contact activation and factor IXa generation in flowing plasma is not inhibited by immobilised anticoagulant active heparin. Consequently, factor IXa-dependent thrombin generation at a downstream located phospholipid membrane was similar, regardless the specific anticoagulant activity of immobilised heparin.
    No preview · Article · Mar 1998 · Thrombosis and Haemostasis
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    ABSTRACT: The effect of local gentamicin release through a vicinal collagen sponge or through preoperative solution-dipping of rat lead samples was investigated in an early-infection model. The efficacy of these methods and their effect on tissue response were determined. It was demonstrated that both methods of local gentamicin release suppress lead-related infectious complications as compared to the control lead, which showed a high presence of inflamed/infected tissues and bacterial growth at each explantation time point. The first day the vicinal collagen sponge was more effective in suppressing the infection than was the solution-dipped lead, probably because there is a faster and higher dose release of gentamicin from the sponge. However, continued implantation time revealed that gentamicin release from the solution-dipped lead was more effective than the sponge. This supports our hypothesis that the presence of lumina are decisive for bacterial growth and persistence of implant-related infections.
    No preview · Article · Jun 1997 · Journal of Biomedical Materials Research

Publication Stats

677 Citations
63.90 Total Impact Points

Institutions

  • 2011
    • Ension
      Pittsburgh, Pennsylvania, United States
  • 1996-2001
    • University of Groningen
      • Department of Medical Biology
      Groningen, Groningen, Netherlands
  • 1995
    • Case Western Reserve University
      • Institute of Pathology
      Cleveland, Ohio, United States
    • Maastricht University
      • Department of Biochemistry
      Maestricht, Limburg, Netherlands