Heparin Solution Research Articles

Collection of Heparinized Plasma by Plasmapheresis

Abstract Background and Objectives: Heparinized plasma can be used for exchange transfusions in neonates and is usually collected by drawing whole blood using heparin as anticoagulant. The heparinized red blood cells and buffy coat cannot be used and are therefore discarded. To collect heparinized plasma more efficiently, a method was developed using an apheresis machine. Materials and Methods: With an MCS3p apheresis machine (Haemonetics), plasma was collected from volunteer donors as anticoagulant, heparin in saline (30,000 IU/I) was added in a 1:9 ratio. The activated partial thromboplastin time (APTT) of the donors was measured before and immediately after the procedure, and various parameters were determined in the collected plasma. Results: In 2 collection cycles, an average of 456±52 ml (mean ± SD; n =20) of heparinized plasma was collected, and 504±57 ml (n=2; donors with a high hemoglobin level) when 3 cycles were performed. The leukocyte and platelet contamination in the plasma (n =2) was 1.11±0.92×106 and 0.05±0.22×109 per unit, respectively, which conformed to national specifications. Sodium levels were normal, but due to dilution of the plasma with heparin solution, potassium and calcium levels were about 20% lower than the serum levels in the donors. The donor APTT values were slightly longer after the procedure than before, but remained all within normal values. Conclusion: For the collection of heparinized plasma, apheresis has the advantage that (1) high‐quality heparinized plasma can be harvested; (2) no blood components need to be discarded; (3) more plasma can be harvested with each donation, and (4) these procedures can be performed more often than whole blood donations.

Prevention of Neoplastic Port Site Implants in Laparoscopy: An Experimental Study

Enthusiasm about the application of videolaparoscopy to oncologic diseases has been limited by the growing number of port site implants. Adult Wistar rats were submitted to 6-7 mm Hg carbonic gas pneumoperitoneum. Rats were randomly divided into two groups: group I rats with tumor (200,000 viable cells of Walker tumor) and group 11 rats with no tumor. The pneumoperitoneum was deflated after 30 min. Group I was further randomized into five groups: no treatment; or abdominal irrigation with saline, heparin, chemotherapy (doxorubicin), or chemotherapy associated with heparin. After a period lasting no more than 18 days, the abdominal wall and intraperitoneal organs macroscopically affected were studied histologically. Chemotherapy groups had no port site implants and were significantly different (p < 0.05) than the no treatment, saline, and heparin solution groups, which had incisional implants at frequencies of 100%, 85.7%, and 82.5%, respectively. Intraperitoneal irrigation with chemotherapy solution was effective in preventing incisional implants in this animal model.

Compatibility of tirofiban HCl with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride during simulated Y-site administration.

To study the compatibility of tirofiban HCl injection 0-05 mg/ml with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride infusion solutions during simulated Y-site administration. Tirofiban HCl, dopamine HCl, famotidine, lidocaine HCl and potassium chloride infusions were each prepared from their respective concentrates as per current clinical preparation instructions in both 0.9% sodium chloride and 5% dextrose solutions at both the minimum and maximum concentrations normally administered. Sodium heparin premixed infusion solutions in 5% dextrose and 0-45% sodium chloride were used as-is. Tirofiban HCl solutions were combined 1:1 (simulated Y-site administration) with the dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride solutions in separate glass containers and polyvinylchloride Y-site infusion lines. Samples were held for 4 h at room temperature under ambient fluorescent light and were assayed for changes in drug content, degradation, pH, appearance and turbidity. Activity of sodium heparin solutions was measured using an aPTT coagulation assay. All mixtures remained clear and colourless with no visual indication of instability, i.e. precipitation. Clarity of solutions was confirmed by turbidometric analysis. There was no significant loss of drug, increase in known degradates, or appearance of unknown drug-related peaks as determined by HPLC. The activity of heparin in heparin-containing solutions remained unchanged. The pH of all test-solutions remained constant. Tirofiban HCl injection 0.05 mg/ml can be co-infused by Y-site administration with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride injection solutions.

INVESTIGAÇÃO DO USO DE HEPARINIZAÇÃO REGIONAL DURANTE ISQUEMIA ARTERIAL TEMPORÁRIA EM COELHOS

O objetivo deste trabalho foi avaliar o efeito da heparinização regional durante a isquemia arterial temporária em coelhos. Os parâmetros avaliados foram a medida do tempo de tromboplastina parcial ativada (TTPa) e a presença ou ausência de trombos ou edema endotelial nos vasos estudados. Foram utilizados 40 coelhos Nova Zelândia, distribuídos em dois grupos de 20 animais. Após dissecção e reparo da artéria ilíaca esquerda, realizou uma arteriotomia e introduziu-se um cateter de polietileno para injeção de solução de heparina no grupo experimento ou de soro fisiológico no grupo controle. O TTPa foi medido no início do experimento e após 90 minutos de isquemia, não sendo encontrado diferenças significantes entre os valores iniciais e ao final do experimento. Na avaliação microscópica não foi encontrada a presença de trombos nos vasos dos animais de ambos os grupos. Em apenas um animal do grupo controle houve a ocorrência de espessamento intimal e desarranjo da camada média, interpretado como edema endotelial, porém este dado não foi significante. Concluiu-se que a injeção intra-arterial de heparina na dose de 60 UI/kg peso não provocou alterações significantes na coagulação sistêmica do coelho, e que na ausência de lesão endotelial não ocorreu trombose dos vasos estudados, com ou sem a utilização de heparina.

Contaminated lithium heparin bottles as a source of pseudobacteraemia due to Pseudomonas fluorescens

Pseudobacteraemia might be responsible for up to 50% of all positive blood cultures and its early recognition is important in order to avoid unnecessary treatment with antibiotics and delay in the search for the true cause of the fever. We describe pseudobacteraemia outbreak of Pseudomonas fluorescens related to contaminated lithium heparin bottles in a paediatric ward. Twelve patients were involved in this outbreak from December 1996–January 1997. All patients had no clinical evidence of sepsis, nevertheless most children were treated with antibiotics. Blood collection bottles were suspected as source of pseudobacteraemia and only lithium heparin bottles were found to be contaminated with P. fluorescencs indistinguishable from the blood isolates taken from these children. Withdrawal of these bottles led to the termination of the pseudobacteraemia. Following discussion with the manufacturer, the contaminated batch of lithium heparin bottles was sent back for testing, and replaced with bottles containing dried lithium heparin. A hazard report was sent to the Medical Devices Agency (MDA). In order to minimize the possibility of this problem occurring again, the manufacturer has informed MDA that all lithium heparin solution is to be filtered to 0·2 microns prior to issue, in order to minimize bacterial contamination. Continued monitoring after the pseudobacteraemia showed no isolates of P. fluorescens from the blood of paediatric patients.

Novel system for real-time ex vivo lactate monitoring in human whole blood

The objective of the study was to evaluate the performance of an amperometric enzyme based lactate sensor and to investigate the possibility of replacing a double lumen catheter based blood withdrawal system with a heparin coated single lumen system. The inner lumen of a double lumen catheter which was placed in a peripheral vein was perfused with heparin solution. The outer lumen was used to collect heparinized blood samples at a defined flow rate. The single lumen system was attached to a heparinized catheter which was also placed in a peripheral vein. The undiluted blood samples were collected at a specified flow rate. A sensor flow chamber incorporating an amperometric thin-film lactate microbiosensor was placed in the sampling line for real-time lactate monitoring. Plasma lactate concentrations were measured during frequently performed hyperlactatemia bicycle ergometer experiments in six healthy volunteers (age 25.8±2.8 years, BMI 22.7±1 kg/m 2). Additionally, plasma lactate was measured in real-time using the lactate sensors. The first three experiments were performed with a double lumen based catheter system whereas the following three experiments were performed with a heparin coated catheter system. The correlation coefficients of sensor readings and laboratory analyzer results in all six experiments were between 0.93 and 0.99, respectively ( P<0.001). The miniaturized lactate sensors showed a linear range up to 25 mmol/l lactate concentration and 95% response times <30 s in undiluted serum. During the experiments maximum lactate concentrations of 14 mmol/l were achieved. Improvements of system performance using heparin coated catheter systems could be shown. The overall SD of the sensor readings compared to laboratory results using three double lumen catheter based systems was 0.91 mmol/l whereas the SD using three heparin coated systems was 0.65 mmol/l. In summary, real-time monitoring of lactate in human whole blood is feasible with such a device and can be improved by using heparin coated catheter systems.

Heparin immobilized on proteins usable for arterial prosthesis coating: growth inhibition of smooth-muscle cells.

Gelatin or a mixture of albumin and gelatin has been proposed for the coating of vascular grafts according to their surface thrombogenicity and biocompatibility, and the possibility of biodegradation. Heparin treatment of hemocompatible surfaces improved the patency of prostheses. In this study, different amounts of heparin were immobilized on these protein gels using a water-soluble carbodiimide [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide]. The results showed a coupling of heparin with gelatin and/or albumin at the surface of the gels, stable for as long as 1 month. From 0.20 to 3.60 microg x cm(-2), heparin could be immobilized. The antiproliferative activity of immobilized heparin was controlled toward bovine smooth-muscle cells grown on these gels. Cell growth inhibition was dose dependent, but the percentages of inhibition were lower at day 8 than at day 4 at any heparin concentration used under experimental conditions. Referring to heparin in solution, immobilized heparin displayed an antiproliferative activity that improved the potential interest for coating.

Studies of Adsorption, Activation, and Inhibition of Factor XII on Immobilized Heparin

The aim of the present investigation was to clarify whether immobilized heparin does, as previously suggested, prevent triggering of the plasma contact activation system. Purified FXII in the absence or presence of antithrombin and/or C1 esterase inhibitor as well as plasma was exposed for 1 to 600 seconds to a surface modified by end-point immobilization of heparin. With purified reagents, a process including surface adsorption and activation of FXII occurred within 1 second. In the presence of antithrombin, the resulting surface-bound α-FXIIa was inhibited within that time. Likewise, the adsorption of native FXII from plasma was a rapid process. However, the inhibition of surface-bound α-FXIIa was slightly slower than with purified components. Nevertheless, neither β-FXIIa nor FXIa were found in the plasma phase. Exposure of a surface prepared from heparin molecules, lacking antithrombin binding properties, to plasma resulted in surface-bound α-FXIIa within 1 second. In the liquid phase, β-FXIIa was detected after 2.5 seconds and, 12 seconds later, FXIIa and FXIa in complex with the C1 esterase inhibitor appeared. Addition of heparin to plasma prior to surface exposure did not prevent activation of surface-bound FXII, nor did it increase the β-FXIIa inhibition rate and prevent FXI activation in plasma, although β-FXIIa and FXIa-AT complex formation occurred. It is concluded that surface-immobilized heparin, unlike heparin in solution, effectively inhibits the initial contact activation enzymes by an antithrombin-mediated mechanism, thereby suppressing the triggering of the intrinsic plasma coagulation pathway.

INHIBITION OF PLATELET DEPOSITION WITH LOCAL DELIVERY OF HEPARIN USING A DOUBLE BALLOON CATHETER

Heparin is an effective agent in the treatment of unstable angina and myocardial infarction. The clinical utility of heparin is limited by bleeding complications. This study was performed to determine whether static delivery of heparin could effectively inhibit further platelet deposition. Thrombogenic graft segments were incorporated into chronic arteriovenous shunts in pigs. Autologous platelets were labeled with 111Indium. Platelet deposition was quantitated with gamma camera imaging. The grafts were exposed to blood flow for 15 min in order to induce platelet deposition on the thrombogenic surface. Heparin was delivered locally either by direct exposure or with a double balloon catheter. After a 15 minute exposure period, the heparin solution was removed and subsequent platelet deposition was monitored for 90 minutes. Heparin, administered with the double balloon catheter in doses as low as 12.5 U, effectively inhibited further platelet deposition. An intravenous injection of 100 U of heparin, the highest dose use for local delivery, did not perturb bleeding time or the activated partial thromboplastin time. In conclusion, platelet deposition can be inhibited with static local delivery of heparin at doses that are not associated with systemic bleeding. © 1997 Elsevier Science Ltd

Vascular Endothelial Growth Factor Enhances Vascularization in Microporous Small Caliber Polyurethane Grafts

Neoarterial regeneration in an implanted small caliber vascular prosthesis is complexly controlled by many structural and biologic factors, such as cytokines. The authors designed an artificial graft, which was prepared as follows. Segmented polyurethane tubular film (inner diameter, 1.5 mm; wall thickness, 100 μ; length, 20 mm), in which micropores (pore size, 100 μ) were fabricated by an excimer laser ablation technique, were coated with a mixed solution of photore-active gelatin and heparin with or without cytokines (vascular endothelial growth factor [VEGF]: 5 or 50 μg/ml, basic fibro-blast growth factor [bFGF]: 1 μg/ml). These coated grafts were irradiated by ultraviolet light, and were implanted in aortas of rats for 4 weeks; the VEGF (5 μg/ml) group, n = 6; the bFGF group, n = 6; the VEGF (5 μg/ml)/bFGF group, n = 11; the VEGF (50 μg/ml)/bFGF group, n = 5; and the control group, n = 9. Control grafts were treated without cytokines. Endothelial coverage was greater for the cytokine immobilized groups (50–60%) than for the control group (30%). At the midportion of the triple VEGF immobilized group, many capillaries were seen in the neoarterial intima, and in the micropores, although such capillaries were rarely observed in the bFGF and control groups. Thus, impregnation of VEGF in the gelatinous layer of grafts enhanced transanastomotic tissue ingrowth and transmural capillary ingrowth. ASAIO Journal 1997; 43:M330-M534.

Efficacy of normal saline solution versus heparin solution for maintaining patency of peripheral intravenous catheters in children

Objectives Literature reports support the use of normal saline solution for maintaining patency of peripheral intermittent intravenous infusion devices (PIID) in the adult population; however, there are limited data regarding this policy in the pediatric population. The purpose of this study was to establish the effects of heparin flush and saline solution flush solutions in maintaining patency of infusion devices in the pediatric population, and to establish cost-saving implications related to both procedures. The specific aims of the study included the following: (1) to determine the efficacy of normal saline solution flush for peripheral IV access devices for the pediatric population, and (2) to establish cost-saving implications related to normal saline solution versus heparin flush for PIIDs in terms of pharmacy costs and costs related to nursing time. Methods The study was a prospective, randomized, doubleblind controlled trial of flushing solutions. The control group ( n = 77) received 3 ml of a 10 units heparin/ml normal saline solution IV flush. The experimental group ( n = 73) received 3 ml of normal saline solution only for the IV flush. Routine hospital procedure for flushing was followed during the study period. Results Descriptive and correlation statistics were used to analyze the data; ξ 2, t test, and analysis of variance were calculated. There were no significant differences between the two groups for demographics or complications. Annual cost savings were computed for both procedures with an estimated annual savings of nursing time and unit cost of solutions equaling $27,594. The savings per procedure was estimated at $9.45. Discussion This study provided support for the efficacy of normal saline solution as an alternative to heparin solutions for the maintenance of peripheral IV devices. Implications include elimination of risks associated with heparin (drug incompatibilities, thrombosis syndrome, hypersensitivity reactions, local tissue damage, and iatrogenic hemorrhage); decreased potential for infection associated with breaks in the integrity of the IV system; substantial money savings as a result of the change to normal saline solution realized by the patient and the institution; and decreased nursing time. By simplifying the procedure, nurses have more time to provide aspects of nursing care to patients.

Local drug delivery with porous balloons in the rabbit: assessment of vascular injury for an improvement of application parameters.

Sufficient intramural drug concentrations with the use of porous balloon catheters can be achieved with additional vascular trauma only. However, effective delivery of a potent drug even in deeper layers of the vessel wall might outweigh these traumatic side effects. Given the porous balloon catheter, the parameters of injection pressure and applied fluid volume will influence the interventional result. We tested a 2.5-mm porous balloon (35 75-micron pores) in the right carotid artery of New Zealand rabbits and used injection pressures of 1, 2, and 5 atm and fluid volumes of 2 and 4 ml of low-molecular-weight heparin solution in combination with the different parameters (n = 5 animals/group). In 50 rabbits, an intimal fibromuscular plaque was induced by using the electrostimulation model. Balloon dilatation and then application of the porous balloon was performed in 30 animals, 10 animals were only electrostimulated, and 10 animals served as a control group with balloon dilatation only. The vessels were excised 7 d after intervention, stained, and analyzed histomorpologically. Anti-Xa assays revealed the extent of systemically escaped drug, and serial cuts allowed for exact determination of vessel wall injuries. Effective local drug delivery could not be achieved with an injection pressure of less than 2 atm. Specific pressure-driven effects such as jet injuries could be identified. When the pressure was high enough for disruptive drug delivery (> or = 2 atm), fluid volumes of 4 ml led to loose elastic membranes and local thickening within the media. Sufficient intramural drug distribution using porous balloon catheters can be achieved with low injection pressures. Different fluid volumes strongly determine the extent of additional vascular injury.

Local drug delivery with porous balloons in the rabbit: Assessment of vascular injury for an improvement of application parameters

Objectives: Sufficient intramural drug concentrations with the use of porous balloon catheters can be achieved with additional vascular trauma only. However, effective delivery of a potent drug even in deeper layers of the vessel wall might outweigh these traumatic side effects. Given the porous balloon catheter, the parameters of injection pressure and applied fluid volume will influence the interventional result. Methods We tested a 2.5-mm porous balloon (35 75-μm pores) in the right carotid artery of New Zealand rabbits and used injection pressures of 1, 2, and 5 atm and fluid volumes of 2 and 4 ml of low-molecular-weight heparin solution in combination with the different parameters (n = 5 animals/group). In 50 rabbits, an intimal fibromuscular plaque was induced by using the electrostimulation model. Balloon dilatation and then application of the porous balloon was performed in 30 animals, 10 animals were only electrostimulated, and 10 animals served as a control group with balloon dilatation only. The vessels were excised 7 d after intervention, stained, and analyzed histomorpologically. Anti-Xa assays revealed the extent of systemically escaped drug, and serial cuts allowed for exact determination of vessel wall injuries. Results Effective local drug delivery could not be achieved with an injection pressure of less than 2 atm. Specific pressure-driven effects such as jet injuries could be identified. When the pressure was high enough for disruptive drug delivery (≥2 atm), fluid volumes of 4 ml led to loose elastic membranes and local thickening within the media. Conclusions Sufficient intramural drug distribution using porous balloon catheters can be achieved with low injection pressures. Different fluid volumes strongly determine the extent of additional vascular injury. Cathet. Cardiovasc. Diagn. 41:308–314, 1997. © 1997 Wiley-Liss, Inc.

DNA binding characteristics of CrtJ. A redox-responding repressor of bacteriochlorophyll, carotenoid, and light harvesting-II gene expression in Rhodobacter capsulatus.

Previous genetic analysis indicated that the photosynthesis gene cluster from Rhodobacter capsulatus coded for the transcription factor, CrtJ, that is responsible for aerobic repression of bacteriochlorophyll, carotenoid, and light harvesting-II gene expression. In this study, we have heterologously overexpressed and purified CrtJ to homogeneity and shown by gel mobility shift assays that CrtJ is biologically active. DNase I footprint analysis confirms molecular genetic studies by showing that CrtJ binds to conserved palindromic sequences that overlap the -10 and -35 promoter regions of the bchC operon. Graphs of the percentage of DNA bound versus protein concentration show sigmoidal curves, which is highly indicative of cooperative binding of CrtJ to the two palindromic sites. A binding constant for interaction of CrtJ with the palindrome that spans the -10 region was calculated to be 4.8 x 10(-9) M, whereas affinity for the palindrome that spans the -35 region was found to be 2.9 x 10(-9) M. Binding of CrtJ to the bchC promoter region was also found to be redox-sensitive, with CrtJ exhibiting a 4.5-fold higher binding affinity under oxidizing versus reducing conditions.

Heparin coating of human breast carcinoma cells in vivo

Mast cells, the only source of heparin in the body, are common in breast carcinoma. Due to metachromatic staining of heparin-proteoglycans released from the mast cells toluidine blue may stain connective tissue a reddish-purple. This study shows that tumour cells in the vicinity may also be coated with metachromatic substance. Such bl vivo coating does not appear to have been reported previously. In experimental studies in vitro coating has been described following suspension of mouse tumour cells in a heparin solution and preincubation of ascitic tumour cells in heparin has given reduction in survival time after transplantation. In human breast carcinoma stromal metachromasia may under certain circumstances be indicative of poor prognosis. The biological implications of in vivo tumour cell coating with heparin are under investigation.

VASCULAR ENDOTHELIAL GROWTH FACTOR ENHANCES VASCULARIZATION IN MICROPOROUS SMALL-CALIBER POLYURETHANE GRAFTS

Neoarterial regeneration in an implanted small caliber vascular prosthesis is complexly controlled by many structural and biologic factors, such as cytokines. The authors designed an artificial graft, which was prepared as follows. Segmented polyurethane tubular film (inner diameter, 1.5 mm; wall thickness, 100 microns; length, 20 mm), in which micropores (pore size, 100 microns) were fabricated by an excimer laser ablation technique, were coated with a mixed solution of photoreactive gelatin and heparin with or without cytokines (vascular endothelial growth factor [VEGF]: 5 or 50 micrograms/ml, basic fibroblast growth factor [bFGF]: 1 microgram/ml). These coated grafts were irradiated by ultraviolet light, and were implanted in aortas of rats for 4 weeks; the VEGF (5 micrograms/ml) group, n = 6; the bFGF group, n = 6; the VEGF (5 micrograms/ml)/bFGF group, n = 11; the VEGF (50 micrograms/ml)/bFGF group, n = 5; and the control group, n = 9. Control grafts were treated without cytokines. Endothelial coverage was greater for the cytokine immobilized groups (approximately equal to 50-60%) than for the control group (approximately equal to 30%). At the midportion of the triple VEGF immobilized group, many capillaries were seen in the neoarterial intima, and in the micropores, although such capillaries were rarely observed in the bFGF and control groups. Thus, impregnation of VEGF in the gelatinous layer of grafts enhanced transanastomotic tissue ingrowth and transmural capillary ingrowth.

Formulation of a flush solution of heparin, vancomycin, and colistin for implantable access systems in oncology

Introduction: Because of the increased use of im plantable access systems, the incidence of blood stream and catheter infections associated with these systems has concomitantly increased. Classically, he parin-lock flush solutions were used to prevent thrombosis; more recently, vancomycin was added to the solution to prevent infections caused by Gram- positive bacteria, particularly coagulase-negative Staphylococci. Disorders due to Gram-negative organ isms have now appeared in oncologic patients. We therefore tested the addition of colistin to heparin- vancomycin solutions. Colistin was chosen for its good activity against Gram-negative bacteria (98% susceptibility in our hospital), its good tolerance due to low systemic passage, and its low cost. Methods: We developed formulations contain ing heparin (100 IU/mL) and various concentrations of vancomycin (10-500 μg/mL) and colistin (10-100 μg/mL) in 0.9% NaCl. Each sterile solution was tested for physical and chemical compatibility (spectropho tometry, nuclear magnetic resonance, and pH mea surements) and its antibacterial activity (against ox acillin-resistant Staphylococcus aureus, Enterococcus faecium, Klebsiella pneumoniae exhibiting broad- spectrum betalactamase (BSBL), imipenem-resistant Pseudomonas aeruginosa) for 2 months at 4°C and at room temperature. Results: The most suitable combination of drugs is heparin (100 IU/mL), vancomycin (100 μg/mL), and colistin (100 μg/mL). This flush solution main tains activity when stored at 4°C for up to 1 month. Conclusions: We feel that the combination of heparin, vancomycin, and colistin can be used as a flush solution for indwelling catheters.

Perioperative antibiotic, steroid, and nonsteroidal anti-inflammatory agents in cataract intraocular lens surgery

Ophthalmologists continue to choose topical antibiotics and corticosteroids more frequently than injectable agents for their current cataract surgical techniques. The preoperative use of povidone-iodine 5% and the postoperative use of impregnated soft contact lenses have helped augment our therapeutic armamentarium. NSAIDs play an important role in decreasing postoperative convalescence with fewer side effects. The intracameral administration of heparin and antibiotic solutions is discussed.

A randomized clinical trial of oxidized regenerated cellulose adhesion barrier (Interceed, TC7) alone or in combination with heparint

To compare the efficacy of heparin-saturated oxidized regenerated cellulose absorbable adhesion barrier, Interceed (TC7; Johnson and Johnson Medical Inc., New Brunswick, NJ) to oxidized regenerated cellulose alone for the prevention of postoperative adhesions. Clinical trial. By random assignment, one ovary was wrapped in oxidized regenerated cellulose, and the contralateral ovary was wrapped in oxidized regenerated cellulose saturated with a heparin solution (1,000 U/mL). Forty women with defects on both ovaries due to adhesiolysis and/or ovarian cystectomy. Adhesion formation and raw ovarian surface area were assessed at second-look laparoscopy 10 days to 16 weeks later. At the second-look laparascopy-adhesions were present on 52.5% (21/40) of the ovaries treated with oxidized regenerated cellulose plus heparin and in 65% (26/40) of the contralateral ovaries treated with oxidized regenerated cellulose alone. For ovaries treated with oxidized regenerated cellulose plus heparin, the raw surface area was reduced from 9.41 +/- 1.27 cm2 (mean +/- SE) at laparotomy to 1.33 +/- 0.52 cm2 at second-look laparoscopy. The corresponding figures for ovaries treated with oxidized regenerated cellulose alone were from 10.24 +/- 1.08 to 1.92 +/- 0.54 cm2, respectively. The mean difference between the reductions in raw surface area (85.9% for oxidized regenerated cellulose plus heparin; 81.3% for oxidized regenerated cellulose alone) was not significantly different from zero (difference = - 0.24 cm2; 95% confidence interval = -2.56 to 3.04). Adding heparin did not enhance significantly the adhesion-reducing capacity of oxidized regenerated cellulose adhesion barrier when applied to ovarian surfaces after cystectomy and/or ovariolysis at laparotomy. This conclusion is subject to the possibility of a type II error.

Heparin-chitosan complexes stimulate wound healing in human skin.

The effect of heparin ionically linked to chitosan on the stimulation of re-epithelialisation of full thickness wounds in human skin was investigated in an in vitro model. After seven days of incubation, heparin-chitosan gel stimulated 9/10 of the full thickness wounds to re-epithelialise compared with only 3/10 of the wounds that were covered with chitosan gel or membrane, and none of the wounds incubated without gel or membrane or with heparin solution alone. Both dermal and epidermal cells were viable after the incubation time. Furthermore, the stimulatory effect of the heparin-chitosan complexes depended on the concentration of heparin in the complex. We hypothesise that these effects are caused by stabilisation and activation of growth factors that bind to immobilised heparin.