Endoscopic application of hemostatic thrombin-gelatin matrix (FloSeal®) in anticoagulated pigs

Abstract

Flexible endoscopy is the method of choice for the diagnosis and therapy of upper gastrointestinal bleeding, but there are still problems during therapy of patients with coagulation disorders. FloSeal^® is a hemostatic matrix largely independent of the body's own clotting system. A newly developed endoscopic applicator for FloSeal^® was tested in a survival study on pigs with impaired clotting. In a total of eight pigs ulcerous lesions Forrest Ib were induced and the bleeding stopped by applying FloSeal^®. Thirty minutes before intervention six pigs were given full weight-adjusted heparinization or a maximum dose of ASS in advance. The Hb course was monitored over the next 48 hours and a postmortem examination was performed. In each case, FloSeal^® was successfully applied and all bleedings could be stopped. In both groups (except the control group) spontaneous extraintestinal bleeding occurred, but in only one case in the ASS group a gastrointestinal bleeding happened. The Hb course was stable in all other animals. FloSeal^® can also be used endoscopically using the applicator being presented here for the first time. It is suited for primary hemostasis of excavated sources of bleeding especially in situations where coagulation is impaired.     

Attachment and proliferation of fibroblast cells on polyetherurethane urea derivatives

Interactions of novel polyetherurethane urea derivatives with fibroblast cells as well as with plasma proteins were investigated. Fibronectin, which is a cell adhesion protein, was found to be very active in attaching fibroblast cells onto a heparinized polyetherurethane urea: its activity was found to be strongly dependent on the surface properties of the material. Fibronectin was easily adsorbed by the heparinized polyetherurethane urea, but the degree of its adsorption to the material in competition with other proteins was so low that cell attachment to polyetherurethane ureas was decreased by heparinization. Different degrees of cell attachment onto different materials due to different adsorptivities of plasma proteins were considered. Proliferation of fibroblast cells was suppressed on cationic polyetherurethane urea but unaffected on other derivatives of polyetherurethane urea. Since specific suppression of cell proliferation was not observed on the heparinized polyetherurethane urea, the latter material was expected to be useful as a long-term antithrombogenic material in vivo.     

Extracorporeal carbon dioxide removal performed with surface-heparinized equipment in patients with ARDS

To avoid the drawbacks of systemic anticoagulation during prolonged extracorporeal circulation in patients with adult respiratory distress syndrome (ARDS) a heparinization technique has been developed by which partially degraded heparin can be covalently end-point attached to the surface of the equipment constituting the extracorporeal circuit (Carmeda Bio-Active Surface, CBAS) thereby localizing the anticoagulatory effect. Since 1986 we have used extracorporeal circuits and membrane lungs coated with the CBAS for extracorporeal lung assistance (ECLA) in 14 patients suffering from ARDS. The patients were on ECLA for 3 to 55 days with a survival rate of 43%. Our experience so far is that by using equipment coated with CBAS it is possible to perform long-term extracorporeal circulation with a minimum of intravenously administered heparin, thus avoiding the risk of major coagulation defects.     

Assessment of biomaterials as components of a reciprocating dialyser during canine dialysis

A recently reported device, the sorbent suspension reciprocating dialyser (SSRD), was investigated for use as a test system for biocompatibility of dialyser components. The device is easy to assemble and operate, and allows minimal blood contact with foreign material outside of dialyser components. Its constant pressure/ variable flow rate operation allows quantification of degree of clotting of dialyser versus time. The effect of heparinization of the blood distribution gaskets (BDG) of the device on performance and dialyser lifetime was investigated. Heparin was bound to the surface of polyethylene gaskets by immersion in a solution of tridodecylmethylammonium chloride (TDMAC)-heparin complex for several hours. Gaskets were then assembled in an SSRD which was then used for experimental dialysis in dogs with AV shunts. Dialysers assembled using non-heparinized gaskets were used as controls. Blood coagulation tendency was quantified by the activated clotting time (ACT) and partial thromboplastin time (PTT), and these values correlated with the rate of clotting of the device. Heparinization of the gaskets resulted in the prevention of clotting in the dialyser until the final minutes of dialysis in all cases, in contrast to the constant decay of blood fill volume and evidence of clotting in the non-heparinized cases. However, dialyser lifetime was not significantly increased by gasket heparinization. At normal initial values of ACT (80–95 s) dialyser clotting occurred in 10–15 mia In tests with non-heparinized gaskets and systemically heparinized dogs, values obtained in the ACT test were observed to decrease during dialysis, indicating the disappearance of heparin from the blood. Both ACT and PTT tests show promise as predictors of dialyser lifetime.     

肝素化胶原/壳聚糖多孔支架的制备及其血管化的研究

本研究旨在构建一种能快速血管化的人工真皮替代物。用冻干法制备了胶原／壳聚糖多孔支架，并对其进行肝素化，观察此支架的结构特征、亲水性、体外降解性和组织相容性，同时将血管生成素引入到此支架，对复合有血管生成素的肝素化支架的体内血管化进行了初步研究。结果表明，肝素化胶原／壳聚糖多孔支架具有合适的三维多孔结构、良好的吸水性和较理想的酶解稳定性，体内实验表明，此支架具有良好的组织相容性，血管生成素可加快支架的血管化。     

急性ST段抬高型心肌梗死患者提前肝素化的疗效评价及风险观察

目的探讨急性ST段抬高型心肌梗死(STEMI)患者提前肝素化的疗效及风险。方法选取2019年5月至2020年5月我院收治的160例STEMI患者作为研究对象,随机分为两组各80例。治疗组给予提前肝素化PCI术治疗,对照组给予常规肝素化PCI术治疗。比较两组的TIMI血流分级、不良事件发生率以及治疗前后的症状评分、 LVEF。结果术后,治疗组的TIMI血流0~1级率低于对照组,3级率高于对照组(P <0.05)。治疗后,两组的症状评分均低于治疗前,LVEF水平均高于治疗前(P<0.05);治疗组的症状评分低于对照组,LVEF水平高于对照组(P <0.05)。治疗组的不良事件发生率低于对照组(P <0.05)。结论 PCI术提前肝素化可以提高灌注效果,有效缓解STEMI患者的病情,改善患者心功能,改善预后,且具有较高的安全性。     

Prolonged total extracorporeal lung assistance without systemic heparinization

A 16-year-old female developed severe ARDS in her single remaining lung following pneumonectomy for blunt trauma. Total extracorporeal lung assist (ECLA) for 40 days using a covalently heparin-coated circuit proved lifesaving. Systemic heparinization was not applied, as the heparinized surface by itself prevented clotting of the extracorporeal circuit. Systemic primary fibrinolysis developed but was not associated with major bleeding. A veno-right ventricular cannulation technique was used and maximum venous drainage for the extracorporeal circulation was achieved by elevating the bed 50 cm from the floor. This allowed extracorporeal blood flow (ECBF) approaching cardiac output (CO) and complete extracorporeal replacement of lung function. After 40 days, lung recovery allowed discontinuation of ECLA. Five days later the patient suffered serious lung collapse and was operated for a bronchopleural fistula. The patient was extubated 4 weeks after terminating ECLA and discharged in good condition 5 weeks later.     

Experimental evaluation of the V-point heparin-bonding system applied to a dense-membrane artificial lung during 24-hour extracorporeal circulation in beagles

Heparin was covalently bonded to a hollow-fiber dense-membrane artificial lung and circuit using a silane coupling agent and polyethyleneimine as a spacer. This study investigated whether the novel artificial lung could sustain prolonged extracorporeal lung assist (ECLA) by venoarterial bypass in beagles using minimal anticoagulants. We maintained ECLA for 24 h in 3 groups of minimal systemic heparinization, heparinization with the new anticoagulant nafamostat mesilate, and without any systemic anticoagulant. The results were assessed from the functional performance of the artificial lung and by macroscopic and microscopic examination after the experiments. Artificial lung function, hemodynamics, hemogram, and platelet aggregation activity were well maintained in all groups. There was no plasma leakage from the artificial lung. Although several clots were observed in stagnant areas of the artificial lungs and circuits, there was no clot formation inside the artificial lung in any group. This highly biocompatible, heparin-bonded dense-membrane artificial lung performed well and safely during prolonged ECLA with blood clotting times less than 120 s.     

Comparison of a new heparin-coated dense membrane lung with nonheparin-coated dense membrane lung for prolonged extracorporeal lung assist in goats

Thrombosis and bleeding are major complications in cases of prolonged extracorporeal lung assist (ECLA) with an artificial-membrane lung. Antithrombogenic treatment of the artificial-membrane oxygenator and circuits is indispensable for safe ECLA. The efficacy of a new heparin-coated membrane lung with minimal systemic heparinization was evaluated for 7 days and compared with a nonheparin-coated membrane lung in goats. The animals were randomly assigned to either the heparin-coated membrane group (HM group, n = 5) or nonheparin-coated membrane group (NHM group, n = 5). Activated coagulation time (ACT) during ECLA was controlled to below 150 s in the HM group, and to near 200 s in the NHM group. All goats in the HM group were sustained on ECLA for 7 days, but two goats in the NHM group died on the 4th and 6th days, respectively. The mean systemic administration rate of heparin during ECLA was 22.4 +/- 4.4 U/kg/h in the HM group and 39.0 +/- 10.0 U/kg/h in the NHM group. There was a significant difference between the two groups (P < 0.05). The oxygen transfer rate, the Pco(2) difference, the perfusion resistance, and platelet counts showed no significant changes. There was no plasma leakage from the artificial lung. Although several clots were observed in the stagnant areas of the artificial lung, they did not lead to deterioration of the function of the artificial lung. The excellent antithrombogenicity, gas exchange ability, and durability of this new artificial lung with circuits might contribute to successful prolonged ECLA with minimal systemic heparinization.