頁籤選單縮合
題 名 | A Protaming Bio-Reactor for Extracorporeal Heparin Removal: Development, in Vitro Modeling, and in Vivo Testing |
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作 者 | Byun,Youngro; Wang,Tanya; Kim,Jae-seung; Yang,Victor C.; | 書刊名 | 醫學工程 |
卷 期 | 9:1 1997.02[民86.02] |
頁 次 | 頁41-48 |
分類號 | 410.1644 |
關鍵詞 | |
語 文 | 英文(English) |
英文摘要 | Extracorporeal blood circulation (ECBC) has been employed in many important clinical situations such as renal dialysis and cardiopulmonary bypass. All these applications require heparin anticoagulation to prevent clotting in the devices. Systemic heparinization, however, results in a high incidence of bleeding complications. To overcome this problem, it is generally accepted in clinical practice to administer protamine, a heparin antagonist, at the conclusion of the heparin therapy to neutralize the anticoagulant effect of heparin. Unfortunately, intravenous administration of protamine at times causes serious or even fatal cardiovascular responses. We propose an approach that could simultaneously prevent both heparin and protamine induced complications. The approach consists of placing a bio-reactor device containing immobilized protamine (termed "protamine bio-reactor") at the distal end of the ECBC procedure where the blood re-enters the patient. The protamine bio-reactor would selectively remove the heparin after it has exerted its anticoagulant effect in the extracorporeal circuit and before it returns to the patient. The protamine bio-reactor would also prevent protamine from entering the patient, thereby minimizing the toxic effects of protamine. A prototype protamine bio-reactor was developed by coupling protamine onto the inner lumen of cellulose hollow fibers, using the cyanogen bromide activation method. A systemic investigation of variables affecting protamine immobilization was conducted to optimize the coupling process. Using this optimized procedure, bio-reactors containing 1 to 120 mg of immobilized protamine per gram of fiber weight was readily prepared. In vitro characterization of the protamine bioreactor showed that heparin adsorption on the bioreactor followed the Langmuir adsorption model, with an adsorption constant of 0.4 mL/mg and a saturation capacity of about 8.9 mg heparin per gram of fiber. A numerical model basied on a plug flow reactor (PFR) was developed for this protamine bioreactor, and the theoretical dta predicted by such a model correlated well with the in vitro experimental results. In vivo studies involving dogs and a femoral arteriovenous bypass circuit were also conducted. The results showed that at a blood flow of 100 mL/min, the bioreactor removed more than 50% of administered heparin in 10 minutes. While a rapid protamine injection produced profound hypotensive responses in dogs, the use of the protamine bioreactor did not elicit any statistically significant changes in all of the hemodynamic parameters monitored. Since the protamine bioreactor would eventually become saturated, the future system is envisioned to consist of a sensor-directed, bio-feedback, two protamine bio-reactor system for simultaneous heparin removal and reactor re-generation. |
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