TY - JOUR
T1 - A protamine bio-reactor for extracorporeal heparin removal
T2 - In vitro modeling, function assessment, and future direction
AU - Wang, Tanya
AU - Byun, Youngro
AU - Kim, Jae Seung
AU - Liang, Junfeng
AU - Yang, Victor C.
PY - 2001
Y1 - 2001
N2 - Heparin, employed during extracorporeal blood circulation (ECBC) procedures (e.g. cardiopulmonary bypass), is often associated with a high incidence of bleeding complications. Protamine, employed in heparin neutralization, at times causes severe adverse reactions. To overcome this clinical dilemma, we previously proposed an approach that placed a blood filter device with immobilized protamine (termed a "protamine bio-reactor") at the distal end of the ECBC circulation. The protamine bioreactor would externally remove heparin using immobilized protamine, thereby simultaneously eliminating both heparin and protamine-induced complications. Both in vitro and in vivo experiments have demonstrated the feasibility and utility of this approach. In order to design an efficient protamine bio-reactor, the relationships between the reactor capacity and initial heparin concentration (CRO), protamine loading, saturation concentration (CS), reactor size (N, number of fibers), and flow rate needed to be established. The object of this investigation was to develop a numerical model that could be used to optimize the protamine bio-reactor for future studies. Protamine was immobilized to cellulose hollow fibers using a cyanogen bromide activation method. The maximum amount of immobilized protamine on the fibers was estimated to be 1620mg protamine/g fiber, whereas the maximum reactor capacity (CS) was estimated to be 8.9 mg heparin/g fiber. By utilizing the plug flow reactor model, the heparin binding constant (ka was determined from experimental data to be 2.8 × 103 M-1 min-1. Based on targeted values for CS and ka, the numerical model provided a performance assessment for an optimized protamine bio-reactor under real clinical situations of hemodialysis (HD) and cardiopulmonary bypass (CPB). This assessment led to a conclusion that a two bio-reactor, bio-feedback system would in the future achieve a most effective heparin removal for real clinical situations.
AB - Heparin, employed during extracorporeal blood circulation (ECBC) procedures (e.g. cardiopulmonary bypass), is often associated with a high incidence of bleeding complications. Protamine, employed in heparin neutralization, at times causes severe adverse reactions. To overcome this clinical dilemma, we previously proposed an approach that placed a blood filter device with immobilized protamine (termed a "protamine bio-reactor") at the distal end of the ECBC circulation. The protamine bioreactor would externally remove heparin using immobilized protamine, thereby simultaneously eliminating both heparin and protamine-induced complications. Both in vitro and in vivo experiments have demonstrated the feasibility and utility of this approach. In order to design an efficient protamine bio-reactor, the relationships between the reactor capacity and initial heparin concentration (CRO), protamine loading, saturation concentration (CS), reactor size (N, number of fibers), and flow rate needed to be established. The object of this investigation was to develop a numerical model that could be used to optimize the protamine bio-reactor for future studies. Protamine was immobilized to cellulose hollow fibers using a cyanogen bromide activation method. The maximum amount of immobilized protamine on the fibers was estimated to be 1620mg protamine/g fiber, whereas the maximum reactor capacity (CS) was estimated to be 8.9 mg heparin/g fiber. By utilizing the plug flow reactor model, the heparin binding constant (ka was determined from experimental data to be 2.8 × 103 M-1 min-1. Based on targeted values for CS and ka, the numerical model provided a performance assessment for an optimized protamine bio-reactor under real clinical situations of hemodialysis (HD) and cardiopulmonary bypass (CPB). This assessment led to a conclusion that a two bio-reactor, bio-feedback system would in the future achieve a most effective heparin removal for real clinical situations.
KW - Bio-feedback system
KW - Heparin removal
KW - Mathematical modeling
KW - Protamine bio-reactor
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M3 - Article
AN - SCOPUS:0035682424
SN - 1068-0659
VL - 6
SP - 133
EP - 149
JO - International Journal of Bio-Chromatography
JF - International Journal of Bio-Chromatography
IS - 2
ER -