Ex vivo evaluation of a Taylor-Couette flow, immobilized heparinase I device for clinical application

Efficient and safe heparin anticoagulation has remained a problem for conti nuous renal replacement therapies and intermittent hemodialysis for patient s with acute renal failure, To make heparin therapy safer for the patient w ith acute renal failure at high risk of bleeding, we have proposed regional heparinization of the circuit via an immobilized heparinase I filter, This study tested a device based on Taylor-Couette flow and simultaneous separa tion/reaction for efficacy and safety of heparin removal in a sheep model, Heparinase I was immobilized onto agarose beads via cyanogen bromide activa tion. The de,ice, referred to as a vortex flow plasmapheretic reactor, cons isted of two concentric cylinders, a priming volume of 45 ml, a microporous membrane for plasma separation, and an outer compartment where the immobil ized heparinase I was fluidized separately from the blood cells, Manual whi te cell and platelet counts, hematocrit, total protein, and fibrinogen assa ys were performed. Heparin levels were indirectly measured via whole-blood recalcification times (WBRTs). The vortex flow plasmapheretic reactor maint ained significantly higher heparin levels in the extracorporeal circuit tha n in the sheep (device inlet WBRTs were 1.5 times the device outlet WBRTs) with no hemolysis, The reactor treatment did not effect any physiologically significant changes in complete blood cell counts, platelets, and protein levels for up to 2 hr of operation. Furthermore, gross necropsy and histopa thology did not show any significant abnormalities in the kidney, liver, he art, brain, and spleen.