In-vitro Blood Flow Models for the Assessment of Device Thrombosis
Yüklə 59,47 Kb. Pdf görüntüsü
|
- Bu səhifədəki naviqasiya:
- Virchow’s Triad Flow Blood Surface
- Blood Flow Surface
- Assessment of Device Thrombosis
- MERITS OF IN-VITRO FLOW MODELS
- LIMITATIONS OF IN-VITRO FLOW MODELS
- Device Thrombosis
- Blood reservoir 37˚C
- Devices Polymer Tubing (1/8” ID) Pump
- Relative Device Thrombosis Assessed In-vitro and In-vivo
- Roller pump. External flow=1-3 L/min
|
In-vitro Blood Flow Models for the Assessment of Device Thrombosis Sivaprasad (SP) Sukavaneshvar, Ph.D. Vice President, Thrombodyne, Inc. Research Faculty Department of Pharmaceutics University of Utah Salt Lake City, UT Virchow’s Triad Flow Blood Surface Vascular wall (Endothelium) Device
Biomaterial Proteins
Cells Streamlined Disturbed Slow/stagnant Fast
Fluid Dynamics Shear Stress Platelet activation Normal velocity Platelet adhesion & aggregation Residence time Coagulation and consolidation Vorticity Platelet aggregation (fluid phase)
Virchow’s Triad
Blood Flow Surface Flow In-vitro Blood flow Models
Device surface
Blood Assessment of Device Thrombosis Surface
characterization In-vitro static blood contact studies
Clinical studies
In-vitro flow model studies In-vivo animal studies
In-vitro Blood Flow Model Configuration 37˚C
Pump Device Blood reservoir Polymer Tubing 37˚C
Variations: Branched flow, Single pass, Chandler loop, etc. Test
Control/predicate In-vitro Blood Flow Models: Key Features • Relative assessment of thrombosis and related processes • Fresh, anticoagulated whole blood – Heparin, citrate (recalcified), hirudin • Blood flow conditions approach clinical use – Flow rate and conduit size • Experiment time: ~hours
In-vitro Blood Flow Models: Key Features • Measured output – Macroscopic thrombus ( Weight, Visual analysis, Radiolabeling) – Microscopic components (SEM) – Fluid phase biomarkers – Thromboemboli – Device dysfunction caused by thrombus (occlusion) • Test conditions selected to focus on the device and minimize the impact of other model components – Surface/Volume ratio – Edge effects
MERITS OF IN-VITRO FLOW MODELS • Useful template for comparing device thrombosis under similar conditions • Some control over blood parameters • Control of other important parameters (e.g. flow)* • Quantification of thrombosis LIMITATIONS OF IN-VITRO FLOW MODELS • Experiment duration • Absence of long-term effects – Blood vessel wall-device interactions – Comprehensive hemostatic pathways (e.g. lytic pathway)
– Inflammatory and foreign body response • Need anticoagulation • Control of other parameters (e.g. flow)!
EXAMPLES Device Thrombosis Device geometry (flow disturbance) Vascular response Surface modification Blood reactivity ?
Coronary Stents Model Configuration(s) Conventional model Peristaltic pump
Blood Reservoir Stent Polymer
conduit Branched flow model Flow probe Initial flow rate: 75 ml/min Heparin: 1 U/ml Expt. Time: 60-90 min Conduit: 3.2 mm ID 111-In labeled platelets THROMBUS ON STENTS Uncoated (control) Coating A Coating B Thrombotic Occlusion Flowrate
ml/min 75 50 25 0 15 30 45 60 75 Time (min) Coating B Control
Coating A Thrombus Accumulation % of
control 100
75 50 25 0 Control
Coating B Coating A ONE PASS CONFIGURATION Blood reservoir 37˚C Useful for assessing thrombosis and embolism on small devices: Stents, distal embolic protection … Circumvents recirculation & recounting of released emboli Less extraneous blood activation Limited range of flow rate, time, and number of simultaneous devices to be tested due to blood volume constraints
37 ° C Hemodialysis Cartridge 37˚C
Pump Cartridge Blood reservoir Dialysis tubing 37˚C
A P B P Flow rate: 300-400 ml/min Heparin: 2-3 U/ml 111-In labeled platelets Hemodialysis Cartridge Thrombotic Occlusion A 10 20 30 40 50 P-Po (mm Hg) 50 100
150 Time (min) B
Relative Device Thrombosis Assessed In-vitro and In-vivo Coronary Stents From Kocsis, et al. Journal of Long Term effects of Medical Implants 2000 In-vitro flow model Baboon 2 hr ex-vivo shunt Clinical studies Uncoated
coated Catheters (PICCs) From Smith, et al., Sci Transl Med 2012 Control Test
Control Test
Control Test
Control Test
IN-VITRO FLOW MODEL CANINE IN-VIVO JUGULAR IMPLANT (~4 hours) Roller pump. External flow=1-3 L/min Roller
pump 37˚C 37 ° C Internal flow 300 ml/min Roller
pump 37˚C 37 ° C Internal flow 300 ml/min Hemodialysis Catheters coated control Hemodialysis Catheters From Lotito, et al. ASN 2006 IN-VITRO FLOW MODEL SHEEP IN-VIVO IMPLANT (up to 30 days) Uncoated Coated
Uncoated Coated
% of Uncoated % of Uncoated 100 50
50 In-vitro Blood Flow Models Summary
• Useful template for comparing device thrombosis under similar conditions – Relative Assessment – Universal/absolute acceptance criteria elusive • Has Limitations – Long-term biological processes – Pre-conditioning? • Model Configuration – Clinical conditions and in-vitro framework – Anticoagulation, flow conditions, time, objective Yüklə 59,47 Kb. Dostları ilə paylaş:
|