title: Preclinical biocompatibility assessment of the EVAHEART ventricular assist device: coating comparison and platelet activation.
abstract: Thromboembolism and bleeding remain significant complications of ventricular assist device (VAD) support. Increasing the amount of biocompatibility data collected during preclinical studies can provide additional criteria to evaluate device refinements, while design changes may be implemented before entering clinical use. Twenty bovines were implanted with the EVAHEART centrifugal VAD for durations from 30 to 196 days. Titanium alloy pumps were coated with either diamond-like carbon or 2-methoxyethyloylphosphoryl choline (MPC). Activated platelets and platelet microaggregates were quantified by flow cytometry, including two new assays to quantify bovine platelets expressing CD62P and CD63. Temporally, all assays were low preoperatively, then significantly increased following VAD implantation, before declining to a lower, but still elevated level over 2-3 weeks. MPC-coated VADs produced significantly fewer activated platelets after implant trauma effects diminished. Three animals receiving no postoperative anticoagulation had similar amounts of circulating activated platelets and platelet microaggregates as animals receiving warfarin anticoagulation. Two new methods to quantify bovine activated platelets using antibodies to CD62P and CD63 were characterized and applied. These measures, along with previously described assays, were able to differentiate between two biocompatible coatings and assess effects of anticoagulation regimen in VAD preclinical testing.
authors.affiliation: Bioengineering Department, University of Pittsburgh, 100 Technology Drive, Pittsburgh, PA 15219, USA.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Snyder
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsukui
authors.forename: Shin'Ichiro
authors.initials: S
authors.lastname: Kihara
authors.forename: Takehide
authors.initials: T
authors.lastname: Akimoto
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Litwak
authors.forename: Marina V
authors.initials: MV
authors.lastname: Kameneva
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamazaki
authors.forename: William R
authors.initials: WR
authors.lastname: Wagner
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D015703:Antigens, CD / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D002417:Cattle; D020099:Coated Materials, Biocompatible / Q000009:adverse effects; D005434:Flow Cytometry; D006353:Heart-Assist Devices / Q000009:adverse effects; D006470:Hemorrhage / Q000097:blood / Q000209:etiology; D006801:Humans; D008422:Materials Testing; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D013923:Thromboembolism / Q000097:blood / Q000209:etiology
chemical_list: D000925:Anticoagulants; D015703:Antigens, CD; C554586:CD63 protein, human; D020099:Coated Materials, Biocompatible; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30