A genetically engineered, nonthrombogenic cellular lining for LVADs: in vitro preconditioning before in vivo implantation.
Because of the clinical success of left ventricular assist devices (LVADs) used for short-term "bridge to transplant" and the limited availability of donor organs, heart assist devices are being considered for long-term implantation as an alternative to heart transplantation. In an effort to improve biocompatibility, our laboratory has developed a nonthrombogenic cellular lining from genetically engineered smooth muscle cells (GE-SMC) for the Thermocardiosystems Heartmate LVAD. Smooth muscle cells have been transduced with the gene for endothelial nitric oxide synthase (NOS III) and produce NO at concentrations that reduce platelet deposition and smooth muscle cell proliferation when tested in vitro. In this investigation, the adhesive capabilities of GE-SMC linings were examined. An in vitro circulatory loop was designed to expose cell lined LVADs to in vivo operating conditions. Cumulative cell loss from cell lined LVADs was less than 10% after 24 hours of flow. Using a protocol for "preconditioning" the cell lining within the mock circulatory loop, the first implantation of an LVAD containing a genetically engineered SMC lining was successfully implemented in a bovine model. Results from this 24 hour study indicate that the flow-conditioned cellular lining remained intact with no evidence of thromboembolization and only minimal changes in coagulation studies.
Tock
C L
CL
Vascular Cell Biology, The Texas Heart Institute, Houston, 77030, USA.
Bosley
J P
JP
Parnis
S M
SM
Clubb
F J
FJ
Macris
M P
MP
Frazier
O H
OH
Scott-Burden
T
T
D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured; D005818:Genetic Engineering; D006353:Heart-Assist Devices; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000648:ultrastructure; D011140:Polyurethanes; D019919:Prosthesis Implantation; D011673:Pulsatile Flow; D013927:Thrombosis / Q000517:prevention & control*; D014025:Titanium; D018487:Ventricular Dysfunction, Left / Q000601:surgery*
D011140:Polyurethanes; D014025:Titanium