Donald J. Lyman

Effects of a vascular graft/natural artery compliance mismatch on pulsatile flow

Attempts have been made to correlate small-diameter vascular graft patency with compliance matching between the graft and the host artery. Without knowledge about the mechanisms of failure by compliance mismatch, however, such correlations remain empirical. We have developed a flow system which mimics the flow in peripheral arteries and techniques to model a compliance mismatch in a straight elastic tube, as might occur with vascular repair. Our goal was to investigate one proposed mechanism of graft failure by compliance mismatch, that of a blood flow disturbance. Flow visualization experiments showed that, under pulsatile flow, a compliance mismatch caused trapping of 40 microns microspheres at the wall near the distal or downstream anastomosis. This suggests that the presence of a microscopic flow separation or stagnant zone in vivo may contribute to the intimal hyperplasia and thrombosis seen in failed grafts.

Gas permeability of various block copolyether—urethanes

Abstract The effect of chemical structure and fabrication variables on the gas permeability of several block copolyether—urethane—urea and copolyether—urethane membranes was determined. It was found that the gas permeability of the copolyether—urethane—ureas increased in a linear manner with an increase in the polypropylene glycol segment molecular weight. Copolymers with a polyethylene glycol segment were found to be less permeable than those with propylene glycol segments. This may be due to the ability of polyethylene glycol to crystallize. For both copolymer systems, the type of chain extender used affected gas permeability. Again, these effects may be due to the degree of phase separation and to the nature of chain packing with the different extenders (i.e., the better the packing the lower the permeability). Changes in casting solvent, or the addition of salts such as LiBr or urea, had only minor effects on gas permeability.

Fourier Transform Infrared Attenuated Total Reflection Analysis of Human Hair: Comparison of Hair from Breast Cancer Patients with Hair from Healthy Subjects

A comparative study of Fourier transform infrared attenuated total reflection (FTIR-ATR) spectra of 32 scalp and pubic hair samples from individuals diagnosed with breast cancer and those who were negative for breast cancer showed increases in the β-sheet/disorder structures (relative to α-helix structures) and C–H lipid content of hair from breast cancer patients. Thus, the presence of breast cancer appears to alter the hair growth process, resulting in changes in the composition and conformation of cell membrane and matrix materials of hair fiber. These appear to be consistent with the changes observed in X-ray diffraction patterns for hair from breast cancer patients. A blind study of 12 additional hair samples using these FTIR-ATR spectral differences as markers correctly identified all four hair samples from cancer patients (100%). Two of these samples were from breast cancer patients. Of the remaining two samples analyzing positive for cancer, one was from a prostate cancer patient and one from a lung cancer patient. Thus, it appears that the mechanism that alters hair fiber synthesis in the three types of cancer may be similar. The blind study incorrectly identified as positive for cancer three hair samples from two apparently healthy individuals and one patient considered cured from prostate cancer.

Effects of an Artery/Vascular Graft Compliance Mismatch on Protein Transport: A Numerical Study

Small-diameter vascular graft failure by intimal hyperplasia and thrombosis may result from flow disturbances and disruption of chemical transport in the fluid at the distal anastomosis, because of compliance mismatch between the graft and host artery. In previous studies, lower-than-normal wall shear stress (WSS), particle trapping, and high particle residence times were observed at the distal anastomosis due to a pulsatile tubular expansion effect caused by nonuniform radial deformations. This study was undertaken to examine effects of compliance and radius mismatch on the distribution of a model protein released at the graft–fluid interface. Finite element simulations of end-to-end vascular grafting were performed under pulsatile flow, using fluid–structure coupling to give physiologic wall displacements. Results showed that protein is convected smoothly downstream in a uniform compliant tube. A compliance mismatch disturbed the transport, causing positive and negative gradients in the concentration profile at the distal anastomosis. This was seen when the graft and artery radii were matched at zero pressure and at mean arterial pressure; low WSSs were only observed in the former case. Thus the distal intimal hypertrophy seen in noncompliant grafts may be caused partly by decreased WSS, and partly by concentration gradients of dissolved chemicals affecting chemotaxis of cells.

Effect of Temperature on the Conformation of Extended α-Keratin

Attenuated total reflection Fourier transform infrared (ATR/FT-IR) spectra of wet horse hair α-keratin indicate that the conformation of extended α-keratin is affected by the water temperature. Extension of the wet horse hair in 21 °C water gives rise to parallel β-sheet structures, thus suggesting that the original α-helical structure is also parallel. In contrast, extension of the wet horse hair α-keratin in 95 °C water gives rise to anti-parallel β-sheet structures (consistent with reported literature where X-ray diffraction was used), suggesting that disulfide interchange and/or increased chain mobility at elevated temperatures plays a role in altering the secondary structure.

Vascular graft healing: I. FTIR analysis of an implant model for studying the healing of a vascular graft

FTIR analysis of sequential biopsy samples of the primary and replacement segments obtained from 70 to 80-cm long carotid-femoral bypass grafts implanted bilaterally in the dog indicate that the healing pattern is similar over the entire length of these grafts. Preliminary analysis of the spectra also indicates that the major developments in the formation of the biological layer appear to occur during the first 4 weeks after implantation. Collagen IV could be detected by both FTIR and antibody staining in the 8-week samples. Thus, this study supports the application of FTIR attenuated total reflectance to determine the components of the biological tissue that forms on an implanted vascular graft surface.

Surface Infrared Spectroscopy

Infrared spectroscopy traditionally involved determination of the electromagnetic radiation absorbed by an organic compound as a function of the wavelength of radiation transmitted through the entire sample thickness. The infrared region of electromagnetic radiation includes wavelengths from 7.8 × 10-5 to 1 × 10-1 cm, although the mid-infrared region generally studied includes wavelengths from 2.5 × 10-4 to 5 × 10-3 cm.

Predicting the compliance of small diameter vascular grafts from uniaxial tensile tests

The compliance hypothesis states that the compliance of vascular grafts should match that of the host artery for optimal patency. Although this has not been proven, the literature shows that much effort has gone into measuring compliance. Uniaxial circumferential tensile tests are simpler than compliance tests, but do not give the compliance (a multiaxial property) directly. Therefore, we have used mechanical models to correlate the two. Simple models suffer from inappropriate simplifying assumptions. In a clinically useful range, a Laplace law model and an incremental elasticity model do not predict the compliance from the rigidity as well as does a model derived from finite elasticity. This latter model has helped locate sources of errors. Variations in graft thickness, diameter, and anisotropy may be responsible for scatter in the experimental correlations between compliance and uniaxial rigidity.

Vascular graft healing. II. FTIR analysis of polyester graft samples from implanted Bi-grafts

FTIR-ATR analysis has shown that the 4-step process for preclotting polyester vascular grafts results in a uniform and reproducible fibrin coating of the polyester fibers. Western blot analyses have shown that FN and VEGF are also present in this fibrin coating. FTIR-ATR analyses of explanted grafts indicate that, while the in vivo healing of these preclotted polyester grafts proceed through the inflammation, proliferation, and remodeling phases of normal wound healing, these phases are modified. Because the fibrin coating provides a nonporous barrier between peri-graft tissue and the flowing blood, these molecular changes are controlled by the interactions of blood-borne constituents with the lumenal surface of the preclotted graft. Also, a well prepared preclotted polyester graft shows a minimal inflammatory response. After implantation, the fibrin preclot is more than 90% gone by the fifth day. However, the proliferation phase, involving synthesis of new protein and polysaccharide materials to replace the fibrin, appears to have begun by the third day. Detection of collagen I in the 5-day explants suggests that the overlapping remodeling phase of healing has begun. Protein and saccharide materials continue to be synthesized and remodeled, and, by the tenth day, collagen IV is detected. By 14-days post-implantation, there is an increase in collagen IV and cellular membrane lipids. Because collagen IV is an indicator of the presence of endothelial cells, some of these cellular membranes must be of endothelial origin. Thus, it appears that FTIR-ATR can be a useful tool in the study of vascular healing.

The parallel helices of the intermediate filaments of α-keratin

Recent Fourier transform infrared spectroscopy (FTIR) with attenuated total reflection technique (ATR) has been applied to alpha-keratin fibers (horse-hair) extended in water both at 21 and 95 degrees C. Infrared absorption bands in the Amide 1 region indicated that at extensions to 40-50% strain in water at 21 degrees C alpha-helices had completely disappeared and parallel beta-sheets were formed [Appl. Spectrosc. 55 (2001) 552]. However, when the hair fibers were extended to the same strain at 95 degrees C in water the result was the formation of anti-parallel beta-sheets. These results suggest that the relatively more stable anti-parallel beta-state [Polymer 10 (1969) 810] is only attained in extended alpha-keratin fibers at elevated temperatures and must result from major molecular rearrangement. It was concluded that the alpha-helices in the intermediate filaments (IFs) of alpha-keratin fibers must be parallel. This is in contrast to the previously accepted orientation of anti-parallel alpha-helices, based primarily on findings of X-ray diffraction studies of the structure of beta-keratin in highly extended fibers [Polymer 10 (1969) 810; Keratins, IL: Thomas Springfield (1972); Nature 316 (1985) 767].