The Tensile and Viscoelastic Properties of Aortic Valve Leaflets Treated with a Hyaluronidase Gradient
- 255 Downloads
When diseased, aortic valves are typically replaced with bioprosthetic heart valves (BPHVs), either porcine valves or bovine pericardium that are fixed in glutaraldehyde. These replacements fail within 10–15 years due to calcification and fatigue, and their failure coincides with a loss of glycosaminoglycans (GAGs). This study investigates this relationship between GAG concentration and the tensile and viscoelastic properties of aortic valve leaflets. Aortic valve leaflets were dissected from porcine hearts and digested in hyaluronidase in concentrations ranging from 0 to 5 U/mL for 0–24 h, yielding a spectrum of GAG concentrations that was measured using the uronic acid assay and confirmed by Alcian Blue staining. Digested leaflets with varying GAG concentrations were then tested in tension in the circumferential and radial directions with varying strain rate, as well as in stress relaxation. The GAG concentration of the leaflets was successfully reduced using hyaluronidase, although water content was not affected. Elastic modulus, the maximum stress, and hysteresis significantly increased with decreasing GAG concentration. Extensibility and the radius of transition curvature did not change with GAG concentration. The stress relaxation behavior and strain-rate independent nature of the leaflet did not change with GAG concentration. These results suggest that GAGs in the spongiosa lubricate tissue motion and reduce stresses experienced by the leaflet. This study forms the basis for predictive models of BPHV mechanics based on GAG concentration, and guides the rational design of future heart valve replacements.
KeywordsAortic valve Glycosaminoglycans Hyaluronidase Mechanical testing Stress relaxation Viscoelasticity
This work was supported by a predoctoral fellowship to Hubert Tseng, and a Grant-in-Aid from the American Heart Association Southwest Affiliate. The authors thank Christopher A. Durst, Ph.D., Rice University, for his help conducting the uronic acid assay.
- 2.Bhatia, A., and I. Vesely. The effect of glycosaminoglycans and hydration on the viscoelastic properties of aortic valve cusps. Conf. Proc. IEEE Eng. Med. Biol. Soc. 3:2979–2980, 2005.Google Scholar
- 10.Eckert, C. E., R. Fan, B. Mikulis, M. Barron, C. A. Carruthers, V. M. Friebe, N. R. Vyavahare, and M.S. Sacks. On the biomechanical role of glycosaminoglycans in the aortic heart valve leaflet. Acta Biomater. 2012; Epub ahead of print.Google Scholar
- 11.Ferrans, V. J., T. L. Spray, M. E. Billingham, and W. C. Roberts. Structural changes in glutaraldehyde-treated porcine heterografts used as substitute cardiac valves. Transmission and scanning electron microscopic observations in 12 patients. Am. J. Cardiol. 41:1159–1184, 1978.CrossRefGoogle Scholar
- 15.Hammermeister, K. E., G. K. Sethi, W. G. Henderson, C. Oprian, T. Kim, and S. H. Rahimtoola. A comparison of outcomes in men 11 years after heart-valve replacement with a mechanical valve or bioprosthesis. Veterans Affairs Cooperative Study on Valvular Heart Disease. N. Engl. J. Med. 328:1289–1296, 1993.CrossRefGoogle Scholar
- 21.Ludoweig, J., B. Vennesland, and A. Dorfman. The mechanism of action of hyaluronidase. J. Biol. Chem. 236:333–339, 1961.Google Scholar
- 26.Missirlis, Y. F., and M. Chong. Aortic valve mechanics—Part I: material properties of natural porcine aortic valves. J. Bioeng. 2:287, 1978.Google Scholar
- 38.Simionescu, D. T., J. J. Lovekamp, and N. R. Vyavahare. Degeneration of bioprosthetic heart valve cusp and wall tissues is initiated during tissue preparation: an ultrastructural study. J. Heart Valve Dis. 12:226–234, 2003.Google Scholar
- 39.Simionescu, D. T., J. J. Lovekamp, and N. R. Vyavahare. Glycosaminoglycan-degrading enzymes in porcine aortic heart valves: implications for bioprosthetic heart valve degeneration. J. Heart Valve Dis. 12:217–225, 2003.Google Scholar
- 47.Vesely, I., J. E. Barber, and N. B. Ratliff. Tissue damage and calcification may be independent mechanisms of bioprosthetic heart valve failure. J. Heart Valve Dis. 10:471–477, 2001.Google Scholar
- 49.Yamagata, T., H. Saito, O. Habuchi, and S. Suzuki. Purification and properties of bacterial chondroitinases and chondrosulfatases. J. Biol. Chem. 243:1523–1535, 1968.Google Scholar