title: Mechanical loading of bovine pericardium accelerates enzymatic degradation.
abstract: Bioprosthetic heart valves fail as the result of two simultaneous processes: structural deterioration and calcification. Leaflet deterioration and perforation have been correlated with regions of highest stress in the tissue. The failures have long been assumed to be due to simple mechanical fatigue of the collagen fibre architecture; however, we have hypothesized that local stresses-and particularly dynamic stresses-accelerate local proteolysis, leading to tissue failure. This study addresses that hypothesis. Using a novel, custom-built microtensile culture system, strips of bovine pericardium were subjected to static and dynamic loads while being exposed to solutions of microbial collagenase or trypsin (a non-specific proteolytic enzyme). The time to extend to 30% strain (defined here as time to failure) was recorded. After failure, the percentage of collagen solubilized was calculated based on the amount of hydroxyproline present in solution. All data were analyzed by analysis of variance (ANOVA). In collagenase, exposure to static load significantly decreased the time to failure (P < 0.002) due to increased mean rate of collagen solubilization. Importantly, specimens exposed to collagenase and dynamic load failed faster than those exposed to collagenase under the same average static load (P = 0.02). In trypsin, by contrast, static load never led to failure and produced only minimal degradation. Under dynamic load, however, specimens exposed to collagenase, trypsin, and even Tris/CaCl2 buffer solution, all failed. Only samples exposed to Hanks' physiological solution did not fail. Failure of the specimens exposed to trypsin and Tris/CaCl2 suggests that the non-collagenous components and the calcium-dependent proteolytic enzymes present in pericardial tissue may play roles in the pathogenesis of bioprosthetic heart valve degeneration.
authors.affiliation: Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: J C
authors.initials: JC
authors.lastname: Ellsmere
authors.forename: R A
authors.initials: RA
authors.lastname: Khanna
authors.forename: J M
authors.initials: JM
authors.lastname: Lee
mesh_terms: D000818:Animals; D001673:Biodegradation, Environmental; D002114:Calcinosis; D002417:Cattle; D017364:Collagenases / Q000378:metabolism; D046508:Culture Techniques / Q000295:instrumentation / Q000379:methods; D006350:Heart Valve Prosthesis; D008838:Microcomputers; D010496:Pericardium / Q000473:pathology / Q000502:physiology*; D011475:Prosthesis Failure; D013314:Stress, Mechanical; D013718:Tensile Strength; D014357:Trypsin / Q000378:metabolism; D016474:Weight-Bearing
chemical_list: D014357:Trypsin; D017364:Collagenases