Thermomechanical stability of heart valve collagen: Differences with valve type and age, and implications for remodeling

Heart valves remain functional while undergoing approximately 35 million open/close cycles per year. While the four valves are loaded at the same frequency, the cardiac cycle, the magnitude of loads is different. This thesis identifies differences in collagen (the primary structural component of valves) structure that exist between the four valves and the age-related changes that occur in the collagen structure of heart valves.;Valves under higher in vivo load denatured at a lower temperature than did those under lower load, suggesting a relationship between molecular stability and in vivo mechanical load. The denaturation temperatures of valvular tissues decreased with age revealing an age-related destabilization of the collagen molecule in heart valves. Total enzymatic crosslinking also decreased with age in valvular tissues, unlike any other previously reported collagenous tissue in which total crosslinking reportedly increases. The enthalpy of denaturation and proline hydroxylation did not change with age, suggesting that the observed age-related destabilization is not a function of a reduction in the bond rupture energy required for thermal denaturation. The proposed mechanism for this age-related destabilization is altered molecular packing. A decrease in denaturation temperature, with no change in the enthalpy of denaturation, following acetic acid treatment of valvular tissues demonstrated the molecular destabilization of collagen in heart valves via an induced increase in molecular spacing.;This thesis increases our understanding of heart valve physiology and connective tissue structure/function relationships. It has important application to the tissue engineering of valve replacements and our understanding of, and treatment strategies for, valvular pathologies.;Assessing samples from the four valves (mitral, aortic, tricuspid and pulmonary) of cattle from four age groups (fetal, young, adult and old), hydrothermal isometric tension testing was used to capture denaturation temperature and half-time of load decay data. Differential scanning calorimetry was used to assess the onset and peak temperatures of denaturation as well as the specific enthalpy of denaturation, both with and without prior acetic acid treatment: used to increase molecular spacing. The moles of enzymatic crosslinks per mole of collagen were assessed using high performance liquid chromatography.