Nitrite-Induced Cross-Linking Alters Remodeling and Mechanical Properties of Collagenous Engineered Tissues

Cumulative damage to long-lived connective tissue proteins play a key role in the development of age-related human diseases such as cardiovascular stiffening and age-related macular degeneration. The processes that result in the accumulation of increasingly insoluble, undigestible damaged collagen are only partially known. Nonenzymatic glycation (NEG) is one such process and has been linked to the development of diabetic-related complications and aging. An additional novel mechanism particularly relevant to smoking- and inflammation-related diseases involves the nonenzymatic nitrite (NEN) modification of connective tissue proteins. The present study was undertaken to examine the effects of NEN of fibrillar type I collagen on cell-mediated remodeling and mechanical properties of collagenous tissues. Using a modification of an in vitro fibroblast-populated collagen gel model system developed in our laboratory, we tested two hypotheses: NEN reduces the ability of primary adult cardiac fibroblasts to remodel type I collagen gels; NEN reduces the deformability of type I collagen gels subjected to mechanical testing. The results show that NEN impairs both cell-mediated remodeling and mechanical deformability in collagenous engineered tissues. Furthermore, these mechanical changes correlate with the degree of cross-linking as determined by SDS-PAGE. Thus, we concluded that NEN reactions may contribute to alterations in the biomechanical properties of collagen-containing tissues consistent with the age-related functional decline observed in human disease.     

Transient unifascicular, bifasicular and trifascicular block: electrophysiologic correlations in a patient with rate-dependent left bundle branch block and transient right bundle branch block.

Correlations of the His to ventricular (H-V) conduction time were made with the surface electrocardiogram during normal intraventricular conduction, unifascicular block (right bundle branch block), bifascicular block (left bundle branch block) and trifascicular block (right and left bundle branch block) in a patient with rate-dependent left bundle branch block who had transient right bundle branch block during recording of the His bundle electrogram. The results provide a functional confirmation of the theory that a prolonged H-V time is a manifestation of trifascicular disease.