Mechanosensitive connective tissue: potential influence on heart rhythm

Connective tissue is an essential component of cardiac histo-architecture. In particular the sinus node region of the healthy heart is rich in fibrous connective tissue l. The distinctive division of sino-atria1 node cells in multiple strands of different size reported in the original first description of the node by Keith and Flack 2 appears to be brought about by cardiac fibroblasts forming sheet-like extensions that enwrap groups of pacemaker cells 3. According to different quantitative studies, connective tissue occupies between 45% 4 and 73% 5 of the volume of the sinus node in man. A number of pathological states is associated with excessive growth of fibrous tissue in other parts of the heart. These pathologies include focal scar development in regions of myocardial ischaemia and infarction, or more scattered fibrosis induced by inflammation during rheumatic heart disease and other processes. The predominant contribution of fibroblasts to post-traumatic atria1 or ventricular restoration is based on their sustained proliferative potential in the adult organism, while myocyte proliferation is confined mainly to fetal periods of development t6,71. Cardiac fibroblasts are known to be mechanosensitive. They respond to mechanical stimulation by changes in gene expression and collagen synthesis in vivo 8,9 and in vitro lo. This generative response to changes in the mechanical environment is assumed to find clinical expression in fibrosis induced by pressure overload l l and tissue dilatation 121. Recently, cardiac fibroblasts have been implicated as a possible alternative substrate for some forms of cardiac mechano-electric feedback [13 observed in the sino-atria1 node region and in cardiac scar tissue 14. This short