CELLULAR AND EXTRACELLULAR REMODELING WITH THE DEVELOPMENT AND RECOVERY FROM TACHYCARDIA-INDUCED CARDIOMYOPATHY - CHANGES IN FIBRILLAR COLLAGEN, MYOCYTE ADHESION CAPACITY AND PROTEOGLYCANS

The myocardial extracellular matrix (ECM) is composed of three importa nt constituents: (1) fibrillar collagen, (2) a basement membrane, and (3) proteoglycans. Structural or compositional changes in these ECM co mponents may affect left ventricular (LV) function as well as influenc e overall LV geometry. Accordingly, this study examined the relationsh ip between changes in these ECM components to changes in LV function a nd geometry which develop with the progression and regression from sup raventricular tachycardia-induced cardiomyopathy (SVT). LV function an d specific components of the ECM were studied in pigs with SVT cardiom yopathy (SVT:atrially paced 240 bpm, 3 weeks; n = 7), or after a 4-wee k recovery from SVT cardiomyopathy (post-SVT; n = 6), and in controls (n = 7). LV fractional shortening fell by 60% and end-diastolic dimens ion increased by 47% with SVT compared to controls. While LV fractiona l shortening normalized with post-SVT, end-diastolic dimension remaine d 40% higher than controls. Collagen concentration fell by 22% and sal t extractable collagen, which reflects collagen cross-linking, increas ed by 41% with SVT compared to controls. Collagen concentration increa sed by 20%, collagen extraction normalized, and levels of collagen typ e III mRNA increased by 42% with post-SVT Isolated myocyte adhesion ca pacity to basement membrane substrates laminin, fibronectin, and colla gen type TV were examined. SVT resulted in over a 50% reduction in myo cyte adhesion for all of the basement membrane components compared to controls. A normalization in isolated myocyte adhesion capacity was ob served in post-SVT. The relative content and distribution of the ECM p roteoglycan chondroitin sulfate was examined using immunohistochemistr y. With SVT, the density of this proteoglycan increased around individ ual myocytes. With post-SVT, the relative distribution of chondroitin sulfate returned to control levels, Thus, SVT cardiomyopathy was assoc iated with reduced collagen concentration and cross-linking, diminishe d myocyte basement membrane adhesion capacity, and increased proteogly cans. Recovery from SVT cardiomyopathy resulted in increased collagen concentration, and a normalization of myocyte adhesion capacity and pr oteoglycan distribution. These results suggest that changes within the ECM are a dynamic process and accompany the LV systolic and diastolic function as well as ventricular and myocyte remodeling during the pro gression and regression from cardiomyopathic disease. (C) 1996 Academi c Press Limited