Extracellular matrix arrangement in the papillary muscles of the adult rat heart. Alterations after doxorubicin administration and experimental hypertension.

In the present study, we analyzed the components of the extracellular matrix (ECM) and its arrangement at the level of the papillary muscles in the adult rat heart using light and transmission and scanning electron microscopy techniques. Our results reveal that after a single dose (6 mg/kg) of dexorubicin to cause a significant decrease and disorganization of the endomysium and perimysium in the first week after injection, affecting the endomysial struts and perimysial strands. Degenerating myocytes and alterations of the coiled perimysial fibers were characteristic 4 weeks after treatment. After 8 weeks, ultrastructural alterations at the level of the plasma membrane of the myocytes and adjacent collagen network were present in the tip of the papillary muscles. These alterations may be responsible for the inefficiency of the valvular apparatus as an initial factor implicated in doxorubicin-induced congestive heart failure. Experimental hypertension, produced by constriction of the abdominal aorta, induced hypertrophy of the left ventricle, with increased perimysium and endomysium of the ECM at the level of the papillary muscles 4 weeks after aortic banding. Interstitial and perivascular fibrosis were observed 8 weeks after surgical treatment, and macrophages around the degenerating myocytes were characteristic 16 weeks after treatment. These alterations of the ECM network have been correlated with their possible implication in ventricular biomechanical properties.