. Changes in extracellular collagen matrix alter myocardial systolic performance. Am J Physiol Heart Circ Physiol 284: H122-H132, 2003;10.1152/ajpheart.00233.2002.-The purpose of this study was to test the hypothesis that acute disruption of fibrillar collagen will decrease myocardial systolic performance without changing cardiomyocyte contractility. Isolated papillary muscles were treated either with plasmin (0.64 U/ml, 240 min) or untreated and served as same animal control. Plasmin treatment caused matrix metalloproteinase activation and collagen degradation as measured by gelatin zymography, hydroxyproline assays, and scanning electron microscopy. Plasmin caused a significant decrease in myocardial systolic performance. Isotonic shortening extent and isometric developed tension decreased from 0.17 Ϯ 0.01 muscle length (ML) and 45 Ϯ 4 mN/mm 2 in untreated muscles to 0.09 Ϯ 0.01 ML and 36 Ϯ 3 mN/mm 2 in treated muscles (P Ͻ 0.05). However, plasmin treatment (0.64 U/ml, 240 min) did not alter shortening extent or velocity in isolated cardiomyocytes. Acute disruption of the fibrillar collagen network caused a decrease in myocardial systolic performance without changing cardiomyocyte contractility. These data support the hypothesis that fibrillar collagen facilitates transduction of cardiomyocyte contraction into myocardial force development and helps to maintain normal myocardial systolic performance. hypertrophy; matrix metalloproteinases; heart failure; muscle; plasmin MANY AUTHORS (3,17,25,35) have hypothesized that the extracellular matrix (ECM) fibrillar collagen network facilitates transduction of cardiomyocyte contraction into myocardial force development and shortening and that changes in collagen may also alter myocardial systolic performance. The basis for this hypothesis is partly because pathological states, which result in the development of systolic dysfunction and congestive heart failure, are associated with significant changes in fibrillar collagen (8,11,13,29,34,36,37). However, these same pathological processes simultaneously change several other cellular and extracellular factors, which can also play a causal role in the development of systolic dysfunction and congestive heart failure (1). In addition, the specificity with which a decrease in collagen can be linked causally to a decrease in systolic function is uncertain because some pathological processes that increase collagen as well as some that decrease collagen can result in systolic dysfunction (8,11,13,29,34,36,37).Therefore, it is not intuitively obvious whether and to what extent changes in ECM myocardial fibrillar collagen can alter systolic function or contribute to the development of congestive heart failure in pathological states. Determining whether collagen degradation plays a mechanistic role in altering systolic function requires an experiment designed to cause an acute, isolated change in collagen without significantly changing any of the cellular determinants of systolic function. Accordingly, the purpose of this study was...

To determine whether and to what extent one component of the extracellular matrix, fibrillar collagen, contributes causally to abnormalities in viscoelasticity, collagen was acutely degraded by activation of endogenous matrix metalloproteinases (MMPs) with the serine protease plasmin. Papillary muscles were isolated from normal cats and cats with right ventricular pressure overload hypertrophy (POH) induced by pulmonary artery banding. Plasmin treatment caused MMP activation, collagen degradation, decreased the elastic stiffness constant, and decreased the viscosity constant in both normal and POH muscles. Thus, whereas many mechanisms may contribute to the abnormalities in myocardial viscoelasticity in the POH myocardium, changes in fibrillar collagen appear to play a predominant role.

Malignant phyllodes tumors are an uncommon breast tumor in clinical practice of surgery. The study population consisted of five consecutive patients. Each patient had complete clinical follow-up with annual mammograms and physical examination in a specialized breast clinic. They were surgically treated for with malignant phyllodes tumor of the breast. All patients are alive and well with a complete follow-up. The first 2 patients had a fine needle aspiration cytology and were surgically treated by a simple mastectomy. The remaining 3 patients were preoperatively diagnosed with core needle biopsy. These 3 patients were treated with a wide excision of the phyllodes tumor with at least a 1-cm margin of normal breast tissue. Mammography was 100% accurate in demonstrating a dense breast mass. In each patient ultrasound suggested heterogeneous internal echoes present in each malignant phyllodes tumor. Fine needle aspiration cytology was of no value in the diagnosis of a phyllodes tumor. Core needle biopsy is highly reliable in establishing a preoperative diagnosis. The most helpful clinical observation of a malignant phyllodes tumor was rapid growth and enlargement, which is frequently noted by the patient.