Mature male Sprague-Dawley rats were subjected to an isoproterenol-induced myocardial infarction. Animals were sacrificed on a daily basis in order to assess the temporal changes in prolyl hydroxylase activity and collagen metabolism during the acute stages of myocardial necrosis and repair. Total myocardial hydroxyproline, as an indexof collagen content, increased promptly and markedly, beginning on day 4, and remained elevated thereafter. The incorporation of (14Cl)-proline into definitive hydroxyproline of mature collagen was also increased. The activity of the enzyme prolyl hydroxylase, which regulates the rate of conversion of proline to hydroxyproline in collagen, was elevated by day 2, remained high through day4, and then declined to a relatively constant but still slightly elevated level throughout the period of repair. It is believed that changes in these parameters of collagen metabolism reflect changes in myocardial fibroblastic cell and ground substance pertinent to fundamental aspects of repair of the injuried myocardium.
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Recent investigations have suggested that the microenvironment of a hemopoietic organ may influence the cellular development within that organ. For example, Trentin ( 1 ) has proposed a concept of hemopoietic inductive microenvironments (HIM) which determine the line of differentiation to be followed by the pluripotential stem cells. Patt and Maloney ( 2 ) have suggested that local regulatory mechanisms are operative in cellular proliferation in the bone marrow, and the importance of the s t r o m in erythropoiesis also has been emphasized by Brecher et al, ( 3 ) .Recently, McCuskey et at. (4) have reported changes in the murine splenic microenvironment during erythropoietic suppression and regeneration and considered the microenvironment to be divided into three compartments: a microvascular compartment composed of arterioles, capillaries, sinusoids, and venules; a connective tissue compartment composed of cells, fibers, and ground substances; and the neural elements associated with the blood vessels and the stroma. In these studies, di,fferences were found in vivo between the microcirculation of erythropoietically-active spleens of normal mice and the erythropoietically-suppressed spleens of polycythemic mice. The spleens of polycythemic mice had limited blood flow through the splenic sinusoids with most sinusoids storing blood. Histochemical analysis of the connective tissue compartment indicated that the red pulp of the erythropoietically-suppressed spleens Suppontied in part by NIH Grant, AM-10507. 2 Recipient NIH Research Career Development Award AM-42370.
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