Lymphocytes infiltration induces dysfunction in autoimmune myocarditis: role of SRS-A

In this paper it was examined whether it could reproduce "in vitro", some of the myocardial dysfunction see "in vivo" in autoimmune myocarditis. The isolated atria from mice hyperimmunized with heart exhibited a lymphomononuclear cell infiltration and alteration in contractility: dysrhythmia and decrease in tension. These alterations highly resembled that triggered by spleen lymphocytes from autoimmune myocarditis mice, when they reacted with normal atria. This effect appears to be specific since cells sensitized to an irrelevant antigen were inactive, and was not secondary to allogenic interaction. The free-cell supernatant of autoimmune cells was inactive, point out the requirement of lymphocyte-heart contact. The most likely effectors of lymphocytes-induced alteration of atria contractility were T-lymphocytes. Beta-lymphocyte subset had no effect. Inhibitors of lipoxygenase(s) pathway of arachidonic acid metabolism, inhibited induced alterations of contractility and the SRS-A receptor blocker, FPL-55712 improved cardiac function. In addition LTC4 release was increased either in autoimmune myocarditis hearts and in normal hearts challenged with autoimmune cells; the hearts proving to be responsible of leukotriene synthesis. Normal or immune cells alone failed to release LTC4. Lipoxygenase(s) inhibitors diminished LTC4 release while indomethacin could not reverse the effect. It is concluded that mononuclear cells infiltrates occurring in hearts with autoimmune myocarditis mice are related to cardiac impairment, being critical in the myocardial dysfunction etiology. The way suggested for these phenomena to take place is, at least in part, the harmful effect of SRS-A released by hearts when specific antigens of myocardial tissue are recognized by autoimmune cells.