The human heart as a shock organ in anaphylaxis.

Human mast cells, by elaborating vasoactive mediators and cytokines, are the primary effector cells of anaphylaxis. A body of evidence implicates human heart mast cells (HHMCs) in anaphylaxis. These cells have been identified perivascularly, in dose proximity to myocytes and in the arterial intima in human heart tissue. The membrane surface of mast cells from human heart tissue of patients undergoing cardiac transplantation expresses the high affinity receptors for IgE (FcepsilonRI) and C5a receptors. Activation of HHMCs in vitro with anti-IgE or anti-FcepsilonRI induced the release of preformed mediators (histamine, tryptase and chymase) and the de novo synthesis of LTC4 (approximately equal to 18 ng/10(6) cells) and PGD2 (approximately equal to 18 ng/10(6) cells). Complement activation and anaphylatoxin formation occur during anaphylaxis in human. C5a caused rapid release of histamine and tryptase from HHMCs. These cells are activated in vitro by therapeutic (general anaesthetics, protamine, etc.) and diagnostic agents (radio contrast media, etc.) that may cause non-IgE-mediated anaphylactic reactions. Administration of low concentrations of histamine and cysteinyl leukotrienes in subjects undergoing diagnostic catheterization caused significant systemic and coronary haemodynamic effects. Taken together, these results indicate that the human heart can be both the site and the target of anaphylactic reactions.