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Characterization of a myocardial depressant factor in meningococcal septicemia
Nazima Pathan1, Colin Sandiford, Sian E Harding
1Department of Pediatrics, Imperial College of Science, Technology and Medicine, London, UK.
Objective:
Identification and characterization of myocardial depressant factors present in meningococcal septicemia.
Design:
Laboratory investigation of myocardial depression that used isolated cardiac myocytes as an model of cardiac contractile function.
Setting:
University hospital and laboratories.
Patients:
Children with severe meningococcal septic shock requiring intensive care.
Animals:
Myocytes obtained from adult male Sprague-Dawley rats.
Interventions:
Serum samples obtained from the acute phase of sepsis were evaluated for the presence of myocardial depressant activity. Further characterization of the myocardial depressant factor was undertaken by using cell culture supernatants from whole blood and peripheral blood mononuclear cells that had been exposed to heat-killed meningococci.
Measurements And Main Results:
Myocardial depressant activity was measured by using isolated rat left-ventricular myocytes. Changes in amplitude of contraction and in the speed of contraction and relaxation were determined after cells were exposed to various stimuli. Serum from patients with meningococcal disease had myocardial depressant activity. This activity was also present in whole blood and peripheral blood mononuclear cells exposed to meningococci. Myocardial depressant activity was found to be heat stable, proteinaceous, and of a molecular weight range of 10-25 kDa. The activity did not elevate concentrations of cyclic guanylic acid. Lipopolysaccharide-binding protein augmented the release of myocardial depressant factor by peripheral blood mononuclear cells exposed to meningococci.
Conclusions:
Myocardial depression in meningococcal sepsis is mediated in part by circulating myocardial depressant factors. Myocardial depressant factors are also released when whole blood or peripheral blood mononuclear cells of healthy donors are exposed to heat-killed meningococci. Release of the factors appears to be mediated through endotoxin-induced activation of peripheral blood mononuclear cells, since lipopolysaccharide-binding protein augments release in a dose-responsive manner. Partial physicochemical characterization of the factors has been achieved.