We have previously described a subpopulation of patients with septic shock who had a reversible depression of radionuclidedetermined left ventricular ejection fraction (EF). To investigate the mechanism of this myocardial depression, an in vitro model of mammalian myocardial cell performance was established employing primary spontaneously beating rat myocardial cells. The contraction of a single cardiac cell was quantitated by recording the changes in area occupied by the cell during contraction and relaxation. In 20 septic shock patients during the acute phase, the mean left ventricular EF was decreased (mean = 033, normal mean = 0.50), and serum obtained during this acute phase induced a mean (±standard error of the mean) 33±4% decrease in extent and 25±4% decrease in velocity of myocardial cell shortening during contraction (P < 0.001). In contrast, serum obtained from 11 of these same patients before shock (n = 2) or after recovery (n = 9) of the left ventricular EF (mean = 0.50) showed a return toward normal in extent and velocity of shortening (P < 0.001). Sera from 17 critically ill nonseptic patients, from 10 patients with structural heart disease as a cause for a depressed EF, and from 12 healthy laboratory personnel, induced no significant changes in in vitro myocardial cell performance. In 20 patients during the acute phase of septic shock, the decreased EF in vivo demonstrated a significant correlation (r = +0.52, P < 0.01) with a deerease in the extent of myocardial cell shortening in vitro. The quantitative and temporal correlation between the decreased left ventricular EF and this serum myocardial depressant substance argues for a pathophysiologic role for this depressant substance in producing the reversible cardiomyopathy seen during septic shock in humans.

A B S T R A C T The mechanism of protection of typespecific antipneumococcal antibody and complement in bacteremia was investigated with purified rabbit antibody and a guinea pig model of pneumococcal bacteremia. IgG and IgM were isolated from the sera of rabbits immunized with type 7 pneumococci (Pn), and their binding to Pn was quantitated. The number of antibody-binding sites on the pneumococcal capsule was also determined. Pn were incubated with various amounts of the immunoglobulin preparations before intravenous injection into nonimmune guinea pigs. Whereas 120 molecules of IgM per Pn were sufficient to enhance bloodstream clearance of Pn, 1,400 molecules of IgG per bacterium were required to produce this effect. As the amount of either IgG or IgM added to the Pn was increased, the rate of bloodstream clearance accelerated. In striking contrast, >1,000 molecules of IgM had no effect on the rate of clearance in C4-deficient guinea pigs, which cannot activate complement via the classic pathway. Similarly, 5,000 molecules of IgG had only minimal effect in C4-deficient guinea pigs, and 24,000 molecules of IgG had no effect in guinea pigs depleted of complement by cobra venom factor. Thus, the in vivo opsonic effects of both IgG and IgM anticapsular antibody are mediated via their ability to activate complement.IgG anti-pneumococcal cell wall antibody, raised by intravenous injection of rabbits with unencapsulated Pn, had no effect on the rate of bloodstream clearance This work was presented in part at the 20th Interscience

Most investigators believe that the pulmonary endothelial damage that is characteristic of the adult respiratory distress syndrome (ARDS) requires the action of neutrophils. In a retrospective review of patients with ARDS, we looked for cases that had developed in patients who already had neutropenia. Four clinical criteria were required for the diagnosis of ARDS: the occurrence of a precipitating event, diffuse bilateral pulmonary infiltrates on a chest x-ray film, a normal intravascular volume (as reflected by a wedge pressure of less than 18 mm Hg), and arterial hypoxemia. During 2 1/2 years, 11 patients fulfilled these clinical criteria, had severe neutropenia that antedated the onset of ARDS, and had pulmonary histologic specimens obtained during the early stages (less than seven days) of clinical respiratory distress. Five of these specimens showed diffuse alveolar damage without evidence of infectious pneumonitis (the histopathological finding characteristic of ARDS), and none had a neutrophil infiltrate. We conclude that ARDS can occur in the setting of severe neutropenia, without pulmonary neutrophil infiltration.

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