Role of endotoxemia in cardiovascular dysfunction and mortality. Escherichia coli and Staphylococcus aureus challenges in a canine model of human septic shock.

Abstract

Using different types of bacteria and a canine model simulating human septic shock, we investigated the role of endotoxin in cardiovascular dysfunction and mortality. Either Escherichia coli (a microorganism with endotoxin) or Staphylococcus aureus (a microorganism without endotoxin) were placed in an intraperitoneal clot in doses of viable or formalin-killed bacteria. Cardiovascular function of conscious animals was studied using simultaneous radionuclide heart scans and thermodilution cardiac outputs. Serial plasma endotoxin levels were measured. S. aureus produced a pattern of reversible cardiovascular dysfunction over 7-10 d that was concordant (P < 0.01) with that of E. coli. Although this cardiovascular pattern was not altered by formalin killing (S. aureus and E. coli), formalin-killed organisms produced a lower mortality and less myocardial depression (P < 0.01). S. aureus, compared to E. coli, produced higher postmortem concentrations of microorganisms and higher mortality (P < 0.025). E. coli produced significant endotoxemia (P < 0.01), though viable organisms (versus nonviable) resulted in higher endotoxin blood concentrations (P < 0.05). Significant endotoxemia did not occur with S. aureus. Thus, in the absence of endotoxemia, S. aureus induced the same cardiovascular abnormalities of septic shock as E. coli. These findings indicate that structurally and functionally distinct microorganisms, with or without endotoxin, can activate a common pathway resulting in similar cardiovascular injury and mortality.

Molecular Events in the Cardiomyopathy of Sepsis

“…However, one of the most striking findings in the study was that depression of the left ventricular ejection fraction, as well as the observed acute left ventricular dilatation, were reversible and returned to normal levels after 7 to 10 days in surviving patients (13). This was later confirmed in further patient studies and experimental settings (14)(15)(16)(17). In more recent studies, predominantly using echocardiography, cardiac dysfunction during sepsis and septic shock has been confirmed (18)(19)(20)(21).…”

High Mobility Group Box 1 Induces a Negative Inotropic Effect on the Left Ventricle in an Isolated Rat Heart Model of Septic Shock A Pilot Study

“…[3][4][5] Several previous studies have shown that sepsisassociated cardiac dysfunction is primarily related to circulating myocardial depressant factors, including tumor necrosis factor (TNF)-. 15 However, because TNF-is a sentinel, rapid-response cytokine and is removed from the circulation several days before the resolution of myocardial dysfunction, it is clear that there are other mediators involved.…”

Toll-Like Receptor 2 Mediates Staphylococcus aureus –Induced Myocardial Dysfunction and Cytokine Production in the Heart

“…1 Experimental studies indicate that the pattern of cardiac dysfunction observed in Gram-negative sepsis is also encountered in Grampositive sepsis. 2 Supporting these finding are clinical data showing that ejection fraction recorded in humans with Gram-positive or Gram-negative sepsis does not differ significantly. 3,4 Although these studies suggest that Grampositive and Gram-negative bacteria activate analogous signaling pathways in the heart, progress in the treatment of sepsis-induced myocardial depression has been hampered by a poor understanding of the molecular mechanisms involved in this condition.…”