Distinct functional activities in canine septic shock of monoclonal antibodies specific for the O polysaccharide and core regions of Escherichia coli lipopolysaccharide.

Monoclonal antibodies (MAbs) specific for O polysaccharide or core oligosaccharide/lipid A of Escherichia coli O111:B4 lipopolysaccharide (LPS) were compared in canine septic shock. Animals received O-specific, core-specific, or control murine IgG2a MAbs (or saline) before intraperitoneal implantation of an E. coli O111:B4-infected clot. Animals were further randomized to ceftriaxone or saline. O-specific MAb significantly reduced bacteremia and endotoxemia but not serum tumor necrosis factor. Core-specific MAb significantly increased mean arterial pressure from day 4 to 28 (P = .02). In dogs not receiving ceftriaxone, survival was enhanced by O-specific MAb (4/5) compared with core-specific MAb (0/5) and control (1/8) (P = .03). Survival rates were similar (P = .22) but survival was prolonged in antibiotic-treated animals also receiving O-specific MAb (P = .02 vs. core-specific MAb and controls) or core-specific MAb (P = .08 vs. controls). These data support the complex role of LPS in sepsis and the discrete functional effects of MAbs specific for different elements of LPS.

Myocardial energy metabolism and morphology in a canine model of sepsis.

The mechanism responsible for sepsis-induced myocardial depression is not known. To determine if sepsis-induced myocardial depression is caused by inadequate free energy available for work, we studied myocardial energy metabolism in a canine model of sepsis. Escherichia coli-infected (n = 18) or sterile (n = 16) fibrin clots were implanted intraperitoneally into beagles. Myocardial function and structure was assessed using radionuclide ventriculograms, echocardiograms, and light and electron microscopy. The adequacy of energy metabolism was evaluated by comparing catecholamine-induced work increases [myocardial O2 consumption (MVO2) and rate pressure product (RPP)] with a simultaneously obtained estimate of intracellular free energy [phosphocreatine-to-adenosine triphosphate ratio (PCr:ATP)] determined by 31P-magnetic resonance spectroscopy. When compared with control animals, septic animals had a decrease in left ventricular ejection fraction (EF, P < 0.0001) on day 1 and fractional shortening (FS, P < 0.0003) on day 2 after clot implantation. On day 2, neither septic nor control animals had statistically significant decreases in PCr:ATP, despite catecholamine-induced increases in MVO2 and RPP (mean maximal increases in septic animals 135 +/- 31 and 51 +/- 10%, respectively). Light and electron microscopic findings showed that hearts of septic animals, compared with control animals, had a greater degree of morphological abnormalities. Thus, in a canine model of sepsis with alterations in myocyte ultrastructure and documented myocardial depression (decreased EF and FS), intracellular free energy levels (PCr:ATP) were maintained despite catecholamine-induced increases in myocardial work (increased MVO2 and RPP), suggesting high-energy synthetic capabilities are not limiting cardiac function.

Plasma exchange does not improve survival in a canine model of human septic shock.

Whether plasma exchange would improve survival in antibiotic-treated canines with septic shock was investigated. Escherichia coli O86H8 (1.4 X 10(10)) was surgically implanted as an intraperitoneal clot in 18 two-year-old (10-12 kg) purpose-bred beagles. Beginning 4 hours after surgery, all animals received cefoxitin and gentamicin for 5 days. Three treatment groups were defined: 1) a no apheresis, or control group, (n = 6); 2) a sham apheresis group, whose whole blood plasma was removed, separated, and then transfused (n = 6); and 3) a plasma exchange group from whom blood and plasma were removed and separated, to whom the blood was returned, and in whom infected plasma was replaced with compatible fresh-frozen canine plasma (n = 6). For the sham apheresis and plasma exchange groups, a commercial blood cell processor was used to separate 1.5 blood volumes of plasma at 5 and 24 hours after surgery. Serial radionuclide left ventricular ejection fractions and femoral and pulmonary arterial catheter hemodynamics were measured simultaneously in awake animals. All six animals in the plasma exchange group died. In both the sham and control groups, only one of six animals survived. Survival times were ordered (median in hours) (control [372 h] > sham apheresis [48 h] > plasma exchange [24 h] [p < 0.038]). Decreases in mean cardiac index and mean arterial pressure (from before apheresis to after) at 5 to 7 hours after surgery were ordered (plasma exchange > sham apheresis > control; p < 0.03). Thus, plasma exchange in this controlled trial of septic shock was associated with decreased survival and worsened hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)