Lipopolysaccharide- and superantigen-modulated superoxide production and monocyte hyporesponsiveness to activating stimuli in sepsis.

The effects of acute and prior exposure to lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB) on superoxide release by monocytes were examined in control subjects and in patients with sepsis and septic shock during the acute stage and recovery. High doses of LPS, PMA (phorbol 12-myristate 13-acetate), and SEB stimulated monocyte superoxide release in control subjects (P < 0.05). Pretreatment of normal monocytes with these doses of LPS, PMA, and SEB induced significant hyporesponsiveness to subsequent challenge (P < 0.01), and evidence of cross-tolerance was observed. Monocytes isolated from patients with sepsis and septic shock demonstrated high spontaneous superoxide release compared with those of control subjects (P < 0.05). Stimulation of patient monocytes with LPS or SEB resulted in less superoxide production than that spontaneously released by controls (P < 0.01). In patients recovering from their initial infection, spontaneous superoxide release was less than that released during acute stage. In addition, the superoxide release in response to the same stimuli was significantly increased when compared with release during the acute stage (P < 0.05). These data demonstrate that both LPS and SEB induce hyporesponsiveness to LPS- or SEB-stimulated superoxide release. A similar pattern of hyporesponsiveness was observed during sepsis that may represent a mechanism for modulating the inflammatory response during severe infections.

Comparison of cardiovascular effects of tiletamine-zolazepam, pentobarbital, and ketamine-xylazine in male rats.

We allocated 35 male Sprague-Dawley rats into 7 groups and anesthetized each by using one of the following regimens: ketamine 50 mg+xylaxine 5 mg; ketamine 75 mg+xylazine 5 mg; pentobarbital 45 mg; and Telazol 30, 40, 50, and 60 mg/kg; supplemental doses were used as required. Respiratory rate, heart rate, mean arterial pressure, cardiac index, and stroke index were measured every 30 min for 4 h. The Telazol groups showed a dose-dependent increase in duration of anesthesia. Duration of anesthesia was significantly shorter for the ketamine and pentobarbital groups than for any of the Telazol doses. Heart rate showed a dose-dependent decrease among the Telazol groups, but overall heart rate in these groups was higher than in the ketamine and pentobarbital groups. Mean arterial pressure in the Telazol 40 and 50 groups was significantly higher than the pentobarbital and higher ketamine groups yet lower than that of the Telazol 60 group. Overall animals anesthetized with Telazol showed the highest cardiac index, ketamine intermediate, and pentobarbital the lowest; cardiac index was higher in the Telazol 50 group than in either the Telazol 30 or pentobarbital groups. The pentobarbital group exhibited the lowest stroke index, whereas ketamine-treated animals had an intermediate stroke index. These differing effects of anesthetics on cardiovascular parameters must be considered when choosing an anesthesia regimen or comparing data from different studies. In our model, the Telazol 40 and 50 groups appeared to exhibit the fewest adverse cardiovascular effects.

Mechanisms of platelet-neutrophil interactions and effects on cell filtration in septic shock.

ABSTRACT-We examined the mechanisms and the adhesive molecules mediating platelet-neutrophil adhesion in patients with septic shock. Neutrophils, platelets, and platelet poor plasma (NPPP) were isolated from 12 normal volunteers. Platelets and neutrophils were stimulated with platelet poor plasma (SPPP) removed from 12 patients in septic shock. Cell adhesion was assessed by filtration through 5-microm pore filters and by flow cytometry. Blocking monoclonal antibodies were used against the platelet and neutrophil surface receptors glycoprotein complex IIb/IIla, P-selectin, ICAM-2, CD11a, CD11b, and CD18. The filtration pressure (Pi) of cells suspended in SPPP was significantly greater than that of cells suspended in NPPP (24 +/- 1.0 mmHg vs. 14 +/- 1.0 mmHg; P< 0.05). The difference between the Pi of cells suspended in SPPP or NPPP (deltaPi SPPP-NPPP) in the presence of monoclonal antibodies anti-CD41, anti-CD62P, abciximab, anti-CD11a, anti-CD11b, and anti-CD18 was significantly less than the APi SPPP-NPPP of cell suspensions without the addition of these monoclonal antibodies (P < 0.01). The greatest reduction in Pi occurred when platelet receptor P-selectin was blocked simultaneously with the CD11b receptor on the neutrophil as compared to all other single blocking monoclonal antibodies or combinations of monoclonal antibodies. The mean fluorescence of activated platelet CD63-PE binding to neutrophils suspended in SPPP was significantly greater than that of cells suspended in NPPP (780 +/- 130 Ifu vs. 295 +/- 35 Ifu; P < 0.05). The greatest attenuation in mean fluorescence occurred by blocking the P-selectin receptor on the platelet simultaneously with CD11b receptor on the neutrophil. We conclude that platelet-neutrophil aggregation is increased in septic shock. This aggregation is mediated by the interaction of multiple platelet and neutrophil surface receptors. The platelet receptor P-selectin and the neutrophil receptor CD11b/CD18 appear to play the most important role in these interactions.