Radiodetoxified endotoxin-induced tolerance alters monocyte but not neutrophil CD11b and CD18 expression in response to lipopolysaccharide.

OBJECTIVES: To test the hypothesis that pretreatment with radiodetoxified endotoxin (RDE) may mitigate the deleterious effects of subsequent infection, in part by modifying leukocyte adhesion receptor expression, and to investigate the cellular mechanisms of endotoxin tolerance induced by RDE. DESIGN: To assess the effect of RDE pretreatment on mortality from bacterial peritonitis, rats were implanted with an intraperitoneal, barium-fecal inoculum at intervals of 0, 1, 3, and 5 days after RDE injection. Experiments were then conducted to test the effect on leukocyte adhesion receptor expression. Two groups of mice received saline solution, and one group, RDE. After 72 hours, one group received saline solution (saline/saline group), the others, lipopolysaccharide (LPS) (saline/LPS and RDE/LPS groups). Peripheral leukocytes were obtained 1 hour after injection and were analyzed for CD11b and CD18 expression by flow cytometry. SETTING: Laboratory animal study. RESULTS: Survival rates were not improved in rats that were pretreated with RDE 0 and 24 hours before inoculum (0% and 7%, respectively). In rats that were pretreated 72 hours and 120 hours before inoculum, 47% (P < .01) and 60% (P < .01) survived, respectively. CD18 expression on polymorphonuclear leukocytes increased twofold in the RDE/LPS (mean +/- SEM, 300.3 +/- 32.9) and the saline/LPS (mean +/- SEM, 360.4 +/- 59.9) groups compared with controls (mean +/- SEM, 176.4 +/- 18.9) (P < .05). CD11b expression on polymorphonuclear leukocytes increased threefold in the RDE/LPS (mean +/- SEM, 91.3 +/- 8.1) and the saline/LPS (mean +/- SEM, 89.8 +/- 11.4) groups compared with controls (mean +/- SEM, 32.1 +/- 1.8) (P < .05). CD18 expression on monocytes decreased in the saline/LPS group (mean +/- SEM, 134.2 +/- 14.2) and was unchanged in the RDE/LPS group (mean +/- SEM, 200.2 +/- 17.2) compared with controls (mean +/- SEM, 217.6 +/- 16.5) (P < .05). CD11b expression on monocytes decreased in the saline/LPS group (mean +/- SEM, 25.8 +/- 2.2) and was unchanged in the RDE/LPS group (mean +/- SEM, 36.4 +/- 0.9) compared with controls (mean +/- SEM, 39.7 +/- 3.9) (P < .05). CONCLUSIONS: Radiodetoxified endotoxin reduces mortality rates from bacterial peritonitis when given at least 72 hours prior to a bacterial inoculum. Tolerance to subsequent LPS challenge is associated with an abrogation of the reduced peripheral monocyte CD11b and CD18 expression observed in native LPS-stimulated mice but is not associated with changes in polymorphonuclear leukocyte CD11b and CD18 expression. The mechanism of the observed RDE-induced monocyte hyporesponsiveness to LPS and its possible protective effect is uncertain and requires further investigation.

Leukocyte CD11b and CD18 expression are increased in blood salvaged for autotransfusion.

To investigate whether activated leukocytes are present in salvaged blood, we measured complete blood counts and quantified the surface expression of the leukocyte adhesion receptors CD11b and CD18 in salvaged blood and arterial blood from six male patients undergoing elective abdominal aortic aneurysm repair. Salvaged blood contained 5,450 +/- 1010 leukocytes/microL and 7600 +/- 6200 platelets/microL and had a hematocrit of 50.6 +/- 3.7%. CD 11b expression was 3.3 +/- 0.5 fold higher on neutrophils and 3.8 +/- 1.0 fold higher on monocytes from salvaged blood compared with arterial blood (P < 0.05 for both). CD18 expression was increased 3.2 +/- 0.2 fold on neutrophils and 2.5 +/- 0.4 fold on lymphocytes (P < 0.05) in salvaged compared to arterial blood (P < .05). Monocyte expression of CD18 was increased 4.50 +/- 1.1 fold in salvaged blood, but this difference was not statistically significant. We conclude that a substantial number of activated leukocytes are present in salvaged blood. Because activated leukocytes could potentially be detrimental to the recipient, our findings raise theoretical concerns about the use of salvaged blood and emphasize the need for further refinement of the procedure.

High porosity PTFE improves endothelialization of arterial grafts without increasing early thrombogenicity.

OBJECTIVE: High porosity (HP) (90 micron internodal distance) PTFE grafts were implanted into the carotid and femoral arteries of dogs to investigate early thrombogenicity, patency, and endothelialization. EXPERIMENTAL DESIGN: Standard PTFE (STD) grafts (30 micron internodal distance) were used as controls. 12 HP and 12 STD grafts were implanted into 6 dogs. Indium-111 labeled platelets were infused intravenously after graft implantation. A graft platelet accumulation index (GPAI) was calculated as the ratio of radioactive emission from the PTFE grafts excised at 48 hours to the emission from a native arterial segment. Another 12 HP and 12 STD grafts were implanted into femoral and carotid arteries to assess patency and endothelialization at 4 and 18 weeks. RESULTS: There was no significant difference in the GPAI of the HP and STD grafts at either the carotid (HP = 31.5 +/- 9.7, STD = 30.6 +/- 11.8; p > 0.05) or femoral (HP = 34.0 +/- 5.0, STD = 31.5 +/- 7.9; p > 0.05) positions. Combined data (carotid and femoral HP vs. carotid and femoral STD) also did not demonstrate a difference in GPAI (HP = 32.8 +/- 7.5, STD = 31.1 +/- 9.6; p > 0.05). Patency rates were the same at 4 weeks (75%), but greater in the HP grafts at 18 weeks (HP = 75%, STD = 37%; p > 0.05). No difference was noted in the percentage of graft endothelialization at 4 weeks (HP = 5.2 +/- 5.8, STD = 5.0 +/- 4.0; p > 0.05), however, at 18 weeks the HP graft had significantly more endothelial coverage compared to STD grafts (HP = 75.2 +/- 13.9, STD = 22.6 +/- 9.5; p < 0.01). CONCLUSIONS: Given that HP PTFE is no more thrombogenic than STD PTFE, and that it provides superior endothelialization, HP grafts should continue to be developed and studied for potential clinical use.

Vascular access surgery as an outpatient procedure.

Construction of a vascular access site for hemodialysis has traditionally been done on an inpatient basis or more recently in a hospital operating room as a 1-day admission. Over 18 months we performed 49 vascular access procedures on 45 patients in a freestanding ambulatory surgical center. Four patients had an arteriovenous radiocephalic autogenous fistula constructed, 30 patients had a polytetrafluoroethylene (PTFE) prosthesis inserted as an arteriovenous bridge graft, 11 patients had a planned reconstruction of a previously placed graft, 1 patient had a false aneurysm corrected, 1 patient had a chronically infected graft removed, and 2 patients had a thrombectomy. All procedures were in the upper extremities except for one femorosaphenous PTFE graft and one excision of a false aneurysm in a thigh prosthesis. Only one patient, an 84-year-old woman, required hospitalization following the outpatient procedure because she was unable to care for herself. No postoperative infection had occurred at 1 month follow-up. A left upper extremity graft performed at another inpatient facility was removed because of infection. The protocol for outpatient vascular access surgery includes preoperative evaluation of the patient for determination of the access site within a week of operation; duplex scan of subclavian veins if central venous lines have been in place for more than 2 weeks; scheduling surgery for the afternoon or morning following routine hemodialysis; obtaining a hemoglobin level, serum/electrolyte study, and an ECG following the last hemodialysis; parenteral antimicrobial prophylaxis; local infiltration anesthesia with standby; a minimum of 1 hour of observation in the recovery room; and a repeat hematocrit study prior to discharge.(ABSTRACT TRUNCATED AT 250 WORDS)