Response to immunization after partial and total splenectomy

Survival after infection from Streptococcus pneumoniae in both animals and man is influenced by the amount of splenic tissue. We investigated the effect of differences in splenic weight upon the antibody response to immunization and the effect of immunization upon survival after pneumococcal challenge. Young Sprague-Dawley rats had either sham operation, hemisplenectomy, splenectomy with splenic autotransplantation, or total splenectomy. Nine weeks later, rats were immunized with a heat- and formalin-killed type-specific pneumococcal vaccine. Antibody response measured by radioimmunoassay was similar in all operative groups and was significantly higher than in nonimmune rats (P less than 0.01). Splenic weight was less after hemisplenectomy or autotransplantation than in sham-operated animals (P less than 0.01). Immunization improved survival after live pneumococcal challenge in rats that had autotransplantation and total splenectomy (P less than 0.001). Our results demonstrate that splenic weight does not affect the antibody response to pneumococcal immunization in rats. Immunization improves survival after bacterial challenge in susceptible animals and minimizes the detrimental effect of reduction in splenic mass.     

Reimmunization and splenic autotransplantation: A long-term study of immunologic response and survival following pneumococcal challenge

Splenic autografts have phagocytic function and increase survival after experimental sepsis. The long-term effect of transplant viability, phagocytic capacity, and immunologic responsiveness were evaluated. Rats were divided into experimental groups: control, splenectomized, and splenic autotransplant rats. Approximately one-half of the rats were immunized against pneumococcus. Twelve months later, the rats were reimmunized, and the pneumococcal antibody titers were measured. The effect of operation and immunization was determined by challenging rats with intravenously administered pneumococci. Bacterial clearance from the bloodstream was measured and mortality recorded. Spleens were weighed and examined histologically. In unimmunized rats, pneumococcus was cleared from the bloodstream of control rats, whereas splenectomized and splenic autotransplant rats demonstrated a progressive increase of pneumococci in the bloodstream. However, splenic autotransplant rats grew fewer bacteria after challenge (P < 0.05). All control rats survived. Thirty-three percent of splenic autotransplant rats were alive, but significantly fewer splenectomized rats (6%) survived (P < 0.05). After reimmunization, highest antibody titers were noted in control rats (P < 0.05). Splenic autotransplant rats had higher antibody titers than did splenectomized rats (P < 0.05). Reimmunized splenic autotransplant rats had greater survivorship (71%) when compared with reimmunized splenectomized rats (26%) (P < 0.003). At 1 year, transplants were smaller than control spleens (P < 0.001), although histologic integrity was maintained. Splenic autotransplantation results in better phagocytic function, improved response to reimmunization, and increased survival after pneumococcal challenge and may be an important measure in preventing postsplenectomy sepsis.     

Heterotopic splenic autotransplantation in prevention of overwhelming postsplenectomy infection.

An experimental study was undertaken to evaluate the protective effect of heterotopic splenic autotransplantation in weanling rats. Rats were divided into three experimental groups: splenectomy, control, and splenic autotransplantation. Rats were challenged with i.v. type I pneumococcus. Bacterial bloodstream clearance and survival were determined. Splenic bacterial uptake was measured by determining the isotopic activity of technetium-99m-labeled pneumococci. Autoradiographs and material stained with hematoxylin and eosin and Gram strains were examined for histologic features. All autografts survived and were histologically compatible with normal splenic tissue. Bloodstream clearance of pneumococci was significantly greater in rats with splenic autotransplantation. Splenic autografts had 10 to 30 times greater uptake of pneumocci than did the liver. Rats with autotransplantation had a prolonged survival time. Heterotopic splenic autotransplantation may prove to be an important adjunctive surgical measure in the treatment of children undergoing splenectomy.     

Splenic tissue autotransplantation in rabbits: no restoration of host defense

BACKGROUND: The loss of spleen may increase the incidence of overwhelming sepsis. To prevent this, splenic autotransplantation has been performed in humans and experimental animals. However, there is still controversy about the effectiveness of regenerated splenic tissue in preventing infection. This study explored the effectiveness of splenic tissue autotransplantation in restoring host defense. MATERIALS AND METHODS: Rabbits were divided into three groups: splenic autotransplantation, sham operation, and total splenectomy. Histomorphology, T-lymphocyte count, serum lysozyme levels, hemolysin titers, and pneumococcal clearance were observed as read-out parameters over 24 weeks. RESULTS: Histological study showed that the white pulp was poorly developed and central arterioles were missing in the regenerated splenic tissue of the autotransplanted rabbits. The weight of regenerated spleens recovered 6 months later in the splenic autotransplantation group was 11% of that in the sham operation group and was significantly less than the weight at implantation. There was no significant difference in the number of T lymphocytes or level of serum lysozyme between the three groups. A poor antibody response by the rabbits in the splenic autotransplantation and total splenectomy groups was noted after the primary intravenous administration of sheep red blood cells compared to those of sham operation group. After the challenge with type 3 pneumococci intravenously, pneumococcal clearance from the bloodstream in the splenic autotransplantation group did not differ significantly from that in the total splenectomy group, but was markedly delayed compared with that in the sham operation group. CONCLUSIONS: The low quantity and poor quality of the regenerated splenic tissue contribute to the inferior immunoprotective ability of animals autotransplanted with one-third of the original spleen. This suggests that the regenerated spleen cannot compensate for the immunological function of the original one, especially host resistance to infection.     

Splenic phagocytic function after partial splenectomy and splenic autotransplantation

We investigated splenic reticuloendothelial activity after splenic preservation procedures to determine their effect upon the phagocytic function of the spleen. We performed the following procedures in Sprague-Dawley rats: sham laparotomy, total splenectomy, hemisplenectomy, subtotal splenectomy, or total splenectomy with intraperitoneal splenic autotransplantation. At nine weeks after operation, phagocytic function of the spleen was determined by measuring radiocolloid uptake. Mean (+/- SEM) splenic phagocytic indices for sham laparotomy (41.2 +/- 2.9), hemisplenectomy (44 +/- 2.9), and subtotal splenectomy (43.2 +/- 5.2) were similar; however, the phagocytic index was reduced markedly after autotransplantation (15.8 +/- 2.2). These data demonstrate that the phagocytic function of the spleen after hemisplenectomy and subtotal splenectomy correlates highly with the weight of the splenic remnant; however, phagocytic function after autotransplantation remains reduced even after accounting for differences in splenic weight.     

Immunologic function against infection in splenic autotransplanted mice

The increasing recognition of the danger of overwhelming postsplenectomy infection (OPSI) has led surgeons to attempt to maintain splenic function after spleen injury. One technique they use when splenorrhapy or partial splenectomy are not feasible is the deliberate autotransplantation of splenic tissue. But the amount of splenic tissue necessary to prevent OPSI remains controversial, and opinions differ about the importance of the location and size of the splenic fragments implanted. The mice were divided into five groups, I. splenectomy, II. splenectomy +30% of the spleen implanted intraperitoneal site, III. splenectomy +50% implanted intraperitoneally, IV. splenectomy +50% implanted subcutaneously and V. Sham operation. This study assessed the blood flow of the splenic tissue, increasing weight of splenic mass, histology, the serum level of the immunoglobulins (IgG, IgA, and IgM), pneumococcal antibody titers after vaccination, and survival after intravenous pneumococcal challenge. This study demonstrated that intraperitoneal transplantation showed better regeneration and afforded better protection from OPSI than subcutaneous transplantation. And 30 to 50 percent of the whole splenic tissue mass protected against experimental pneumococcal sepsis. The splenic autotransplants developed in volume and blood supply after 8 weeks, and immunologic function against infection recovered at the same time.     

Pulmonary antipneumococcal defenses after hemisplenectomy

Conservative splenic surgery such as partial splenectomy is advocated for splenic injuries, since splenectomy predisposes individuals to overwhelming sepsis with encapsulated organisms, of which Streptococcus pneumoniae is the most frequently isolated. The respiratory route is argued to be the most likely portal of entry of pneumococci; however, little data exist on the interaction of the spleen and pulmonary defense mechanisms against pneumococcal invasion. We studied the effect of splenectomy, 50% splenectomy (hemisplenectomy), 25% splenectomy, and sham operation on in vivo clearance of live pneumococci from the lungs of male CD-1 mice following an aerosol challenge of pneumococci. Splenectomy impaired pneumococcal clearance from mouse lung pairs and allowed for increased translocation of live pneumococci to tracheobronchial lymph nodes compared to sham-operated controls. Preservation of splenic mass by partial splenectomy improved lung clearance and allowed for fewer bacteria to be cultured from tracheobronchial lymph nodes compared to splenectomized animals. Clearance of live pneumococci from the lungs and survival were directly proportional to the amount of splenic tissue remaining. Splenic factors probably exist which regulate reticuloendothelial cell function throughout the host. Maintaining adequate splenic mass, therefore, is an important consideration when operating for splenic trauma.     

Optimal site and amount of splenic tissue for autotransplantation.

Clinical and basic studies have documented a high susceptibility to pneumococcal infection in asplenic humans and animals. It has been suggested that autotransplantation of splenic tissue might be a method of providing host resistance when total splenectomy is necessary. However, the effect of splenic autograft has remained controversial. This study was performed to evaluate the most effective site and amount of splenic autograft using rats. Rats were divided into five groups for the purpose of determining the site of splenic autotransplantation: splenectomy, sham operation, implantation into the omental pouch, intraperitoneal implantation, and intramuscular implantation. For determining the amount for autotransplantation, the rats were divided into seven groups: splenectomy, sham operation, and implantations of 25, 50, 100, 200, or 300 mg of splenic tissue. All animals were challenged with Streptococcus pneumoniae type 6, 16 weeks after surgery. Howell-Jolly bodies appeared postsplenectomy, but disappeared in the implanted rats 16 weeks after the operation. Histologically, the implanted tissue was indistinguishable from that of a normal spleen. Pneumococcal clearance from the bloodstream and survival rate were significantly higher in rats implanted in the omental pouch as compared with splenectomized rats. Intraperitoneal and intramuscular implanted rats did not show a significant difference from the splenectomized rats. More than 50% of splenic tissue for autograft showed a significant increase in pneumococcal clearance and survival rate as compared with that of splenectomized rats. It was suggested that the most effective site of autotransplantation is the omental pouch and approximately 50% of the whole spleen would be necessary for prevention from sepsis.     

Serum antibody responses to pneumococcal vaccine after splenic autotransplantation

Immunization with pneumococcal capsular polysaccharide vaccines is advocated after splenectomy; however, experimental and clinical data suggest an impaired antibody response in splenectomized individuals. This study examined the value of splenic autotransplantation at various sites in augmenting the antibody response to Type III pneumococcal capsular polysaccharide in mice immunized 3 months after operation. Splenectomy resulted in impaired antibody responses compared to sham-operated mice (p less than 0.001) using an enzyme-linked immunosorbent assay. Mice with intraperitoneal splenic autotransplants, but not mice with subcutaneous or intramuscular transplants, had greater antibody responses compared to splenectomized mice (p less than 0.05). Antibody responses were elevated only in mice autotransplanted with 50% or more of the original splenic mass. Since autotransplantation of splenic tissue augments the antibody response to pneumococcal capsular polysaccharides, the combination of splenic autotransplantation and pneumococcal vaccination may confer more protection than either modality alone in individuals who must undergo splenectomy.     

Penicillin and natural immunity protect against postsplenectomy sepsis

Prophylactic penicillin, splenic autotransplantation, and immunization using pneumococcal vaccine have all been shown to reduce the incidence and mortality of postsplenectomy sepsis. However, little is known regarding the effect of penicillin in established infection or the effect of prior infection in either asplenic controls or animals with autotransplanted splenic tissue. An animal model with bacterial introduction via the lungs was used to investigate the effect of penicillin, splenic autotransplantation, and previous exposure to the infecting organism on the mortality of postsplenectomy sepsis. One hundred fifty-nine rats underwent either sham celiotomy, intraperitoneal splenic autotransplantation, or splenectomy. Twelve weeks postoperatively all animals were challenged using Streptococcus pneumoniae delivered transtracheally. Half of each group received procaine penicillin by intramuscular injection for 5 days beginning 24 hr post bacterial inoculation and mortality was observed. Eight weeks later surviving rats that had received penicillin were reinoculated with the same organism and mortality was again observed. Splenic autotransplantation reduced the early mortality in postsplenectomy sepsis. Prior bacterial exposure reduced the mortality in postsplenectomy sepsis, even in splenectomized animals. Treatment with penicillin produced a marked reduction in mortality even when administration was postponed for 24 hr after bacterial inoculation.     

Decreased phagocytic capacity of autotransplanted splenic tissue

Background: Asplenic patients have an increased risk of infections. Operations such as autotransplantation have been proposed to restore functional splenic tissue after splenectomy, but the protective value of this tissue is unclear. Immune responses such as production of antibody remain impaired in humans and animals even when such tissue is present, and clearance of particles from the blood is reported to be less efficient than by normal spleen tissue. The present study investigated the phagocytic capacity of cells in the regenerated tissue in vitro, free of the confounding effects of hepatic clearance. Methods: Single cell suspensions were prepared from splenic tissue from rats 6 months after splenic autotransplantation or sham operation. Phagocytosis of killed, fluorescein‐labelled bacteria was measured by flow cytometry. Results: Autotransplanted tissue contained fewer phagocytic cells than normal tissue, and these cells phagocytosed less per cell. Phagocytosis by spleen cells was dependent on heat‐labile opsonic factors. Conclusions: Autotransplanted splenic tissue does not restore the phagocytic capacity lost following splenectomy.     

Immune response capacity after human splenic autotransplantation: restoration of response to individual pneumococcal vaccine subtypes

OBJECTIVE: To evaluate features of general immune function, in particular the restoration of the humoral immune response to pneumococcal capsular polysaccharides, in humans undergoing a spleen autotransplantation after splenectomy because of trauma. SUMMARY BACKGROUND DATA: After splenectomy, patients have an increased risk of overwhelming infection or sepsis involving encapsulated bacteria such as pneumococci. The value of human spleen autotransplantation after splenectomy because of trauma has long been questioned. Mononuclear phagocyte system function appeared to be similar to that in splenectomized persons. The presence of specific antipneumococcal antibodies would allow other parts of the mononuclear phagocyte system, such as those in the liver, to phagocytose opsonized bacteria. METHODS: Ten consecutive patients undergoing splenectomy followed by autotransplantation were compared with the next 14 consecutive patients undergoing splenectomy alone. After a minimum of 6 months, the patients were vaccinated with 23-valent pneumococcal vaccine. Blood samples were taken at the time of vaccination and after 3 and 6 weeks for antipneumococcal capsular polysaccharides IgM and IgG enzyme-linked immunosorbent assay against types 3, 4, 6, 9, 14, and 23. Splenic regrowth was evaluated by scintigraphy. RESULTS: Surprisingly, several of the nonautotransplanted patients showed scintigraphic activity, indicating the presence of either accessory spleens or traumatic seeding (splenosis). Significant antibody titer increases (more than twofold) were found for both IgM and IgG in the autotransplanted patients. Splenectomized-only patients showed no significant increase in Ig levels in patients without splenic regrowth and partial improvement in patients with splenosis/accessory spleens. CONCLUSIONS: Considering this significant antipneumococcal antibody increase, spleen autotransplants can be expected to permit an adequate humoral response to pneumococcal infections and presumably also to other TI-2 antigens, and to protect against overwhelming postsplenectomy infection or sepsis.     

Intraportal splenic autotransplantation in rats: Feasibility and effectiveness

This experiment was designed to see whether or not normal host resistance to infection could be reestablished in splenectomized animals by intraportal autotransplantation of homogenized splenic tissue. Part I studied the feasibility of the technique. Within 1 hr of splenectomy, 16 adult Lewis rats received an intraportal injection of autogenous splenic tissue which had been passed through a 500-μm screen. Five rats died acutely from hemorrhage at the site of injection. The others tolerated the infusion well, both acutely and chronically. The animals developed only transient elevations in liver enzymes; chronic portal hypertension did not occur. Histologically, splenic tissue could be demonstrated within terminal portal venules. Part II assessed the effectiveness of intraportal splenic autotransplantation. Eight to twelve months after splenectomy, autotransplantation, or sham operation, 103 Sprague-Dawley rats were challenged with intravenous boluses of 10⁵ to 10⁸ pneumococci. Mortality was 91% for splenectomized animals, 88% for animals bearing autotransplants, and 59% for controls. Thus intraportal splenic autotransplantation is technically feasible in rats. The grafts are well tolerated by the liver, and splenic tissue is preserved in intimate contact with the blood stream. Even after 8 to 12 months, however, such autografts are not capable of providing normal protection against massive pneumococcemia.     

The effects of splenectomy and splenic implantation on alveolar macrophage function

The effect of splenectomy on the ability of alveolar macrophages of young and adult rats to phagocytize Pneumococci, Types 3 and 14, and Pseudomonas aeruginosa was studied. Young animals showed a significant (15%) decrease in the phagocytosis of pneumococci type 14, 4 weeks after splenectomy. This depression increased to 30% in 6 weeks' time. Such depression was also noted when young splenectomized rat alveolar macrophages were challenged with Pseudomonas aeruginosa but not with type 3 pneumococci 6 weeks postsplenectomy. Three months following splenectomy in young animals, the rats were grown and they seemed to regain their normal phagocytic activity against pneumococci type 14. Adult rats also showed no alteration in their phagocytic activity against type 3 pneumococci. Autoimplantation of the spleen had a protective effect on the phagocytosis of type 14 pneumococci, and a nonsignificant effect on that of type 3. The present study postulates a modulatory role of the spleen on alveolar macrophage function. Splenectomy may cause the impairment of local lower respiratory immune function, making lungs vulnerable to specific bacterial invasion. Such splenic modulatory effect on alveolar macrophage phagocytic function seems to be age and antigen specific.     

Overwhelming pneumococcal infection in rats immediately after splenectomy

A rat model was used to evaluate the possibility that a nonspecific factor of splenic origin, promoting opsonization and/or antibody production, could affect the susceptibility to pneumococci after splenectomy. Streptococcus pneumoniae type 1 4 × 10³ CFU was injected intravenously in Sprague-Dawley rats. In Experiment I, two groups of previously splenectomized rats (15 at 7 weeks and 15 at 14 weeks of age) were challenged with pneumococci at the age of 15 weeks. All these rats succumbed with no difference in survival time between the two groups. In contrast, the entire control group of 10 nonsplenectomized (sham-operated) rats challenged peroperatively with pneumococci survived. In experiment II, 62 animals were divided into two equal groups. One group was splenectomized when 9 weeks old, and the other was subjected to omental resection (sham operation) at the same time. Two weeks later splenectomy was performed on previously oment-resected animals and the remaining animals were sham-operated. At the second operation all animals were challenged with pneumococci. In each group 74% died and survival times did not show any difference between the two groups. In experiment III splenectomy was performed on 37 9-week-old rats. Two weeks later 20 of these were subjected to omental resection, and in the remaining 17, intraabdominal deposition of homologous dispersed splenic tissue was carried out. Peroperatively, pneumococci were injected intravenously. No difference between the two groups as regards mortality rate or survival times was registered. These experiments revealed no factor remaining briefly after splenectomy that could affect the susceptibility to intravenous injection of Streptococcus pneumoniae type 1.     

Immunization with heat-killed pneumococci, but not pneumococcal capsular polysaccharides, improves survival in splenectomized mice

Immunization with pneumococcal capsular polysaccharides (pn PS) is advocated after splenectomy to decrease the risk of overwhelming sepsis. The clinical and experimental evidence for the benefit of immunization after splenectomy is controversial. Various reports in the literature have claimed a benefit of immunization after splenectomy, but careful review of methodologies reveals that heat-killed pneumococci (pn) were used to immunize the experimental animals. Since we have not been able to protect splenectomized (splx) mice by immunization with pn PS, we compared survival after live pneumococcal aerosol challenge and antibody (Ab) responses in splx and sham splx mice immunized with either pn PS or heat-killed pn. Immunization with either heat-killed type 3 pn or pn type 3 PS improved survival in sham-splx mice compared to saline controls (p less than 0.001). Only immunization with heat-killed type 3 pn improved survival in splx mice (p less than 0.001), while pn PS had no effect on survival compared to saline splx controls. Ab responses to pn type 3 PS measured by enzyme linked immunosorbent assay were depressed in splx mice compared to sham-splx mice regardless of the method of immunization. Sham-splx mice immunized with heat-killed pn had higher Ab levels compared to mice vaccinated with pn PS (p less than 0.001) suggesting an adjuvant effect in sham-splx mice. The data suggest that immunization with pn PS may not be beneficial to a splx host. Improved survival after immunization with heat-killed bacteria in splx mice may be related to Ab responses to antigens other than the capsular polysaccharide.     

Splenic autotransplantation: determination of the optimum amount required for maximum survival

Splenic salvage in cases of traumatic or iatrogenic injuries may require autotransplantation of splenic fragments when splenorrhaphy or partial splenectomy is not possible. There are no studies which address the issue concerning the optimal amount of spleen to be transplanted in order to yield maximal survival in a model of pneumococcal sepsis. This study uses a Sprague-Dawley rat model to attempt to clarify this issue. Animals were divided into seven groups: control, total splenectomy, 25, 40, 60, 80, and 100% omental pouch autotransplantation. These animals were challenged with intravenous Streptococcus pneumonia Type I after 24 weeks, and mortality and blood culture results were monitored. Transplants were recovered and weights were compared with the weights originally transplanted. Survival and blood culture results were seen to improve in a linear quantitative fashion as the amount of spleen autotransplanted increased up to 80%, after which no further improvement was seen. This data supports the autotransplantation of 80% of the spleen in the Sprague-Dawley rat as the optimum amount to achieve maximal survival in a model of pneumococcal sepsis.     

Splenic autotransplantation provides protection against fatal sepsis in young but not in old rats.

Splenectomy increases the risk of contracting infections with high mortality. Thus, splenic tissue should be repaired orthotopically whenever possible. If all attempts fail, splenic autotransplantation might be a suitable method for splenic salvage. The protective function of such transplants in adults has been questioned, leading to a decreased frequency of splenic autotransplantations. However, the regeneration of splenic tissue is better in the young organism than in the old, suggesting that the protection provided by regenerated splenic tissue might be more reliable in children than in adults. In addition, children are at a higher risk in the case of overwhelming postsplenectomy sepsis. The protection warranted by regenerated splenic tissue after autotransplantation at different ages was examined using a highly standardized animal model. Sham operation, splenectomy, and splenic autotransplantation were performed on adult, weanling, and newborn rats, and Streptococcus pneumoniae was applied intranasally 9 months after the operation. After pneumococcal challenge about 80% of the splenectomized animals in the different age groups died of infection, whereas only 20% of the sham operated rats died. Regenerated splenic tissue resulting from splenic autotransplantation performed on adult or weanling rats demonstrated no protective function. However, in newborn rats with transplanted splenic tissue, both survival rate and survival time were increased significantly. Determination of lymphocyte subsets in the blood did not allow the protective role of splenic transplants to be predicted. This study indicates that disappointing results of splenic autotransplantation in adult patients should not lead to false pessimism about the role of this operation in children.     

Methods of splenic preservation and their effect on clearance of pneumococcal bacteremia.

The intravascular clearance of type 3 Streptococcus pneumoniae was studied in Sprague-Dawley rats. Sham celiotomy was performed on 20 animals while another 20 rats underwent splenectomy. Four weeks later, bacteremia was induced by intraperitoneal (IP) injection of S. pneumoniae. Serial cultures of peripheral blood were obtained. Splenectomy produced significant impairment of intravascular clearance of bacteria compared to that noted among control animals (p less than 0.01). Eighty animals were divided into four equal groups: I--splenectomy, II--50% splenectomy with the upper half left in situ connected to the short gastric vessels, III--50% splenectomy with the lower half left in situ connected to the hilar vessels, and IV--splenectomy with implantation of splenic fragments. Pneumococcus was administered IP 16 weeks later. Rats were killed 6 hours after bacterial challenge. Residual splenic tissue was weighed. There was significantly less splenic tissue in Groups II-IV than noted in sham animals after 16 weeks (p less than 0.01). The type of partial splenectomy did not significantly affect the weight of residual splenic tissue 16 weeks later. Implantation did yield viable splenic tissue, though the amount proved significantly less than that resulting from either type of partial splenectomy (p less than 0.01). Mean bacterial counts with time for short gastric (Group II) and hilar (Group III) remnant animals were significantly different from those for the asplenic (Group I) rats (p less than 0.02 and p less than 0.001, respectively). Animals with splenic implants (Group IV) were not significantly different from asplenic rats (Group I). Animals with hilar splenic remnants proved significantly different from those with short gastric splenic remnants (p less than 0.01). Partial splenectomy offers protection against pneumococcal bacteremia, though preservation of the hilar blood supply affords the most benefit. The utility of splenic implantation remains unproven.     

Influence of splenectomy, partial splenectomy and splenic artery ligation on E. coli sepsis in rats

Male Sprague-Dawley rats were allocated to four groups--sham operation, partial splenectomy, splenic artery ligation or total splenectomy, and 4 weeks after the operation 3 x 10(8) colony-forming units of Escherichia coli were injected intraperitoneally. Among the splenectomized rats the mortality was significantly (p less than 0.02) increased compared with the controls, while both partial splenectomy and splenic artery ligation did not influence survival. Blood clearance and organ (liver, spleen and lungs) uptake of intravenously injected, radiolabelled, heat-killed E. coli were determined 1 hour after the intraperitoneal challenge. Splenectomy caused a significant decrease in blood clearance. Splenic uptake of radiolabelled E. coli was significantly reduced following partial splenectomy and splenic artery ligation. The splenic operations increased hepatic uptake expressed per gram tissue. Splenectomy thus resulted in reduced blood clearance and increased mortality in Gram-negative sepsis, while the reduced splenic uptake following partial splenectomy or splenic artery ligation did not influence blood clearance of E. coli or mortality.