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.     

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.     

Does survival depend on the amount of autotransplanted splenic tissue?

Susceptibility to Streptococcus pneumoniae infection was studied in 11 groups of rats allocated to sham operation, splenectomy, or splenic autotransplantation of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the removed spleen. Three months later, all rats were exposed intravenously to type 1 Streptococcus pneumoniae (median lethal dose, LD50, for control group). Survivors were killed 13 days after the bacterial challenge. Autopsy showed that more splenic tissue was recovered in rats that received less than 50% splenic tissue compared with those that received 50% or more. More survivors were found among sham-operated rats (47.5%; 95% confidence intervals, 32 to 68) and rats that had 40% splenic tissue implanted (35%; confidence interval, 20 to 54) or those that were found to have regenerated 40% splenic tissue. We conclude that 40% of the spleen should be autotransplanted to protect the rat optimally against infection after splenectomy.     

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.     

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.     

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 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.     

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.     

脾切除对肺内细菌清除和移位的影响

目的:探讨脾切除对肺内细菌清除及移位的影响,同时观察自体脾组织移植的应用效果.方法:将Wistar大鼠90只随机分为假手术组、脾切除组和半脾移植组,采用肺炎球菌悬液雾化吸入方法攻击动物,观察肺组织学病变,肺内细菌清除和移位状况.结果:脾切除组动物肺组织严重充血肿胀,炎性细胞浸润少,肺内细菌清除功能降低,细菌向肺门淋巴结移位和侵入血流加快,与假手术组比较有显著性差异(P<0.05),但半脾移植组动物能基本恢复对肺炎球菌的抵抗能力.结论:脾切除后动物肺抗菌功能降低,而自体脾组织移植是保留脾功能的有益术式.     

Intraperitoneal splenic implants do not alter clearance of pneumococcal bacteremia

The effect of intraperitoneal splenic autotransplants was studied in Sprague-Dawley rats. Twenty animals underwent total splenectomy. Splenectomy was performed in another group of 20 rats, after which the spleen was diced into 15 pieces and replaced within the leaves of the small bowel mesentery. Twelve weeks later pneumococcal bacteremia was induced by intraperitoneal injection of 5 X 10(6) Streptococcus pneumoniae. Quantitative blood cultures were obtained from the tail vein 15, 30, 45, 60, 90, and 240 minutes after injection. Mean bacterial counts with time for animals bearing splenic autotransplants were not significantly different from completely asplenic rats. At autopsy, all animals receiving splenic implants were found to have viable splenic tissue among the leaves of the small bowel mesentery. This study shows that even allowing 12 weeks for maximal regeneration, splenic autotransplants fail to significantly alter the clearance of an established bacteremia.     

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.     

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.     

The value of partial splenic autotransplantation in patients with portal hypertension: a prospective randomized study.

HYPOTHESIS: Splenic autotransplantation plays a role in preserving immune function of the spleen in patients with portal hypertension and liver cirrhosis. DESIGN: Prospective randomized study. SETTING: University hospital. PATIENTS: Twenty patients (19 men and 1 woman; aged 33-80 years) suffering from portal hypertension and liver cirrhosis were randomly allocated into 2 groups. Each group consisted of 10 patients. INTERVENTIONS: All patients underwent modified Sugiura operation. In the control group, splenectomy was performed, while partial splenic autotransplantation into the retroperitoneal space was additionally completed in the splenic autotransplantation group. MAIN OUTCOME MEASURES: Serum tuftsin and IgM were measured preoperatively and 2 months after surgery. Dynamic scintigraphy with technetium Tc 99m-labeled heat-damaged erythrocytes was performed at 2-month intervals during the 8-month follow-up. RESULTS: There was no statistical difference in the mortality of the groups. The preoperative levels of serum tuftsin and IgM showed no statistical difference between groups. However, although these measures had decreased remarkably in the control group 2 months after operation (P<.001 for serum tuftsin; P =.04 for serum IgM), they remained stable in the splenic autotransplantation group (P =.25 for serum tuftsin; P =.12 for serum IgM). Four patients within the splenic autotransplantation group showed positive scanning of the transplanted splenic fragment during follow-up, whereas there was no positive scanning in the control group. CONCLUSION: Our results suggest that partial splenic autotransplantation can preserve immune function of the spleen, as measured by serum levels of tuftsin and IgM, in patients with portal hypertension and liver cirrhosis.     

腹膜后自体脾移植术在肝硬变门静脉高压症治疗中的临床研究

目的　观察腹膜后自体脾移植联合食管下段横断术治疗肝硬变门静脉高压症的临床效果。方法　将20例肝功能Child A、B级的肝硬变门静脉高压症患者随机均分为自体脾移植组和切脾组。自体脾移植组采用自体带蒂脾组织腹膜后移植联合改良的食管下段横断术,切脾组则采用脾切除联合改良的食管下段横断术。以患者术前的情况为对照,在术后2~6 个月观察患者的一般情况、脾扫描、肝功能、血清促吞噬素(tuftsin)及IgM水平。结果　术后第6天切脾组死亡1例,术后第10天脾移植组出现再出血1 例。自体脾移植组术后血清tuftsin、IgM水平高于切脾组,差异有显著性意义(P<0.01),而对肝功能无明显影响。结论　腹膜后自体脾移植能维持脾脏的基本免疫功能,且能长期存活,在临床上推广应用是可行的。     

Relative merits of partial splenectomy, splenic reimplantation, and immunization in preventing postsplenectomy infection.

Partial splenectomy, splenic autotransplantation, and immunization with pneumococcal vaccine have been reported to protect patients against overwhelming postsplenectomy infection, and this study was undertaken to evaluate these therapeutic alternatives. For this purpose 136 rats were divided into experimental groups: 34 controls, 34 splenectomy, 34 partial splenectomy, and 34 splenic autotransplantation animals. Five weeks after operation, two-thirds of the animals were immunized with killed pneumococci. The effects of operation and immunization were studied by challenging the animals intravenously with pneumococci. Pneumococcal antibody titers were determined, and phagocytic uptake of pneumococci by the spleen and liver was measured. Immunization impressively increased the survival rate in all groups. At low-challenge doses autotransplantation prolonged survival. At higher-challenge doses only partial splenectomy increased survival. Partial splenectomy and control animals had higher antibody titers than did splenectomy and autotransplantation rats. Animals with the highest antibody titers had the greatest splenic and hepatic phagocytic uptake of pneumococci. Partial splenectomy was more efficient in removing pneumococci than was autotransplantation. Thus immunization is one of the most important factors contributing to survival after splenectomy. Partial splenectomy is preferable to splenic autotransplantation because it is associated with higher antibody titers after immunization, better pneumococcal splenic uptake, and improved survival rates.     

自体脾移植联合食管横断吻合术治疗肝硬化门静脉高压症

目的 探讨腹膜后自体脾移植联合食管横断吻合术治疗肝硬化门静脉高压症的临床疗效.方法 将2003年1月至2006年12月收治的36例肝硬化门静脉高压症患者随机分为自体脾移植组(n=18)和脾切除组(n=18),自体脾移植组接受脾切除、食管横断吻合及自体脾移植术,脾切除组接受脾切除、食管横断吻合术.于术前及术后2～6个月定期观察两组患者的一般情况、行脾脏放射性核素扫描,同时检测肝功能、血清促吞噬素(Tuftsin)及IgM水平,并行组间及手术前后比较分析.结果 自体脾移植组患者术后2个月血清Tuftsin和IgM水平与术前比较无明显差异(P0.05),而脾切除组患者术后2个月血清Tuftsin和IgM水平较术前明显降低(P<0.05);自体脾移植术对患者肝功能无明显影响;术后2个月放射性核素扫描证实移植脾于腹膜后存活.结论 自体脾移植对保留机体脾脏免疫功能具有重要价值,腹膜后自体脾移植联合食管横断吻合术治疗肝硬化门静脉高压症的临床效果确切,值得推广应用.     

脾切除对脂质代谢影响的实验研究

目的 探讨脾切除对脂质代谢的影响,以及保留部分和自体脾移植是否对脂质代谢产生有益的作用。方法 将３５只大鼠随机均分为普通饮食组（ＯＦ）、高胆固醇饮食组（ＡＣＦ）、脾切除＋高胆固醇饮食组（ＳＴ）、部分脾切除＋高胆固醇饮食组（ＨＳＴ）、脾切除＋自体脾移植＋高胆固醇饮食组（ＳＴＳＡ）。观察血脂变化。结果 ＡＣＦ组血清甘油三酯（ＴＧ）,胆固醇（ＣＨＯＬ）呈升高趋势。ＳＴ组血清ＴＧ,ＣＨＯＬ进一步升高,高密     

Splenic resection or heterotopic transplantation of splenic tissue as alternatives to splenectomy. Regeneration and protective effect against pneumococcal septicemia

In 82 male Sprague-Dawley rats, divided into eight groups according to surgical procedure performed (total splenectomy, sham operation and six different modes of splenic conservation), resistance to intravenous injection of 4 X 10(3) CFU of Streptococcus pneumoniae type I was evaluated 16 weeks after the surgical procedures. Significant regeneration of the spleen and almost normal resistance to pneumococci was seen 16 weeks after a two-thirds resection. Pieces of the spleen, implanted subcutaneously or into the greater omentum, also showed marked regeneration; though survival time was prolonged, the mortality among these animals following injection with pneumococci did not, however, differ from that of totally splenectomized animals. Dispersed splenic tissue, injected subcutaneously, intramuscularly, or retroperitoneally, showed less sign of regeneration and had no effect on mortality or survival time in partially vis-à-vis totally splenectomized rats.     

The Effects of Splenectomy and Splenic Autotransplantation on Plasma Lipid Levels

Purpose: Atherosclerosis observations after splenectomy for trauma and hypersplenism suggests a possible role for the spleen in lipid metabolism. The authors examined the effects of splenectomy on serum lipids in rats and also cholesterol-fed rats with experimental atherosclerosis. Methods: This study was designed on rats. The rats were divided into five groups: splenectomy, normal diet (SP-N, n: 8), splenectomy, cholesterol-fed groups (SP-C, n: 8), splenic autotransplantation after splenectomy, normal diet (SA-N, n: 8), splenic autotransplantation after splenectomy, cholesterol-fed groups (SA-C, n: 8) and sham groups (n: 8). Total triglyceride, total cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein), and VLDL (very low-density lipoprotein) levels were determined in 40 rats. The rats were classified into five groups based on the surgical procedures. The spleens were removed and then the rats were fed a normal diet in Group SP-N (n = 8). The spleens were removed and then the rats were fed a diet containing 1% cholesterol in Group SP-C (n = 8). Splenectomy and splenic autotransplantations were performed and then the rats were fed a normal diet in Group SA-N (n = 8). Splenectomy and splenic autotransplantations were performed and then the rats were fed a diet containing 1% cholesterol in Group SA-C (n = 8). The rats were sham-operated in the control group (Group S, n = 8). An active splenic function was shown in rats that underwent splenic autotransplantation in both groups by using Technicium 99 m sulphurcolloide sintiscan on day 30. Blood lipid levels were repeated 6 months later. Results: There was no difference between pre- and postoperative lipid levels in the sham group and SA-N group (p >.05). All lipid levels including HDL were increased significantly in SP-C group (p <.05). Also VLDL and total tryglyceride levels were increased significantly in SP-N and SA-C groups (p <.05). Conclusions: This study showed that the spleen might have an important effect on lipid metabolism and splenic autotransplantation may be protective in conditions with increased lipid levels.     

Splenic autotransplantation for treatment of portal hypertension.

BACKGROUND: When total splenectomy is unavoidable it is important to preserve splenic function in some form in order to prevent the complications of asplenism. Splenic autotransplantation is a good alternative in such cases. We describe the use of splenic autotransplantation for the treatment of portal hypertension. METHODS: We carried out total splenectomy on 31 patients (21 men, 10 women), ranging in age from 21 to 68 years, with schistosomal portal hypertension. From each removed spleen, we took 20 fragments and implanted them on the greater omentum. This procedure was combined with abdominal portal-variceal disconnection. Transgastric running suture of the lower esophageal and gastric varices completed the treatment of portal hypertension. All patients underwent clinical, hematologic, immunologic and scintigraphic assessment. The results with respect to morbidity and mortality, and hematologic and immunologic findings were compared with those in 36 patients submitted to other splenic procedures. RESULTS: There was no complication related to the splenic implants and none of the patients died. Hematologic and immunologic findings were normal. Scintigraphy registered images of splenic tissue in all cases. CONCLUSION: The implantation of splenic fragments on the greater omentum seems to be a safe and useful procedure for maintaining splenic function after total splenectomy.