Biomedical subjects

Thalachallour Mohanakumar

Publications and source records attributed to Thalachallour Mohanakumar.

18 recordsLinked to original sources

PubMed2006

Elevated soluble CD30 correlates with development of bronchiolitis obliterans syndrome following lung transplantation.

BACKGROUND: The long-term function of lung transplants is limited by chronic rejection (bronchiolitis obliterans syndrome, BOS). Due to lack of specific markers, BOS is diagnosed clinically. Because there is strong evidence that alloimmunity plays a significant role in the pathogenesis of BOS, we investigated whether soluble CD30 (sCD30), a T-cell activation marker, would correlate with BOS. METHODS: Sera collected serially from BOS+ (n = 20) and matched BOS- (n = 20) lung transplant (LT) patients were analyzed for sCD30 by enzyme-linked immunosorbent assay. Pretransplant sera and sera from normal donors were also analyzed. RESULTS: PreLT levels were comparable to normal subjects. However, posttransplant there was a significant elevation in sCD30 levels during BOS development in all BOS+ patients, compared to BOS- (mean 139.8+/-10.7 vs. 14.8+/-2.7 U/ml, P < 0.001). sCD30 levels declined in the BOS+ patients but were still elevated compared to BOS- (48.52+/-5.04 vs. 7.19+/-2.9, P < 0.0001). CONCLUSIONS: We conclude that sCD30 may represent a novel marker to monitor the development of BOS.

Adult↗

PubMed2006

Induction of IL-10 suppressors in lung transplant patients by CD4+25+ regulatory T cells through CTLA-4 signaling.

T cell-mediated autoimmunity to collagen V (col-V), a sequestered yet immunogenic self-protein, can induce chronic lung allograft rejection in rodent models. In this study we characterized the role of CD4+ CD25+ regulatory T cells (Tregs) in regulating col-V autoimmunity in human lung transplant (LT) recipients. LT recipients revealed a high frequency of col-V-reactive, IL-10-producing CD4+ T cells (T IL-10 cells) with low IL-2-, IFN-gamma-, IL-5-, and no IL-4-producing T cells. These T(IL-10) cells were distinct from Tregs because they lacked constitutive expression of both CD25 and Foxp3. Expansion of T IL-10 cells during col-V stimulation in vitro involved CTLA-4 on Tregs, because both depleting and blocking Tregs with anti-CTLA4 F(ab')2 mAbs resulted in loss of T IL-10 cells with a concomitant increase in IFN-gamma producing Th1 cells (TIFN-gamma cells). A Transwell culture of col-V-specific T IL-10 cells with Th1 cells (those generated in absence of Tregs) from the same patient resulted in marked inhibition of IFN-gamma and proliferation of T(IFN-gamma) cells, which was reversed by neutralizing IL-10. Furthermore, the T IL-10 cells were HLA class II restricted because blocking HLA class II on APCs resulted in the loss of IL-10 production. Chronic lung allograft rejection was associated with the loss of Tregs with a concomitant decrease in T IL-10 cells and an increase in T IFN-gamma cells. We conclude that LT patients have col-V-specific T cells that can be detected in the peripheral blood. The predominant col-V-specific T cells produce IL-10 that suppresses autoreactive Th1 cells independently of direct cellular contact. Tregs are pivotal for the induction of these "suppressor" T IL-10 cells.

Antigens, CD↗

PubMed2006

IL-12 p80 is an innate epithelial cell effector that mediates chronic allograft dysfunction.

RATIONALE: Bronchiolitis obliterans syndrome is the leading cause of chronic lung allograft dysfunction. We have demonstrated that respiratory viral infection is a bronchiolitis obliterans syndrome risk factor and virus-dependent injury induces expression of innate airway epithelial genes belonging to the interleukin (IL)-12 family. Thus, we hypothesized that epithelial cell IL-12 family members could mediate lung allograft dysfunction. OBJECTIVES: We used mouse and human allograft specimens to evaluate the role of epithelial cell IL-12 family members in allograft dysfunction associated with and without viral infection. METHODS: Murine and human IL-12 family members were characterized and manipulated in allografts and then correlated with epithelial cell injury, immune cell accumulation, and collagen deposition. RESULTS: In a mouse model of lung transplantation, concurrent viral infection and allogeneic transplantation increased epithelial injury and this was followed by exaggerated accumulation of macrophages and collagen deposition. This virus-driven allograft dysfunction was associated with an epithelial innate response manifested by a synergistic increase in the production of the macrophage chemoattractant IL-12 p80 (p80), but not IL-12 or IL-23. Blockade or overexpression of donor epithelial p80 resulted in a corresponding abrogation or enhancement of macrophage accumulation and allograft dysfunction. We extended these findings to human recipients with viral infection and transplant bronchitis and again observed excessive epithelial p80 expression that correlated with increased macrophage accumulation. CONCLUSIONS: These experiments support a role for an enhanced epithelial innate response as a central process in allograft dysfunction and identify the macrophage chemoattractant p80 as an innate epithelial effector of disease progression.

Animals↗

PubMed2006

Respiratory viral infection in obliterative airway disease after orthotopic tracheal transplantation.

BACKGROUND: The long-term survival after human lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Clinically, community-acquired respiratory viral infections have been correlated with an increased incidence of BOS. The goal of this study was to investigate the role of respiratory viral infections in chronic lung allograft rejection using the murine orthotopic tracheal transplantation model. METHODS: Eighty orthotopic tracheal transplants were performed using BALB/c and C57BL/6 mice. Recipient mice were infected intranasally with Sendai virus (SdV), a murine parainfluenza type I virus. Experiments altering the infectious dose, infection time, harvest time, allogeneic response, and viral response were performed. Tracheal allograft rejection was monitored using percent fibrosis and lamina propria to cartilage ratio measurements. Interferon-gamma ELISPOT analysis against irradiated donor (BALB/c) splenocytes was used as immunologic indicator of alloreactivity after transplantation. RESULTS: Sendai virus infection revealed a dose-dependent transient suppression of alloreactivity with a decrease in tracheal allograft fibrosis and frequency of alloreactive T cells at 30 days. This immunosuppression was reversed by day 60, leading to increased tracheal allograft fibrosis with a concomitant increase in the frequency of interferon-gamma producing alloreactive T cells. Pretransplant sensitization with donor antigens prevented the initial suppression of alloreactivity due to SdV infection. Furthermore, pretransplant immunization against SdV infection resulted in rapid clearing of the infection and reduced the immunopathology of rejection. CONCLUSIONS: Respiratory viral infections can cause enhanced tracheal allograft rejection despite the initial phase of transient immunosuppression. Early treatment or vaccination against the respiratory infections may represent a viable intervention to reduce the risk of chronic rejection.

Animals↗

PubMed2006

Chimerism after vascularized limb versus bone marrow transplantation.

This study used quantitative PCR in the murine model to compare the ability of a limb allograft vs. a comparable dose of marrow suspension to induce chimerism. Female C57Bl/6 mice received a vascularized hindlimb allograft, a comparable dose of 5 x 10 (6) donor bone marrow cells, or a standard dose (20 x 10 (6)) of marrow suspension from male Balb/c donors. All recipients were treated with a regimen based on CD40 costimulation blockade and T cell depletion. Y chromosome-specific quantitative PCR was used to measure chimerism. Most recipients of limb allografts demonstrated low levels of chimerism after 1 week (3/4) and 1 month (3/4). Most recipients of 5 x 10 (6) marrow cells had low levels of chimerism at 1 week (4/6) and only 1/5 after 1 month. All recipients of 20 x 10 (6) cells except one demonstrated either low or high levels of chimerism after 1 week (5/5) and 1 month (5/6). The marrow component of a limb allograft is thus more effective at inducing microchimerism compared to a comparable dose of bone marrow suspension.

Animals↗

PubMed2005

The significance of a single episode of minimal acute rejection after lung transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) remains the leading obstacle to better long-term outcomes after lung transplantation. Acute rejection has been identified as the primary risk factor for BOS, but the impact of minimal acute rejection, especially a solitary episode, has usually been discounted as clinically insignificant. METHODS: We performed a retrospective cohort study of 259 adult lung transplant recipients to determine the risk of BOS associated with a single episode of A1 rejection, without recurrence or subsequent progression to a higher grade. The cohort was divided into 3 groups based on the severity of acute rejection (none, single episode of A1, and single episode of A2). We determined the risks of BOS stages 1, 2, 3, and death for each group using univariate and multivariate Cox regression analyses. RESULTS: A solitary episode of A1 rejection was a significant risk factor for BOS stages 1 and 2, but not stage 3 or death, in the univariate analysis. Multivariate Cox regression models confirmed that the risk of BOS attributable to a single episode of A1 rejection was independent of other potential risk factors, such as community acquired respiratory viral infections, number of HLA mismatches, and cytomegalovirus pneumonitis. Likewise, univariate and multivariate analyses demonstrated that a single episode of A2 rejection was a significant risk factor for all stages of BOS but not death. CONCLUSIONS: A single episode of minimal acute rejection without recurrence or subsequent progression to a higher grade is a significant predictor of BOS independent of other risk factors.

Adult↗

PubMed2005

Induction of obliterative airway disease in murine tracheal allografts by CD8+ CTLs recognizing a single minor histocompatibility antigen.

The role of minor histocompatibility Ag (mHAg)-specific CD8+ CTLs in the pathogenesis of chronic lung allograft rejection (bronchiolitis obliterans syndrome) remains to be elucidated. Thus, the goal of this study was to define the role of a single mHAg mismatch at the polymorphic H13 allele in the development of obliterative airway disease (OAD) after murine heterotopic tracheal transplantation. The H13a and H13b alleles encode for the SSVVGVWYL (SVL9) and SSVIGVWYL (SIL9) mHAgs, respectively, presented in the context of the H2Db MHC class I molecule. Toward this, C56BL/10SnJ (H13a) tracheal allografts were transplanted into congenic B10.CE-H13b Aw(30NX)/Sn (H13b) recipients. The allografts were harvested at 30, 60, and 90 days after transplantation, and OAD lesions (epithelial damage, cellular infiltration, and luminal fibrosis) were confirmed histologically. Selected groups of mice were immunized (s.c.) or tolerized (i.v.) with the SVL9 peptide before transplantation. This single mHAg mismatch induced the development of OAD within 90 days. SVL9 immunization significantly accelerated the kinetics of the OAD lesions. In contrast, SVL9 tolerization completely abrogated the development of OAD. This was correlated with a complete abrogation of H13a-specific CD8+ CTL responses with a significant reduction in the frequency of IFN-gamma-producing CTLs and the activation of TGF-beta-producing CD8+ T cells. In conclusion, a single mHAg mismatch can induce the development of OAD. These data also suggest that mHAg-reactive CD8+ CTLs may play an important role in the pathogenesis of chronic lung allograft rejection in humans.

Animals↗

PubMed2005

Effects of Schwann cells and donor antigen on long-nerve allograft regeneration.

Nerve allotransplantation has been used successfully in human subjects to restore function after traumatic nerve injury and avoid subsequent limb amputation. However, due to the morbidity associated with nonspecific immunosuppression, this reconstructive approach has been limited to patients with particularly severe nerve injuries. It would be desirable to broaden the indications for such procedures through development of less toxic antirejection therapies. A miniature swine model of nerve transplantation was used to investigate the effects of preoperative ultraviolet-B (UV-B)-irradiated donor alloantigen portal venous infusion and injection of cultured major histocompatibility complex (MHC)-matched Schwann cells into the nerve graft. The transplanted ulnar nerves were harvested at 20 weeks. Histomorphometry showed marked enhancement in nerve regeneration through allografts injected with Schwann cells. Serial mixed lymphocyte assays demonstrated suppression of the recipient immune response to the donor antigen after pretreatment, but no additional neuroregenerative effect of donor alloantigen pretreatment.

Animals↗

PubMed2005

Prolonged cold-preservation of nerve allografts.

The goal of this study was to determine the effect of varying durations of cold-preservation on the immunogenicity of nerve allografts and their subsequent ability to facilitate neuroregeneration across a short nerve gap. Allografts preserved for 1, 4, and 7 weeks were compared to untreated allografts and isografts. There was a shift from an interferon-gamma-producing cellular response (untreated allografts) to an absence of response (7-week cold-preserved allografts and isografts). There were no detectable alloantibodies by flow cytometry. Histomorphometry distal to the graft showed robust regeneration in the isograft and 7-week cold-preserved groups when compared to the untreated allograft group. Increasing duration of cold-preservation diminished the cellular immune response. This cold-preservation does not preclude subsequent nerve regeneration across a short nerve graft. Prolonged cold-preservation of nerve allograft tissue could serve as a means to produce unlimited graft material for use in peripheral nerve reconstruction.

Animals↗

PubMed2005

Inhibition of obliterative airway disease development following heterotopic murine tracheal transplantation by costimulatory molecule blockade using anti-CD40 ligand alone or in combination with donor bone marrow.

INTRODUCTION: Obliterative airway disease (OAD) development in heterotopic murine tracheal allografts, a model of obliterative bronchiolitis after lung transplantation, is immunologically mediated. Whether tolerance induction by the administration of anti-CD40 ligand monoclonal anti-body (MR-1) alone or in conjunction with donor-derived bone marrow cells (BMCs) can prevent the development of OAD was tested in this study. METHODS: BALB/c tracheal allografts were heterotopically transplanted into C57BL/6 recipients. Group 1 received no treatment. Group 2 received multiple infusions of donor BMCs intravenously. Group 3 was administered MR-1 intraperitoneally. Group 4 received donor BMCs and MR-1. Allografts were harvested at several time points post-transplantation and examined for the development of OAD. RESULTS: Group 1 developed cellular infiltration and epithelial damage by Day 15 post-transplant and OAD by Day 28, evidenced by complete obliteration of the tracheal lumen. Group 2 developed OAD with similar kinetics to Group 1. Group 3 had no evidence of OAD at 28 days. At Days 45 to 90, moderate cellular infiltration, epithelial metaplasia, and a minimal narrowing of the tracheal lumen were evident. OAD developed by Day 120. Group 4 mice had patent tracheal lumens even at 120 days post-transplantation, with only mild epithelial metaplasia and luminal narrowing noted. CONCLUSIONS: The administration of MR-1 alone in combination with infusions of donor bone marrow cells significantly attenuated the development of OAD. Tolerance-inducing regimens such as this deserve further investigation in the prevention of post-lung transplant obliterative bronchiolitis following human lung transplantation.

Animals↗

PubMed2005

Interleukin-1beta is prominent in the early pulmonary inflammatory response after hepatic injury.

BACKGROUND: Acute lung injury and inflammation can occur after hepatic ischemia/reperfusion or cryoablation. The etiology of this response is uncertain although it involves NF-kappaB-mediated cytokine release from the liver. METHODS: Inflammation-specific complementary DNA microarrays were utilized to evaluate cytokine upregulation in mouse lung at 4 hours after partial-volume hepatic cryoablation with a recirculating liquid N(2) probe. Hierarchical cluster analysis was performed to identify candidate genes. On the basis of these results, an enzyme-linked immunosorbent assay for interleukin-1beta (IL-1beta) was conducted on serum and pulmonary parenchymal specimens. The time course of IL-1beta transcriptional upregulation in the liver and lungs was evaluated by quantitative reverse transcription/real-time polymerase chain reaction. RESULTS: Starting with a pool of 35 genes generated from normalization and variation filtration, unsupervised hierarchical clustering clearly distinguished lungs of hepatic cryo-injured mice from controls. Genes from the IL-1-family were prominent in the signature. IL-1beta was demonstrable in serum within 2 hours postinjury (218 +/- 89 pg/mL vs 0 at baseline, P = .01). In the lung, IL-1beta was more than 4-fold greater at 4 hours than at baseline. Real-time polymerase chain reaction showed a transcription peak of IL-1beta at 30 minutes in the liver, whereas expression in the lungs remained low until 60 minutes, then continued to increase through 4 hours. CONCLUSIONS: Microarray analysis identified cytokines of the IL-1 family as central components of acute lung injury after hepatic cryoablation. IL-1beta levels increased in both serum and lung tissue over 4 hours after liver injury. Expression of IL-1beta peaked early in the injured liver remnant, followed by subsequent increases in the lungs. Targeted intervention against IL-1beta may ameliorate liver-mediated lung injury.

Animals↗

PubMed2005

Minimal acute rejection after lung transplantation: a risk for bronchiolitis obliterans syndrome.

Bronchiolitis obliterans syndrome (BOS) is a major cause of lung allograft dysfunction. Although previous studies have identified mild to severe rejection (grade>or=A2) as a risk factor for BOS, the role of minimal rejection (grade A1) remains unclear. To determine if A1 rejection by itself is a risk factor for BOS, we performed a retrospective cohort study on 228 adult lung transplant recipients over a 7-year period. Cohorts were defined by their most severe rejection episode (none, A1 only, and >or=A2) and analyzed for the subsequent development and progression of BOS using univariate and multivariate time-dependent Cox regression analysis. In the univariate model, the occurrence of isolated minimal rejection was a risk factor for all stages of BOS. Similarly, multivariate models that included HLA mismatch, cytomegalovirus pneumonitis, community acquired viral infection, underlying disease and type of transplant demonstrated that A1 rejection was a distinct risk factor for BOS. Furthermore, the associated risk with A1 rejection was slightly greater than the risk from >or=A2 and treatment of A1 rejection decreased the risk for subsequent BOS stage 1. We conclude that minimal rejection is associated with an increased risk for BOS development and progression that is comparable to A2 rejection.

Adolescent↗

PubMed2004

Respiratory viral infections are a distinct risk for bronchiolitis obliterans syndrome and death.

Bronchiolitis obliterans syndrome (BOS) is the major obstacle to long-term survival after lung transplantation, in part because its pathogenesis is poorly understood and treatment options are limited. To identify unique risk factors for BOS and death, we performed a retrospective cohort study on 259 consecutive adult lung transplant recipients over a 5-year period. The demographic and clinical characteristics of this population were analyzed for an association between BOS or death and potential risk factors, including community-acquired respiratory viral (CARV) infections, acute rejection, and cytomegalovirus pneumonitis. Respiratory syncytial virus, parainfluenza, influenza, and adenovirus accounted for 21 CARV infections. Univariate and multivariate time-dependent Cox regression analyses demonstrated that this CARV group was more likely to develop BOS, death, and death from BOS. Furthermore, these trends were more pronounced in patients with evidence of lower respiratory tract-CARV (lower-CARV) infections. Notably, the CARV and lower-CARV infections were risk factors for BOS, death, and death from BOS distinct from the risk attributable to acute rejection. Identification of CARV and lower-CARV infections as BOS and mortality risk factors has important clinical implications and may provide insight into disease pathogenesis and accelerate the development of novel treatment strategies to modify post-CARV BOS.

Bronchiolitis Obliterans↗

PubMed2004

Anti-CD40 ligand monoclonal antibody induces a permissive state, but not tolerance, for murine peripheral nerve allografts.

Anti-CD40 ligand monoclonal antibody prevents the interaction between CD40 and its T-cell-based ligand, thereby resulting in selective inhibition of T cell costimulation without pan-T-cell suppression. This antibody has found application in several animal models of solid organ transplantation. This study investigated use of anti-CD40 ligand antibody to promote acceptance of nerve allografts. In Experiment 1, 40 BALB/cj mice with tibial nerve transplants were administered anti-CD40 ligand antibody, a control antibody, or no treatment. In Experiment 2, 40 BALB/cj mice underwent the same regimen as in Experiment 1, but were later challenged with a second nerve allograft 3 weeks after discontinuation of treatment. Animals treated with anti-CD40 ligand antibody in Experiment 1 exhibited improved functional recovery and greater mean fiber count, fiber density, and percent nerve fiber than animals treated with control antibody or no antibody (P < 0.05). These permissive effects on nerve regeneration were associated with immune unresponsiveness on Elispot assay. The benefit of anti-CD40 ligand therapy did not persist after withdrawal of treatment (Experiment 2). Active blockade of the CD40 costimulatory pathway with murine anti-CD40 ligand antibody therefore induces a permissive state conducive to nerve regeneration across allografts but does not establish long-term tolerance.

Animals↗

PubMed2003

Chronic rejection: failure of immune regulation.

Current strategies for immunosuppression following organ transplantation focus on the prevention of acute rejection. As new generations of immunosuppressants have been developed, acute rejection rates have diminished markedly. The new challenge, then, is to prevent the devastating complications of chronic rejection, which have remained largely unchanged over the decades. The process of chronic rejection is a complex one, and it is likely that most, if not all, components of the immune system play some role in the long-term, smoldering failure of organs following transplantation. Through a better understanding of their individual contributions as well as interactions, new strategies may be developed to overcome this problem. We present here an overview of the major immune components thought to be involved in chronic rejection.

Animals↗

PubMed2002

Proapoptotic Bax is hyperexpressed in isolated human islets compared with antiapoptotic Bcl-2.

BACKGROUND: Apoptosis is a well-documented pathway for islet cell death. One potential mechanism is overexpression of death-promoting Bax compared with antiapoptotic Bcl-2 in islets. METHODS: We isolated islets from 10 human pancreata and measured the expression of Bax mRNA and Bcl-2 mRNA by real-time quantitative polymerase chain reaction; islet and pancreas expression of Bax, Bcl-2, activated caspase-3, and cleaved poly (ADP-ribose) polymerase were also assessed by immunohistochemistry. Islet cell apoptosis was evaluated by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) assay and by flow cytometry. RESULTS: The mean (+/-SE) level of Bax mRNA was 336+/-79 copies per nanogram of total RNA, and the level of Bcl-2 mRNA was 36+/-10 (P=0.001). A positive correlation existed between islet expression of Bax mRNA and Bcl-2 mRNA (P=0.001). The islet Bax to Bcl-2 ratio was 10.8+/-1.3 and 1.71+/-0.3 for the spleens (P=0.0001). Bax mRNA (P=0.04), but not Bcl-2 mRNA, was expressed at a higher level in islets compared with spleens. Human islets contained large numbers of cells expressing Bax protein, whereas only infrequent islet cells expressed Bcl-2 protein, activated caspase-3, and poly (ADP-ribose) polymerase. The apoptotic index was 5% by TUNEL assay, and the percentage of apoptotic islet cells was 9.7+/-2.5% by flow cytometry. Sections of human pancreas before islet isolation showed islet staining for Bax but not Bcl-2. CONCLUSIONS: Our finding that isolated human islets express Bax at a higher level compared with Bcl-2 suggests a molecular mechanism for islet cell death by apoptosis. We hypothesize that reducing islet expression of Bax, or regulating its activation, will help preserve islet cell mass after islet transplantation.

Adult↗

PubMed2002

Identification of HLA-A3-restricted CD8+ T cell epitopes derived from mammaglobin-A, a tumor-associated antigen of human breast cancer.

Mammaglobin-A is highly overexpressed in breast cancer cell lines and primary breast tumors. This pattern of expression is restricted to mammary epithelium and metastatic breast tumors. Thus, mammaglobin-A-specific T cell immune responses may provide an important approach for the design of breast cancer-specific immunotherapy. The purpose of our study was to define the T cell-mediated immune response to mammaglobin-A. We determined that the frequency of mammaglobin-A-reactive CD8+ and CD4+ T cells in breast cancer patients is significantly higher than that observed in healthy female controls using limiting dilution analyses (p = 0.026 and p = 0.02, respectively). We identified 8 mammaglobin-A-derived 9-mer peptides with the highest binding affinity for the HLA-A3 molecule (Mam-A3.1-8) using a computer-assisted analysis of the mammaglobin-A protein sequence. Subsequently, we determined that CD8+ T cells from breast cancer patients reacted to peptides Mam-A3.1 (23-31, PLLENVISK), Mam-A3.3 (2-10, KLLMVLMLA), Mam-A3.4 (55-63, TTNAIDELK) and Mam-A3.8 (58-66, AIDELKECF) using an IFN-gamma enzyme-linked immunospot assay. A CD8+ T cell line generated in vitro against HLA-A*0301-transfected TAP-deficient T2 cells loaded with these peptides showed significant cytotoxic activity against the Mam-A3.1 peptide. This CD8+ T cell line showed a significant HLA-A3-restricted cytotoxic activity against mammaglobin-A-positive but not mammaglobin-A-negative breast cancer cells. In summary, our study identified four HLA-A3-restricted mammaglobin-A-derived epitopes naturally expressed by breast cancer cells, indicating the immunotherapeutic potential of this novel antigen for the treatment and prevention of breast cancer.

Breast Neoplasms↗

PubMed2002

Effect of age on thrombosis and morbidity in the mouse-limb transplantation model.

Murine models of limb transplantation have been recently described. Because of the technical challenge, non-technical factors that influence the success rate and are easily controlled should be considered. This study investigated the effect of recipient animal age on anastomotic thrombosis, morbidity, and mortality. Twelve allogeneic heterotopic hindlimb transplants were performed using the femoral vessels with end-to-end arterial and end-to-side venous anastomoses. Group 1 (n=8) consisted of 2 to 3-month-old mice weighing 17 to 20 g, and Group 2 (n=7) included 7 to 8-month-old mice weighing 24 to 27 g. In Group 1, 6/8 (75 percent) transplants were successful, while in Group 2, only 1/7 (14 percent) allografts survived (p<0.05). A statistically significant difference in the incidence of vascular compromise of the ipsilateral recipient hindlimb was also noted (p<0.01). The authors conclude that although smaller, juvenile, inbred mice have a higher anastomotic patency rate, with greater collateral vasculature in the hindlimbs, and are therefore more suitable for limb transplantation research.

Age Factors↗