Objective To explore immunosuppressive effect and sappan L （WECSL） in heart transplantation of rats. Methods mechanism of watery extract of caesalppinia Wistar rats （donor） heart allografts were transplanted into the abdomen of SD rats （receptor）. Ninety-six SD rats were divided into four groups （24 rats in each group）. Control group： olive oil（8ml/kg·d） treated; group A： cyclosporine A （CsA,5ml/kg·d） treated; groupB： WECSL（37.5g/kg·d） treated; group C： WECSL（25g/kg·d） plus semidose of CsA（2.5mg/kg·d） treated. Median survival time of heart allografts and the histological changes of allografts were examined. Messenger ribonucleic acid （mRNA） of interleukin-2（IL-2）, interleukinf-10（IL-10） in the myocardium were determined by reverse transcription polymerase chain reaction （RT-PCR）, serum level of IL-2 and IL-10 were determined by enzyme-linked immunosorbent assay （ELISA） at 3, 7 days after surgery. Results Compared with control group, median survival time of heart allografts in group A, group B, group C was prolonged （P〈0. 01）, lymphocyte infiltration and myocyte necrosis were relieved, mRNA expression of IL-2 in allografts was lower, mRNA expression of IL-10 was higher （P〈0.01）. The serum levels of IL-2 in group A 3,7days after surgery and in group B, group C 3 days after surgery was lower than that in control group （P〈0.01）. The serum levels of IL-10 in group A 7days after surgery and in group B 3 days after surgery was higher than that in control group （P〈0. 05）. Conclusion Acute rejection of rat heart transplantation can be effectively suppressed by WECSL, Th1 to Th2 polarization induced by WECSL is observed.
目的总结心脏移植和双肺移植供体心肺同时摘取的经验。 方法解放军第一八一医院心脏中心2012年完成3例同一供体心肺同时摘取，分别完成心脏移植和双肺移植各3例。3例供体为脑死亡，阻断供体升主动脉和主肺动脉后，同时灌注保护液，心脏保护应用组氨酸-色氨酸-酮戊二酸心脏停搏液（HTK液），肺保护应用低钾右旋糖酐液（LPD液）；供体心肺热缺血时间为5 min，供心冷缺血时间分别为252 min、323 min和375 min，供体肺冷缺血时间分别为610 min、679 min和738 min；3例心脏移植均采用双腔静脉吻合法，3例肺移植均采用序贯式双肺移植。 结果3例心脏移植均存活；肺移植2例存活，1例死亡。存活患者出院后生活质量良好，随访8～13个月未出现感染、急性排斥反应等并发症。 结论供体心肺同时摘取，同时灌注后分别修剪并再次灌注，分别保存运输，心脏移植和双肺移植可取得满意效果。
Objective To insure early detection and hence efficient prevention of allograft rejection in transplanted heart, investigate possible applications of NAD(P)H fluorescence components analysis at the level of living cardiac cells to propose new approaches for diagnosis of rejection. Methods NAD(P)H was studied for noninvasive fluorescent probing of the mitochondrial function. Human cardiomyocyte were isolated from one additional endomyocardial biopsy (EMB) of 14 pediatric patients with heart ransplantation. Rat cardiomyocyte (n=5, 13-14 week old) were also isolated by the same approach for human myocytes. Autofluorescence(AF) was recorded in living cardiomyocytes following excitation with 375 nm UVlight and detection by spectrallyresolved time correlated single photon counting (TCSPC), based on the simultaneous measurement of the fluorescence spectra and lifetimes. Rat cardiac cells were divided into four groups: normoxic condition, normoxia with Rotenone, ischemic condition and ischemia with Rotenone. Comparison of cardiomyocyte AF between human and rat; compared kinetics of rat cardiomyocytes AF in normoxic conditions to ischemiamimicking ones, induced at physiological temperatures by reducing cell pH and oxygen content; comparison of cardiomyocyte AF dynamic changes in transplanted pediatric patients presenting either no rejection (R0) or mild rejection (R1). Results We have achieved appropriate isolation of living cardiomyocytes from human biopsies, as well as from rat cardiac tissues and determined their AF. At least a 3-exponential decay with 0.5-0.7ns, 1.9-2.4 ns and 9.0-15.0 ns lifetime pools is necessary to describe human cardiomyocyte AF within 420560 nm spectral range. Rat cardiomyocyte steadystate AF in ischemiamimicking condition was significantly increased when compared normoxic ones (Plt;0.05); application of Rotenone induced a significant increase in AF intensity in ischemic and normoxic condition, however no significant difference between the two groups (Plt;0.05).Human cardiomyocyte AF was found significantly lower in comparison to experimental rat model in the same condition(Plt;0.05). A correlation between changes in steadystate NAD(P)H fluorescence and rejection grades was found when comparison of R1 to R0. R1 showed significantly increased fluorescence intensity (Plt;0.05), without change in the spectra shape, results can be comparable to the effect of ischemiamimic conditions. Conclusion Our studies clearly demonstrated that spectrallyresolved fluorescence spectral analysis coupled to fluorescence lifetime are high sensitive approaches to examine mitochondrial metabolic oxidative state directly in living human cardiomyocytes with good reproducibility. Human cardiomyocytes are more metabolically active than the rat ones, while this activity (and thus ATP production) seems lowered during rejection process. In perspective, the advantage of this method is the possibility of its combination to multiphoton confocal microscopy, which can result in the adaptation of this approach directly to tissue biopsy, as well as in vivo directly via cardiac catheterization without the necessity of cell isolation. This approach provides promising new tool for clinical diagnosis and treatment of allograft rejection, and will enhance our knowledge about cardiomyocyte oxidative metabolism and/or its dysfunction at a cellular level.
Objective To explore the impact of SARS-CoV-2-positive donors on the prognosis of heart transplant recipients. MethodsThe Medline, EMbase, CENTRAL, CNKI, Wanfang Data, VIP and China Biology Medicine from inception to May 2023 were searched by computer for studies about impact of SARS-CoV-2-positive donors on the prognosis of heart transplant recipients. The data were extracted from all the relevant literatures, and the quality of the data was assessed using the Newcastle-Ottawa Scale (NOS). All statistical analyses were conducted by the Stata 11.0 software. Results A total of 10 studies (NOS score ranging from 5 to 9 points) involving 643 patients were enrolled. The pooled results demonstrated that the pooled mortality of heart transplant recipients from SARS-CoV-2-positive donors was 4% (95%CI 2% to 5%). And the incidence of composite outcome, regarding graft failure, rejection and death as poor prognosis, was 7% (95%CI 5% to 9%). Besides, compared with recipients from SARS-CoV-2-negative donors, the pooled odds ratio (OR) value of death of SARS-CoV-2-positive donors was 0.68 (95%CI 0.38 to 1.22, Z=1.28, P=0.200). The pooled OR value of rejection rate was 0.41 (95%CI 0.27 to 0.64, Z=3.97, P<0.005). For the composite outcome, the pooled OR value was 0.50 (95%CI 0.37 to 0.69, Z=4.30, P<0.005). In addition, there was no statistical difference in the length of hospital stay between heart transplant recipients from SARS-CoV-2-positive donors and negative donors (SMD=–0.03, 95%CI –0.22 to 0.15, Z=0.36, P=0.720). Conclusion The application of heart from SARS-CoV-2-positive donor for transplantation is safe and feasible. However, further prospective studies with longer follow-up are still needed to verify its impact on long-term outcomes.
Objective Tolerogenic DCs (Tol-DCs), a group of cells with imDC phenotype, can stably induce T cells low-reactivity and immune tolerance. We systematically reviewed the adoptive transfusion of Tol-DCs induced by different ways to prolong cardiac allograft survival and its possible mechanism. Method MEDLINE (1966 to March 2011), EMbase (1980 to March 2011), and ISI (inception to March 2011) were searched for identification of relevant studies. We used allogeneic heart graft survival time as endpoint outcome to analyze the effect of adoptive transfusion of Tol-DC on cardiac allograft. By integrating studies’ information, we summarized the mechanisms of Tol-DC in prolonging cardiac grafts. Results Four methods were used to induce Tol-DC in all of the 44 included studies including gene-modified, drug-intervened, cytokine-induced, and other-derived (liver-derived amp; spleen-derived) DCs. The results showed that all types of Tol-DC can effectively prolong graft survival, and the average extension of graft survival time for each group was as follows: 22.02 ± 21.9 days (3.2 folds to control group) in the gene modified group, 25.94 ± 16.9 days (4.3 folds) in the drug-intervened groups, 9.00 ± 8.13 days (1.9 folds) in the cytokine-induced group, and 10.69 ± 9.94 days (2.1 folds) in the other-derived group. The main mechanisms of Tol-DCs to prolong graft survival were as follows: a) induceT-cell hyporeactivity (detected by MLR); b) reduce the effect of cytotoxic lymphocyte (CTL); c) promote Th2 differentiation; d) induce Treg; e) induce chimerism. Conclusion For fully MHC mismatched allogeneic heart transplant recipients of inbred mouse, adoptive transfusion of Tol-DC, which can be gene-modified, drug-intervened, cytokine-induced, spleen-derived or liver-derived, can clearly prolong the survival of cardiac allograft or induce immune tolerance. Gene-modified and drug-induced Tol-DC can prolong graft survival most obviously. Having better reliability and stability than drug-induction, gene-modification is the best way to induce Tol-DCs at present. One-time intravenous infusion of 2 × 106 Tol-DC is a simple and feasible way to induce long-term graft survival. Multiple infusions will prolong it but increase the risk and cost. Adoptive transfusion of Tol-DC in conjunction with immunosuppressive agents may also prolong the graft survival time.
Objective To simplify surgical technique andincrease postoperative survival rate, sleeve anastomosis technique combined cuff technique was used in developing the model of cervical heart transplantation in rats. Methods In this model, the hearts from 25 male SD rats were transplanted into the neck of Wistar rats by anastomosing the donor innominate artery to the recipient right common carotid artery by use of sleeve technique, and the donor pulmonary artery to the recipient right external jugular vein by use of cuff technique. After operation,the rats were treated with cyclosporine A (1.5mg/kg, q.d.), transplanted hearts were followed by daily inspection or palpation and the allograft survival time was more than 3 days as the standard of successful operation. Results The mean operative time was (48.7±3.4) min, with a successful rate of 88%(22/25). Complications were anastomotic hemorrhage( 1 case) and thrombosis(2 cases). During the followup period, 6 rats died of pulmonary infection, abscess in the neck,liver or bladder tumor. The remaining 16 transplanted hearts survived more than3 months. Conclusion The modified operation have advantages ofless operative procedure, shorter operation and ischemia time and easier monitoring of graft function.
Objective To establ ish the modified model of cervical heterotopic cardiac transplantation in rats for investigation of cardiac chronic rejection. Methods Forty healthy male Wistar rats, aged 10 weeks, weighing 250-300 g, were appl ied as the donor group, and forty healthy male SD rats, aged 10 weeks, weighing 300-350 g, served as the recipient group. The donors’ pulmonary artery was anastomosed to the reci pients’ right external jugular vein by non-suture cuff technique while the donors’ innominate artery was anastomosed to the recipients’ right common carotid artery by suture microvascular anastomosis. All recipients received cyclosporin to prevent acute allograft rejection. Results Forty consecutive successful transplantations were performed. Neither anastomosis leakage nor vessel obstruction occurred. The total operation time was 40-50 minutes. The time of cuff vascular anastomosis was 2-3 minutes and that of microvascular anastomosis was 9-12 minutes. All recipients survived for more than 30 days and all allografts were examined at 30 days after the transplantation. Pathological manifestations of allograft vessels were chronic rejection. Conclusion This modified model of cervical heterotopic cardiac transplantation is simple, practical and highly reproducible and is appl icable for investigation of chronic rejection in various organ transplantation studies.
ObjectiveTo analyze the short- and long-term therapeutic effects of heart transplantation in children. MethodsA retrospective study was conducted on recipients and donors who underwent heart transplantation at the 7th People’s Hospital of Zhengzhou from May 2018 to August 2023, analyzing their clinical characteristics, surgical data, postoperative complications, and survival rates. ResultsA total of 22 children underwent heart transplantation, including 14 males and 8 females, with a median age of 13.5 (10.0, 15.0) years and a median weight of 41.9 (30.5, 55.4) kg. The primary diseases included: dilated cardiomyopathy in 16 patients, hypertrophic cardiomyopathy in 1 patient, myocardial dysplasia in 3 patients, right ventricular dysplasia in 1 patient, and congenital heart disease with abnormal coronary artery origin in 1 patient. The median age of the donors was 21.0 (13.0, 29.0) years, and the median weight was 50.5 (47.3, 75.0) kg. The blood types of the donors and recipients were the same, with type A in 10 patients, type B in 5 patients, type O in 5 patients, and type AB in 2 patients. Before transplantation, all children had a New York Heart Association cardiac function grade Ⅳ, with 1 patient assisted by intra-aortic balloon pump (IABP), 3 patients assisted by extracorporeal membrane oxygenation (ECMO), 2 patients assisted by continuous renal replacement therapy (CRRT), and 2 patients on mechanical ventilation. Nine patients met the criteria for emergency child status allocation, and the panel reactive antibody level in the patients was<10%. The median cold ischemic time of the donor heart was 355.0 (262.0, 395.5) min, the median aortic cross-clamping time was 45.0 (38.3, 51.3) min, the median mechanical ventilation time was 22.5 (16.8, 52.5) h, the median postoperative hospital stay was 29.5 (20.0, 43.0) d, and the median intensive care unit stay was 6.0 (5.0, 8.3) d. After surgery, 4 patients were assisted by ECMO, 2 patients by CRRT, and 7 patients developed complications, including lung fungal infection in 6 patients, liver and kidney dysfunction in 1 patient, local wound non-union and mediastinal infection in 1 patient, and multiple organ failure in 1 patient. Kaplan-Meier curve analysis showed that the survival rates of children after surgery were 91.3% at 1 year and 3 years; the survival rates of adult heart transplant recipients at our center were 86.7% and 73.8% at 1 year and 3 years, respectively, indicating that the survival rate of children with heart transplantation was higher than that of adult patients. ConclusionHeart transplantation is an effective treatment for end-stage heart failure in children, and the short- and long-term survival rates of children with heart transplantation are superior to those of adults. There are still many difficulties to be solved in pediatric heart transplantation, requiring joint efforts from society and the medical community.