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.
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 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.
Heart transplantation remains the most effective treatment for patients with end-stage heart failure. Over the past decade, significant advancements have been made in the field of heart transplant surgery. However, the enormous demand from heart failure patients and the severe shortage of available donor hearts continue to be major obstacles to the widespread application of heart transplantation. With the development of donor heart recovery, preservation, and evaluation techniques, the use of extended criteria donors and donation after circulatory death has increased. These technological advancements have expanded the safe ischemic time and geographic range for donor heart procurement, significantly enlarging the donor pool and driving a rapid increase in heart transplant cases. Concurrently, many new techniques have emerged in heart transplant surgery and perioperative management, particularly the rapid advancements in mechanical circulatory support and artificial intelligence, which hold the potential to revolutionize the field. This article reviews and discusses the current status and major surgical advancements in adult heart transplantation in the United States, aiming to provide insights and stimulate ongoing exploration and innovation in this field.
Objective To report the experiences using orthotopic heart transplantation （HTX） to treat a patient with primary cardiac pheochromocytoma （PCT）. Methods On June 2, 2005, a 48-year-old woman received orthotopic HTX because she suffered from cardiac PCT which can not be resected. The procedure for the recipient was uneventful. The aortic crossclamp time was 95 min, assist circulation time 64 min. Results Twenty days after the operation, the patient was discharged without any events, and serum norepinepherine dropped to 1. 339 ng/ml, and urinary norepinepherine 108μg/24h. Conclusion Orthotopic HTX is an effective treatment for cardiac PCT when it cannot be resected.
Objective To study efficiency and security of the recombinant adenoviralmediated gene transfer to the donor heart during the heart transplantation. Methods A total of 140 healthy male Wistar rats,aged 10 weeks, weighing 200250 g, were equally divided into the donor group and the recipient group, and then 70 rats in the recipient group were randomly andequally divided into 2 subgroups: the gene transfer group and the control group. The rat model of heterotopic heart transplantation(Abdomen)was developed, the donor hearts were removed and their coronary arteries were perfused with 800 μlof the recombinant adenoviral vectors encoding the β-galactosidase gene（Ad-LacZ）. The grafts were stored in the 4℃ cold saline solution for 30 minutes, and then the syngeneic transplant was performed. In the control group, saline of tales doses was perfused. The donor hearts were harvested at 3, 5, 7, 14, and 28days (n=7)after transplantation, and the β-galactosidase activity was assessed by the X-gal staining. At 28 days the major organs of the recipients were tested by the histopathological analysis and the polymerase chain reaction of the adenoviral E1A sequences. Results The successful gene transfer of the βgalactosidase gene was demonstrated in the adenovirus-perfused hearts, with no staining in the control group. The gene expression reached a peak level at 3, 5 and 7 days, and the averaged numbers of the total βgalactosidase positive staining cells per slice were 66.4±23.1, 91.3±32.4 and 68.7±22.7, respectively, with no significant difference between the groups (Pgt;0.05). At 14 days the gene expression gradually declined (32.1±13.9), and the significant difference was found when compared with that at 3, 5 and 7 days (Plt;0.05). At 28 days the cells positive for β-galactosidase were sparse (3.9±3.4), and the gene transfer was significantly less efficient compared with that at 3, 5, 7 and 14 days (Plt;0.05). The major organs of the recipients were not affected seriously at 28 days. No virus spread to other organs in this experimental protocol. Conclusion The ex vivo adenoviralmediated gene transfer intracoronarily to the donor heart during the heart transplantation is feasible and safe.
Objective To summarize and analyze the clinical outcomes and experiences of continuous renal replacement therapy(CRRT) in patients with acute renal insufficiency after heart transplantation. Methods There were 39 patients received orthotopic heart transplantation from September 2007 to September 2008 in Fu Wai hospital. Seven cases required the use of PRISMA CRRT machine (Gambro Healthcare,Inc.) because of acute renal insufficiency after heart transplantation, and received continuous venovenous hemodiafiltration(CVVHDF) treatment via M100 blood filter (hemofilters). Activated coagulation time (ACT) was maintained in 160200 s. Results Six survivals with New York Heart Association (NYHA)Ⅰdischarged ，1 case died of multiple system organ failure (MSOF) and severe infection. The time of CRRT was 48658 h, with an average of 252 h. Seven patients were oliguric or anuric during CRRT, but hemodynamics and internal environment were stable. After stopping CRRT, the creatinine level rose to 267.1±68.5 μmol/L， then the creatinine level decreased to normal range with urine increasing gradually. Postoperative glomerular filtration rate (GFR) was 56.5±19.0 ml/min， and there was no statistical significance compared with preoperative GFR（Pgt;0.05）. Six survivals were followed up for 513(9.7±3.8)months，and their creatinine level was in normal range(90.6±26.7 μmol/L). There was no statistical significance compared with the creatinine level at discharge (83.2±26.5 μmol/L, Pgt;0.05）. Conclusion The prognostic outcomes of patients with acute renal insufficiency after heart ransplantation are excellent after using CRRT. No significant renal dysfunction is found.
ObjectiveTo explore the correlation between perioperative blood transfusion and acute kidney injury (AKI) after heart transplantation.MethodsA retrospective study was performed on 67 patients who underwent heart transplantation in the Department of Cardiac Surgery, Guangdong Provincial People's Hospital from January 2016 to December 2018, and finally 63 patients were included according to the exclusion criteria. There were 53 males and 10 females with an average age of 44.3±12.9 years. Twenty patients who adopted continuous renal replacement therapy (CRRT) after heart transplantation were divided into a RT group and the other 43 patients who did not use CRRT were divided into a non-RT group. Baseline characteristics, perioperative blood transfusion data and clinical prognosis were compared between the two groups.ResultsThe preoperative baseline characteristics of the two groups were basically the same. There were significant differences in perioperative infusion of red blood cells and plasma, postoperative 24 h bleeding and re-exploration (P<0.05) between the two groups. The area under the receiver operating characteristic (ROC) curve was 0.923 (95%CI 0.852 to 0.995, P<0.001). The ROC curve showed that perioperative infusion of red blood cells more than 18 mL/kg would increase the incidence of AKI after heart transplantation.ConclusionPerioperative blood transfusion is closely related to AKI after heart transplantation. The more blood transfusion is in clinics, the higher incidence of renal injury is and the worse prognosis is. It is suggested that various blood-saving measures can be carried out.
Allogeneic mouse model of peritoneal heart transplant is a microscopic surgery on small animal with complex techniques. For a beginner, a learning curve of this surgical technique has to be experienced. The learning curve contains three stages:(1) to be familiar with the local anatomy of either donor or recipient mouse; (2) to be capable of collecting donor heart and well preparing the major peritoneal vessels of recipient; (3) to be skillful in the anastomosis of major vessels. The bottleneck of the learning curve is the valid skill of vascular anastomosis. The stepwise essentials are to "understand, be familiar, be accurate, and be quick" in the learning curve.
Objective To investigate the rat model of cardiac allograft vasculopathy after heart transplantation in rat abdominal cavity. Methods Forty Wistar rats and 40SDrats were divided into control group and experiment group randomly pair-matching. Rat model ofheterotopic heart transplantation was developed. Low doseCyclosporine A were injected into the abdominal cavity in experiment group, while the control group had not received the Cyclosporine A. Transplant hearts were harvested at two weeks and four weeks post-operatively and changes of coronary artery were observed by light microscope. Results There were no alteration of tunica intima of coronary artery in control group at two weeks and four weeks post-transplantation. Tunica intima of coronary artery increased in thickness at two weeks post-transplantation in experiment group and concentric circular change occurred at four weeks post-transplantation. Lumen of coronary artery constricted transparent and cardiac allograft vasculopathy occurred. Conclusion This animal model is reliable of cardiac allograft vasculopathy.
