Objective To investigate the effect of interleukin-10 （IL-10） gene transfer on expression of CD44, selectin-E, lymphocyte function associated antigen-1 （LFA-1）, vascular cell adhesion molecule-1 （VCAM-1） in mice heart transplantation rejection. Methods Model of mice cervical heterotopic heart transplantation was set up, 96 mice were divided into three groups with random number table, control group： heart transplantation between C57 mice; transplant group： heart from BALB/C mice transplant to C57 mice; IL-10 group： IL-10 was transfected on BALB/C mice isolated heart for 1 hour, then transplanted to C57 mice. The messenger ribonucleic acid （mRNA） level expression of CD44 ,selectin-E ,LFA-1 ,VCAM-1 and IL-10 were measured by reverse transcription-polymerase chain reaction （RT-PCR） at the 5th day after transplantation. Results The mRNA level expression of CD44, selectin-E ,LFA-1 ,VCAM-1 in transplant group were significantly increased than those in control group （P〈0.01）. The mRNA level expression of CD44, selectin-E, LFA-1 ,VCAM-1 in IL-10 group were significantly decreased than those in transplant group （P〈0.01）. Conclusion IL-10 gene transfer is able to decrease the expression of CD44, selectin-E,LFA-1 ,VCAM-1 and suppress the heart transplantation rejection in mice.
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.
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 analyze the relation between preoperative pulmonary artery pressure(PAP) and postoperative complications in heart transplant patients, and summarize the experience of perioperative management of pulmonary hypertension (PH), to facilitate the early period heart function recovery of postoperative heart transplant patients. Methods A total of 125 orthotopic heart transplant patients were divided into two groups according to preoperative pulmonary arterial systolic pressure(PASP) and pulmonary vascular resistance(PVR), pulmonary [CM(1583mm]hypertension group (n=56): preoperativePASPgt;50 mm Hg or PVRgt;5 Wood·U; control group (n=69): preoperative PASP≤50 mmHg and PVR≤5 Wood·U. Hemodynamics index including preoperative cardiac index (CI)，preoperative and postoperative PVR and PAP were collected by SwanGanz catheter and compared. The extent of postoperative tricuspid regurgitation was evaluated by echocardiography. Postoperative pulmonary hypertension was treated by diuresis，nitrogen oxide inhaling，nitroglycerin and prostacyclin infusion, continuous renal replacement therapy(CRRT)and extracorporeal membrane oxygenation(ECMO). Results All patients survived except one patient in pulmonary hypertension group died of multiorgan failure and severe infection postoperatively in hospital. Acute right ventricular failure occurred postoperatively in 23 patients, 10 patients used ECMO support, 10 patients with acute renal insufficiency were treated with CRRT. 124 patients were followed up for 2.59 months，7 patients died of multiple organ failure, infection and acute rejection in follow-up period, the survivals in both groups have normal PAP, no significant tricuspid regurgitation. No significant difference in cold ischemia time of donor heart, cardiopulmonary bypass(CPB) and circulation support time between both groups; but the patients of pulmonary hypertension group had longer tracheal intubation time in comparison with the patients of control group (65±119 h vs. 32±38 h, t=2.17，P=0.028). Preoperative PASP，mean pulmonary artery pressure(MPAP) and PVR in pulmonary hypertension group were significantly higher than those in control group, CI was lower in pulmonary hypertension group ［PASP 64.30±11.50 mm Hg vs. 35.60±10.20 mm Hg; MPAP 43.20±8.50 mm Hg vs. 24.20±7.20 mm Hg; PVR 4.72±2.26 Wood·U vs. 2.27±1.24 Wood·U; CI 1.93±0.62 L/（min·m2） vs. 2.33±0.56 L/（min·m2）; Plt;0.05］. Postoperative early PASP, MPAP and PVR in pulmonary hypertension group were significantly higher than those in control group (PASP 35.40±5.60 mm Hg vs. 31.10±5.70 mm Hg, MPAP 23.10±3.60 mm Hg vs. 21.00±4.00 mm Hg, PVR 2.46±0.78 Wood·U vs. 1.79±0.62 Wood·U; Plt;0.05). Conclusion Postoperative right heart insuficiency is related to preoperative pulmonary hypertension in heart transplant patients. Donor heart can quickly rehabilitate postoperatively by effectively controlling perioperative pulmonary hypertension with good follow-up results.
Objective To summarize the experiences of donor heart procurement of heart transplantation so as to improve the efficiency of donor heart protection. [WTHZ]Methods [WTBZ]From April 2002 to October 2006, sixtyone patients with endstage heart disease had undergone orthotopic heart transplantation. Donors were all male brain deaths, aged from 21 to 53, and 5 of them were older than 40. There were 6 cases in which the weight difference between donor and recipient＞20%, and the rest ≤±20%. Fortyfive cases had the same ABO blood type, and 16 had matching ABO blood type. Four donor hearts were procured under the condition of stable hemodynamics and enough oxygen after brain death(typeⅠ), fortyfour donor hearts were procured under the condition of brain death with acute hemorrhage and hypovolemia (typeⅡ), and 13 donor hearts were procured under the condition of brain death with cardiac arrest (typeⅢ). Twenty cases underwent standard transplantation procedure, one underwent total heart transplantation procedure and 40 underwent bicaval transplantation procedure. The donor heart cold ischemic period ranged from 52 to 347 min（92±31 min）, and 13 cases were more than 240 min. Results Two cases died of low cardiac output syndrome on 7th and 9th day after operation respectively, and their donor heart cold ischemic period were 327 and 293 min respectively. The rest of patients all recovered and discharged. One died of acute rejection on 18th month after operation because of rejecting immunosuppressive agents, and 1 died in traffic accident on 23rd month after transplantation. The rest 57 cases survived 6-59 months(mean 35 months), and had good life quality with NYHA cardiac function classification in 0-I grade. Conclusions Heart transplantation with donor aged over 40 may also have satisfactory results. Patients with endstage dilated cardiomyopathy can procure donor heartsfrom donors with heavy weight. Using different techniques to procure donor hearts may furthest reduce myocardial injury. Donor hearts which have been protected by myocardium protecting liquid for a long time should be used with caution.
The shortage of donor heart and the lack of satisfactory donor heart are embarrassing heart transplantation. With the development of the study of the effects of thyroid hormone（TH） on cardiovascular system, amazing achievement has been obtained. TH could improve the quality of donor heart, increase successful rate and reduce mortality of heart transplantation. In the mean time ,some donor hearts that could not be used originally had been used after TH application, thus expanded donor pool. TH has been a routine treatment measure in heart transplantation in many heart centers. The application of TH in heart transplantation has been reviewed in this article.
Objective To investigate the effect of alltrans retinoic acid (atRA) on proliferative artery disease after heart transplantation. Methods Heterotopic heart transplantation model was established by Ono model with 16 inbred healthy male Wistar rats as donors and 16 SD rats as recipients. The rats were divided into chronic rejection group and atRAtreated group by complete random design, and there were 8 rats in each group. Rats in chronic rejection group were given Cyclosporine A 10 mg/(kg·d) by subcutaneous injection after operation, and those in atRAtreated group were given Cyclosporine A 10 mg/(kg·d) in the same way and atRA 10mg/(kg·d) by gavage. The transplanted hearts of rats were taken out 60 days after the transplantation. HE stain, masson stain and Van Gieson were done to analyze the rejection of transplanted hearts, the degree of vascular stenosis and myocardial fibrosis respectively.Immunohistochemistry was used to test proliferating cell nuclear antigen (PCNA). Results The area of myocardial fibrosis in chronic rejection group was obviously larger than that in atRAtreated group（63.99%±11.91% vs.34.68%±6.34%）, and there was significant difference between two groups（t=8.377，P=0.000）. The index of vascular stenosis in chronic rejection group was higher than that in atRAtreated group（62.86±17.18 vs. 40.10±8.20）. Vascular stenosis in atRAtreated group alleviated significantly, and there was significant difference between two groups（t=3.913, P=0.006）. The PCNA positive cells in chronic rejection group were obviously more than that in atRAtreated group（60.17±17.74 vs. 33.96±8.65）, and there was significant difference between two groups（t=5.387, P≤0.001）. There was a positive correlation between the PCNA positive cell ratio and the index of vascular stenosis（r=0.854, P=0.007）. Conclusion Alltrans retinoic acid can inhibit vascular disease after heart transplantation by cell proliferative pathway.
Heart transplantation is a most efficacious therapy for end-stage heart failure, but acute rejection (AR) is the biggest problem to threat longer-term survival of post-transplant patients. Currently, endomyocardial biopsy is the gold standard for the diagnosis of AR. Due to limited sample size and different tissue locations, this invasive examination may cause sampling error and significant difference between biopsy-based diagnosis and AR severity. Therefore, we need a noninvasive and repeatable method to accurately diagnose and monitor AR after heart transplantation. Cardiovascular magnetic resonance can not only observe histological changes directly from the imaging when AR occurs, but also monitor and make diagnosis of AR by evaluating T2 relaxation time, cell labeling, cardiac functional parameters and morphological changes.
Abstract:Objective To investigate immunoinh.ibitory effects of paclitaxel on acute rejection of allogeneic heart transplantation in rats. Methods Heterotopic abdominal cardiac transplantation was performed from Wistar rats to SD rats. Seventy recipients were randomly divided into five groups,14 rats in each group. Control group： rats didn＇t receive any immunoinhibitory drug; group Ⅰ ： low-dose paclitaxel （0.75 mg/kg · d） was injected intraperitoneally; group Ⅱ ： high-dose paclitaxel （1.5 mg/kg ·d） was injected intraperitoneally; group Ⅲ ： cyclosporin A（CsA, 5 mg/ kg·d） was administered orally; group Ⅳ ： low-dose paclitaxel （0. 75 mg/kg · d） was injected intraperitoneally in combination with CsA （5 mg/kg · d administered orally）. General conditions of recipient, allograft survival and pathologic lesion at 7th day posttransplantation were observed. Results Allograft survival in treating groups were significantly prolonged compared with control group （P〈 0. 05）. Moreover, allograft survival in group IV was significantly prolonged compared with those in group Ⅰ and group Ⅲ （P〈0.05）. On 7th day posttransplantation, cardiac allograft looked swollen and International Society for Heart and Lung Transplantation （ISHLT） score was 3 or 4 in control group; cardiac allograft beat vigorously, showed pink in color and felt tender in group Ⅰ and group Ⅱ , ISHLT-score was 2 or 3. Compared to control group, pathologic lesion of grafts in group Ⅰ and group Ⅱ were significantly relieved （P〈0.05）. Cardiac allograft beat well and ISHLT-score was 2 in group Ⅲ. Cardiac allograft looked as normal and beat vigorously, ISHLT-score was less than 2 in group IV ; the protective effects on cardiac allograft was better than those in group Ⅰ and group Ⅱ （P〈0. 05）. Conclusion Paclitaxel could obviously suppress acute rejection and prolong survival of rat cardiac allograft. Paclitaxel and CsA has synergistic effect on prevention acute rejection.
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.