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.
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.
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.
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 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 investigate the effects of human recombinant hepatocyte growth factor(rh-HGF) on the expression of c-Met in intima of allograft vessels after cardiac transplantation in rats. Methods Heterotopic heart transplantation were established in abdominal cavity with eighty Wistar rats and forty SD rats. Donors’ cardiac grafts from Wistar rats were transplanted to SD rats(allograft) or Wistar rats(isograft).Sixty recipient rats were divided into three groups, control group：20 Wistar rats were injected with normal saline 1ml/kg·d intraperitoneally after transplantation; cyclosporine A (CsA) group:20 SD rats were injected with CsA 5mg/kg·d intraperitoneally on operation day; rhHGF group:20 SD rats were injected with rh-HGF 500μg/kg·d and CsA 5mg/kg·d intraperitoneally on operation day. The cardiac grafts were harvested at the 15th day and 60th day after transplantation. The crosssection of vascular tissues were used for immunohistochemistrical staining of c-Met, and investigated the expression of c-Met messenger ribonucleic acid (mRNA ) in intima of allograft vessels by reverse transcriptionpolymerase chain reaction(RT-PCR). The pathologic changes of allograft coronary vessels were observed with histopathological method. Results The allograft coronary arteries showed minimal intimal thickening, the endothelium and internal elastic lamina remained almost intact in rh-HGF group after transplantation.The expression of c-Met and c-Met mRNA in intima of allograft vessels after transplantation in rhHGF group were significantly higher than those in CsA group and control group（expression of c-Met at 60d: 1.85±0.26 vs. 0.96±0.10, t=8.491,P=0.000;1.85±0.26 vs. 0.58±0.03, t=13.725,P=0.000; expression of c-Met mRNA at 60d: 192±0.22 vs. 0.88±0.07, t=11.940,P=0.000;1.92±0.22 vs. 0.42±0.02,t=19.206,P=0.000）. Conclusion rh-HGF may prevent the progression of cardiac allograft vasculopathy through upregulating the expression of c-Met to stimulate endothelial cell repair and growth.
Abstract: Human leukocyte antigen (HLA) is the key antigen mediating rejection and panel reactive antibody (PRA) represent anti-HLA antibodiesin circulation. HLA typing and PRA testing are carried out generally before organ transplantation. With research on the relationship among HLA, PRA and heart transplantation developing, the value of HLA typing and PRA testing in heart transplantation has received more attention and their clinical using strategy has been improved. This article will review the strategy of HLA typing, the clinical value of HLA typing, time-selection in HLA typing, reason and mechanism of rising PRA, clinical sense of PRA testing and treatment of sensitized patients.
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 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.
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.