Immunologically induced coronary artery stenosis in allografts after heart and heart-lung transplantation in rats

The role of the lung in suppressing immunologically induced coronary artery stenosis after heterotopic allograft transplantation was studied in rats. Thirty-nine recipients were divided into two groups: untreated and treated. The untreated group was divided into two subgroups — the heart allograft TH group and the heart-lung allograft THL group. The treated group was divided further into four subgroups depending on when the graft was harvested, after 30 days or 60 days (T_30-H and T_30-HL group, and T_60-H, T_60-HL, respectively). Rejection was assessed by Lurie's classification. The percent of intraluminal stenosis (PIS) was determined by planimetry. All treated animals received cyclospolin A 10 mg/kg/day intramuscularly for 20 days. In the untreated group, heart-lung allograft survival was longer than heart allograft survival. In the treated group, all grafts were still beating when the animals were killed. The rejection grade score in the T_30-H and T_30-HL groups were lower than those in the T_60-H or T_60-HL groups. The PIS in the THL group was slightly lower than that in the TH group. However the PIS increased over time in both the TH and THL groups. This study demonstrates that the lung suppresses but does not abolish immunologically induced coronary atherosclerosis-like occlusive lesions after cardiac transplantation.     

Predictors of Chronic Kidney Disease in Long-Term Survivors of Lung and Heart-Lung Transplantation

Renal insufficiency is common after non-renal organ transplants. The predictors of long-term renal outcomes are not well established. A total of 219 lung and heart-lung transplant recipients surviving more than 6 months after transplantation were studied to determine predictors of time to doubling of serum creatinine and end-stage kidney disease (ESKD) with death as a competing risk. Median follow-up was 79 months (range 9-222 months). Baseline estimated glomerular filtration rate (GFR) was 96.3+/-34.5 mL/min/1.73 m2. One hundred twenty-two recipients (55%) doubled their serum creatinine, 16 (7.3%) progressed to ESKD and 143 (65%) died. The majority of recipients who survived >6 years had a GFR<60 mL/min at both 1 and 7 years. Most of the loss of renal function occurred in the first year post-transplant. Older age at transplant, lower GFR at 1 month and cyclosporine use in the first 6 months predicted shorter time to doubling of serum creatinine when death was handled as a competing risk. Based on this prevalence data and using GFR decay and death as study endpoints, we offer sample size estimates for a prospective, interventional trial that is aimed at slowing or preventing the progression of kidney disease.     

Lung and heart-lung transplantation

Unilateral lung transplantation has become a successful method for the treatment of end-stage pulmonary disease, whereas double-lung transplantation has provided benefit to patients with nonfibrotic lung disease such as emphysema and cystic fibrosis. In the past 5 years, 16 single-lung and 13 double-lung transplantations have been performed by the Toronto Lung Transplant Group in patients with end-stage lung disease. Seven perioperative and two late deaths have been recorded so far. Since the introduction of heart-lung transplantation at Stanford in 1981 and at Pittsburgh in 1982 for the treatment of Eisenmenger's syndrome and terminal pulmonary vascular disease, more than 350 combined heart-lung transplantations have been carried out throughout the world. Presently, the 2-year actuarial survival is about 62%. The long-term results have not yet reached the same level of success as those of cardiac transplantation alone. Although several factors have played a role in this difference, a prominent cause has been the lack of a reliable and simple method for pulmonary protection against prolonged ischemia. Most of the techniques proposed against ischemia can be classified as normothermic or static hypothermic cardiopulmonary preservation. The use of the normothermic method has not always been successful. For this reason, interest has now been directed toward the potential for hypothermic preservation of the heart-lung bloc and the use of free-radical scavenger therapy in the reduction of reperfusion injury.     

Lung and heart-lung transplantation

This report is a brief summary on current events related to lung and heart-lung transplantation. Eleven patients have undergone transplantation of the heart and both lungs at Stanford University. The ages ranged from 22-45, the average age being about 36 years, and included were four females and seven males. The diagnosis was primary pulmonary hypertension in three and Eisenmenger syndrome--congenital heart disease with pulmonary hypertension--in eight. Eight patients are living and well, two to more than 24 months after transplantation of the heart and both lungs. All these patients were discharged and are fully rehabilitated, which is an important consideration. There have been three operative deaths, one was secondary to two previous operations that made our operation much too long, another was secondary to the use of intravenous cyclosporine, and the third was related to the poor maintenance of the donor lung. Three of the eleven patients were catheterized following the transplant from six months to a year after transplantation, and the pulmonary artery pressure and pulmonary vascular resistance were absolutely normal in all three of these individuals. Of course the plan is to go ahead with further catheter studies at yearly intervals in all of the patients. The last patient underwent transplantation in January, 1983. I think no matter how effective or how ingenious the medical staff is with artificial organs, it will be a long time before these early results of transplantation of the heart and both lungs can be matched by any types of artificial organ implants.     

Lung transplantation after hematopoietic stem cell transplantation

Whitson BA, Shelstad RC, Hertz MI, Kelly RF, D’Cunha J, Shumway SJ. Lung transplantation after hematopoietic stem cell transplantation.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01482.x.
© 2011 John Wiley & Sons A/S. Abstract: Introduction: Pulmonary insufficiency following bone marrow transplant (BMT) is common and has significant associated mortality. Lung transplantation (LTX) is the only viable treatment for patients with end‐stage pulmonary disease, but LTX after BMT is an uncommon event given the medical candidacy of the potential recipients. We sought to evaluate the short‐ and long‐term outcomes of LTX in BMT recipients. Methods: We performed a retrospective evaluation of our institution’s longitudinal LTX and BMT databases. Demographic and outcomes variables were collected. Results: We identified 639 LTX from January 1, 1988, through December 31, 2009, and 5525 BMT from program inception, March 21, 1974, through December 31, 2009. From the cross‐referenced cohort, we identified four patients who had BMT followed by LTX. Our series was composed of two men and two women, with a mean age of 32.3 yr (range, 20–59 yr). Single LTX were performed in two recipients (50%). All patients had significant and expected morbidities related to their transplant immunosuppression. Three patients (75%) required cardiopulmonary bypass at the time of LTX. The two recipients who underwent bilateral LTX required open chest management and subsequent tracheostomy. All patients are still alive at follow‐up (range, 19–119 months, median 39.5). Conclusion: Our study demonstrates that LTX in the setting of BMT is a high‐risk operation with the potential for a tumultuous perioperative course. Despite this, good outcomes and survival are obtainable in carefully selected patients. Selection factors include clinically stable patients without active sepsis and preoperative optimization of nutrition in anticipation of a prolonged recovery. An experienced multidisciplinary team approach and a protocol‐driven management plan are paramount for successful outcomes in this challenging population.     

Anaesthesia for combined heart and lung transplantation

In December 1983, Harefield Hospital started a programme for combined heart and lung transplantation. Fifty-two transplants have been successfully performed, with 36 survivors (April 1986). Patient selection and anaesthetic management of both donor and recipient are discussed. Two case histories are presented which illustrate the principles of anaesthetic management and postoperative care.     

Heart-lung transplantation —Harefield experience

One hundred and fifty-nine combined heart and lung transplantations were performed on 152 patients at Harefield Hospital from 1980 to February 1988. The age of the recipients ranged from 10 weeks to 52 years. The transplantation was indicated for pulmonary vascular disease on 106 patients (69.7 per cent), and for parenchymal lung disease on 46 patients (30.3 per cent). Eisenmenger syndrome was the commonest disease that required the heart-lung transplantation. A combination of cyclosporin A and azathioprine was administered for immunosuppression therapy postoperatively, and oral steroids were not routinely used. The hospital mortality rate was 32.2 per cent, and 103 patients were discharged from the hospital. The first-year actuarial survival rate was 64 per cent, and the second-year was 61 per cent. Although pulmonary deterioration due to obliterative bronchiolitis was a serious late complication, most of the recipients enjoyed a good quality of life after transplantation. Heart and lung transplantation offers the patient a chance of marked improvement both in survival and in quality of life. This report is the gist of a paper read by M.H.Y. at the 88th Annual Meeting of the Japan Surgical Society, Niigata, Japan, 1988     

Lung transplantation: state of the art and current practice

This article is a reflection of the present status of lung transplantation in the UK and worldwide and its transformation of end-stage lung disease. In its infancy, it was swept along by the determination and drive of surgical pioneers. Amongst them the names Demikhov, Hardy, Schumway, Cooley, Reitz, Cooper and Patterson have exemplified the surgeons' drive to bring lung transplantation to clinical fruition. With long-term survivors of heart–lung transplantation (HLTx) from 1981, single lung transplantation (SLT) from 1983 and bilateral lung transplantation (BLTx) from 1986, this decade saw the true genesis of clinical lung transplant programmes. In the modern era, research into donor organ regeneration with ex vivo lung perfusion (EVLP) and retrieval of lungs from non-brain dead donors (DCD transplantation), drug improvements in immunosuppression, technique improvements with ECMO and off-pump surgery have constantly pushed the boundaries and consistently seen a rise in lung transplantation year on year and it now exceeds cardiac transplant activity despite falling numbers of organ donors.     

Ganciclovir prophylaxis after lung and heart-lung transplantation

Abstract Cytomegalovirus (CMV) infection causes both acute and chronic allograft damage. The aim of this study was to analyze the utility of ganciclovir in preventing CMV infection in pulmonary allografts. Thirty five consecutive lung (LTX) and heart-lung (HLTX) transplant patients were studied from 1990 to 1996 CMV prophylaxis was started in January 1995. Recipients with CMV-positive serology received ganciclovir on postoperative days (POD) 7–28. Acyclovir was given on POD 29–90. Recipients with CMV-negative serology received ganciclovir on POD 7–90 if the serology of the donor was positive. CMV was demonstrated by rapid cell vial culture and/or detecting CMV-specific antigens in bronchoalveolar lavage (BAL) samples. The time point of the first BAL fluid specimen exhibiting CMV was estimated using the Life Table method. BAL samples of all the recipients without ganciclovir treatment became positive for CMV, whereas two of the 11 patients with ganciclovir administration remained negative. Ganciclovir significantly ( P < 0.05) delayed but did not absolutely prevent CMV infection after LTX and HLTX.     

肺移植治疗终末期肺病18例报告

陈静瑜郑明峰朱艳红胡春晓何毅军王永功周敏陆国础陆明华【摘要】目的探讨国内开展临床肺移植的可行性以及目前存在的主要问题。方法2002年9月至2005年4月共完成临床肺移植18例,其中肺气肿9例、肺纤维化5例、矽肺1例、支气管肺扩张1例、肺淋巴管平滑肌瘤病1例及室间隔缺损合并艾森曼格综合征1例。受者术前均为重症呼吸衰竭,长期靠呼吸机依赖3例。手术方式为:单肺移植15例(左肺移植9例,右肺移植6例),其中2例受者的供肺为同一供者同期的左、右单肺,有1例为左侧供肺植入右胸腔,1例为体外循环下室间隔缺损修补后行右肺移植;非体外循环下序贯式双侧单肺移植3例。结果术后短期内死亡3例,1例于术后15d死于急性排斥,1例于术后30d死于感染后多脏器功能衰竭,1例术后36d死于肺梗死。其余15例均痊愈出院,肺功能明显改善,生存1年以上3例,生存2年以上2例,中位生存时间10个月。结论肺移植是治疗各种终末期肺病的有效的手段;但术后的缺血再灌注损伤、排斥反应和感染仍是肺移植短期死亡的主要原因。     

Thoracic organ transplantation

This article presents an overview of factors associated with thoracic transplantation outcomes over the past decade and provides valuable information regarding the heart, lung, and heart-lung waiting lists and thoracic organ transplant recipients. Waiting list and post-transplant information is used to assess the importance of patient demographics, risk factors, and primary cardiopulmonary disease on outcomes.
The time that the typical listed patient has been waiting for a heart, lung, or heart-lung transplant has markedly increased over the past decade, while the number of transplants performed has declined slightly and survival after transplant has plateaued. Waiting list mortality, however, appears to be declining for each organ and for most diseases and high-severity subgroups, perhaps in response to recent changes in organ allocation algorithms. Based on perceived inequity in organ access and in response to a mandate from Health Resources and Services Administration, the lung transplant community is developing a lung allocation system designed to minimize deaths on the waiting list while maximizing the benefit of transplant by incorporating post-transplant survival and quality of life into the algorithm. Areas where improved data collection could inform evolving organ allocation and candidate selection policies are emphasized.     

心肺移植3例

目的 总结3例心肺移植的经验.方法 2003年7月至2012年8月,3例终末期心肺疾病患者施行心肺移植手术.1例先天性房间隔缺损伴艾森曼格综合征,心功能Ⅳ级;1例扩张性心肌病伴中重度肺动脉高压,心功能Ⅲ～Ⅳ级;1例左心室双出口合并室间隔缺损伴肺动脉主干及左、右分支狭窄,心功能Ⅲ～Ⅳ级.心肌保护液均为UW液;肺保护液均加入前列腺素E1,Euro-Collin液1例,低钾右旋糖酐液2例.术前给予赛尼派或巴利昔单抗、术中甲基泼尼松龙、术后环孢素/他克莫司+泼尼松+骁悉抗排斥治疗.术中严密止血.移植术后严格消毒、隔离,加强呼吸道护理.例2患者术毕至术后31天胸液量14 640ml,术后40天内应用纤维支气管镜吸痰13次,同时使用广谱抗生素及抗真菌药物控制感染.结果 3例患者全部痊愈出院.1例术后4年10个月因慢性排异反应引起的阻塞性支气管炎、肺功能衰竭死亡;1例术后68天因突发脑血管意外死亡;1例目前健在,已生存1年余.结论 妥善保护心肺功能,术中认真止血,手术操作精细,术后加强防治感染,重视应用纤维支气管镜和合理的抗排斥治疗是心肺移植成功的重要因素.     

Lung transplantation in patients with coal workers' pneumoconiosis

Patients with coal workers' pneumoconiosis (CWP) can develop chronic respiratory failure and require lung transplantation. A retrospective review was performed of the 712 referrals and 143 patients undergoing unilateral or bilateral lung transplantation at the University of Kentucky Medical Center between January 1999 and July 2009. Twenty-one of the 712 referrals (3%) had a diagnosis of CWP with eight patients eventually undergoing lung transplant (six single, two bilateral). The mean age of the cohort was 53 ± 5 (mean ± SD) yr (range 45-59). There was no increased risk of perioperative or postoperative complications. Six patients (75%) remain alive after a mean follow-up of 1013 ± 857 d with the two deaths attributable to sepsis 683 and 145 d after transplant, respectively. There were no pulmonary complications because of the native lung in patients after a single lung transplant, with otherwise good clinical outcomes seen after lung transplantation.     

Lung and heart-lung transplantation. Evolution and new applications.

Heart-lung transplantation (HLT) and lung transplantation (LT) are effective treatment modalities for patients with advanced pulmonary parenchymal or vascular disease. Lung transplantation offers potential advantages over HLT, including reduced pretransplant waiting time and improved efficiency of organ utilization, and is currently being offered to patients formerly treated by HLT. To explore the relative merits of these procedures, the authors examined the results in 44 procedures (23 HLT and 21 LT) in 42 patients transplanted at their institution. Heart-lung transplant recipients included 20 adults and three children (ages 5,5 and 3). Most HLT patients had primary pulmonary hypertension (PPH) (n = 9) or Eisenmenger's syndrome (ES) (n = 8). Twenty-two of twenty-three patients have been long-term survivors (mean follow-up = 17.8 months, Kapaln-Meier survival at 12 months = 85%). Obliterative bronchiolitis (OB) has occurred in five patients (22%), and all have died. Of 21 LTs in 19 patients, nine had obstructive and eight had restrictive lung diseases. Three single-LT (SLT) patients had PPH, and one had ES secondary to a ventricular septal defect. Mean pulmonary artery pressures fell from 55 +/- 6 mm Hg before SLT to 21 +/- 3 mm Hg after SLT; p less than 0.001. Three pediatric patients (ages 4, 10, 17, and 17[re-transplant]) have undergone four SLTs. With mean follow-up of 6.4 months, LT patients have survival at 12 months of 80% (Kaplan-Meier). Lung transplant patients wait a far shorter time for their transplant than do HLT patients (166 vs. 384 days, p less than 0.03). Three patients (19%) have evidence of OB after SLT, with one death. By virtue of equal intermediate-term outcomes, shorter waiting times, and better use of donor organs in comparison with HLT, LT should be offered whenever possible to patients with end-stage pulmonary parenchymal or vascular disease. The authors' pediatric LT and HLT experience (7 treatments in 6 patients) is the largest reported to date and demonstrates the utility of these procedures in this group. Chronic rejection (OB) remains the greatest impediment to long-term survival in both LT and HLT pts.     

Functional and metabolic effects of propafenone in the rat heart-lung preparation

The effects of propafenone on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation. Propafenone 0.3, 3 or 30µg·ml^–1 was administered 5min after the start of perfusion. Heart rate decreased in the 30µg·ml^–1 group significantly following the drug administration. The highest dose of propafenone (30µg·ml^–1) reduced cardiac output significantly, and this dose was associated with a higher incidence of arrhythmias than the other groups. Although there were no significant differences in myocardial lactate and glycogen concentrations among groups, ATP content in the 30µg·ml^–1 group was significantly less than that in the control group. As therapeutic plasma concentration of propafenone is about 0.6 (range 0.06 to 1.0) µg·ml^–1, 30µg·ml^–1 is 50 times greater than its concentration. These results suggest that the negative inotropic and chronotropic effects of propafenone are almost same with those of lidocaine which we have previously reported.(Kashimoto S, Oguchi T, Nakamura T, et al.: Functional and metabolic effects of propafenone in the rat heart-lung preparation. J Anesth 5: 392–395, 1991)