Cardiac Transplantation Following Storage of the Donor Heart by a Portable Hypothermic Perfusion System

Four patients have undergone heterotopic heart transplantation with donor hearts stored by a portable hypothermic perfusion system. Total ischemic periods ranged from 6 hours 55 minutes to 16 hours 50 minutes. One heart, transplanted into a patient who had acutely rejected a previous graft, suffered accelerated, irreversible, acute rejection within five days, associated with strong antibody formation; donor heart function was never good. In the 3 remaining patients, donor heart function was good after initially being poor for a few hours in 2 patients. One patient died of long-term rejection after 6 months and 1 of tuberculous meningitis after 10 months; 1 remains alive at 15 months.Neither preservation of the donor heart for periods in excess of approximately 4 hours nor the use of continuous hypothermic perfusion as a method of preservation appears to have been reported previously in the context of the clinical situation.     

Further cardiac transplant procedures in patients with heterotopic heart transplants

Seven patients with heterotopic heart transplants have undergone further heart transplant procedures. In 5, the first heterotopically placed donor heart was excised and replaced with the second donor heart. In 2, the first heterotopic donor heart was left in situ and the patient's own heart (then nonfunctioning) was excised and replaced by the second donor heart; thus, these patients underwent orthotopic transplantation and were left with two donor hearts. The decision to perform retransplantation in a patient undergoing irreversible acute rejection is usually straightforward, but the timing of a further transplant procedure in a patient with advanced graft arteriosclerosis may present a difficult problem. Two of the 7 patients in this series died of infectious complications within the first 3 months after retransplantation. A third patient acutely rejected the second donor heart within 5 days, but survived an additional 17 months with the support of his own cardiomyopathic heart. Four patients remain alive and well between 5 and 36 months following the second transplant and between 17 and 54 months following the first transplant procedure.     

Pancreatic transplantation without duodenum in the dog

Our study has shown that it is possible to maintain normal exocrine and endocrine function in pancreatic heterotopic auto- and allotransplants without duodenum in the dog using a small periampullary duodenal cuff sutured directly to jejunal mucosa. The described technic has been used to prepare human cadaver donors and further clinical trials are anticipated.     

A new solid-state, long-life, lithium-powered pulse generator

A pulse generator powered by lithium iodide and using hybrid circuitry eliminates many of the causes of premature failure of pulse generators. The lithium iodide power source is completely dry, produces no gas, has no significant self-discharge, shows no catastrophic failure, is most efficient at body temperature, and loses power in a gradual fashion, thus giving months of foreknowledge of impending failure. The hybrid circuitry eliminates most soldered connections, which increases efficiency, reduces sources of failure, and allows a smaller pulse generator to be produced. The entire system can be hermetically sealed because no outlet for gas is required. The calculated in vitro life of this system is greater than 10 years, while a conservative estimate of in vivo life is 5 years.     

The Professor Merry Lecture: Endings and beginnings

Organ transplantation has become an established and worthwhile treatment for many otherwise intractable conditions in many countries around the world. For example, over 4000 patients have benefited from heart or lung transplants (or both) since the first heart transplant in Australia or New Zealand was carried out in 1984. However, there is thought to be a worldwide shortage of donors relative to the number of organs needed. Many people, notably many of those involved with situations in which organ donation might be possible, value the opportunity to contribute organs. This has led to interest in expanding the criteria for donation. Standard criteria donation (SCD) involves the formal diagnosis of brain death, and conservative criteria for donor eligibility. Extended criteria donation allows slightly more liberal eligibility criteria, thought acceptable in light of improved results in SCD. In donation after cardiac death (DCD), an alternative approach to increasing the pool of available donors, a formal diagnosis of brain death is not required. The formal diagnosis of brain death is very reliable, but prognosis in less definitive manifestations of severe brain damage is less so, as illustrated by numerous anecdotal reports. There is a tension between providing enough time between withdrawal of treatment and declaration of death for reasonable confidence to be maintained in the process of DCD and the desirability of keeping warm ischemic time to a minimum in the interest of organ survival. In Australia and New Zealand, DCD is undertaken only in the context of planned withdrawal of support in intensive care units (Maastricht category 3). There has been a considered and carefully implemented approach to DCD, and the educational initiatives associated with its introduction may have had incidental benefit to the SCD program as well. It is, nevertheless, important that all involved are cognizant of the practical and ethical issues at stake.     

Outwitting evolution*

Cooper DKC. Outwitting evolution.
Xenotransplantation 2010; 17: 171–180. © 2010 John Wiley & Sons A/S. Abstract: The author pays tribute to those who stimulated him to follow a career in clinical cardiothoracic surgery and experimental transplantation. Highlights of his career have been in contributing to (i) the first hypothermic perfusion storage of the donor heart to be used successfully in clinical practice, (ii) hormonal therapy in the management of the brain‐dead potential organ donor, (iii) the identification of Galα1,3Gal as the major antigenic target for primate natural anti‐pig antibodies, (iv) the 2‐ to 6‐month survival of α1,3‐galactosyltransferase gene‐knockout hearts transplanted into baboons, and (v) the 3‐ to 12‐month normoglycemia following the transplantation of islets from CD46‐transgenic pigs into diabetic monkeys. Many friends have been made through a mutual interest in transplantation, particularly through the activities of the International Xenotransplantation Association (IXA). The author thanks the many mentors, colleagues, and research fellows with whom it has been his great privilege and pleasure to work during the past several decades, and readily acknowledges that it is largely their contributions that have enabled him to receive the honor of Honorary Membership of the IXA.     

Pediatric ventricular assist devices: Bridge to a new era of perioperative care

Pediatric ventricular assist devices (VADs) are evolving as a standard therapy for end stage heart failure in children. Major recent developments include the increased use of continuous flow (CF) devices in children and increased experience with congenital heart disease (CHD) and outpatient management. In the current and future era anesthesiologists will encounter more children presenting for VAD implantation, subsequent procedures and heart transplantation. Successful perioperative management requires an understanding of the interaction between the patient's physiology and the device and a framework to troubleshoot problems. This review focuses on CF devices, VAD support for CHD and perioperative management of pulsatile and CF devices in the pediatric population.     

Consistent protection from pancreatitis in canine pancreas allografts treated with 5-fluorouracil

A consistent protection from pancreatitis and a significant prolongation of survival was observed in canine pancreas allograft recipients treated with azathioprine and 5-FU. Dogs that were treated only with azathioprine did not survive nearly as long as the treated dogs and pancreatitis and peritonitis were the cause of death in more than 50% of the animals. Untreated animals survived an average of 5 days and most of the animals died as a consequence of severe pancreatitis or an associated infectious process.     

Pediatric cardiac surgery: an historical appreciation

Many of the early, classic pediatric cardiac surgical operations were named after their originators. Some of these continue to be performed in the original form, many in modified form and some are obsolete. The development of many of these important early operations is reviewed and they are placed in the context of their times.     

Modification of bicaval anastomosis: an alternative technique for orthotopic cardiac transplantation

We describe an alternative technique for orthotopic cardiac transplantation (OCT), which we use to combine the advantages of the conventional technique (Lower and Shumway) and the bicaval anastomosis. The modified technique was utilized in 31 consecutive patients undergoing heart transplantation by one surgeon in our hospital since 1998.     

Anesthesia for major general surgery in neonates with complex cardiac defects

Centers with large cardiac workloads may be presented with neonates who need major general surgery before correction or palliation of a serious cardiac defect. This is still a rare situation with only three short case reports available in the medical literature ( 1–3 ). We have reviewed the anesthetic and analgesic regimens of 18 such neonates who presented to the Birmingham Children's Hospital in the 4-year period 2004–2007. These children require meticulous preoperative evaluation and although it might be anticipated that they would pose a serious challenge to anesthetists, in reality with thorough investigation, preparation, and careful management, they tolerate general anesthesia well. These children may be transferred to centers of specialist pediatric cardiac anesthesia to be benefited from experience obtained there.     

The Youngest Successful Heart Transplant in the U.K.: A Case Report

We report a case of dilated cardiomyopathy in a 7 year-old boy who was assessed and treated medically, but failed to respond. A successful orthotopic cardiac transplantation was performed.     

Mortality as an outcome measure following cardiac surgery for congenital heart disease in the current era

Mortality following cardiac surgery for congenital heart disease is rare in the current times. In this review article, we explore current mortality rates, factors associated with mortality, and pitfalls in the use of mortality as a measure for assessing outcomes following congenital heart surgery.     

Carvedilol improves functional class in patients with severe left ventricular dysfunction referred for heart transplantation

PURPOSE: Limited options are available to improve the functional class of patients awaiting cardiac transplantation. We assessed the effect of carvedilol on New York Heart Association (NYHA) class, heart rate (HR), blood pressure (BP), jugular venous pressure (JVP), electrolytes and renal function in patients with markedly decreased left ventricular (LV) function referred for cardiac transplantation assessment. METHODS: Sixty-one patients (age = 52 +/- 12 yr, EF = 23 +/- 7%, VO2 max = 16 +/- 5 mL/kg/min) referred to the cardiac transplant clinic were reviewed before and after the addition of carvedilol (starting dose 3.125 mg twice daily to target dose of 25 mg twice daily) to usual heart-failure therapy. Over a 1-yr period, at each visit prior to initiation, at baseline initiation visit and at each follow-up visit, NYHA class, BP, HR, JVP, electrolytes, and renal function were obtained. Statistical analysis was performed using random effects regression approach. A multiple logistic regression analysis was performed on 52/61 patients to determine possible associations between NYHA improvement and the following patient characteristics: sex, etiology of cardiomyopathy, initial NYHA class, and dose of carvedilol. RESULTS: Three patients died (2 after stopping carvedilol) and 3 were transplanted. Median follow-up was 100 d. Sixteen patients reached the target dose after a mean of 137 d (2.75 visits). Estimated time-to-target dose is 8 months (5.6 visits). BP tended to increase (p = 0.07 for change in trend) with no change in JVP, electrolytes or renal function. HR decreased 6 +/- 3 b.p.m. (p = 0.03). Of 14 patients NYHA class I/II at baseline, none were class III/IV at last follow-up visit. Of 47 patients NYHA class III/IV at baseline, 25 were class I/II, and 22 were class III/IV at last follow-up (p < 0.001). Multiple logistic regression analysis did not demonstrate any factor predictive of subsequent NYHA class improvement. CONCLUSIONS: Despite less than target doses in most patients, a favorable effect of carvedilol on functional class in patients with severe congestive heart failure (CHF) referred for transplant was observed. Those with good functional status remained stable and those with poor functional status improved or remained stable. No baseline patient characteristic predicted improvement. The shortage of donor organ requires optimal use of medical regimens which may improve functional class while awaiting transplantation and which may delay the necessity for heart transplantation. Therefore, addition of carvedilol to usual medical therapy may be beneficial even in patients with severe LV dysfunction and poor NYHA classification.     

Clinical outcome and quality of life of patients surviving 20 years or longer after heart transplantation

To evaluate outcome and quality of life (QoL) in ≥20 years survivors after heart transplantation. Patients surviving ≥20 years with a single graft were retrospectively reviewed. Heterotopic, multiorgan and retransplantations were excluded. QoL was evaluated using the SF‐36 survey. Eight hundred and twenty‐seven heart transplants were performed from 1981 to 1993, and among these, 131 (16%) patients survived ≥20 years; 98 (75%) were male and mean age at transplant was 43 ± 13 years. Conditional survival in these 20 years survivors was 74.1 ± 4.3% at 23 years and 60.9 ± 5.3% at 25 years (45 deaths, 34%). Forty‐four (34%) patients suffered rejection ≥2R. Conditional survival free from rejection ≥2R was 68 ± 4.1% at 5 years and 66.4 ± 4.2% at 10 years. Thirty‐five (27%) patients had cardiac allograft vasculopathy (CAV) grade 2–3. Conditional CAV‐free survival was 76 ± 3.8% at 20 years and 72.1 ± 4% at 25. Sixty‐nine (53%) patients developed malignancy, mostly skin cancers. Conditional malignancy‐free survival was 53.5 ± 4.4% at 20 years and 45.2 ± 4.6% at 25 years. At latest follow‐up, 24.0 ± 3.0 years after transplantation, mean left ventricular ejection fraction was 62 ± 11% and mean physical and mental scores were 57 ± 23 and 58 ± 21, respectively. Sixteen per cent of heart recipients survived ≥20 years with good ventricular performance and QoL. CAV and malignancies account for late morbidity and mortality.