The advantage of heterotopic cardiac transplantation over orthotopic cardiac transplantation in the management of severe acute rejection

Barnard, Christiaan N.; Losman, Jacques G.; Curcio, Christian; Sánchez, Héctor Alan Mendoza; Wolpowitz, A; Barnard, M.S.

doi:10.1016/s0022-5223(19)41191-4

Cited by 53 publications

(20 citation statements)

References 10 publications

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“…Both organs were beating asynchronously and their respective shares of the combined cardiac output depended on the ever changing two preloads (or the respective parts of the cardiac cycles both hearts were in). The telemetric pressure data of the donor left ventricle, of the recipient ascending aorta (distal to the end-toside anastomosis), support the assumption and Our implantation procedures precisely followed those used in human patients [7][8][9][10][11]. Under clinical conditions, the recipient's own heart function was of course limited; the long-standing results were however good and proved that the donor organs within the right chest could maintain the recipients' circulation.…”

Section: Discussionsupporting

confidence: 58%

“…The donor organs increased in size most probably due to humoral rejection reactions and sequelae of thrombotic microangiopathy, although additional growth cannot be excluded (M. Mohiuddin, personal communication), compressing most of the right lung within the narrow chests of the baboons. There is strong evidence, however, that allogeneic heterotopic heart transplantation has worked reliably over many years, albeit with slightly inferior results when compared to orthotopic procedures [7][8][9][10][11]. Lifelong anti-coagulation with coumadins or the new oral anti-thrombin/factor Xa inhibitors would be necessary in a clinical setting, where the patient's native left ventricular ejection fraction is impaired.…”

Section: Discussionmentioning

confidence: 99%

“…These experiments were terminated although two recipients were in good condition, one in reduced general condition. In three cases, side effects of rejection treatment, mainly due to bortezomib, contributed to the negative outcome (experiments 7,8,9). These were severe anaemia, leuko-, thrombo-cytopenia, hypoproteinaemia causing whole body oedema.…”

Section: Survival Groupmentioning

confidence: 99%

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Pre‐clinical heterotopic intrathoracic heart xenotransplantation: a possibly useful clinical technique

Abicht

Mayr

Reichart³

et al. 2015

Xenotransplantation

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Background: As a step towards clinical cardiac xenotransplantation, our experimental heterotopic intrathoracic xenotransplantation model offers a beating and ejecting donor heart while retaining the recipient 0 s native organ as a backup in case of graft failure. Clinically applicable immunosuppressive regimens (IS) were investigated first, then treatments known to be effective in hypersensitized patients or those with recalcitrant rejection reactions. Methods: Consecutive experiments were carried out between 2009 and 2013. Twenty-one genetically modified pigs (GGTA1-knockout/hCD46/ AE thrombomodulin, in one case HLA-E instead) were used as donors. In all experiments, two cycles of immunoabsorption reduced preformed antibodies. Recipient baboons were divided into two groups according to IS regimen: In group one (n = 10), pre-treatment started either one (anti-CD20) or four weeks (anti-CD20 plus the proteasome inhibitor bortezomib) prior to transplantation. The extended conventional (as for allotransplantation) immunosuppressive maintenance regimen included anti-thymocyte globuline, tacrolimus, mycophenolate mofetil, methylprednisolone and weekly anti-CD20. In group two (n = 11), myeloablative pre-treatment as in multiple myeloma patients (long and short regimens) was added to extended conventional IS; postoperative total thoracic and abdominal lymphoid irradiation (TLI; single dose of 600 cGY) was used to further reduce antibody-producing cells. Results: In the perioperative course, the surgical technique was safely applied: 19 baboons were weaned off extracorporeal circulation and 17 extubated. Nine animals were lost in the early postoperative course due to causes unrelated to surgical technique or IS regimen. Excluding these early failures, median graft survival times of group 1 and 2 were 18.5 (12-50) days and 16 (7-35) days. Necropsy examination of group 1 donor organs revealed hypertrophy of the left ventricular wall in the six longer-lasting grafts; myocardial histology confirmed preclinical suspicion of humoral rejection, which was not inhibited by the extended conventional IS including intensified treatments, and signs of thrombotic microangiopathy. Grafts of group 2 presented with only mild-to-moderate features of humoral rejection and thrombotic microangiopathy, except in one case of delayed rejection on day 17. The other experiments in this group were Jan-Michael Abicht, terminated because of untreatable pulmonary oedema, recurring ventricular fibrillation, Aspergillus sepsis, as well as a combination of a large donor organ and late toxic side effects due to TLI. Conclusions: Longer-term results were difficult to achieve in this model due to the IS regimens used. However, we conclude that heterotopic intrathoracic heart transplantation may be an option for clinical xenotransplantation.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Survival Groupmentioning

confidence: 99%

See 1 more Smart Citation

Pre‐clinical heterotopic intrathoracic heart xenotransplantation: a possibly useful clinical technique

Abicht

Mayr

Reichart³

et al. 2015

Xenotransplantation

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“…The heterotopic thoracic approach may increase the level of safety for this procedure. It was shown in the past that even during a severe rejection crisis with temporary failure of the transplant, the residual function of the recipients' native hearts was able to bridge to a successful treatment of rejection [12]. However, this possible advantage needs to be confirmed in a study combining the heterotopic thoracic pig-to-baboon heart transplantation with a cardiac failure model [10].…”

Section: Discussionmentioning

confidence: 99%

First experience with heterotopic thoracic pig-to-baboon cardiac xenotransplantation

Bauer¹,

Postrach²,

Thormann³

et al. 2010

Xenotransplantation

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This is the first description of a heterotopic thoracic pig-to-baboon heart transplantation. The procedure combines the advantages of a working heart model with the safety of heterotopic transplantation. In contrast to orthotopic transplantation, the recipient heart can assist the donor heart during episodes of rejection. We believe that the heterotopic thoracic model may accelerate the progress into the clinical application of cardiac xenotransplantation. However, successful combination of this heterotopic transplantation with an experimental model of cardiac failure may be needed before this technique can be promoted to clinical trials.

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“…After just two successful cases, the procedure was modified so that the transplanted heart could support both of the recipient's ventricle^.^ Barnard's interest in the heterotopic procedure was based on his experiences with orthotopic transplantation in which the heart of the donor had failed intraoperatively from inadequate ex-vivo preservation or from persisting pulmonary hypertension and postoperatively due to uncontrolled rejection. 6 Because most other transplant centers were influenced by Norman Shumway and associates who performed orthotopic procedures, the South African experience in which 56 heterotopic procedures were performed between 1974 and 1983 is unique and provides interesting comparison^.^ Today indications for heterotopic cardiac transplantation are individualized as a result of lessons learned about its benefits and drawbacks. special advantages in preserving the recipient's own ventricles.…”

Section: Introductionmentioning

confidence: 99%

Heterotopic Cardiac Transplantation: Current Status

Griffith¹,

Kormos²,

Hardesty³

1987

J Cardiac Surgery

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Heterotopic cardiac transplantation first introduced by Bernard in 1974 currently is rarely used as the procedure of choice when orthotopic cardiac transplantation can be considered. Specific indications for heterotopic cardiac transplantation include elevation of pulmonary vascular resistance and availability of a small or poorly functioning donor organ for a mortally ill recipient. Most cardiac transplant centers have abandoned its routine use because the recipient's diseased and poorly functioning heart remains as a potential source for embolism, infection, and continued angina, because the operative procedure is more complicated. Pulmonary complications are common due to compressive atelectasis of the right lung. Experience indicates that the heterotopic procedure is useful for those selected individuals in whom the orthotopic procedure is not appropriate and that rates of survival are nearly equal.

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The advantage of heterotopic cardiac transplantation over orthotopic cardiac transplantation in the management of severe acute rejection

Cited by 53 publications

References 10 publications

Pre‐clinical heterotopic intrathoracic heart xenotransplantation: a possibly useful clinical technique

Pre‐clinical heterotopic intrathoracic heart xenotransplantation: a possibly useful clinical technique

First experience with heterotopic thoracic pig-to-baboon cardiac xenotransplantation

Heterotopic Cardiac Transplantation: Current Status

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