Aortic arch replacement with a beating heart: a simple method using continuous 3-way perfusion.

We describe a simplified 3-way perfusion strategy that could be used in complex aortic procedures, which ensures continuous end-organ perfusion and minimizes the potential risks of cardiac, cerebral and peripheral ischaemic complications.

Hyperacute lung rejection in a pig-to-human transplant model: the role of anti-pig antibody and complement.

BACKGROUND: The physiology of hyperacute rejection of pig lung by human blood and the role of antispecies antibody and complement in this phenomenon have not previously been characterized. METHODS: Human blood was perfused through an ex vivo pig heart-lung preparation. In the treatment groups, blood was either unmodified or modified to deplete alternative pathway complement (heat treatment), anti-pig antibody, or both. Control experiments were performed with unmodified and heat-treated pig blood. Physiologic parameters, organ survival, and immunohistology were the primary outcome measures assessed. RESULTS: Pig lung was consistently damaged by human blood within 45 min (median 20 min), as evidenced by elevated pulmonary vascular resistance and parenchymal injury. Immunohistologic studies of perfused lungs showed prominent deposition of IgM and classical pathway component, C4, and weaker deposition of alternative pathway component, properdin. Heat treatment did not impede the rise in pulmonary vascular resistance or significantly prolong survival. Depletion of anti-pig antibody prolonged survival (median 90 min) and attenuated the rise in pulmonary vascular resistance. Antibody absorption, combined with heat treatment of plasma, prevented the elevation in pulmonary vascular resistance and yielded median graft survival (210 min) similar to pig blood perfusion (approximately 240 min). CONCLUSIONS: These results show that elevated pulmonary vascular resistance and pulmonary parenchymal injury are mediated at least in part by antispecies antibody and heat-sensitive pathways. They are consistent with the hypothesis that complement activation contributes significantly to acute lung damage in the pig-to-human species combination.

Orthotopic heart transplantation in a transgenic pig-to-primate model.

BACKGROUND: Previous studies demonstrated that hearts from transgenic pigs expressing human decay-accelerating factor (hDAF) were not hyperacutely rejected when transplanted heterotopically into the abdomen of cynomolgus monkeys. This study examines orthotopic transplantation of hDAF transgenic pig hearts into baboon recipients. METHODS: Orthotopic xenogeneic heart transplantation was performed using piglets, transgenic for hDAF, as donors. Ten baboons were used as recipients and were immunosuppressed with a combination of cyclophosphamide, cyclosporine, and steroids. RESULTS: Five grafts failed within 18 hr without any histological signs of hyperacute rejection. Pulmonary artery thrombosis induced by a size mismatch was observed in two of these animals. The other three recipients died because of failure to produce even a low cardiac output and/or dysrhythmia. The remaining five animals survived between four and nine days. One animal died of bronchopneumonia on day 4. Three xenografts stopped beating on day 5 due to acute vascular rejection. The longest survivor was killed on day 9 with a beating, histologically normal xenograft, because of pancytopenia. CONCLUSIONS: The results reported here demonstrate that hDAF transgenic pig hearts are not hyperacutely rejected when transplanted into baboon recipients. Orthotopically transplanted transgenic pig hearts are capable of maintaining cardiac output in baboons. An optimum immunosuppressive regimen is the subject of ongoing research.

Life supporting function for over one month of a transgenic porcine heart in a baboon.

BACKGROUND: Inhibition of hyperacute rejection (HAR) and sustained graft survival have been demonstrated in a pig-to-primate model of heterotopic cardiac xenotransplantation using pigs transgenic for human Decay Accelerating Factor (hDAF). Building on this work, an orthotopic model has been developed. This case records 39-day cardiac xenograft function in a life-supporting capacity with clinically applicable immunosuppression. METHODS: Using a heart from an hDAF transgenic pig, an orthotopic cardiac transplant was performed on an adult baboon. The immunosuppressive regimen consisted of induction with a short course of cyclophosphamide, followed by maintenance therapy with cyclosporine A, mycophenolate mofetil and a tapering course of corticosteroids. Post-operative monitoring included daily anti-pig hemolytic antibody titer surveillance and endomyocardial biopsy. RESULTS: The animal survived 39 days and was active and energetic throughout its postoperative course, remaining free of signs of cardiopulmonary failure. Endomyocardial biopsy performed on post-operative Day 36 revealed only patches of sub-endocardial fibrosis with no signs of active rejection. The baboon succumbed to an acute cardiopulmonary decompensation immediately following administration of medication via oral gavage. Post-mortem histopathology demonstrated well-preserved myocardial architecture with small foci of mild humoral rejection. CONCLUSIONS: This case documents the longest survival recorded to date of a discordant orthotopic cardiac xenograft and illustrates that the hDAF transgene combined with a clinically acceptable maintenance immunosuppressive regimen enables sustained, life-supporting function of porcine cardiac xenografts in non-human primates. The inhibition of hyperacute rejection and the subsequent control of humoral and cellular rejection for over 1 month demonstrated in this experiment represent significant progress in the development of a viable strategy for clinical xenotransplantation.

Coronary artery bypass grafting nine years after cardiac transplantation.

Angina and increasing exertional dyspnea developed in a 53-year-old man 9 years after cardiac transplantation. Left heart catheterization revealed severe proximal triple coronary artery disease, and he underwent surgical revascularization. Now 18 months after the operation he continues to be free of symptoms.

Extrusion of Teflon aortic pledgets from a sternal wound six years after cardiac surgery.

We present a case of a cardiac surgery patient with a persistent low-grade discharge from his sternal wound for over six years. It finally healed when some suture material and Teflon felt pledgets were extruded. These had been used intraoperatively to close the aortic cannulation site. The extrusion of prosthetic material from this site after this length of time has never been described.

A comparison of the performance of pig hearts perfused with pig or human blood using an ex-vivo working heart model.

The pathophysiology of xenograft hyperacute rejection is still poorly understood although it is believed to involve complement fixation to vascular endothelium, probably as a result of the presence of naturally occurring anti-species antibodies. Hyperacute rejection of pig hearts by human blood was studied in an ex-vivo working heart model. Cardiac performance and immunological reactions occurring in the perfusing blood were studied. Stroke work performed by pig hearts perfused with human blood and their survival (median 47 min: n = 10) was significantly reduced compared to survival (median 158 min: n = 10) and stroke work performed by pig hearts perfused with pig blood. Decomplementation of human blood resulted in improved performance and duration of the action (median survival > 240 min: n = 10) of hearts. Quantitative differences were seen in complement fixation between the groups. Our data demonstrate the central role of complement in the destruction of pig-to-man xenografts.

The rationale for xenotransplantation as a solution to the donor organ shortage.

This paper describes the current level of activity in organ transplantation and illustrates that human organ donors are never going to be sufficiently numerous to fill the clinical needs of potential organ recipients. Xenografts are proposed as an alternative solution and arguments are presented to suggest that xenografts from primates to man will not be an appropriate organ source in most cases. Finally the possibility of genetically engineering a pig to provide organs for human use is proposed.