Transplantation from non-heart-beating donors.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Khagani.
Explore the source record for details and available documents.
OBJECTIVE: Although airway problems after lung and heart-lung transplantation have been greatly reduced due to changes in surgical technique, excessive granulation tissue at the anastomosis may threaten airway patency. Treatment options include electrocautery, dilation, laser coagulation and stent placement however, recurrence remains a problem. Cryotherapy, the controlled application of extreme cold, is effective at causing cell lysis in granulation tissue and may therefore be effective after lung transplantation for airway problems arising from granulation stenosis. Our objective was to review our experience with cryotherapy as a first-line treatment for airways compromised by granulation tissue after lung and heart-lung transplantation. METHODS: A retrospective analysis of patient records after lung and heart-lung transplantation was performed. A total of 696 patients were identified who received lung or heart-lung transplants, 64 of whom were found to have granulation tissue at the site of airway anastomosis (8.9% of 721 airways at risk). When the granulation tissue was found to narrow the lumen by > or = 50% and affect lung function. RESULTS: The trachea was involved in 5 patients and the main stem bronchus in 16. Each patient required a mean of 2.6 +/- 2.0 cryoapplications. Anatomical results of cryotherapy were judged excellent to good in 15 patients and fair in 6 patients. Eight patients required endobronchial stenting as part of a multimodality treatment. Overall, the post-treatment FEV1 and FVC increased by 34 +/- 36% and 25 +/- 27% from pre-treatment values respectively (P < 0.001). In 13 patients in whom cryotherapy and dilation alone were effective, the FEV1 increased by 41 +/- 43% (range -11 +/- 138%) and the FVC by 28 +/- 29% (range -4 +/- 96%). These changes were also significant (P < 0.001). Changes in these two parameters were positively and significantly correlated (P < 0.01). Acturial survival at 3 and at 5 years were 57 and 43%, respectively (NS compared to total cohort), and median survival was 978 days (range 365-1862). Six patients are alive at a median follow-up of 5.75 years (range 0.6-8.3). CONCLUSIONS: We conclude that cryotherapy is a safe, effective treatment for excessive granulation tissue after lung and heart lung transplantation and may reduce the need for endobronchial stenting and limit recurrence.
Increased experience and knowledge in the field of heart transplantation has resulted in continued expansion of this clinical activity. The same experience has served to identify many problems and provided some answers which are in many instances incomplete. The outstanding problems in heart transplantation are firstly the availability of donor organs, secondly, the limited storage of excised donor hearts and thirdly the conundrum of transplant vascular disease as it is manifested in the coronary arteries of the donor heart. Despite these problems, heart transplantation remains a very effective form of treatment particularly for young, well-motivated patients in end-stage heart failure. Although there is considerable agreement on many of the issues relating to heart transplantation, there are several areas of controversy. Neonatal heart transplantation is one example, though with accumulated experience, acceptance of the procedure has grown. The purpose of this article is to provide an overview of the present situation and to highlight areas of controversy and ignorance which require investigation.
The human gastroepiploic artery has been used as a coronary artery bypass conduit in a limited number of clinical studies. It has been postulated that the capacity of the endothelium to release vasoactive substances may contribute to differing patency rates observed in established bypass grafts. We have now examined endothelial function in the human gastroepiploic artery. Endothelium-dependent relaxations to substance P were observed. A maximum relaxation of 83.25% +/- 8.2% (mean +/- standard error) was attenuated to 48.5% +/- 16.4% in the presence of L-NG-monomethyl-arginine, a specific inhibitor of endogenous nitric oxide synthesis. Removal of the endothelium abolished the relaxations. With a specific radioimmunoassay, concomitant changes in levels of cyclic guanosine 3',5'-monophosphate, the second messenger that elicits smooth muscle relaxation after release of the endothelium-derived relaxing factor, were measured. It was found that the gastroepiploic artery had significantly higher resting and stimulated levels of cyclic guanosine 3',5'-monophosphate than either the internal mammary artery or the saphenous vein. In the presence of the cyclooxygenase inhibitor indomethacin, and indomethacin plus L-NG-monomethylanginine, the maximum relaxation was decreased to 70% +/- 9.5% and 59% +/- 10.8%, respectively. Our data demonstrate that endothelium-derived relaxing factor and prostacyclin may exhibit synergy in the control of vascular tone in this vessel. It is concluded that the endothelium of the gastroepiploic artery has a strong capacity to secrete vasodilators and inhibitors of platelet activity. This could have important influence on long-term patency.
Measurement of the potential difference (PD) across the airways provides an indication of the viability and integrity of the lining epithelium. PD was recorded from the lower airways in "diseased controls" and in patients following heart-lung transplantation. Diseased controls showed a high PD centrally which fell (became less negative) peripherally (trachea -15.8 mV (SEM 1.0), lobar bronchi -12.6 mV (1.2), segmental bronchi -9.8 mV (1.2]. Following heart-lung transplantation (HLT) the profile of PD with airway size was altered in comparison to non-transplanted patients with reduced values in the large airways. Host tracheal values above the anastomosis were similarly reduced. Two episodes of rejection were associated with a lower mean airway PD; no significant changes were found with infection. In patients with cystic fibrosis (CF), values in the donor lung did not differ from those in non-CF transplanted patients up to one year following transplantation, although nasal PD in the host remained elevated. HLT selectively alters the PD profile only of larger airways, which may relate to the interruption of the bronchial arterial supply to these sites.
Knowledge about the distribution and origins of peptide-containing nerves in the innervated and transplanted heart is lacking. Immunohistochemical and histochemical techniques were used to visualize human cardiac innervation before and after transplantation. In the recipient heart cardiac nerve fibers and fascicles displayed immunoreactivity for general neural (protein gene product 9.5 and synaptophysin) and Schwann cell markers (S-100). A major proportion of cardiac nerves displayed neuropeptide tyrosine and tyrosine hydroxylase immunofluorescence staining. Subpopulations of nerves contained somatostatin, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P- or neurokinin-like immunoreactivity, and acetylcholinesterase activity. Tissues from cardiac allografts (5 weeks to 63 months after transplantation) contained nerves and ganglion cells that were acetylcholinesterase positive and immunoreactive for the general neural markers. These nerves were less numerous than in recipient hearts and rarely displayed neuropeptide immunostaining. Atrial natriuretic peptide immunoreactivity was localized to myocardial cells in transplanted hearts as well as explanted recipient and postmortem hearts. While most human cardiac allografts remain functionally extrinsically denervated, they appear to contain viable intrinsic nerves, and myocardial cells retain the capacity to produce atrial natriuretic peptide.
Respiratory tract nerves have cell bodies outside (sensory, sympathetic) and inside (parasympathetic) the organ and contain bioactive peptides. These include calcitonin gene-related peptide and tachykinins (sensory nerves), vasoactive intestinal polypeptide (parasympathetic nerves), and neuropeptide with tyrosine (sympathetic nerves). Because transplantation interrupts the extrinsic nerve supply to the tissues, we have examined transplanted human respiratory tracts (n = 11) removed at retransplantation 2 to 42 months after the primary transplant in order to determine whether any nerves and peptide synthesis persist. As controls to establish nerve distribution in human respiratory tract, tissues were obtained from 10 lung resections and five autopsies. Cryostat sections were immunostained to demonstrate the general neural marker PGP 9.5, neuropeptides, and the catecholamine-synthesizing enzyme tyrosine hydroxylase. Nerves immunoreactive for PGP 9.5 were detected in all transplanted tissues. They were fewer in number overall than in control tissue, significantly so in epithelium of trachea and bronchus where they were present sparsely in only three cases. Nerves immunoreactive for tyrosine hydroxylase were significantly fewer in the transplants. Peptide-immunoreactive nerves were also reduced in number in the transplants, except for vasoactive intestinal polypeptide, which was only significantly changed in blood vessels in the lung. Ganglion cells immunoreactive for tyrosine hydroxylase and neuropeptide with tyrosine were seen in the transplanted tissues in five cases, but never in the control tissues. We conclude that whereas some nerves and neuropeptide synthesis persist after extrinsic pulmonary denervation, potentially significant changes also occur, including the appearance in intrinsic parasympathetic neurones of immunoreactivity for a catecholamine-synthesizing enzyme and a peptide normally found in sympathetic nerves.
Explore the source record for details and available documents.
Explore the source record for details and available documents.