Ultrastructural correlation of endomyocardial biopsy findings with myocardial preservation in human cardiac allografts.
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Biomedical subjects
Publications and source records attributed to U Livi.
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Acute allograft rejection is still a leading cause of both early and late mortality and morbidity after cardiac transplantation. Besides cell-mediated acute rejection, a "humoral" form exists which is more frequent in younger patients in the early postoperative period, and less likely to respond to the usual therapy. Cyclosporine therapy has deeply affected the clinical, laboratory and histological aspects of acute rejection. Though endomyocardial biopsy remains the most reliable diagnostic tool, other noninvasive procedures are of great value for a final diagnosis; among these are electrocardiography and two-dimensional echocardiography, which are the two elective techniques for post-transplantation follow-up in children. The laboratory and immunological assays, on the contrary, share a very low specificity. In conclusion, the diagnosis of acute rejection is still a clinical one, though supported by laboratory and histological evidence. In our experience, the natural evolution of many mild and mild-moderate rejection episodes toward regression does not support an excessive prophylaxis or an early treatment of symptom-free acute rejection. In addition, treatment of rejection must be personal and specific to each patient.
This study was undertaken to characterize the phenotype and function of lymphocytes derived from endomyocardial biopsies in heart transplant patients. To this aim, tissue infiltrating lymphocytes were derived from seven heart transplant patients and were analyzed for the expression of a panel of markers, including CD3, CD4, CD8, CD16, CD56, CD45RA, CD45RO, alpha/beta and gamma/delta T cell receptor, and for their ability to lyse a series of targets, including NK-sensitive K-562 targets, NK-resistant Raji targets, donor related, and unrelated normal splenocytes. Our data show that the majority of cultured lymphocytes expressed the CD3+ phenotype and the alpha/beta T cell receptor. The CD4 and CD8 molecules were heterogeneously expressed among T cell lines tested. Concerning cytotoxic related markers, a significant percentage of cells were CD56+. The evaluation of CD45 isoforms showed that both "naive" and "memory" cells were present among heart TIL. Cytotoxic in vitro studies demonstrated that all our T cell lines showed an efficient cytotoxic machinery when tested against NK-sensitive targets. A marked lysis of donor-related splenocytes was demonstrated in all patients tested. To investigate the role of CD3 and HLA class I molecules in the cytotoxic mechanisms taking place in human heart allograft rejection mechanisms, TIL were assessed for their lytic activity against different targets in the presence of anti-CD3 and anti-HLA class I monoclonal antibodies (mAbs). Although donor-specific cytotoxicity was considerably inhibited by the anti-CD3 mAb, no inhibitory effect was displayed by this antibody on TIL-mediated cytotoxicity against donor-unrelated splenocytes. Anti-HLA class I mAb was able to inhibit both allospecific and nonallospecific cytotoxicity. These data suggest that different types of cytotoxic cells may be propagated from biopsy specimens of heart transplant patients.
A simplified technique has been used to enlarge the aortic annulus in a series of 13 patients undergoing aortic valve replacement. The procedure basically consists of extending the aortotomy incision into the aortic annulus by dividing the commissure between the left and noncoronary sinuses, without involving the anterior mitral leaflet. Wide opening of the commissure is obtained and the resulting defect is closed, preferably using a patch of bovine pericardium sutured to the mitral annulus and aortic wall. This technique is simple, reproducible, avoids opening of the left atrium (reducing the potential bleeding sites), allows insertion of a prosthesis at least two sizes larger than the original annulus, and is also applicable in cases of mitral-aortic valve replacement. Our preliminary results are satisfactory and seem to demonstrate that in many patients, even in the young age group, more complex procedures are often unnecessary when enlargement of the aortic annulus is required.
The shortage of ideal donor hearts has led to an increasing number of would-be heart transplant recipients who die while on the waiting list: an extension of the classical donor criteria seems necessary to expand the donor pool. In this paper, the major controversies on donor selection are presented, along with the clinical results obtained in cardiac transplantation with donor grafts not complying with standard criteria. The extension of donor age over 35 years is supported by the decreased incidence of coronary artery disease (CAD) in the Western world. In our experience, the number of donors over 40 years has increased steadily, without concomitant significant increase in postoperative short- and medium-term mortality after cardiac transplantation. The relative importance of CAD risk factors in the older heart donor is to be weighed out on a case-by-case basis. The performance of coronary angiography in 90% of the donor grafts over 50 years has led to more accurate selection. ECG minor alterations and ECHO diagnosed dyskynesias are of uncertain significance. Localized infection, transitory hypotension, brief cardiac arrest and thoracic trauma do not necessarily contraindicate heart donation. The importance of donor/recipient weight mismatch over 20% is critical only in face of high pulmonary vascular resistance. Prolonged dopamine infusion above 10 micrograms/kg/min may predict poorer function outcome. From our data, severe donor dysionemia may be very hazardous. In conclusion, our experience demonstrates that extended donor criteria do not compromise short- and medium-term clinical results of cardiac transplantation. Nevertheless, several controversial aspects of donor graft selection remain open.
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Since November 1968, 54 patients have undergone excision of an intracardiac myxoma, which was located in the left atrium in 46 (85%), in the right atrium in 6 (11%), and in the right ventricle in 2 (4%). There were 35 female and 19 male patients with a mean age of 48 +/- 14 years (range, 7 to 68 years). Four patients were asymptomatic; the others were seen mostly with exertional dyspnea, palpitation, signs of systemic illness, and syncopal episodes. Before operation, embolic episodes occurred in 13 patients with a left atrial myxoma. There were two early (3.7%) and two late deaths (3.8). Actuarial survival at 20 years is 91% +/- 4%, and most of the current survivors are asymptomatic at a mean follow-up of 6.5 +/- 5 years (range, 0.2 year to 20 years). Noninvasive reevaluation was performed with echocardiographic studies in 44 patients and 24-hour electrocardiographic monitoring in 34. No instances of tumor recurrence were observed, and there was a low incidence of major supraventricular arrhythmias late postoperatively. We conclude that excision of intracardiac myxomas is curative and long-term survival is excellent. The transseptal approach provides adequate exposure and allows complete removal of the tumor regardless of its location.
From November 1985 to August 1989, 105 patients underwent heart transplantation at our institution of whom 8 (7%) underwent heterotopic heart transplantation (HHTx). There were 7 males and 1 female with a mean age of 49 +/- 6 years (range, 41-58 years), 7 of whom had ischaemic cardiomyopathy and 1 had dilated cardiomyopathy. The indications for HHTx were gross donor/recipient size mismatch, unreliable donor heart, elevated pulmonary vascular resistance and the need for urgent transplantation or their combination. HHTx was performed as a left ventricular bypass in 6 patients and as biventricular bypass in 2 combined with various surgical procedures on the native heart in 5. There was one perioperative death with a mean follow-up of the survivors of 17 +/- 10 months (range, 6-30 months). Comparison of preoperative and postoperative (1 year) 2-D echocardiographic studies of the native heart showed haemodynamic stability of the latter with no substantial changes in left ventricular ejection fraction and cardiac index, while left ventricular end-diastolic volume tended to increase in 2 patients. In conclusion, preservation of the native heart allows recovery or growth of a graft considered unsuitable for orthotopic transplantation. Our experience confirms that HHTx may still be considered a valuable alternative to orthotopic transplantation in selected patients, thus expanding donor utilization.
The internal mammary artery (IMA) is currently considered as the graft of choice for myocardial revascularization procedures. We report on two patients who underwent successful coronary artery bypass surgery using retrograde IMA flow. We provide, for the first time, angiographic evidence of late patency of an inverted IMA graft.
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We report a patient in whom orthotopic heart transplantation was performed after late failure of ventricular septation for double-inlet left ventricle. This case shows that orthotopic heart transplantation represents a valid therapeutic alternative in children with previous correction of complex congenital heart defects not amenable to further intracardiac repair.
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