Search PubMed⌕ Search

Biomedical subjects

A Haverich

Publications and source records attributed to A Haverich.

480 records · Page 27Linked to original sources

Predictive implications of bioptic diagnosis in cardiac allografts.

The prognostic value as represented by the predictive implications of the histopathologic bioptic diagnosis in cardiac allografts was studied in a total of 3209 biopsies from 111 patients under triple-drug immunosuppressive therapy after transplantation during a period of more than 2 years (0 to 782 days). The application of the so-called Hannover classification in the histopathologic diagnosis of rejection has revealed that there are certain configurations of histopathologic changes that lead significantly more frequently to the forms of acute rejection (moderate or severe) that require therapy. These are mild acute rejection with retrogressive changes in myocytes and a late-resolving phase of acute rejection with a severe vasculopathy. In cases with the simultaneous presence of the chronic phase of rejection, a slight prolongation of the interval taken by the conversion of these two diagnoses into the therapy-requiring forms of acute rejection could be observed. On average, however, the time interval of conversion of mild acute rejection with retrogressive changes in myocytes and of the late-resolving phase of acute rejection with interstitial vascular reaction into the therapy-requiring forms ranges between 7 and 10 days. Thus a second biopsy should be performed within this time interval.

Antilymphocyte Serum↗

Myocardial calcification after orthotopic heart transplantation.

Two cases with a remarkable similarity in their clinical and histopathologic findings are reported. Both cases involved myocardial calcification found in biopsy material obtained after orthotopic heart transplantation. Myocardial calcification after heart transplantation so far has been described in only one case in the medical literature and thus appears to be a rare entity. Its occurrence is associated with a certain constellation of clinical situations, which include repeated episodes of acute rejection, temporary uremia, periods of septicemia, alcoholism, and cyclosporine and/or steroid therapy.

Biopsy↗

Flush perfusion using Euro-Collins solution vs cooling by means of extracorporeal circulation in heart-lung preservation.

Single-flush perfusion using modified Euro-Collins solution and donor cooling by extracorporeal circulation represent two concepts of lung preservation currently in use for on-site heart-lung transplantation. The question of which technique is better for safe clinical application of heart-lung transplantation, including extended periods of ischemia and distant organ procurement, currently remains undetermined. Eighteen mongrel dogs, divided in three groups, underwent left lung, heterotopic heart transplantation, leaving the right lung and heart of the recipient in place. Donor organs were obtained from size-matched dogs. In all groups, myocardial preservation was achieved using 10 ml/kg cold potassium cardioplegia. Following flush perfusion of the lung (Euro-Collins solution, 60 ml/kg), six dogs were immediately transplanted (group I). Using the same preservation, organs were stored for 6 hours at 4 degrees C in group II. In group III, organs were cooled using extracorporeal circulation until reaching a rectal temperature of 16 degrees C, harvested, and thereafter stored as in group II. After transplantation, blood supply of the donor heart was assured by selective drainage of the superior vena cava into the right side of the donor heart. Outflow was obtained by end-to-side anastomosis of donor and recipient aorta. The dogs were kept anesthetized, and both lungs were ventilated selectively with an FiO2 of 0.4 for 20 hours or until death. During the postoperative course, the donor heart pumped about one third of the entire cardiac output in all groups. The lowest pulmonary vascular resistance of the transplanted lung was observed in group III. Oxygenation of the transplanted lung revealed no impairment in group I compared with the pretransplant values. By contrast, groups II and III showed a slight decrease of oxygenation within acceptable limits. We therefore conclude that both methods of cardiopulmonary preservation evaluated may allow for an extended ischemic time of up to 6 hours before heart-lung transplantation. Pulmonary vascular resistance was significantly lower in the group preserved by extracorporeal circulation, possibly reflecting superior preservation of lung function by this method.

Animals↗

Cytoimmunologic monitoring in early and late acute cardiac rejection.

The absolute concentration of circulating lymphoblasts and prelymphoblasts has been shown repeatedly to closely correlate with acute cardiac rejection in heart transplant recipients. Little information, however, is available with respect to the reliability of this measurement in the late postoperative course. Fifty-two heart transplant recipient operated on from October 1985 through September 1986 were studied with cytoimmunologic monitoring for lymphocyte activation in peripheral blood. Immunosuppressive therapy consisted of azathioprine, cyclosporine, and steroids. Endomyocardial biopsies were obtained at regular intervals. Cytoimmunologic monitoring was performed daily during hospitalization and together with endomyocardial biopsy at outpatient visits. A total of 768 endomyocardial biopsies and 1077 mononuclear concentrates for study of lymphocyte activation were obtained. Concentration of activated cells showed a significant increase during acute rejection. Cytoimmunologic monitoring had an overall sensitivity of 76% and a specificity of 79%. Within 90 days after transplantation cytoimmunologic monitoring showed a sensitivity of 84%, which decreased to 71% beyond 3 months. We therefore conclude that cytoimmunologic monitoring, a noninvasive adjunct for diagnosis of acute allograft rejection, cannot replace routine endomyocardial biopsy, particularly in view of a significant loss in sensitivity in the late postoperative course.

Adolescent↗

Ultrasonic characterization of acute cardiac rejection from temporal evolution of echocardiograms.

Two ultrasonic parameters that characterize cardiac contractile performance were tested for their ability to detect the early stages of acute rejection. Five dogs received heart transplants with a heterotopic abdominal model and were given echographic examinations 1, 4, and 8 days after surgery. The ultrasonic measurements were extracted from pairs of cross-sectional echocardiograms, separated in time by approximately half of a cardiac cycle. The contraction-related changes in the portions of the images corresponding to myocardium were characterized by ratio of mean video amplitude and image-pair correlation. Full-thickness biopsies were taken from the left and right ventricles after each examination so that the correlations between the ultrasonic measurements and the histologic state of the tissue could be determined. Each biopsy was ranked according to the following scale of increasing levels of rejection: 0 (normal), 1 (lymphocyte infiltration), 2 (focal necrosis), 3 (diffuse necrosis), 4 (presence of hemorrhages). The average histologic state for the left ventricle increased from 0.2 +/- 0.4 for the first examination, to 2.0 +/- 0.7 for the second, and 3.6 +/- 0.5 for the third. Similar results were obtained for the right ventricle. The progressions of mean amplitude ratio and correlation were 1.55 +/- 0.14, 1.49 +/- 0.17, 1.19 +/- 0.15, and 0.22 +/- 0.10, 0.28 +/- 0.10, 0.74 +/- 0.25, respectively. Thus in this experiment, these parameters were useful for distinguishing advanced stages of rejection from the normal state and from mild rejection.

Animals↗

Changes of the intramyocardial electrogram after orthotopic heart transplantation.

Heart transplantation, including conventional immunosuppression, has allowed the use of the surface electrocardiogram to detect allograft rejection. With the use of cyclosporine this parameter is no longer sensitive, but voltage of the intramyocardial electrogram has correlated repeatedly with rejection. From July 1983 through February 1986, 98 patients had heart transplantation; 13 of those patients had a telemetry pacemaker simultaneously implanted. In previous studies, daytime dependent variabilities of the sum voltage of the surface electrocardiogram were reported. Therefore intramyocardial electrogram was measured at 7, 10, 13, 16, and 20 hours. In addition, the influence of exercise on intramyocardial electrogram voltage was studied in all patients. Analysis of the diurnal intramyocardial electrogram revealed substantial atrial and ventricular variability of both voltage measurements (p less than 0.05). Also, intramyocardial electrogram voltage was influenced by exercise, as demonstrated by a significant decrease after physical work at 25 W (-8%) and 50 W (-12%); p less than 0.05. Therefore we conclude that a high variability of intramyocardial electrogram may be found diurnally and on exercise testing after heart transplantation in humans. If intramyocardial electrogram is used to detect rejection, it should be applied at comparable hours and with the patients in a controlled resting state.

Adolescent↗

Transposition of the greater omentum for management of mediastinal infection following orthotopic heart transplantation: a case report.

A case of mediastinal infection following orthotopic heart transplantation is presented. A general survey of the available surgical management of this complication is given and an alternative operation involving extra-abdominal transposition of the greater omentum pedicled on the left gastroepiploic vessels is suggested for treating difficult cases.

Enterobacteriaceae Infections↗

Preventive treatment of coronary vasculopathy in heart transplantation by inhibition of smooth muscle cell proliferation with angiopeptin.

BACKGROUND: The underlying mechanism of accelerated coronary vasculopathy in cardiac allografts still remains unclear. Our hypothesis was that inhibition of smooth muscle cell proliferation with the somatostatine analogue Angiopeptin may reduce vasculopathy. METHODS: Fifty-four patients received Angiopeptin injections (1500 micrograms x three times daily subcutaneously) for 21 days after the operation and three additional injections with every rejection treatment. Angiography was performed yearly, and data were compared with a matched historic control group. RESULTS: Actuarial survival was 85% at 1 year and 80% at 2 years, comparable with our results in general (80%/77%). Forty-six long-term survivors could be followed by coronary angiography. At 1 year, vasculopathy was assessed in nine patients (17%). Of the 18 patients investigated at 2 years thus far, an additional three patients were found to have vasculopathy. In the control group vasculopathy was comparable, being 13% after 1 year and 20% after 2 years. A significantly lower incidence of rejections and lower creatinine values were found in the study group within the entire observation period (p < 0.05). CONCLUSIONS: We conclude that Angiopeptin treatment appears to be safe without significant side effects; it may reduce the number of acute rejections, at least during the first year after heart transplantation. However, the results of the 2-year follow-up in the remaining patients would have to be included in assessing the effect of Angiopeptin. Long-term follow-up will be necessary to decide whether Angiopeptin will be helpful in reducing the incidence of transplant vasculopathy.

Actuarial Analysis↗

Euro-Collins flush perfusion in human lung preservation--ultrastructural studies of the preservation quality of the contralateral donor lung in clinical single lung transplantation.

The quality of pulmonary preservation after Euro-Collins flush perfusion was assessed by means of morphometric analysis based on transmission electron microscopy. In five patients undergoing single lung transplantation, the contralateral donor lung that could not be matched for another recipient was studied by means of light microscopy and transmission electron microscopy. While one of the donor lungs was transplanted, the contralateral lung was fixed by airway instillation at the same time and subsequently processed for microscopic examination. Although light microscopy showed an excellent quality of organ preservation, transmission electron microscopy revealed the presence of fine to medium alterations at the level of the air-blood-barrier. In the five contralateral donor lungs, different degrees of the cellular alterations were recorded by morphometric analysis, which correlated with differences observed in the early postoperative course of the patients receiving the other lung, respectively. Although in four of five patients the clinical course showed no complications and extubation was performed within 36 hours after the operation, one patient required artificial ventilation over a period of 10 days because of impaired oxygenation of the transplanted lung. In this patient, morphometric analysis of the air-blood-barrier showed a significantly (p < 0.02) smaller surface fraction of normal type 1 pneumocytes, a significantly (p < 0.05) smaller volume density of the capillary endothelial cells, and a significantly (p < 0.01) higher volume density of type 2 pneumocytes. The alterations of the alveolar epithelium have to be interpreted as a result of influences occurring during the donor's medical history rather than being an effect of preservation and/or ischemia.

Adolescent↗

Functional results after lung retransplantation.

In selected cases with either acute or chronic graft failure after lung or heart-lung transplantation, retransplantation remains the only therapeutic option. Since December 1987, we have performed a total of 110 single lung, bilateral lung, and combined heart-lung transplantations in 102 patients including five early and four late retransplantations in eight patients. Early retransplantation was indicated for severe reperfusion injury after single lung transplantation (n = 2) or heart-lung transplantation (n = 1), for persistent pulmonary hypertension caused by an unrecognized aortopulmonary window (n = 1), for central airway necrosis, and for contralateral pulmonary artery bleeding after bilateral lung transplantation (n = 1). Two of these patients after single lung transplantation were bridged with extracorporeal membrane oxygenation for 9 and 11 days until single lung retransplantation. Three patients underwent late single lung retransplantation 14, 24, and 26 months after single lung transplantation (n = 2) or heart-lung transplantation (n = 1) for chronic rejection, and an additional patient was treated successfully by bilateral lung retransplantation for obliterative bronchiolitis and central airway stenosis 26 months after bilateral lung transplantation. Two patients died 19 and 140 days, respectively, after acute retransplantation because of early graft failure and progressive rejection, respectively, while the other patients were discharged from the hospital. Mortality was 22.2% in the retransplantation group versus 15.1% (11 of 73 patients) undergoing primary single lung transplantation or bilateral lung transplantation (not significant). Patient survival after retransplantation ranged between 159 and 993 days (median, 453 days). Duration of postoperative ventilation was markedly prolonged in patients who underwent retransplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Distinct expression of cell-cell and cell-matrix adhesion molecules on endothelial cells in human heart and lung transplants.

BACKGROUND AND METHODS: Intercellular reactions and cell-matrix interactions are mediated by a number of specific adhesion molecules. For the intravascular reactivity of leukocytes and thrombocytes the endothelial expression of adhesion ligand molecules is of main importance. This condition may be of special relevance for the organ-specific manifestation of immune reactions in heart and lung transplants. The question was investigated as to whether organ-specific differences exist on arterial, venous, and capillary endothelial lining cells in heart and lung transplants and whether this condition is modified during transplant rejection. Transplant biopsy specimens of 24 heart transplant recipients (n = 303) and lung transplant recipients who underwent retransplantation for rejection (n = 4), as well as normal heart (n = 7) and lung tissue (n = 4), were studied. Cell-cell adhesion molecules (intercellular adhesion molecule-1 (CD54) and -2; LFA-3; CD31; vascular cellular adhesion molecule-1; neural cellular adhesion molecule; E-/P-selectin; CD44) and cell-matrix adhesion molecules (very late antigen-1 through -6; CD51) were studied on cryostat sections by means of standard immunohistology. RESULTS: (1) Arterial, venous, and capilary endothelia in lung and heart tissue show a distinct pattern of cell-cell and cell-matrix adhesion molecules: capillary and venous endothelia are in contrast to arterioles negative for vascular cellular adhesion molecule-1 and P-selectin. Arterial endothelia of the lung, in contrast to veins and capillaries, express no receptors for laminin (very late antigen-2 and very late antigen-6). (2) With transplant rejection, an induction of a number of adhesion molecules was noted on all endothelial lining cells in heart and lung transplants (intercellular adhesion molecule-1[CD54], intercellular adhesion molecule-2, lymphocyte function antigen-3, very late antigen-2, and very late antigen-6). Capillaries of the lung, in contrast to heart capillaries, displayed no inducibility of vascular cellular adhesion molecule-1 and E-selectin. In heart transplants, differences between capillaries and arteriovenous endothelia were found for virus-like agent-2 and -3. CONCLUSIONS: These results show a distinct expression of a both cell-cell and cell-matrix adhesion molecules on arterial, venous, and capillary endothelia of heart and lung transplants. This expression may influence the local regulation of leukocyte and thrombocyte adhesion during transplant rejection. Especially lung capillaries show a lack of inducibility for vascular cellular adhesion molecule-1 and E- and P-selectin required for the induction phase of leukocyte adhesion. This lack was not found in heart transplants. This observation may explain differences in intravascular adhesion and infiltration between vessel compartments in hearts and lungs and could be of relevance for therapeutic interventions to modify leukocyte and thrombocyte adhesion, as during transplant rejection and reperfusion damage.

Biopsy↗