Adequate lung preservation for clinical lung transplantation: an important condition for satisfactory graft function.
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Graft Survival↗
Biomedical subjects
A Haverich
Publications and source records attributed to A Haverich.
Successful lung transplantation for posttraumatic adult respiratory distress syndrome after extracorporeal membrane oxygenation support.
A severe adult respiratory distress syndrome after bilateral lung contusion was successfully treated by extracorporeal membrane oxygenation and subsequent double-lung transplantation in a 19-year-old man. The patient is fully rehabilitated 1 year after transplantation.
Adult↗
TPEN, a transition metal chelator, improves myocardial protection during prolonged ischemia.
In view of the hypothesis that free radicals induced damage during ischemia and reperfusion is mediated by transition metals, we investigated the effect of the potent metal chelator TPEN (N,N,N'N'-tetrakis(-)[2-pyridylmethyl]-ethylenediamine) on cardiac function after prolonged myocardial ischemia. Isolated working rat hearts were subjected to 12 hours of cold ischemic arrest followed by reperfusion for 1 hour. The study was carried out on five groups (nine hearts in each): (1) St. Thomas' Hospital cardioplegic solution; (2) St. Thomas' Hospital cardioplegic solution with 7.5 mumol/L TPEN; (3) protection conditions as in group 2, but with TPEN administration during preischemic and reperfusion periods; (4) University of Wisconsin solution; and (5) the same conditions as in group 4 with TPEN administration during the preischemic and reperfusion periods. Significant enhancement of hemodynamic recovery was observed in the presence of TPEN throughout the experiment. The recovery of cardiac output was 24% +/- 4% in group 3, as compared to 12% +/- 4% in group 1 (p < 0.01). The postischemic left ventricular pressure recovery was 57% +/- 4% in group 3, as compared to 18% +/- 7% in group 1 (p < 0.005). The hearts in group 5 recovered, reaching 29% +/- 2% of the preischemic cardiac output and at 65% +/- 2% of the left ventricular pressure recovery (p < 0.05 versus group 3). Lactate dehydrogenase was released throughout the reperfusion. TPEN addition to groups 2 and 3 did not significantly reduce lactate dehydrogenase release; however, TPEN in University of Wisconsin solution and throughout the experiment significantly decreased lactate dehydrogenase release.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphate↗
Intravascular oxygenation for advanced respiratory failure.
Severe acute respiratory failure of varying etiology may require the temporary use of artificial gas exchange devices. So far, extracorporeal membrane oxygenation and extracorporeal carbon dioxide removal have been used successfully for this purpose. A totally implantable intravascular oxygenator (IVOX) recently became available. The authors have used IVOX in three patients who presented with severe respiratory failure secondary to pneumonia (n = 2) and post-traumatic adult respiratory distress syndrome (n = 1). At the time of implantation, all patients had hypoxemia (PaO2 less than 60) despite a 100% inspired oxygen concentration and forced mechanical ventilation. The duration of IVOX therapy ranged from 12 to 71 hr. All patients initially showed improvement in arterial oxygenation, allowing for moderate reduction of ventilator therapy after several hours. In one patient the pulmonary status deteriorated further, and she died from multiple organ failure despite IVOX therapy. One patient could be stabilized but died from other causes. The third patient is a long-term survivor 18 months after IVOX therapy. Gas transfer capabilities of IVOX are limited when compared to extracorporeal membrane oxygenation, and this may restrict its clinical applicability in cases of severe adult respiratory distress syndrome. However, IVOX may be used successfully in selected patients with less severe respiratory failure.
Adolescent↗
Improvement of currently used methods for lung preservation with prostacyclin and University of Wisconsin solution.
After 6 hours of cold ischemia the quality of lung preservation was assessed in a canine heart-lung transplant model comparing three clinically used methods for lung preservation: donor core cooling by means of extracorporeal circulation (group I); pulmonary artery flush perfusion with either Euro-Collins solution after prostacyclin application (group II); or University of Wisconsin solution after donor pretreatment with prostacyclin (group III). In all cases St. Thomas Hospital solution was used for myocardial protection. Heterotopic heart and orthotopic left lung allotransplantation was performed in three groups of six mongrel dogs each according to the method of lung preservation. After transplantation cardiorespiratory function was assessed at FiO2 of 0.4 for a maximum of 12 hours. After surgery, significantly improved oxygenation of the donor lung was observed in groups II and III, compared to group I (p less than 0.01). Between groups II and III, no significant differences were found in the oxygenation during the first 5 hours, but in the later postoperative course pO2 values decreased in group II although they remained stable on a higher level during the entire postoperative course in group III (p less than 0.05). University of Wisconsin solution for lung preservation in combination with prostacyclin donor pretreatment provides superior postoperative oxygenation of the transplanted lung compared to currently used clinical standards represented by donor core cooling and Euro-Collins flush perfusion.
Adenosine↗
Evaluation of the inotropic function at rest and the effect of enoximone in heart transplanted recipients. Assessment by left ventricular endsystolic pressure volume relationship.
Denervation of the heart involves an alteration (density, distribution of beta 1-beta 2-types) of beta-adrenoceptors in long-term follow-up. To elucidate the influence of these changes on left ventricular contractility and to provide an effective alternative treatment to re-transplantation in cases of chronic rejection (coronary vasculopathy-CVP, unspecific myocardial allograft failure-UMAF) a clinical study on 19 male transplant recipients after orthotopic heart transplantation without CVP and UMAF in the non-rejecting state was undertaken. Six male patients served as a control group to compare the systolic function at rest. Left ventricular end-systolic pressure-volume relationships (ESPVR) (k-slope) were registered and computer measured using a conductance catheter-technique under conditions of a transiently occluded vena cava and at a fixed heart rate (atrial pacing) in all patients (n = 25). In the transplanted patient group the acute response of enoximone (0.75 mg/kg) administered intravenously was recorded. The position of the ESPVR in the transplanted hearts were not different as compared to the data obtained from the non-transplanted hearts at rest. The k-slope increased from the baseline data after the acute infusion of enoximone in the transplanted hearts. The dosage of enoximone used produced a significant leftward shift in the ESPVR in most patients (89%). In addition, 42% of the patients showed an insignificant drop in left ventricular systolic pressure. Thus, the baseline contractile characteristics of the heart transplant recipients without chronic rejection and in the non-rejecting state is not obviously different from those in non-transplanted patients at rest independent of the time since operation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Multidrug resistance in heart transplant patients: a preliminary communication on a possible mechanism of therapy-resistant rejection.
Multidrug resistance refers to a complex cellular phenotype, the hallmark of which is cross-resistance to multiple drugs, for example, chemotherapeutic agents, that are unrelated to the selecting agent in structure, cellular target, and mode of action. The expression of this multidrug resistance is connected with the overexpression of P-glycoprotein. By applying the method of immunocytochemical assay, we have demonstrated the appearance of the multidrug-resistant phenotype (P-glycoprotein+ cells, multidrug-resistant cells) in mononuclear cells of the peripheral blood from 32/49 patients receiving triple-drug (azathioprine, steroids, cyclosporine) immunosuppressive therapy after heart transplantation. In the group of patients showing not only the presence of cells with multidrug-resistant phenotype in the peripheral blood, but also a significant increase in the number of these cells during the interval of observation (0 to 767 days)-16/32/49 cases--a significantly increased incidence of acute rejection episodes could be demonstrated. This supports the hypothesis of a possible existence of a therapy-resistant form of acute rejection, with an involvement of mechanisms of multidrug-resistance playing a role in its causal development.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Early diagnosis and effective treatment of pulmonary CMV infection after lung transplantation.
The early diagnosis and effective treatment of cytomegalovirus (CMV) pneumonia remains a keystone for patient survival after lung transplantation. At present, the use of DHPG (ganciclovir sodium) opens the possibility of a potent antiviral therapy. The use of monoclonal antibodies directed to immediate early CMV antigens offers a fast method to detect the early phase of systemic or local viral replication. Five single lung and heart-lung transplant patients at high risk for CMV infection (donor, CMV-positive; recipient, CMV-negative) were monitored by cellular immunohistology for immediate early antigens. Specimens from bronchoalveolar lavage (n = 39) and bronchial biopsies (n = 17), and peripheral blood leukocytes (n = 57) were examined. In peripheral blood leukocytes and bronchial biopsy specimens no CMV-positive cells were detected. The bronchoalveolar lavage analysis of two patients showed immediate early antigen-positive cells after 1 to 3 months. At the same time the patients had clinical symptoms that could also be related to lung rejection. Serologic conversion (CMV-IgM) occurred only 6 days later in one patient with informative follow-up analysis; CMV culture (available 4 to 6 weeks later) confirmed the diagnosis retrospectively. DHPG treatment was started immediately and resulted in CMV antigen negativity in bronchoalveolar lavage fluid after one or two courses (10 mg/kg/day; 14 days). Direct antigen detection offers a fast and specific monitoring of early CMV infection. The implications to the clinical management of lung transplant patients are discussed.
Adult↗
Some aspects of changed histopathologic appearance of acute rejection in cardiac allografts after prophylactic application of OKT3.
The histopathologic findings of therapy-requiring acute rejection in the cardiac allograft observed in endomyocardial biopsy specimens taken from patients under prophylactic administration of OKT3 show certain differences in comparison with the classic description of acute rejection. These differences are characterized above all by a distinctly reduced cellularity of the infiltrates, with a relative decrease of T cells, as well as edema and retrogressive changes, up to necroses of myocytes with marked fragmentation; some patients also have increased vascular reactions. Furthermore, an earlier occurrence of and an increased frequency of changes corresponding to the so-called lymphoma-like lesions ("Quilty" effect) were observed in patients who received immunosuppressive prophylaxis with OKT3. The changed histopathologic findings of therapy-requiring acute rejection under prophylactic application of OKT3 may, to a certain extent, explain the discrepant results reported by different transplant groups with respect to the frequency of rejection episodes and the time when the first episode of therapy-requiring rejection occurs after heart transplantation.
Antibodies, Monoclonal↗
Donor heart-related variables and early mortality after heart transplantation.
Impaired donor heart function after heart transplantation results in the necessity for prolonged catecholamine and ventilatory support of the patient. Subsequently the risk of multiorgan impairment, infection, and rejection will be increased. In this retrospective analysis we tried to identify donor-related risk factors in patients who died early after transplantation. Of 174 patients undergoing heart transplantation from October 1985 through October 1988, 22 (12.6%) died early. Of the total, 39 cases were evaluated retrospectively for donor-related logistic and metabolic factors. All donors were analyzed with respect to the early mortality for age, weight, height, maximum dopamine concentration, thyroid hormone levels, and the duration from brain death until explantation and ischemia. Thirty patients were survivors (group A); nine patients died early (group B). By multiple regression analysis a significant influence (group A vs group B) of donor age, dopamine support, and ischemic time on early mortality could be demonstrated, whereas donor weight and height, hormone levels of triiodothyronine and thyroxine, and duration of brain death showed no correlation. From this limited experience we conclude that use of hearts from older donors with higher catecholamine support and longer ischemic times will result in an increased early mortality. In contrast, no influence of prolonged brain death times and metabolic factors could be demonstrated.
Adult↗
Lung growth after experimental pulmonary transplantation.
Replacement of the heart and both lungs or single lung transplantation has been performed in a few cases of terminal (cardio) pulmonary disease in childhood. It remains unclear whether pulmonary allografts will meet the demands of a growing organism. Six domestic pigs (mean body weight, 24 kg) underwent left lung transplantation from donors of equal weight. Immunosuppression consisted of cyclosporine, azathioprine, and corticosteroids. After the pigs doubled their body weight, growth of the lung was assessed by bronchography and pulmonary angiography. In transplant animals it took 11 weeks (normal animals, 6 weeks) for their weight to double. At that time, the bronchial tree showed similar growth when compared with nontransplant animals of equal weight. The diameter of the left lower lobe bronchus (9.2 +/- 0.4 mm) was significantly greater than that of animals of 24 kg body weight (7.5 +/- 0.3 mm; p less than 0.01) but comparable to that of normal pigs of similar weight (9.0 +/- 0.5 mm). The same applied for length of the left lower lobe bronchus (transplants, 95 +/- 6.7 mm; controls 24 kg, 67 +/- 2 mm [p less than 0.01]; controls 48 kg, 93 +/- 3 mm). Similar growth tendencies were observed in the pulmonary vascular tree. The diameter of the left lower lobe artery was 9.4 +/- 98 mm in 48 kg transplant pigs, compared with 9.7 +/- 1.2 mm in 24 kg control pigs and 8.5 +/- 0.8 mm in 48 kg control pigs. In one case of recurrent severe pulmonary rejection, the lung did not grow. We conclude from this study that growth is retarded by immunosuppression.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiography↗
Comparison of mononuclear cell subpopulations in bronchoalveolar lavage fluid in acute rejection after lung transplantation and Mycoplasma infection in rats.
Acute lung rejection after orthotopic left lung transplantation and Mycoplasma pulmonis infection were studied immunohistologically by bronchoalveolar lavage (BAL) in inbred rats using monoclonal antibodies differentiating lymphocyte and macrophage subpopulations. Twenty transplants in a major histocompatibility complex (MHC)-different strain combination (Brown-Norway/Lewis) were examined 2, 4, and 6 days after transplantation. Thirty isotransplants (Lewis/Lewis) and normal Lewis rats were used as controls. Eight Lewis rats with acute Mycoplasma pulmonis infection and six Lewis rats with chronic Mycoplasma infection also underwent BAL. Mononuclear cell subpopulations were analyzed using a panel of monoclonal antibodies to MHC and macrophage differentiation antigens: ED1 monocyte/macrophages, ED2 inflammatory tissue macrophages, OX19 T lymphocytes, and OX12 B lymphocytes. The following results were obtained: (1) All allotransplants developed acute rejection on day 2, and it advanced until day 6, demonstrating severe perivascular and peribronchiolar infiltration of inflammatory tissue macrophages (ED1+/ED2+): (2) the proportion and number of inflammatory macrophages (ED2+) in BAL fluid increased on day 6; (3) in BAL the proportion and number of T lymphocytes (OX19+) increased more prominently than B lymphocytes (OX12+) on day 6 of acute rejection; (4) in infection with Mycoplasma pulmonis the increase of T lymphocytes (OX19+) in BAL was more prominent than that of B lymphocytes (OX12+). In conclusion, serial analysis of macrophage, T- and B-lymphocyte antigens was performed. The increase of the proportion of inflammatory macrophages (ED2+) and lymphocytes (OX19+, OX12+) in BAL fluid occurred rather late in the rejection response. This limits the use of BAL as an early diagnostic method of allografted lung rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Treatment of rejection after heart transplantation: what dosage of pulsed steroids is necessary?
Histologically proved rejection after heart transplantation is commonly treated with intravenous steroids, 1 gm/day for 3 days. This regimen may result in severe side effects, however, both metabolic and infectious. In a total of 663 rejection episodes, we treated 397 with conventional steroid therapy, 1000 mg per day for 3 days (group 1), 199 with 500 mg/day for 3 days (group 2), and 67 with 250 mg/day for 3 days (group 3). Response to treatment was assessed by control biopsy after 1 week and graded as ongoing, resolving, or resolved rejection. The efficacy of the three regimens showed no significant differences between the groups as determined by the results of the subsequent biopsy. Ongoing rejection, resolving rejection, and resolved rejection, respectively: group 1-3.3%, 66.5%, 30.2%; group 2-8.0%, 66.8%, 25.2%; group 3-4.5%, 73.1%, 22.4%. We conclude that comparable effects, even with a considerable reduction of pulsed steroids, may be obtained in the treatment of cardiac allograft rejection, if triple-drug immunosuppression is used for maintenance therapy. It seems likely that steroid side effects may be decreased without jeopardizing the graft.
Adult↗
Some histopathologic aspects regarding onset of antirejection therapy after heart transplantation.
The histopathologic indication for starting antirejection therapy has so far been given by the diagnosis of moderate rejection in endomyocardial biopsies, that is, rejection with necroses of myocytes and predominantly lymphocytic infiltrates (corresponding to the descriptive diagnosis of moderate rejection in the Stanford classification, grade 4 and more in the Texas classification, and A-3 moderate rejection in the Hannover classification). Our present results, however, have shown that the critical limit for the onset of antirejection therapy may be fixed somewhat higher on the scale of severity of acute rejection and that it may be reasonable to define an affection of more than 20% of the total biopsy material by morphologic changes corresponding to the traditional definition of moderate acute rejection as the decisive histopathologic finding that should induce antirejection therapy. This means that the diagnosis of moderate rejection has to be divided into two groups: (1) A-3a moderate acute rejection not yet requiring therapy that, however, does necessitate bioptic control within 7 to 10 days; (2) A-3b moderate acute rejection requiring antirejection therapy. The introduction of this differentiation of histopathologic diagnoses is not just another sophisticated scientific theorem; its practical significance may be seen in a definitive restriction of the application of antirejection therapy, which means a reduction of the risks and side effects imposed on heart-transplanted patients by chemotherapy and particularly by steroid therapy.
Biopsy↗
Acute humoral rejection: a new entity in the histopathology of heart transplantation.
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Graft Rejection↗
Oxygen free radical scavengers to prevent pulmonary reperfusion injury after heart-lung transplantation.
Oxygen free radical scavengers, such as superoxide dismutase (SOD) and catalase (CAT), have been shown to reduce effectively myocardial reperfusion injury. No such data have been reported for cold global pulmonary ischemia, which is required in heart-lung transplantation. Heterotopic heart-left lung allotransplantation was performed in 18 dogs after single-flush perfusion of the lungs with Euro-Collins solution (60 ml/kg), cardioplegic arrest, and 6 hours of cold global ischemia. Six dogs served as controls. In six other dogs prostacyclin (PGI2) was administered both into the pulmonary artery (20 ng/kg/min) and to the Euro-Collins solution (15 mg/L) before explantation (group A). Grafts in six other dogs were preserved with Euro-Collins solution plus SOD (40,000 U/L) and CAT (100,000 U/L)(group B). In addition, SOD (1 mg/kg) and CAT (1.5 mg/kg) were given intravenously during the first 20 minutes of reperfusion. There was no significant difference in cardiac output, right and left atrial pressures, nor pulmonary arteriolar resistance among the groups. In contrast, left atrial oxygen pressure (PO2) values were best in group B. At all times, PO2 values in animals in groups A and B exceeded those in control animals. Compared with control animals with Euro-Collins solution preservation alone, animals with both PGI2 and SOD/CAT preservation had significantly improved pulmonary function after heart-lung transplantation. Better oxygenation in the SOD/CAT group (group B) suggests an important impact of oxygen free radicals during reperfusion.
Animals↗
Sequential analysis of monomorphic and polymorphic major histocompatibility complex antigen expression in human heart allograft biopsy specimens.
Changes in major histocompatibility complex (MHC) antigen expression after heart transplantation were investigated in 233 cardiac allograft biopsy specimens of 33 patients by means of immunohistologic examination. The altered tissue expression was related to histopathologic and clinical diagnoses. A panel of monoclonal antibodies directed to monomorphic determinants was used for the analysis of MHC antigens, class I (human leukocyte antigens [HLA]-A, B, C, and beta 2 microglobulin) and class II (HLA-DR, HLA-DP, HLA-DQ). Donor and recipient MHC antigen expression (HLA-A and HLA-B) was studied by use of monoclonal antibodies directed to polymorphic epitopes. It was found in 57 of 78 rejection episodes that the induction of class I MHC antigens on the normally negative myocyte membranes was related to the rejection process. Usually the induction was focally associated with lymphocytic infiltrates but in severe rejection was generalized on all myocyte membranes. After effective rejection treatment the class I induction was reversed. Class II (HLA-DR) MHC antigens were induced on most vessel endothelia. During rejection MHC antigens HLA-DP and HLA-DQ also were coexpressed on the endothelia of a few vessels. Donor HLA-A and HLA-B antigens were expressed by endothelial and interstitial cells in comparable density but only in low amounts on myocyte membranes. Recipient interstitial cells infiltrated around vessels with time after transplantation. Most interstitial cells between myofibrils, however, remained those of the donor type until 1 year after transplantation. These results show that cardiac allografts undergo remarkable changes in the expression of MHC antigens during clinical complications after transplantation. Furthermore, the changes in alloantigen composition may influence the clinical course.
Adolescent↗
Early graft failure after heart transplantation: management by extracorporeal circulatory assist and retransplantation.
Early graft failure represents a serious complication after orthotopic heart transplantation. Various modes of extracorporeal mechanical circulatory assistance, however, allow for "bridging" to heart retransplantation in these instances. We report a case of bridging to heart transplantation by means of intraaortic balloon counterpulsation. After transplantation a right ventricular assist device was required because of early graft failure while the intraaortic balloon pump was left in place. A retransplantation was successful, and 13 months after the operation the patient is in New York Heart Association functional class I. The cause of early graft failure, especially the tendency toward failure of the right ventricle, is not well understood and seems to be multifactorial, which suggests that an elevated pulmonary vascular resistance in the recipient possibly represents a considerable risk factor. Bridging to heart retransplantation with the use of extracorporeal blood pumps can be performed effectively.
Assisted Circulation↗