Biomedical subjects
R Pfitzmann
Publications and source records attributed to R Pfitzmann.
Intramyocardial impedance measurements for diagnosis of acute cardiac allograft rejection.
BACKGROUND: Measurements of intramyocardial impedance at high frequencies can indicate alterations in cell membranes and intracellular spaces during acute cardiac allograft rejection. METHODS: Fifteen beagle dogs underwent heterotopic heart transplantation and were immunosuppressed with cyclosporine and methyl prednisolone (MP). Impedance was determined twice daily by means of four screw-in electrodes in the right and left ventricle. Transmyocardial biopsies and the intramyocardial electrogram (IMEG) were performed as reference methods. A total of 23 rejection episodes were induced. When acute rejection was recognized histologically and through IMEG readings, the animals were treated with a bolus of 125 mg of methyl prednisolone over 5 consecutive days. Treatment of rejection was controlled by biopsy and IMEG. RESULTS: All hearts showed a uniform decrease in impedance of about 28.3%+/-5.5% immediately after transplantation, which subsequently reached a stable plateau after 7 to 8 days. Impedance values then remained unchanged as long as rejection was absent. Biopsy findings of grades 1A to 1B (ISHLT) were accompanied by a statistically significant increase in impedance of 12.2%+/-2.5%; of grades 2 to 3A of 19.2%+/-3.2% and of grades 3B to 4 of 27.0%+/-2.9%. Sensitivity was 96%, specificity 91%. Successful treatment of rejection led to a decrease of impedance to the initial levels. CONCLUSIONS: The amount of increase in impedance of high frequencies is a method to stratify acute cardiac allograft rejection into grades like histologically grading. The effectiveness of rejection treatment can also be monitored through impedance measurement. The method is also applicable for telemetric rejection monitoring by means of an implantable device.
Intramyocardial electrogram recordings (IMEG) for diagnosis of cellular and humoral mediated cardiac allograft rejection.
OBJECTIVE: The purpose of this study was to prove the reliability of intramyocardial electrogram (IMEG) recordings for diagnosis and treatment monitoring of (1) cellular and (2) humoral mediated allograft rejection after heart transplantation. MATERIAL AND METHODS: Fifteen beagle dogs underwent heterotopic neck-heart transplantation. Eight of them were previously sensitized through several skin transplantations. IMEG recordings were performed daily. Donor-specific antibodies (IgG, IgM) were determinated in serum daily. Transmyocardial biopsies were performed every two days. RESULTS: In the sensitized group (group I) accelerated rejection occurred under triple drug immunosuppression with cyclosporine A, azathioprine, and cortisone on the fifth postoperative day (range: 4th-5th). All episodes were detected through IMEG diagnosis. In each case rejection could be treated successfully. In the cellular mediated group (group II), the average sensitivity for rejection diagnosis of a single lead was 24% for the unipolar and 42% for the bipolar leads. When the voltages of different leads were summed up the sensitivity rose to 36% (3 unipolar), 81% (3 bipolar) and 100% (all leads). During rejection therapy the IMEG recovered within 24-48 hours. CONCLUSION: The IMEG detects cellular and humoral mediated rejection early and with high reliability. The rejection-related changes of grade 2/3a rejection in IMEG seem to follow a Ofocal patternO similar to the histology. Therefore the recording of several, preferably bipolar, electrode configurations appears to enhance diagnostic reliability.
Pulmonary artery stenosis 5 years after single lung transplantation in primary pulmonary hypertension.
This is a case report about a 56-year-old female patient with primary pulmonary hypertension who underwent single, right lung transplantation. Five years postoperatively she developed signs of right heart failure. History and physical examination suggested pulmonary artery stenosis. Diagnosis was confirmed by pulmonary angiography. Percutaneous placement of a balloon expandable stent normalized pulmonary artery pressure.
[Measuring bioelectric myocardial impedance as a noninvasive method for diagnosis of graft rejection after heart transplantation].
12 beagle dogs underwent neck-heart transplantation and were immunosuppressed with cyclosporine and methylprednisolone. Intramyocardial impedance was determined twice daily with four screw-in electrodes in the right and left ventricle. Transmyocardial biopsies and the intra-myocardial electrogram (IMEG) were performed as reference methods. 19 rejection episodes were induced. When acute rejection was seen in histology the animals were treated with pulsed 125 mg methylprednisolone over 5 consecutive days and immunosuppression was raised to sufficient levels. Successful treatment of rejection was controlled by biopsy. All hearts showed a uniform decrease of impedance of about 28.3% +/- 5.5% immediately after implantation, then reaching a stable plateau after 7 to 8 days. Impedance values then remained unchanged as long as rejection was absent. Biopsy findings of grade 1A to 1B (ISHLT) were accompanied by a statistically significant increase of impedance of 12.2% +/- 2.5%, of grade 2 to 3A of 19.2% +/- 3.2%, and of grade 3B to 4 of 27.0% +/- 2.9%. Sensitivity was 95%, specificity 91%. Successful treatment of rejection led to a uniform decrease of impedance to intramyocardial impedance for high frequencies can reliably indicate alterations of the cell membrane and the intracellular space during acute cardiac allograft rejection. The amount of increase of impedance is a reliable noninvasive parameter to graduate acute cardiac allograft rejection. The success of treatment of rejection can also be monitored by impedance. This noninvasive method is applicable for telemetric rejection monitoring via an implantable device, which would allow continuous rejection surveillance of a patient at home without hospital admission.
Treatment of humoral rejection after heart transplantation.
BACKGROUND: Until a few years ago, the incidence of humoral rejection after heart transplantation was underestimated. These episodes were frequently very aggressive and often fatal, because the maintenance and emergency immunosuppression available at the time only inadequately covered the humoral branch of the immune response. In spite of individual case reports, the effects of blood purification procedures or cyclophosphamide in this situation can only be insufficiently estimated. METHODS: To evaluate this therapy concept, 20 dog-lymphocyte-antigen-matched dogs underwent heterotopic neck-heart transplantation. Fourteen dogs underwent transplantation after having been previously sensitized through multiple skin transplantations, 6 dogs were not sensitized (control). The animals received an induction with 3x 250 mg prednisolone, as well as triple immunosuppression (cyclosporine, azathioprine, and cortisone). Biopsy (light microscopy, immunofluorescence), intramyocardial voltage, electric myocardial impedance (>200 kHz, <10 kHz), and echocardiographic (left ventricular wall thickness, diastolic relaxation velocity) examinations were performed daily to monitor rejection. Rejection therapy was continued for 3 days according to the following regimen: apheresis, cortisone boluses (CB), and cyclophosphamide in group A1 (n = 4), apheresis and CB without cyclophosphamide in group A2 (n = 4), and CB only in group C (n = 6). The subsequent course under triple immunosuppression was then observed. RESULTS: In the sensitized animals the onset of severe humoral rejection on the fifth day deteriorated cardiac function down to 75% (70% to 80%) of the initial values. In groups A1 and A2, apheresis resulted in recovery to near-control values (89% to 94%) within two hours, and indeed to complete recovery (97% to 101%) after the second apheresis, that is, within 1 day. In group C recovery was delayed (2 days) and incomplete (84% to 91 %). After therapy was discontinued, rejection-related functional deterioration recurred immediately in group C, and from 2 to 3 days after apheresis, regardless of whether cyclophosphamide therapy was performed (group A1) or not (group A2). In the control group all animals showed a rejection-free posttransplantation course. CONCLUSIONS: By diluting inflammatory mediators, apheresis leads to a rapid improvement in cardiac function during severe humoral rejection after head transplantation. Neither apheresis nor cyclophosphamide therapy are able to have an immediate positive influence on the activation of the immune cascade and to prevent an ongoing rejection.
Humoral rejection after heart transplantation: reliability of intramyocardial electrogram recordings (IMEG) and myocardial biopsy.
In recent years, as the importance of humoral-mediated rejection has increasingly become recognized, the fact that endomyocardial biopsies (BX) evaluated according to the criteria of the International Society for Heart and Lung Transplantation often produce false-negative results has become a matter of concern. To evaluate the reliability of measuring intramyocardial ECG amplitude (IMEG) and immunofluorescence evaluation (FITC-labeled anti-IgG/ IgM staining) of endomyocardial biopsies (IFM), heterotopic neck-heart transplantation (HTX) was performed on eight beagles previously sensitized through skin transplantations. After HTX, IMEG, echo, and donor-specific antibodies in serum (IgG, IgM) were determined daily and myocardial biopsies (IFM, BX) were performed once every 2 days. Accelerated (humoral) rejection occurred on the 5th (4th-5th) postoperative day and sensitivity of IMEG, IFM, and BX was 100%, 75%, and 12.5%, respectively. In each case rejection was recognized so early that it was possible to initiate therapy with "restitutio ad integrum". Our results show that, as opposed to endomyocardial biopsy (IFM, BX), IMEG diagnosis detected humoral-mediated rejection early and with high reliability.
[Acute graft versus host disease (GvHD) after heart-lung transplantation].
We report on a 28 year old woman with congenital ventricle-septum defect and Eisenmenger-reaction who developed acute GvHD on 10th postoperative day after successful heart-lung transplantation. The patient died on the 34th postoperative day of dissociated brain death after intracerebral bleeding.
Acute graft-versus-host disease after human heart-lung transplantation: a case report.
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[Intramyocardial electrocardiogram (IMEG) in diagnosis of humoral rejection after heart transplantation].
Measuring intramyocardial ECG amplitude is a clinical non-invasive procedure used for diagnosing rejection after heart transplantation. In recent years, as the importance of humoral mediated rejection has increasingly been recognized, the fact that endomyocardial biopsies often produce false negative results due to the absence of lymphocytic infiltrates has become a matter of concern. In order to test the reliability of IMEG diagnosis of this form of rejection, heterotopic neck-heart transplantation was performed on eight beagles which were previously sensitized through several skin transplantations. Over the course of the study IMEG registrations were performed daily as well as echocardiographic examinations to determine left ventricular wall thickness and maximal diastolic relaxation velocity. Donor-specific antibodies in serum (IgG, IgM) were also determined daily. Myocardial biopsies, performed once every 2 days, were examined for the presence of edema and lymphocytic infiltrate (according to the guidelines of the International Society of Heart and Lung Transplantation, ISHLT) and examined under immunofluorescent microscopy of IgG and IgM. Under triple drug immunosuppression with cyclosporine A, azathioprine, and cortisone accelerated rejection occurred on the fifth postoperative day (range: 4th-5th). All eight episodes were detected through IMEG diagnosis (sensitivity 100%), while the myocardial biopsies graded according to ISHLT guidelines indicated only one case of relevant lymphocytic infiltrate (Grade 3A) (sensitivity 12.5%). In each case rejection was recognized so early that it was possible to perform therapy with restitutio ad integrum. This proved that, as opposed to endomyocardial biopsy, IMEG diagnosis detected humoral mediated rejection early and with high reliability. Furthermore, the immediate recovery in IMEG during therapy indicates that the voltage decrease cause by rejection cannot be explained by an irreversible loss of myocardium (myocytolysis), but rather may be due to a quickly reversible functional impairment.
Successful orthotopic liver transplantation for treatment of intrahepatic Osler's disease.
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IL-2 receptor antibody induction increases the risk for chronic rejection after liver transplantation.
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A prospective, randomized trial with quadruple versus dual tacrolimus-based induction after liver transplantation.
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