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Biomedical subjects

H Reichenspurner

Publications and source records attributed to H Reichenspurner.

At least 145 records · Page 8Linked to original sources
PubMed1986

A new model for hetero-orthotopic heart-lung transplantation in the dog.

A method of hetero-orthotopic heart-lung transplantation is described in the dog. The model was developed to study patterns of rejection in the transplanted heart and lung, since the dog will not survive bilateral pneumonectomy and loss of the Hering-Breuer reflex. After removal of the recipient's left lung the donor heart and left lung are explanted en bloc. End-to-end connection is made of both left main bronchi, and the donor aorta is joined end-to-side with the recipient's descending aorta. An atrio-atrial anastomosis is performed between the recipient's left and the donor's right atrium. Four experiments were done to develop the surgical technique and 10 long-term studies were performed to investigate rejection patterns. The average survival rate of these animals was 28.5 +/- 8.3 days, ranging from 5 to 53 days. Causes of death were not due to operative complications. Heterotopic heart-lung transplantation is an uncomplicated surgical method which does not require cardiopulmonary bypass or anticoagulation and allows the investigator to study heart and lung grafts in dogs for long-term periods after surgery. Bronchoscopy, bronchoalveolar lavage, and heart and lung biopsies of both donor and recipient organs can be performed.

Animals↗
PubMed1986

Special control of infection and rejection episodes after four years of cardiac transplantation at the University of Munich.

During the past 4 years, 36 orthotopic heart transplantations and two heart-lung transplantations were performed at Munich University Hospital. Immunosuppressive regimen consisted of cyclosporine A and low dose prednisone. The rejection diagnosis was based on daily cyto-immunological monitoring (CIM) and high frequency electrocardiography. In addition, viral, bacterial, and fungal infections were examined by CIM. The CIM is based on an evaluation of activated lymphocytes, lymphoblasts, and lymphocyte subsets in the mononuclear concentrate isolated from the peripheral blood by Ficoll Hypaque separation. Of the 38 patients, 24 are currently alive from 1 month to 4 years later (including one heart-lung recipient 1.5 years postoperatively). Altogether, 40 rejection episodes occurred among the patients. The diagnosis was based on CIM (sensitivity = 95%) and on endomyocardial biopsies (sensitivity = 95%). Control of rejection therapy was also done by using these methods. When the biopsies showed ongoing acute rejection, additional antithymocyte globulin or antilymphocyte globulin therapy was administered, relative to the CIM results. When using the endomyocardial biopsies for rejection control only, results showed a very low rate of two to three biopsies per patient in the first 3 months postoperatively. In addition, 16 infection periods were detected: five viral, six bacterial, four fungal, and one case of toxoplasmosis. The CIM showed typical hints of these inflammations in 12 cases (sensitivity = 75%) before clinical signs were visible. This immediately led to further diagnostic examinations and specific anti-infectious therapies, which were initiated early.

Journal Article↗
PubMed1983

[Immunologic reactions following heart transplantation and their detection].

Transplantation antigens of the major histocompatibility complex are able to stimulate the rejection of the graft. Class I and class II antigens presented by dendritic cells to the host macrophages are found on parenchymal cells (class I) or combined on all passenger leucocytes. Humoral factors like interleukin 1 produced by the macrophages activate the helper-lymphocyte subpopulation. The cytotoxic effector cells but also antibody producing B-cells receive their signal (interleukin 2) from the helper cells. Cellular and humoral mechanisms attack the vascular endothelium and the endocard first. Typical perivascular infiltrates or antibodies on the sarcolemm of myocard fibres and the intima herald the two types of rejection. The activated lymphocytes and their blast forms recirculate in various amounts in the peripheral blood, reflecting the severity of the event. Hematological evaluation including differentiation of lymphocyte subsets by monoclonal antibodies according to their phenotype seem to be a tool to recognize these mechanisms at an early stage. It is suggested that the optimal therapy and the necessary biopsy can be adjusted even more precisely using this immunological monitoring.

Antibody Formation↗
PubMed1982

[Report on a successful orthotopic cardiac transplantation in Germany].

The first successful heart-transplantation carried out in the Department for Cardiovascular Surgery of the University of Munich, Klinikum Grosshadern is reported. The recipient, 32 years old at the time of operation, had sustained a large antero-lateral-septal myocardial infarction in June 1980; thereafter the left ventricular ejection fraction was severely impaired (e.f. = 19%). Yet, the operation was definitely planned some year later, after the patient had survived an embolus to the right lung, an acute left heart failure and a small ulcer of the stomach. The operation was performed on 8-19-1981. The donor was a 23 year old young man, who had met a fatal motorcycle accident 10 days ago. The man was pronounced dead in the afternoon of the preoperative day according to the criterions of the German Society for Surgery by means of a carotid angiogram. Donor and recipient were well matched in regard to blood group, HLA-A2-System and finally cross-match-test. Transplantation was carried out according to the technique of Lower and Shumway. Immediately p.o., immunosuppressive therapy was started using azathioprine, cortisone and antihuman thymocyte globulin. Two acute rejections were noted, the first from p.o. day 6 to 15, the second from p.o. day 22 to 34. The second acute rejection was complicated by a pneumatosis cystoides intestinii, which caused a change of the immunosuppressive therapy to Cyclosporin A. No further complications were registered in the following p.o. course, the patient is discharged since Christmas 1981.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Mean xenograft survival of 14.6 days in a small group of hDAF-transgenic pig hearts transplanted orthotopically into baboons.

INTRODUCTION: In a discordant orthotopic xenotransplantation model (pig-to-baboon) donor pigs expressing human decay accelerating factor (hDAF) as a regulator of complement activity were used to prevent hyperacute xenograft rejection (HXR). We investigated a modified immunosuppressive therapy consisting of ERL080 (Novartis Pharma AG, Base, Switzerland), cyclosporin A (Neoral), steroids, and a cyclophosphamide (CyP) induction protocol with several reduced doses to prevent acute vascular rejection (AVR). METHODS: Donor hearts were harvested from hDAF-transgenic pigs (18.8 +/- 2.6 kg, Imutran Ltd., a Novartis Pharma AG Company). Four adult baboons (25.6 +/- 2.7 kg) with high titers of xenoreactive antibodies (XAb) served as recipients. Serological and hemodynamic parameters were measured. Finally, myocardial tissue was sampled for histological and immunohistochemical examinations. RESULTS: In the first baboon, an acute graft failure occurred after 1 hour due to preservation injury. The second succumbed after 11.1 day due to an acute renal failure. The third died after 13.1 days of an ileus. The fourth baboon had continuously excellent cardiac function (mean echocardiographic ejection fraction, 69.2%), but succumbed on day 20 due to anemia. Corrected mean xenograft survival (excluding the first baboon because of a technical failure) was 14.6 +/- 2.6 days. XAb decreased after day 3 to constantly low levels (<1:64 titer) after CyP induction. White blood cell count decreased from 10.3 +/- 0.8 to 0.9 +/- 0.3 G/L after day 3. Macroscopically and histologically no typical signs of HXR or severe AVR could be detected. CONCLUSIONS: These results confirm that hDAF transgen blocks HXR in this life-supporting model. AVR was prevented by using a modified quadruple immunosuppressive drug combination (Neoral, ERL080, steroids, and several small single doses of CyP). An optimum "fine-tuning" of immunosuppression is required to achieve the best risk-benefit ratio.

Animals↗
PubMedDate not supplied

Combination of hDAF-transgenic pig hearts and immunoadsorption in heterotopic xenotransplantation of immunosuppressed baboons.

INTRODUCTION: Hyperacute xenograft rejection (HXR) and acute vascular rejection (AVR) after xenotransplantation are triggered by xenoreactive antibodies (XAb) and an activated complement cascade. In a heterotopic (abdominal) xenotransplantation model we combined immunoadsorption (IA, Ig-Therasorb column) and a quadruple immunosuppressive drug therapy in recipient baboons with donor pig hearts transgenic for human decay accelerating factor (hDAF). METHODS: According to XAb titers between 6 and 14 cycles of IA were performed preoperatively in 4 recipient baboons (18.6 +/- 2.5 kg). Hearts of hDAF-transgenic donor pigs (6.1 +/- 1.1 kg, Imutran Ltd., a Novartis Pharma AG Company, Basel, Switzerland) were heterotopically transplanted using the abdominal technique in baboons. Immunosuppression consisted of cyclophosphamide (CyP) induction therapy, ERL080 (Novartis Pharma AG), cyclosporin A (CyA, Neoral), and steroids. Blood levels of mycophenolate, CyA, immunoglobulins (Ig), anti-pig-antibodies, complement factors, and cardiac enzymes were determined. Abdominal electrocardiography (ECG), echocardiography, and palpation were used for monitoring of the pig hearts. Myocardial tissue specimens were examined using immunohistochemistry, light microscope (LM), and electron microscope (EM). RESULTS: Ten cycles of IA alone removed 78% of XAb and accordingly IgM, IgG, IgA, complement C3, and C4. None of the xenografts was hyperacutely rejected, but xenograft failure occurred after 5.0 +/- 1.3 days (range, 2.4-8.0 days) because of an AVR associated with a rapid XAb increase within 24 hours. White blood cell count (10.3 +/- 2.2 G/L) showed a maximum of 13.1 +/- 2.1 (day 1) and constant levels (1.4 +/- 0.3-2.1 +/- 1.3 G/L) between day 3 and 6. Histology (LM/EM) showed massive hemorrhage, necrosis, and vascular thrombi as signs of AVR. CONCLUSION: Although HXR was prevented by using IA and hDAF-transgenic donor hearts, AVR was not avoided due to insufficient immunosuppressive regimen used and a missed postoperative IA treatment as a result of an inefficient control of XAb production.

Adrenal Cortex Hormones↗