Biomedical subjects

A Haverich

Publications and source records attributed to A Haverich.

At least 181 records · Page 10Linked to original sources

PubMed1999

Combined use of prostacyclin and higher perfusate temperatures further enhances the superior lung preservation by Celsior solution in the isolated rat lung.

BACKGROUND: The poor tolerance of the lung to ischemia and reperfusion (IR) still represents one of the limitations in clinically successful lung transplantation. Modified Euro-Collins (EC) is routinely used in lung preservation, but alternative solutions have been developed for improvement of pulmonary preservation. Celsior is an extracellular solution that has significantly reduced the IR-induced pulmonary damage in animal studies. So far, no extensive experimental studies exist concerning the influence of Celsior on pulmonary gas exchange following IR. METHODS: In an extracorporeal rat lung model 10 lungs, each, were preserved with Celsior (CE) and Celsior/prostacyclin (CEPC, 6 microg/100 ml) at 4 degrees and 15 degrees C, each, and compared to low-potassium Euro-Collins (EC-40, 40 mmol/liter potassium). After 2 hours of ischemia lungs were reventilated and reperfused using a roller pump. Oxygenation in terms of oxygen partial tension in the left atrial effluent, pulmonary vascular resistance (PVR), peak inspiratory pressure, and wet/dry ratio were monitored for 50 minutes. Furthermore, edema formation was evaluated by light microscopy. Statistical analysis was performed using ANOVA models. RESULTS: Compared to the EC-40 group, oxygenation was increased and amount of edema was reduced in most Celsior-preserved organs (p<0.032) with exception of the CEPC group at 4 degrees C (p = 0.06). Additional application of prostacyclin did not have any significant effect on oxygenation in the Celsior group. However, after temperature elevation of the CEPC perfusate to 15 degrees C, a superior partial tension of oxygen was observed (p<0.023) in contrast to the 4 degrees C groups CE and CEPC. The lowest PVR was found in the CE 4 degrees C group (p<0.02). CONCLUSIONS: Celsior provides better lung preservation than EC-40 solution. Application of prostacyclin at higher perfusate temperatures results in additional functional improvement. In vivo experiments and ultrastructural analysis are warranted for further evaluation of Celsior in lung preservation.

Animals↗

PubMed1999

Valve-sparing repair after aortic root dissection following heart transplantation.

We describe the case of a 56-year-old male who presented with a Stanford type A dissection limited to the donor aorta 25 days after orthotopic heart transplantation. Transesophageal echocardiography revealed a newly developed aortic regurgitation grade III and a typical intimal tear 1 cm above the commissures. Surgical therapy included replacement of the ascending aorta with an aortic allograft and implantation of the native aortic valve inside the allograft as a modified David procedure.

Aortic Dissection↗

PubMed1999

Lung transplant waiting list: differential outcome of type of end-stage lung disease, one year after registration.

BACKGROUND: Donor lung scarcity, distinct natural courses of the different types of end-stage lung diseases, and lung allocation schemes demand appropriate candidate acceptance for a lung transplant and time of listing. This study was undertaken to investigate the association between type of end-stage lung disease and outcome, 1 year after a lung transplant candidate was put on the waiting list. METHODS: From 1990 to 1995, 1376 adult patients were registered for a first lung (n = 1006) or heart-lung (n = 370) transplantation in Eurotransplant. All patients were followed for at least 1 year. For each type of end-stage lung disease (cystic fibrosis, pulmonary fibrosis, emphysema, pulmonary hypertension, congenital heart disease, and other), chances of transplantation, of death on the waiting list, and of removal for other reasons, 1 year after listing, were calculated with the competing risks method. A multivariate Cox regression model was used to assess the influence of the type of end-stage lung disease on the waiting list outflow among other prognostic variables. RESULTS: Lung transplant candidates with emphysema and with pulmonary fibrosis had the highest chance of a transplant; however, patients with pulmonary fibrosis had also the highest probability of dying while waiting, while the emphysema patients and those with the type "other" had the lowest probability. In the multivariate analysis, the type of end-stage lung disease appeared as an independent prognostic factor for both outcomes. Compared to the patients with cystic fibrosis (reference group), only patients with pulmonary fibrosis had a significantly higher chance of a transplant (RR = 1.50); the lowest chance of death for the emphysema and the "other" patients was confirmed (RR = 0.53 and RR = 0.51, respectively). Recipient size, ABO blood group, country and epoch of listing also had a significant impact on the transplant chance, while country of listing and recipient age were the other factors independently influencing the chance of dying on the waiting list. On the heart-lung waiting list, the type of end-stage lung disease solely affected the chance of death prior to transplant. Compared with cystic fibrosis, pulmonary fibrosis had a significantly higher risk (RR = 2.93), closely followed by pulmonary hypertension (RR = 2.57). Factors crucial for the chance of a heart-lung transplant were recipient size, ABO blood group and country of listing. CONCLUSIONS: The type of end-stage lung disease is a distinctive factor for predicting survival on the lung and heart-lung transplant waiting list, and should be taken into account whenever assessing waiting list outcomes. When developing lung allocation schemes, it is medically justified to incorporate the type of end-stage lung disease.

Adolescent↗

PubMed1999

Improvement of pulmonary preservation with Celsior and Perfadex: impact of storage time on early post-ischemic lung function.

BACKGROUND: Optimal preservation of post-ischemic organ function is a continuing challenge in clinical lung transplantation. METHODS: Using an established extracorporeal rat lung screening model, the results after preservation of 8 lungs, each with the extracellular-type preservation solutions Celsior and Perfadex using ischemic periods of 2 and 4 hours were compared to the results obtained after 2 hours of preservation with low-potassium Euro-Collins with prostacyclin. RESULTS: Oxygenation capacity of all Celsior-preserved organs was significantly higher as compared to LPEC lungs (p < 0.01), and after 4 hours of ischemia, lung preservation in terms of post-ischemic oxygenation ability was significantly higher in the Celsior group compared with Perfadex-protected organs (p < 0.01). CONCLUSION: Especially at extended ischemic times Celsior can provide significantly better pulmonary preservation in terms of oxygenation capacity compared to Perfadex solution, which is associated with a post-ischemic lung function only comparable to preservation with modified Euro-Collins solution.

Animals↗

PubMed1999

Bronchoalveolar lavage in lung transplantation. State of the art.

Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) has become a crucial tool in the management of lung transplant recipients. Detection of pulmonary infectious pathogens by culture, cytology, and histology of BAL, protected brush specimens, and transbronchial biopsies (TBB) is highly effective. Morphologic and phenotypological analyses of BAL cells may be suggestive for certain complications after lung transplantation. For interpretation of BAL findings, the natural course of BAL cell morphology and phenotypology after lung transplantation must be considered. During the first 3 months after pulmonary transplantation, elevated total cell count in BAL and neutrophilic alveolitis are common, representing the cellular response to graft injury and interaction of immunocompetent cells of donor and recipient origin. With increasing time after transplantation the CD4/CD8 ratio decreases due to lowered percentages of CD4 cells in BAL. During bacterial pneumonias, the cellular profile of BAL is characterized by a marked granulocytic alveolitis. Lymphocytic alveolitis with a decreased CD4/CD8 ratio is suggestive of acute rejection, but is also found in viral pneumonias and obliterative bronchiolitis. In the case of a combined lymphocytosis and neutrophilia without any evidence of infection, obliterative bronchiolitis should be considered. Functional analyses of BAL cells can give additional information about the immunologic status of the graft, even before histologic changes become evident but have not been established in routine transplant monitoring. However, functional studies suggest an important role of activated, alloreactive and donor-specific T lymphocytes in the pathogenesis of acute and chronic lung rejection. Investigations of soluble components in BAL have given further insight into the immunologic processes after lung transplantation. In this overview, the characteristics of BAL after lung transplantation will be summarized, and its relevance for the detection of pulmonary complications will be discussed.

Acute Disease↗

PubMed1999

Adhesion molecules in patients after lung transplantation.

Leukocyte adhesion molecules, such as intercellular adhesion molecule (ICAM)-1 and its ligands, are involved in inflammatory processes of the lung. For ICAM-1, differential expression during different kinds of complications after transplantation has been proposed. We analyzed the role of ICAM-1, CD18, CD11a, CD11b, and CD11c during episodes of rejection or infection in patients after lung transplantation and compared the results to episodes without apparent complication. A total of 98 bronchoalveolar lavage (BAL) samples and 90 serum samples were analyzed. ICAM-1, CD18, CD11a, CD11b, and CD11c expressions were detected immunocytochemically on alveolar macrophages. Soluble ICAM-1 was quantified in serum and BAL. In the control group, 49.8 +/- 18% of macrophages stained positive for CD11b. During rejection, the mean of cells showing CD11b on the surface was significantly higher (64.6 +/-11.4%) with no difference compared to episodes of infection (59.7 +/-22.7). All other epitopes were not expressed differently with regard to a normal clinical course or episodes of infection and rejections. In summary, assessment of ICAM-1 and corresponding ligands did not allow for a reliable discrimination between episodes of rejection or infection in lung transplantation.

Adolescent↗

PubMed1999

Exogenous surfactant improves survival and surfactant function in ischaemia-reperfusion injury in minipigs.

Reperfusion injury is the major cause of early morbidity and mortality after lung transplantation. This complication has been experimentally linked to dysfunction of pulmonary surfactant. Therefore, the hypothesis that reperfusion injury might be preventable by exogenous surfactant treatment was tested. Left lungs of minipigs were exposed to 120 min of ischaemia, and the lungs were then reperfused for up to 7 h. Animals were divided into a control group and a surfactant group (n=5 each). The surfactant group received 50 mg x kg(-1) Alveofact intrabronchially via a bronchoscope at the beginning of the ischaemic period. Bronchoalveolar lavage was performed at baseline before ischaemia and 90 min after reperfusion. Surfactant treatment significantly improved short-term survival. Pulmonary vascular resistance increased markedly in control animals leading to right heart failure and death within 3 h after reperfusion whereas the surfactant-treated animals survived the 7 h observation period. After reperfusion, alveolar accumulation of neutrophils and exuded proteins was present in both groups to the same extent. Surfactant activity after reperfusion deteriorated markedly in the control group but was preserved in the surfactant group. In conclusion, early surfactant treatment alleviates the deterioration of surfactant function and improves survival in this minipig model of ischaemia-reperfusion injury.

Animals↗

PubMed1999

Extracorporeal membrane oxygenation -- new developments.

Extracorporeal membrane oxygenation (ECMO) has been used clinically for more than 10 years in pulmonary and cardiopulmonary failure. Intravascular devices were developed and introduced. But, due to lack of efficiency, they did not gain clinical acceptance. However, progress was made in improving the extracorporeal devices in terms of biocompatibility: less traumatizing oxygenators and pumps were developed. In addition heparin coating of the extracorporeal circuit was introduced. The cannulation technique became less invasive due to a transcutaneous approach. New treatment strategies and ventilator techniques were introduced in the last decade for respiratory insufficiency with the implication of less requirement for ECMO. However, these new treatment strategies, like nitric oxide ventilation or surfactant replacement, may be used as cotherapy with ECMO to reduce complications on ECMO or shorten the time ECMO is required. Further technical improvements are evolving like sophisticated pump control systems to reduce negative inlet pressure or pulsatile pump flow. Therefore ECMO devices have become safer and less invasive. Pharmacological cotherapy will both shift the inclusion criteria for ECMO and improve ECMO efficacy and safety.

Equipment Design↗

PubMed1999

Inhaled nitric oxide as a prophylactic treatment against reperfusion injury of the lung.

BACKGROUND: Inhaled Nitric Oxide (NO) has been found to be effective in clinical treatment of reperfusion injury after lung transplantation. This study was designed to determine a possible prophylactic role to reduce severe reperfusion injury. METHODS: In 12 minipigs the left lung was selectively perfused with cold Euro-Collins solution. After 90 minutes of warm ischemia the lungs were reperfused and the contralateral pulmonary artery and main bronchus clamped. Hemodynamic and respiratory parameters were monitored for 7 hours. 6 animals were used as controls. 6 pigs formed the NO group and were ventilated continuously with 40 ppm nitric oxide (NO) starting 30 minutes prior to reperfusion. RESULTS: In the control group right heart failure developed within 1.9 +/- 0.8 hours of reperfusion. Lung compliance was significantly reduced. A significant increase of pulmonary vascular resistance (PVR) was found. All animals of the NO group survived the reperfusion period of 7 hours. PVR was decreased compared to controls (p = 0.03). AaDO2 was lower, but not significantly different. The dynamic compliance of the lung was significantly higher (p = 0.007) in the NO group. CONCLUSIONS: The prophylactic institution of inhaled NO reduces reperfusion injury of the lung. Short-term use of inhaled NO should be adopted as a prophylactic agent after transplantation of lungs preserved in Euro-Collins solution.

Administration, Inhalation↗

PubMed1999

Dissociation of the effects of forskolin and dibutyryl cAMP on force of contraction and phospholamban phosphorylation in human heart failure.

Forskolin and dibutyryl cyclic adenosine monophosphate (cAMP) stimulate force of contraction independent of beta-adrenoceptor stimulation. We studied their effects on force of contraction and phosphorylation of regulatory proteins in isolated electrically driven trabeculae carneae from failing human ventricles. The phosphorylation state of the regulatory protein phospholamban was studied because its phosphorylation usually faithfully follows contractility. For comparison, the phosphorylation state of the inhibitory subunit of troponin was studied. The phosphorylation state was inferred from in vitro phosphorylation of homogenates with cAMP-dependent protein kinase in the presence of radioactive gamma[32P]ATP Proteins were separated by electrophoresis, and radioactivity in the proteins of interest was quantified. The maximal positive inotropic effects occurred at 30 microM forskolin and were attenuated in comparison with the maximal effects to dibutyryl cAMP (1 mM). Both forskolin and dibutyryl cAMP enhanced phospholamban phosphorylation. However, phospholamban phosphorylation in intact trabeculae treated with 30 microM forskolin and 1 mM dibutyryl cAMP was comparable. It is suggested that phospholamban phosphorylation can be dissociated from inotropy at least in isolated trabeculae from failing human hearts.

Adolescent↗

PubMed1999

Ten year survival after heart transplantation: palliative procedure or successful long term treatment?

OBJECTIVE: To investigate the long term outcome and prognostic factors after heart transplantation. SETTING: University hospital. SUBJECTS: 120 heart transplant patients (98 male, 22 female; underlying disease: dilated cardiomyopathy in 69, coronary artery disease in 42, miscellaneous in nine) who had undergone heart transplantation between October 1984 and October 1987. Immunosuppressive treatment was comparable in all patients and rejection episodes were treated in a uniform manner. METHODS: Functional status, quality of life, and potential predictors for long term survival were investigated. RESULTS: Actuarial survival rates were 65% at five years and 48% at 10 years; 58 patients survived > 10 years. The major causes of death were cardiac allograft vasculopathy (39%), acute rejection (18%), infection (11%), and malignancy (11%). Long term survivors had good exercise tolerance assessed by the New York Heart Association classification: 47 (81%) in grade I/II; 11 (19%) in grade III/IV. Echocardiography showed good left ventricular function in 48 patients. On angiography, severe allograft vasculopathy was present in only 16 patients (28%). Renal function was only slightly impaired, with mean (SD) serum creatinine of 148.5 (84.9) micromol/l. Multiple potential predictors of long term survival were analysed but none was found useful. CONCLUSIONS: Heart transplantation represents a valuable form of treatment. Survival for more than 10 years with a good exercise tolerance and acceptable side effects from immunosuppression can be achieved in about 50% of patients.

Adult↗

PubMed1999

Site of pleural drain insertion and early postoperative pulmonary function following coronary artery bypass grafting with internal mammary artery.

STUDY OBJECTIVES: Coronary artery bypass graft (CABG) surgery using the left internal mammary artery (LIMA) impairs postoperative pulmonary function. We studied the changes in pulmonary function and subjective pain relative to the site of chest tube insertion. DESIGN: Thirty patients undergoing CABG surgery using the LIMA were randomized into two groups. Group A (n = 15) received a left chest tube inserted from the midline (subxyphoid). Group B (n = 15) had a tube placed in the sixth intercostal space at the anterior axillary line. All of the patients underwent bedside pulmonary function testing preoperatively and on postoperative days (PODs) 1, 3, and 5. Pain sensation was quantified by a standardized score (1 to 10). RESULTS: A significant impairment of pulmonary function parameters was observed in both groups until POD 5. For group A, the decline in percent predicted (+/-SD) in the vital capacity (VC) from before surgery to POD 5 was, respectively, 92.3+/-30.6% to 56.9+/-12.6% (p < 0.001). For group B, the decline in the VC was from 88.0+/-18.2% to 55.5+/-14.8% (p < 0.001). The FEV1 declined concomitantly in group A from 86.2+/-18.2% to 50.8+/-12.1%, and in group B from 83.5+/-16.4% to 53.9+/-12.5% (p < 0.001). On POD 1, a significantly lower decrease in the VC was measured in group A than in group B, respectively: 45.3+/-15.5% vs 28.6+/-8.7% (p < 0.001). A significantly lower decrease in the FEV1 was also seen in group A than in group B, respectively: 36.9+/-12.9% vs 28.0+/-10.6% (p < 0.05). Pain experienced during deep inspiration was also significantly less in group A than in group B, respectively: 1.2+/-1.1 vs 2.5+/-0.9 (p < 0.01). CONCLUSIONS: Subxyphoid insertion of the pleural drain leads to a significantly lower impairment of pulmonary function and less subjective pain than insertion at the intercostal position. The drainage of the left pleural space is equally effective with both techniques.

Aged↗

PubMed1999

[Lung transplantation in Hanover: an interim balance-sheet after ten years].

BACKGROUND: We reviewed our experience with various forms of lung transplantation (heart-lung [HLTx], bilateral lung [BLTx] and single lung [SLTx]) from December 1987 to September 1998 at Hannover University. PATIENTS: In 258 patients 282 procedures (46 HLTx, 142 BLTx and 94 SLTx) were performed. Major indications were pulmonary fibrosis (n = 73), obstructive lung disease (n = 55), cystic fibrosis (n = 48), primary pulmonary hypertension (PPHT, n = 36), secondary pulmonary hypertension (n = 30) and retransplantation (n = 24). RESULTS: The 1-, 3- and 5-year survival rates in all 258 recipients were 77%, 70% and 63% respectively. Significantly better 1-year survival was noted in patients with cystic fibrosis (90%), pulmonary fibrosis (81%), obstructive lung disease (71%) and secondary pulmonary hypertension (83%) when compared to patients with primary pulmonary hypertension (58%). There was no significant difference in actuarial 1-year survival rates between the different procedures (HLTx 78%, BLTx 77%, SLTx 77%). Bronchiolitis obliterans syndrome (BOS) proved to be the major obstacle for long term survival. Actuarial freedom from BOS was 80% at 1 year and only 45% at 5 years. Various treatment strategies including augmentation of immunosuppression could only temporarily halt the deterioration of lung function in the majority of patients with BOS. CONCLUSIONS: Lung transplantation provides a true therapeutic option for patients with endstage lung disease. However, improved long term outlook will depend on a better understanding and treatment of bronchiolitis obliterans.

Adolescent↗

PubMed1999

[Experimental xenogenic lung transplantation].

Lung transplantation has become a valuable therapeutical option for patients with end stage vascular and parenchymal pulmonary disease. The main limitation is the donor organ shortage, which is for lung transplantation even more pronounced than for other solid organs. Therefore, the search for alternative sources in the field of xenotransplantation as potential bridging to human allograft transplantation has emerged over the last few years. Pulmonary xenotransplantation at this stage is still an experimental procedure. Different concordant and discordant models have been investigated for specific organ functions, but in subhuman models no long-term function could be achieved to date. The purpose of this article is to present recent results in pulmonary xenotransplantation models.

Animals↗

PubMed1998

Long-term outcome of chronic hepatitis B in heart transplant recipients.

BACKGROUND: Hepatitis B is common in organ transplant recipients. It adversely affects the prognosis after liver and kidney transplantation. The long-term outcome of hepatitis B virus (HBV) infection in heart transplant recipients has not been studied before. METHODS: Between July 1984 and June 1993, 436 patients underwent heart transplantation at the Hannover Medical School. A total of 345 patients survived for more than 1 year and were included in this study. Of these, 74 were found to be hepatitis B surface antigen (HBsAg)-positive during follow-up; 69 acquired HBV infection at known time points 25+/-17 months after transplantation, and 5 had already been infected before heart transplantation. Mean follow-up was 105 (range, 25-157) months. RESULTS: Patients developed significant alanine aminotransferase (ALT) elevations after HBV infection, which peaked and then remained above normal. Preinfection levels of ALT were 15.4+/-6.4 U/L, peak values were 71.2+/-47.2 U/L, and mean values after HBV infection were 28.9+/-14.6 U/L. All patients remained HBsAg-positive. Thirteen patients (18%) became HBeAg-negative during follow-up, 10 with negative quantitative HBV-DNA assays. Mean HBV-DNA levels in the remaining patients were 292+/-267 (range, 0-978) pg/ml. Thirty-four patients died during follow-up (45.9%) compared to 78/271 (28.8%) in the control group (P=0.008). Six of the HBsAg-positive patients (17.1%) died of liver failure 6.2-10.6 years (mean, 8.6) after transplantation. Histology of 25 HBsAg-positive patients more than 5 years after infection revealed severe fibrosis or cirrhosis in 14 (56%), mild fibrosis in 9 (36%), and chronic hepatitis without fibroproliferation in 2 (8%). CONCLUSIONS: Hepatitis B infection after heart transplantation leads to chronic liver disease in the majority of the affected patients, causing cirrhosis in more than 55% within the first decade after transplantation. Liver failure is a common cause of death in the infected group of patients. Active HBV vaccination is mandatory for all organ transplant candidates, in particular before heart transplantation.

Adult↗

PubMed1998

[Aortic valve insufficiency in aneurysms of the ascending aorta: functional results following valve-sparing reconstruction].

BACKGROUND AND OBJECTIVE: Changes in geometry of the aortic root, especially a dilatation of the sinotubular junction, are the major causes of aortic valve regurgitation in ascending aortic aneurysm. In valves without structural defect, a valve sparing aortic root reconstruction may be a therapeutic option. Aim of this study was the assessment of functional results, in the early postoperative, and during follow-up, in a large patient cohort from one centre. PATIENTS AND METHODS: Between July 1993 and March 1998, a total of 48 valve sparing operations were performed at Hannover Medical School. Mean age of patients (34 males, 14 females) was 47.4 +/- 19 years. In a prospective design clinical, and echocardiographic examinations were performed pre-, intra and early postoperatively as well as 3.6 and then every 12 months during follow-up. Structural valve changes, systolic pressure gradients as well as the degree of diastolic regurgitation were evaluated. RESULTS: Aortic root reconstruction was successful in all patients; none died perioperatively. Extension of the underlying disease to the aortic arch was present in eleven, acute and chronic dissection of the ascending aorta (type A) in two and three patients, respectively. Echocardiographic follow-up over a mean period of 25.1 +/- 18.3 months (cumulatively 1204 months) revealed stable valve function in 41 patients without (n = 30) or with a minimal (n = 11) regurgitation. In three patients moderate valve regurgitation (grade 2) was observed, three patients (6.3%) had to be reoperated because of a progressive valve failure. Thromboembolic or bleeding complications were not observed. CONCLUSIONS: Valve sparing aortic root reconstruction is a promising alternative to the composite replacement of the ascending aorta. Low perioperative morbidity and mortality rates as well as favourable functional results were demonstrated. Long-term anticoagulation can be avoided. Long-term follow-up will be necessary to assess the definitive role of this new surgical approach.

Adult↗

PubMed1998

Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells.

BACKGROUND: The risk of interspecies transmission of retroviruses during xenotransplantation is suggested by reports of pig endogenous retrovirus (PERV) released from porcine cell lines productively infecting human cell lines in vitro and of infectious PERV being released from pig peripheral blood mononuclear cells after mitogenic stimulation. Endothelial cells are the main interface between a xenograft and the recipient's leucocytes and tissues. METHODS: We have analysed pig primary aortic endothelial cells (PAEC) together with other transplantation-relevant porcine cells and tissues for expression of PERV mRNA. Release of virus particles by PAEC was monitored by reverse transcriptase (RT) activity in the medium of cultured PAEC. Infectivity for human cells was tested by co-cultivation of irradiated PAEC with the human embryonal kidney cell line HEK293 and looking for virus release from the human cells. FINDINGS: PAECs, hepatocytes, lung, and skin from a variety of pig strains and breeds expressed PERV mRNA. PAEC released infectious particles. Co-cultivation of PAEC and HEK293 led to productive infection of the human cells and expression of PERV types A and B. INTERPRETATION: Release of infectious virus from PAEC occurred without mitogenic stimulation, suggesting a serious risk of retrovirus transfer after xenotransplantation.

Animals↗

PubMed1998

Porcine endogenous retrovirus (PERV) was not transmitted from transplanted porcine endothelial cells to baboons in vivo.

The discussion about the clinical risk of zoonoses in xenotransplantation has recently culminated in the demand for a moratorium on clinical organ transplantation using pig donors. The basis for this discussion was a recent report showing a possible trans-species transmission of pig endogenous retrovirus (PERV) by in vitro transfer to human cell lines. At present, it remains unclear if this could also happen in vivo or in the setting of xenotransplantation. Potential in vivo transfer of PERV after xenotransplantation was investigated in an experimental pig-to-baboon cell transplantation model. Baboons were immunosuppressed with high-dose cyclophosphamide (total 45-150 mg/kg) and transplanted with primary porcine aortic endothelial cells (PAEC). Tissue samples (skin, lymph nodes, lung) and peripheral blood leukocytes of 15 baboons, taken about 12-24 months after transplantation of PAEC, were then analyzed by PCR and showed no PERV infection. PERV expression in PAEC was also analyzed: PERV mRNA and reverse transcriptase in the culture supernatant could be detected. In spite of the release of retroviral particles from cultured PAEC, transplantation of these cells into baboon recipients did not result in virus transmission, not even under heavy immunosuppression.

Animals↗