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2.
Int J Surg Case Rep ; 5(5): 256-8, 2014.
Article in English | MEDLINE | ID: mdl-24705636

ABSTRACT

INTRODUCTION: We present a rare case in which both a double cardiac valve replacement was performed as well as a hepatic resection. PRESENTATION OF CASE: We report the case of a 36 year old patient who presented with intra abdominal bleeding thought to have been caused by a liver haemangioma she also had severe autoimmune cardiac valve disease. She underwent a simultaneous right hepatectomy with cardiac valve replacement. DISCUSSION: Management of this challenging case is discussed. CONCLUSION: We advocate the possibility of performing combined operations where both valve replacement and hepatic resection is required.

3.
Eur Respir J ; 39(3): 691-7, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21778169

ABSTRACT

Fundoplication may improve survival after lung transplantation. Little is known about the effects of fundoplication on quality of life in these patients. The aim of this study was to assess the safety of fundoplication in lung transplant recipients and its effects on quality of life. Between June 1, 2008 and December 31, 2010, a prospective study of lung transplant recipients undergoing fundoplication was undertaken. Quality of life was assessed before and after surgery. Body mass index (BMI) and pulmonary function were followed up. 16 patients, mean ± sd age 38 ± 11.9 yrs, underwent laparoscopic Nissen fundoplication. There was no peri-operative mortality or major complications. Mean ± SD hospital stay was 2.6 ± 0.9 days. 15 out of 16 patients were satisfied with the results of surgery post fundoplication. There was a significant improvement in reflux symptom index and DeMeester questionnaires and gastrointestinal quality of life index scores at 6 months. Mean BMI decreased significantly after fundoplication (p = 0.01). Patients operated on for deteriorating lung function had a statistically significant decrease in the rate of lung function decline after fundoplication (p = 0.008). Laparoscopic fundoplication is safe in selected lung transplant recipients. Patient benefit is suggested by improved symptoms and satisfaction. This procedure is acceptable, improves quality of life and may reduce deterioration of lung function.


Subject(s)
Fundoplication , Gastroesophageal Reflux/surgery , Lung Transplantation , Quality of Life , Adult , Body Mass Index , Female , Humans , Laparoscopy , Lung/physiopathology , Male , Middle Aged , Patient Satisfaction , Prospective Studies , Respiratory Function Tests , Surveys and Questionnaires , Treatment Outcome
4.
Br J Anaesth ; 108 Suppl 1: i29-42, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22194428

ABSTRACT

Over the course of the last century, organ transplantation has overcome major technical limitations to become the success it is today. The breakthroughs include developing techniques for vascular anastomoses, managing the immune response (initially by avoiding it with the use of identical twins and subsequently controlling it with chemical immunosuppressants), and devising preservation solutions that enable prolonged periods of ex vivo storage while preserving function. One challenge that has remained from the outset is to overcome the shortage of suitable donor organs. The results of organ transplantation continue to improve, both as a consequence of the above innovations and the improvements in peri- and postoperative management. This review describes some of the achievements and challenges of organ transplantation.


Subject(s)
Organ Transplantation/history , History, 20th Century , History, 21st Century , Humans , Immunosuppression Therapy/history , Immunosuppression Therapy/methods , Organ Preservation/methods , Organ Transplantation/methods , Tissue and Organ Procurement/methods , Tissue and Organ Procurement/trends , Treatment Outcome
5.
Heart ; 96(15): 1217-22, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20639237

ABSTRACT

BACKGROUND: Due to increasing success with repair or palliation in childhood, there is a rapidly growing population of adult patients with complex congenital heart disease who may require transplantation. There remains little data on outcomes of cardiac transplantation in this group. METHODS: 38 orthotopic cardiac transplants were performed in 37 patients (18 men) > or =18 years of age with congenital heart disease (CHD) from 1988 to 2009 in our institution. Outcomes were reviewed using medical records and transplant databases. RESULTS: 15 patients (41%) had univentricular and 22 (59%) biventricular physiology. The biggest group was transposition of the great arteries following atrial switch in eight patients (22%). Six (16%) had no previous surgical intervention. Mean age at transplant was 33.5 years (range 19.1-59.9 years). 11 patients (30%) required additional surgical procedures at transplant. 16 (43%) died, 12 early and 4 late deaths (1.8, 2.4, 2.7 and 7 years). Survival was 70% at 30 days, 68% at 1 year, 58% at 5 years and 53% at 10 and 15 years. Outcome improved in later eras with reduction in 30-day mortality from 50% to 18% and increase in 5-year survival from 50% to 69%. Two patients developed post-transplant lymphoproliferative disease. None required long-term renal replacement therapy. One patient was re-transplanted for cardiac allograft vasculopathy. CONCLUSIONS: While operative mortality following cardiac transplantation for adult congenital heart disease is higher than for other diagnostic groups, long-term survival is good and comparable to patients without CHD. Disappointing early results are improved with increasing experience.


Subject(s)
Heart Defects, Congenital/surgery , Heart Transplantation , Adult , Cause of Death , Female , Heart Defects, Congenital/diagnosis , Humans , Immunosuppression Therapy/methods , Male , Middle Aged , Patient Selection , Postoperative Care/methods , Prognosis , Reoperation , Survival Analysis , Treatment Outcome , Young Adult
6.
Am J Transplant ; 9(6): 1272-8, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19459806

ABSTRACT

Chronic allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is the major cause of morbidity and mortality in human lung transplant recipients. While alloimmunity has a definite role, there is increasing interest in overall allograft injury and subsequent inflammation and remodeling. This review deals with nonalloimmune factors that may potentiate alloimmune injury. We discuss infection and reflux/aspiration as examples of allograft injury, which may lead to chronic loss of graft function and BOS. Surgical and nonsurgical treatments aimed at preventing these insults and improving survival are considered. The need for further evidence, including randomized-controlled trials, to evaluate the role of medical and surgical therapies is emphasized by the current literature.


Subject(s)
Bronchiolitis Obliterans/drug therapy , Bronchiolitis Obliterans/etiology , Lung Transplantation/adverse effects , Azithromycin/therapeutic use , Bronchiolitis Obliterans/physiopathology , Gastroesophageal Reflux/etiology , Gram-Negative Bacterial Infections/complications , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lung Diseases/complications , Lung Diseases/microbiology , Pneumonia/microbiology , Pneumonia, Aspiration/etiology , Transplantation, Homologous/immunology
7.
Atherosclerosis ; 202(2): 612-6, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18589426

ABSTRACT

INTRODUCTION: Increasing age is associated with reduced numbers of circulating endothelial progenitor cells (EPCs). It is unclear whether this relates to depletion or impairment of bone marrow progenitors, or to deficient mobilization signals from aging tissues. In cardiac transplant patients, one previous study has reported an association between circulating EPCs and the risk of cardiac allograft vasculopathy (CAV). We investigated whether increased donor heart age, a strong risk factor for CAV, was associated with reduced circulating EPC numbers in a group of cardiac transplant recipients matched for factors which influence EPC numbers, but with maximally discordant donor heart ages. METHODS: We identified 32 patient pairs, matched for factors known to influence EPC numbers, but who had discordant donor heart ages by at least 20 years. EPCs were quantified using flow cytometry for absolute counts of cells expressing all the combinations of CD45, CD34, CD133 and the kinase domain receptor (KDR). RESULTS: There were no significant differences in the numbers of circulating EPCs between patients with old or young donor heart age. There was no association between the presence of CAV and circulating EPC numbers. CONCLUSIONS: We suggest that the increased susceptibility to CAV of older donor hearts is not mediated via circulating EPCs. Our results are consistent with the theory that the normal age-related decline in EPC numbers relates to bone marrow aging rather than failure of target tissues to induce EPC mobilization.


Subject(s)
Endothelium, Vascular/cytology , Heart Transplantation/statistics & numerical data , Hematopoietic Stem Cells/cytology , Postoperative Complications/epidemiology , Vascular Diseases/epidemiology , Adult , Age Distribution , Aged , Cell Count , Cohort Studies , Female , Flow Cytometry , Humans , Male , Middle Aged , Risk Factors , Tissue Donors , Transplantation, Homologous
8.
BMJ Case Rep ; 20092009.
Article in English | MEDLINE | ID: mdl-21686410

ABSTRACT

In the present study, 4 patients with cystic fibrosis undergoing lung transplantation (from a total of 137) who developed fulminant pseudomembranous colitis are described. Initial presentation was variable and the mortality rate was 50% despite urgent colectomy. In one case the presenting abdominal distension was thought to be due to meconium ileus equivalent. It is concluded that Clostridium difficile colitis may be a difficult diagnosis in patients with cystic fibrosis and follows a fulminant course after lung transplantation.

9.
Transplant Proc ; 40(5): 1796-7, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18589200

ABSTRACT

Mitral valve dysfunction after orthotopic heart transplantation may cause symptoms refractory to medical therapy. In this report, we present a patient who underwent mitral annuloplasty for severe symptomatic mitral valve insufficiency 9 years after heart transplantation, and we critically appraise the literature available for mitral valve dysfunction in this setting. Mitral valve repair, when feasible, should be considered for mitral insufficiency after transplantation to improve functional status and reduce the risk of retransplantation--this is particularly prudent in view of chronic donor shortage.


Subject(s)
Cardiomyopathies/surgery , Heart Transplantation/adverse effects , Mitral Valve Insufficiency/etiology , Mitral Valve Insufficiency/therapy , Myocardial Ischemia/etiology , Myocardial Ischemia/surgery , Adult , Humans , Male , Mitral Valve Insufficiency/diagnosis , Treatment Outcome
10.
Thorax ; 63(8): 725-31, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18487317

ABSTRACT

BACKGROUND: Lung transplantation is an important option to treat patients with advanced cystic fibrosis (CF) lung disease. The outcomes of a large UK cohort of CF lung transplantation recipients is reported. METHODS: Retrospective review of case notes and transplantation databases. RESULTS: 176 patients with CF underwent lung transplantation at our centre. The majority (168) had bilateral sequential lung transplantation. Median age at transplantation was 26 years. Diabetes was common pretransplantation (40%). Polymicrobial infection was common in individual recipients. A diverse range of pathogens were encountered, including the Burkholderia cepacia complex (BCC). The bronchial anastomotic complication rate was 2%. Pulmonary function (forced expiratory volume in 1 s % predicted) improved from a pretransplantation median of 0.8 l (21% predicted) to 2.95 l (78% predicted) at 1 year following transplantation. We noted an acute rejection rate of 41% within the first month. Our survival values were 82% survival at 1 year, 70% at 3 years, 62% at 5 years and 51% at 10 years. Patients with BCC infection had poorer outcomes and represented the majority of those who had a septic death. Data are presented on those free from these infections. Bronchiolitis obliterans syndrome (BOS) and sepsis were common causes of death. Freedom from BOS was 74% at 5 years and 38% at 10 years. Biochemical evidence of renal dysfunction was common although renal replacement was infrequently required (<5%). CONCLUSION: Lung transplantation is an important therapeutic option in patients with CF even in those with more complex microbiology. Good functional outcomes are noted although transplantation associated morbidities accrue with time.


Subject(s)
Cystic Fibrosis/surgery , Lung Transplantation/mortality , Postoperative Complications/etiology , Adolescent , Adult , Airway Obstruction/mortality , Bronchiolitis Obliterans/mortality , Bronchoalveolar Lavage Fluid/microbiology , Child , Cystic Fibrosis/microbiology , Cystic Fibrosis/mortality , Diabetes Complications/mortality , Epidemiologic Methods , Female , Humans , Kidney Diseases/etiology , Kidney Diseases/mortality , Male , Middle Aged , Neoplasms/mortality , Postoperative Complications/mortality , Preoperative Care , Renal Dialysis/statistics & numerical data , Reoperation , Sputum/microbiology , United Kingdom/epidemiology
11.
Am J Transplant ; 8(4): 866-71, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18324978

ABSTRACT

Although smoking cessation is a prerequisite prior to listing for cardiac transplantation, some patients return to smoking after recovery. We have covertly assessed the smoking habits of our cardiac transplant recipients (with ethical approval) since 1993 by measuring urinary cotinine: a level of >500 ng/mL signifying continued tobacco use. We retrospectively analyzed survival, causes of death and the development of graft coronary artery disease (GCAD) with respect to the number of positive and negative cotinine levels. One hundred four of 380 (27.4%) patients tested positive for active smoking at some point posttransplant, and 57 (15.0%) tested positive repeatedly. Smokers suffered significantly more deaths due to GCAD (21.2% vs. 12.3%, p < 0.05), and due to malignancy (16.3% vs. 5.8%, p < 0.001). In univariate analysis, smoking after heart transplantation shortened median survival from 16.28 years to 11.89 years. After correcting for the effects of pretransplant smoking in time-dependent multivariate analysis, posttransplant smoking remained the most significant determinant of overall mortality (p < 0.00001). We conclude that tobacco smoking after cardiac transplantation significantly impacts survival by accelerating the development of graft vasculopathy and malignancy. We hope that this information will deter cardiac transplant recipients from relapsing, and intensify efforts in improving cessation rates.


Subject(s)
Heart Transplantation/adverse effects , Smoking/adverse effects , Adult , Biomarkers/urine , Coronary Disease/epidemiology , Coronary Disease/mortality , Cotinine/urine , Heart Transplantation/mortality , Humans , Neoplasms/epidemiology , Neoplasms/mortality , Smoking/epidemiology , Smoking/urine , Survival Analysis , Tobacco Use Disorder/complications , Tobacco Use Disorder/urine , Treatment Failure
12.
Am J Transplant ; 7(1): 83-90, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17227559

ABSTRACT

Sympathetic discharge and hypertensive crisis often accompany brain death, causing neurogenic pulmonary edema. Progressive systemic inflammatory response develops, which can injure the lung further. We investigated whether (a) early hemodynamic injury during donor brain death increases reperfusion injury after lung transplantation and (b) delaying lung recovery would augment reperfusion injury further, because of the progressive systemic inflammatory response in the donor. Brain death was induced by intracranial balloon inflation in rats, with or without alpha-adrenergic blockade pretreatment to prevent the hypertensive crisis. Another group of rats had a sham procedure. Lungs were retrieved 15 min after brain death or sham procedure and reperfused using recipient rats. In a fourth group, brain death was induced and the lungs were retrieved 5 h after brain death and reperfused. Postreperfusion, lungs retrieved early from untreated brain-dead donors developed more severe reperfusion injury, as assessed by functional parameters and inflammatory markers, than those from sham or alpha-blockade-treated donors. Lungs retrieved late from brain-dead donors had similar inflammatory markers after reperfusion to those retrieved early, but significantly lower pulmonary vascular resistance. Early hemodynamic damage during donor brain death increases reperfusion injury after lung transplantation. Delaying retrieval may allow the lung to recover from the hemodynamic injury.


Subject(s)
Brain Death/pathology , Delayed Graft Function/etiology , Lung Transplantation/adverse effects , Tissue Donors , Vascular Diseases/pathology , Animals , Hypertension , Inflammation , Lung/pathology , Male , Models, Animal , Rats , Rats, Wistar , Reperfusion Injury/pathology , Vascular Diseases/etiology
13.
Thorax ; 62(6): 554-6, 2007 Jun.
Article in English | MEDLINE | ID: mdl-16601087

ABSTRACT

Pseudomembranous colitis is an uncommon complication in patients with cystic fibrosis, despite the use of multiple high-dose antibiotic regimens and the frequency of hospital admissions. Four patients from a total of 137 patients with cystic fibrosis undergoing lung transplantation are described who developed fulminant pseudomembranous colitis. Initial presentation was variable and the mortality rate was 50% despite urgent colectomy. In one case the presenting abdominal distension was thought to be due to meconium ileus equivalent. It is concluded that Clostridium difficile colitis may be a difficult diagnosis in patients with cystic fibrosis and follows a fulminant course after lung transplantation.


Subject(s)
Cystic Fibrosis/complications , Enterocolitis, Pseudomembranous/etiology , Lung Transplantation , Postoperative Complications/etiology , Adult , Cystic Fibrosis/diagnostic imaging , Enterocolitis, Pseudomembranous/diagnostic imaging , Female , Humans , Male , Postoperative Complications/diagnostic imaging , Tomography, X-Ray Computed
14.
Thorax ; 60(10): 872-4, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16055614

ABSTRACT

BACKGROUND: A biologically plausible link between gastro-oesophageal reflux (GOR), aspiration, and lung allograft dysfunction has been suggested, but there is no systematic evidence indicating the presence of gastric contents in the lung. We have tested the hypothesis that pepsin, as a marker of aspiration, is detectable in bronchoalveolar lavage (BAL) fluid of allograft recipients who had not reported symptoms of GOR. METHODS: Standardised 3 x 60 ml surveillance BAL fluid samples from 13 chronologically sequential stable lung allograft recipients without chronic rejection (10 patients treated with a prophylactic proton pump inhibitor) were studied. Lavage supernatants were assayed by an ELISA based on a monospecific goat antibody for pepsin/pepsinogen. Pepsin levels were compared with those from four normal volunteer controls. RESULTS: Pepsin levels were measurable in all allograft recipients, in keeping with gastric aspiration (median 109 ng/ml (range 35-1375)). In the control group the pepsin levels were below the limit of detection. Treatment with a proton pump inhibitor was not correlated with pepsin levels. There was no correlation between BAL fluid neutrophils and pepsin levels. CONCLUSION: These data demonstrate lung epithelial lining fluid concentrations of pepsin in lung allograft recipients which are much higher than blood reference levels, with no detectable pepsin in controls. This provides direct evidence of gastric aspiration, which is potentially injurious to the allograft.


Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , Lung Transplantation , Pepsin A/analysis , Pneumonia, Aspiration/diagnosis , Adult , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Pepsinogens/analysis , Pneumonia, Aspiration/etiology , Transplantation, Homologous
15.
Thorax ; 60(10): 865-71, 2005 Oct.
Article in English | MEDLINE | ID: mdl-15972366

ABSTRACT

BACKGROUND: Obliterative bronchiolitis in chronic rejection of lung allografts is characterised by airway epithelial damage and fibrosis. The process whereby normal epithelium is lost and replaced by fibroblastic scar tissue is poorly understood, but recent findings suggest that epithelial cells can become fibroblasts through epithelial-mesenchymal transition (EMT). It is hypothesised that EMT occurs in lung allografts and plays a potential role in airway remodelling. METHODS: Sixteen stable lung transplant recipients underwent bronchoscopy with bronchoalveolar lavage (BAL), endobronchial biopsies, and bronchial brushings. Biopsy sections were stained for the fibroblast marker S100A4. Brushings were cultured on collagen, stained with anti-S100A4, and examined for further EMT markers including matrix metalloproteinase (MMP) zymographic activity and epithelial invasion through collagen coated filters. RESULTS: A median 15% (0-48%) of the biopsy epithelium stained for S100A4 in stable lung transplant recipients and MMP-7 co-localisation was observed. In non-stimulated epithelial cultures from lung allografts, S100A4 staining was identified with MMP-2 and MMP-9 production and zymographic activity. MMP total protein and activity was increased following stimulation with transforming growth factor (TGF)-beta1. Non-stimulated transplant epithelial cells were invasive and penetration of collagen coated filters increased following TGF-beta1 stimulation. CONCLUSIONS: This study provides evidence of EMT markers in lung allografts of patients without loss of lung function. The EMT process may represent a final common pathway following injury in more common diseases characterised by airway remodelling.


Subject(s)
Epithelial Cells/pathology , Lung Transplantation , Mesoderm/pathology , Adult , Biopsy/methods , Bronchiolitis Obliterans , Bronchoalveolar Lavage Fluid/cytology , Female , Fibroblasts/pathology , Humans , Immunohistochemistry , Male , Matrix Metalloproteinases/analysis , Middle Aged , Phenotype , Staining and Labeling
16.
Transplant Proc ; 37(2): 977-80, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15848596

ABSTRACT

Renal, hepatic, and lung allografts are compromised by aggressively deteriorating function. This chronic process is produced by an overall burden of organ damage, but the pathophysiology remains poorly understood. Rates of chronic rejection in the lung, for example, have not substantially improved over the last decade, despite new immunosuppressive drugs and improvements in surgical procedure. We present a hypothesis that epithelial-to-mesenchymal transition is a common cause of chronic allograft failure. Research in this area may provide insights into chronic rejection of kidney, liver, and lung allografts that impact on future therapeutic strategies.


Subject(s)
Epithelial Cells/pathology , Heart Transplantation/pathology , Kidney Transplantation/pathology , Lung Transplantation/pathology , Mesoderm/pathology , Cell Differentiation , Humans , Transplantation, Homologous/pathology , Treatment Failure
17.
Thorax ; 59(5): 434-7, 2004 May.
Article in English | MEDLINE | ID: mdl-15115876

ABSTRACT

BACKGROUND: Donor organ shortage severely limits lung transplantation as a therapeutic option, yet many potential donor lungs are deemed unsuitable by clinical selection criteria. METHODS: Of 39 consecutive potential donor lungs, 14 were accepted and 25 excluded by clinical selection criteria. All were evaluated prospectively by clinical assessment, bronchoscopy, and bronchoalveolar lavage (BAL) to evaluate objectively the discrimination of pulmonary infection and injury. RESULTS: Accepted donors were significantly younger than those excluded (mean (SD) age 36.7 (15.3) years v 49.5 (13.2) years; p = 0.009, unpaired t test) and were more likely to have suffered traumatic brain death (50% v 20%; p = 0.07, Fisher's exact test). Oxygenation (PaO(2):FiO(2)) was higher in accepted donors than in excluded donors (median (range) 63.2 (48-82.5) kPa v 43.1 (7.7-71.7) kPa; p = 0.0001, Mann-Whitney test). Positive formal BAL culture was more frequent in accepted donors (75%) than in those excluded (43%; p = 0.1, Fisher's exact test). There was no significant difference in the percentage and concentration of neutrophils in BAL fluid between accepted and excluded donors (median (range) 37.9 (0-96.9)% and 44.6 (0-1190)x10(3)/ml v 36 (1-98.1)% and 46 (0.2-1457)x10(3)/ml), nor in the BAL fluid concentration of tumour necrosis factor-alpha (140 (0-340) pg/ml v 160 (0-760) pg/ml) or interleukin 8 (810 (33-17 600) pg/ml v 540 (0-15 110) pg/ml). CONCLUSION: Current selection criteria are poor discriminators of pulmonary injury and infection and lead to the exclusion of potentially usable donor lungs.


Subject(s)
Lung Transplantation/methods , Lung/physiology , Tissue Donors , Tissue and Organ Procurement/methods , Adult , Humans , Middle Aged , Prospective Studies , Tissue and Organ Procurement/standards
19.
Pediatr Transplant ; 7(1): 59-63, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12581330

ABSTRACT

We report on survival, rejection, lymphoma and renal function following cardiac transplant using a steroid-free maintenance immunosuppressive regimen. We have performed 73 cardiac transplants in 71 children under 16 yr of age in the last 12 yr. There were eight perioperative and four late deaths giving actuarial survival of 88, 88, 85 and 70% at 1, 2, 5 and 10 yr, respectively. A total of 11 (15.3%) children had one episode of rejection (grade 3) in the first 6 months; one died and one was re-transplanted because of rejection. There was only one episode of late rejection (8 yr post-transplant) because of low drug levels in a patient with lymphoma and sepsis. This patient did not survive. Three other children (5.6%) also developed lymphoma and recovered but one died subsequently of graft failure. Four children have developed severe renal failure (glomerular filtration rate GFR <30 mL/min/m2). Two have not survived and one is expected to commence dialysis soon. The remainder have mild to moderate renal impairment. We report excellent survival and low rejection rates without use of long-term steroids. However the doses of cyclosporin used have had a significant effect on renal function in many cases.


Subject(s)
Heart Transplantation , Immunosuppressive Agents/therapeutic use , Methylprednisolone/therapeutic use , Adolescent , Azathioprine/therapeutic use , Child , Child, Preschool , Cyclosporine/therapeutic use , Graft Rejection , Heart Transplantation/adverse effects , Heart Transplantation/mortality , Humans , Infant , Prednisolone/therapeutic use , Retrospective Studies , Survival Rate
20.
J Thorac Cardiovasc Surg ; 122(6): 1162-6, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11726891

ABSTRACT

OBJECTIVE: This study investigated the effects of cardiopulmonary bypass on neutrophil expression of chemokine receptors, CXCR1 and CXCR2, and the beta2 integrin CD11b. METHODS: Ten patients undergoing coronary artery grafting with cardiopulmonary bypass were studied. Blood samples were collected preoperatively, before bypass, at termination of bypass, and 12 to 18 hours postoperatively. In vitro studies were performed on control subjects to determine changes in the surface expression of CXCR1, CXCR2, and CD11b on stimulation with interleukin 8. Receptor expression was measured by flow cytometry. Plasma levels of interleukin 8 from the patients were determined by enzyme-linked immunoassay. RESULTS: After bypass, CXCR2 expression fell by 66% (P <.0001) and remained low postoperatively (P <.0001). CXCR1 expression persisted at preoperative levels. CD11b expression increased significantly after bypass (P <.0001), returning to prebypass levels postoperatively. In vitro studies showed a dose-related fall of both CXCR1 (P <.0001) and CXCR2 expression (P <.0001) and a significant rise in CD11b expression (P <.0001). Plasma interleukin 8 increased significantly after bypass (P <.0001), remaining elevated 12 to 18 hours postoperatively (P =.02). Correlations between interleukin 8 levels and CXCR2 expression (P <.0001) and CD11b expression (P <.03) were demonstrated. CONCLUSIONS: CXCR2 expression is significantly down-regulated after bypass; in contrast, CXCR1 expression remains unchanged. In addition, whereas interleukin 8 is an important determinant of both CXCR1 and CXCR2 expression in vitro, it only correlates with CXCR2 and CD11b expression in vivo. This has implications in the search for antagonists against CXC chemokines and their receptors.


Subject(s)
Cardiopulmonary Bypass , Neutrophils/metabolism , Receptors, Interleukin-8A/metabolism , Receptors, Interleukin-8B/metabolism , Coronary Artery Bypass , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Humans , Interleukin-8/blood , Macrophage-1 Antigen/metabolism , Male , Middle Aged
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