Long-term follow-up of a patient with JAG1-associated retinopathy.

PURPOSE: To report the long-term structural and functional changes in the posterior segments of an adult with an unusual retinal dystrophy caused by a novel mutation in JAG1. METHODS: A 33-year-old female underwent comprehensive ophthalmic examination, including best corrected visual acuity (BCVA) measurement, dilated fundus imaging (wide-angle fundus colour and short wavelength autofluorescence imaging), macular and peripheral spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG) at baseline and 10 years later at the age of 43. The patient also underwent systemic review with detailed cardiac, brain and renal investigations. During follow-up, genetic analysis using whole-exome sequencing was performed on the patient and her parents to identify disease-causing variants. RESULTS: The patient's main complaint was of a recent onset of bilateral photophobia and blurred vision in the left eye. On examination, the most striking retinal finding was of bilateral well-demarcated, anterior circumferential chorioretinal atrophy with scattered pigment clumping from the mid periphery to the ora. In addition, she had posterior pole RPE hypopigmentation, peripapillary chorioretinal atrophy, left macular choroidal folds and retinal vasculature tortuosity with atypical branching. Her retinal electrophysiology was consistent with a cone rod photoreceptor dystrophy and left macular dysfunction. Ten years later, her BCVA, the anterior circumferential chorioretinal atrophy and her visual field constriction all remained stable. Her retinal electrophysiology demonstrated deterioration of left rod function, while cone dysfunction remained stable. Macular function deteriorated in both eyes. During follow-up, she was also noted to have progressive aortic root dilatation, posterior embryotoxon and an x ray diagnosis of butterfly vertebrae. Whole-exome sequencing revealed a novel c.2412C > A p.(Tyr804Ter) truncating mutation in JAG1 that was predicted to be pathogenic and suggested a diagnosis of Alagille syndrome. CONCLUSION: This is the first report of the long-term detailed follow-up of a patient with Alagille syndrome whose most striking ophthalmic finding was bilateral well-demarcated, anterior circumferential chorioretinal atrophy. During follow-up, this finding remained stable, suggesting that this may be developmental in origin. This is in contrast with the progressive deterioration in the posterior pole retinal and macular function.

Outcomes of lung transplantation in adults with bronchiectasis.

BACKGROUND: Lung transplantation is a well-established treatment for end-stage non-cystic fibrosis bronchiectasis (BR), though information regarding outcomes of transplantation remains limited. Our results of lung transplantation for Br are reported here. METHODS: A retrospective review of case notes and transplantation databases was conducted for patients that had underwent lung transplantation for bronchiectasis at the Freeman Hospital between 1990 and 2013. RESULTS: Fourty two BR patients underwent lung transplantation, the majority (39) having bilateral sequential lung transplantation. Mean age at transplantation was 47.1 years. Pre-transplantation osteoporosis was a significant non-pulmonary morbidity (48%). Polymicrobial infection was common, with Pseudomonas aeruginosa infection frequently but not universally observed (67%). Forced expiratory volume in 1 second (% predicted) improved from a pre-transplantation mean of 0.71 L (22% predicted) to 2.56 L (79 % predicted) at 1-year post-transplantation. Our survival results were 74% at 1 year, 64% at 3 years, 61% at 5 years and 48% at 10 years. Sepsis was a common cause of early post-transplantation deaths. CONCLUSIONS: Lung transplantation for end-stage BR is a useful therapeutic option, with good survival and lung function outcomes. Survival values were similar to other bilateral lung transplants at our centre. Pre-transplantation Pseudomonas infection is common.

Transventricular Cardioscopic Release of a Trapped Prosthetic Mitral Valve Leaflet.

Trapped prosthetic valve leaflets are a rare but challenging complication. A 68-year-old male patient had previously undergone redo aortic valve replacement. Postoperatively, he decompensated with severe mitral regurgitation, requiring extracorporeal membrane oxygenation and a salvage mitral valve replacement via right thoracotomy with very difficult access. This procedure was complicated by a trapped valve leaflet. He recovered well initially but presented 2 years later with worsening heart failure due to mitral stenosis and rising pulmonary artery pressures. Due to the high risk of sternotomy and right thoracotomy, a transventricular cardioscopic release of the trapped mitral valve leaflet was undertaken by left minithoracotomy. The procedure was successful, and the patient was discharged home on day 12. This novel minimally invasive approach, which does not require myocardial preservation, is ideal for high-risk patients with this rare complication and has not previously been described. We hope that by sharing our experience, others will consider this innovative approach.

Do older surgeons have safer hands? A retrospective cohort study.

BACKGROUND: For complex surgical procedures a volume-outcome relationship can often be demonstrated implicating multiple factors at a unit and surgeon specific level. This study aims to investigate this phenomenon in lung transplantation over a 30-year period with particular reference to surgeon age and experience, cumulative unit activity and time/day of transplant. METHODS: Prospective databases identified adult patients undergoing isolated lung transplantation at a single UK centre between June 1987 and October 2017. Mortality data was acquired from NHS Spine. Individual surgeon demographics were obtained from the General Medical Council. Student t-test, Pearson's Chi-squared, Logistic Regression, and Kaplan-Meier Survival analyses were performed using Analyse-it package for MicrosoftExcel and STATA/IC. RESULTS: 954 transplants (55.9% male, age 44.4 ± 13.8 years, 67.9% bilateral lung) were performed, with a median survival to follow-up of 4.37 years. There was no difference in survival by recipient gender (p = 0.661), between individual surgeons (p = 0.224), or between weekday/weekend procedures (p = 0.327). Increasing centre experience with lung transplantation (OR1.001, 95%CI: 1.000-1.001, p = 0.03) and successive calendar years (OR1.028, 95%CI: 1.005-1.052, p = 0.017) was associated with improved 5-year survival. Advancing surgeon age at the time of transplant (mean, 48.8 ± 6.6 years) was associated with improved 30-day survival (OR1.062, 95%CI: 1.019 to1.106, p = 0.003), which persisted 5 years post-transplant (OR1.043, 95%CI: 1.014-1.073, p = 0.003). Individual surgeon experience, measured by the number of previous lung transplants performed, showed a trend towards improved outcomes at 30 days (p = 0.0413) with no difference in 5-year survival (p = 0.192). CONCLUSIONS: Our study demonstrates a relationship between unit volume, increasing surgeon age and survival after lung transplantation. A transplant volume: outcome relationship was not seen for individual surgeons.

A human model of bilateral pulmonary vein sampling to assess the effects of one-lung ventilation on neutrophil function.

BACKGROUND: Neutrophil activation drives lung complications after cardiopulmonary bypass (CPB). Evidence suggests the healthy, ventilated lung may beneficially re-condition pro-inflammatory neutrophils. However, evidence in humans is lacking, due to a paucity of good models. CPB with simultaneous central venous and bilateral pulmonary vein sampling provides an opportunity to model effects of one-lung ventilation. The study's primary objectives were to establish a model of intra-operative, bilateral pulmonary vein sampling and to determine whether neutrophil function differed after passing through inflated or deflated lungs. METHODS: Seventeen patients having "on pump" coronary artery bypass grafting (CABG) with one-lung ventilation (in two cohorts with tidal volume 2ml kg-1 and FiO2 0.21, or tidal volume 4 ml kg-1 and FiO2 0.5 respectively) were recruited. Cohort 1 consisted of 9 patients (7 male, median age 62.0 years) and Cohort 2 consisted of 8 male patients (median age 65.5 years). Recruitment was via prospective screening of scheduled elective and non-elective CABG procedures with cardiopulmonary bypass. Each patient had five blood samples taken-central venous blood pre-operatively; central venous blood pre-CPB; central venous blood post-CPB; pulmonary venous blood draining the ventilated lung post-CPB; and pulmonary venous blood draining the deflated lung post-CPB. Neutrophil phagocytosis and priming status were quantified. Plasma cytokines were measured. RESULTS: Phagocytosis and priming were not significantly different in neutrophils returning from the ventilated lung as compared to the non-ventilated lung. Plasma IL-6, IL-8 and IL-10 were significantly elevated by CPB. CONCLUSIONS: The intra-operative, bilateral pulmonary vein sampling model provides unique opportunities to assess biological effects of interventions to one lung, with the other lung acting as an internal control. Single-lung ventilation during CPB had no significant effects on neutrophil function.

Extended trans-septal versus left atrial approach in mitral valve surgery: 1017 patients' experience.

OBJECTIVE: The mitral valve may be accessed directly through the left atrium but visualisation can sometimes be challenging. A trans-septal interatrial approach provides better exposure and easy access for concomitant tricuspid procedures especially in difficult cases. This retrospective study evaluates the safety and effectiveness of the extended vertical trans-septal approach (EVTSA) for routine mitral valve exposure. METHOD: 1017 consecutive patients undergoing an isolated primary mitral valve procedure (repair/replacement) through a median sternotomy were retrospectively studied between 2000 and 2015. Up to 135 patients were operated by EVTSA (group A) while 882 patients underwent a traditional left atrial (LA, group B) approach. RESULTS: There were 135 patients (M/F=56/79) in group A and 882 patients (M/F=398/484) in group B. Logistic EuroSCORE was significantly lower in EVTSA group (0.61 vs 0.90, p=0.000001). In the LA group there were more patients with preoperative transient ischaemic attack or stroke (94 vs 6, p=0.005). Cumulative cross-clamp time was 82 (44-212) min (EVTSA group) and 78 (30-360) min (LA group) (p=0.271) while cardiopulmonary bypass time was 107 (58-290) and 114 (43-602) min, respectively (p=0.121).Postoperative blood loss was 415 mL (EVTSA) vs 427 mL (LA) (p=0.273). No significant difference was found in the incidence of postoperative atrial fibrillation (p=0.22) or heart block requiring permanent pacemaker (p=0.14). CONCLUSION: In our opinion, EVTSA to the mitral valve is safe and reproducible. It gives excellent exposure of the mitral valve under all circumstances without any significant increase in cross-clamp or bypass time, postoperative arrhythmia, heart block/pacemaker rate or bleeding.

ISHLT Consensus Statement on adult and pediatric airway complications after lung transplantation: Definitions, grading system, and therapeutics.

Airway complications remain a major cause of morbidity and mortality after cardiothoracic transplantation. The reported incidence of airway ischemic complications varies widely, contributed to by the lack of a universally accepted grading system and standardized definitions. Furthermore, the majority of the existing classification systems fail to integrate the wide range of possible bronchial complications that may develop after lung transplant. Hence, a Working Group was created by the International Society for Heart and Lung Transplantation with the aim of elaborating a universal definition of adult and pediatric airway complications and grading system. One such area of focus is to understand the problem in the context of a more standardized consensus of classifying airway ischemia. This consensus definition will have major clinical, therapeutics, and research implications.

Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion.

Objectives: Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. Methods: In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. Results: Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1ß and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1ß concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. Conclusions: This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study.

Lung Transplant With Cardiopulmonary Bypass: Impact of Blood Transfusion on Rejection, Function, and Late Mortality.

BACKGROUND: Allogeneic blood transfusion has been associated with immune modulation in other solid organ transplants. Within cardiothoracic surgery, allogeneic blood transfusion is associated with greater postoperative morbidity and mortality. We investigated the impact of allogeneic blood transfusion on rejection, function, and late mortality within lung transplantation. METHODS: A retrospective review was made of 311 adult patients who underwent bilateral lung transplantation with cardiopulmonary bypass from 2003 to 2013. Patients were stratified based on the amount of blood products transfused within 24 hours of transplantation. Kaplan-Meier methods and multivariate Cox proportional hazards models were used for time to first rejection/death and all-cause mortality analyses. RESULTS: In all, 174 men and 137 women (mean age 41.4 ± 14.0 years) utilized a median number of 3 units (range, 0 to 40) of red blood cells (RBC), 2 units (range, 0 to 26) of fresh frozen plasma (FFP), and 1 unit (range, 0 to 7) of platelets within the first 24 hours of transplantation. Time to first treated rejection/death was not statistically different whether patients were transfused with more or less than the median number of units of RBC (unadjusted p = 0.233, adjusted hazard ratio [HR] 1.02, 95% confidence interval [CI]: 0.75 to 1.40, p = 0.177), FFP (unadjusted p = 0.146, adjusted HR 1.29, 95% CI: 0.95 to 1.76, p = 0.108), or platelets (unadjusted p = 0.701, adjusted HR 0.74, 95% CI: 0.47 to 1.15, p = 0.177). Rate of rejection and number of rejection episodes per patient at 1 year after transplant were not statistically different. Forced expiratory volume in 1 second expressed as percentage of forced vital capacity at 3 and 6 months was similar for all groups. Unadjusted early all-cause mortality was not influenced by RBC (p = 0.162) or FFP (p = 0.298) but was significantly different with more platelets (p = 0.032). Adjusted 10-year mortality showed no significant differences for RBC (HR 1.12, 95% CI: 0.70 to 1.79, p = 0.645), FFP (HR 1.24, 95% CI: 0.78 to 1.97, p = 0.356), or platelets (HR 1.49, 95% CI: 0.84 to 2.64, p = 0.172.). CONCLUSIONS: All blood products administration regardless of amount transfused did not appear to affect early rejection outcomes or forced expiratory volume in 1 second expressed as percentage of forced vital capacity at 3 and 6 months. Use of RBC and FFP had no effect on survival. However, greater platelet usage appeared to adversely affect early but not late mortality.

International Expert Consensus on Sutureless and Rapid Deployment Valves in Aortic Valve Replacement Using Minimally Invasive Approaches.

OBJECTIVE: To define the benefit of sutureless and rapid deployment valves in current minimally invasive approaches in isolated aortic valve replacement. METHODS: A panel of 28 international experts with expertise in both minimally invasive aortic valve replacement and rapid deployment valves was constituted. After thorough literature review, the experts rated evidence-based recommendations in a modified Delphi approach. RESULTS: No guideline could be retrieved. Thirty-three clinical trials and 9 systematic reviews could be identified for detailed text analysis to obtain a total of 24 recommendations. After rating by the experts 12, final recommendations were identified: preoperative computed tomographic scan as well as intraoperative transesophageal echocardiography are highly recommended. Suitable annular sizes are 19 to 27 mm. There is a contraindication for bicuspid valves only for type 0 and for annular abscess or destruction due to infective endocarditis. The use of sutureless and rapid deployment valves reduces extracorporeal circulation and aortic cross-clamp time and leads to less early complications as prolonged ventilation, blood transfusion, atrial fibrillation, pleural effusions, paravalvular leakages and aortic regurgitation, and renal replacement therapy, respectively. These clinical outcomes result in reduced intensive care unit and hospital stay and reduced costs. The use of sutureless and rapid deployment valves will lead to a higher adoption rate of minimally invasive approaches in aortic valve replacement. Respect should be taken to a necessary short learning curve for both sutureless and minimally invasive programs. CONCLUSIONS: Sutureless and rapid deployment aortic valve replacement together with minimally invasive approaches offers an attractive option in aortic valve placement for patients requiring biological valve replacement.

Sutureless, rapid deployment valves and stented bioprosthesis in aortic valve replacement: recommendations of an International Expert Consensus Panel.

OBJECTIVES: After a panel process, recommendations on the use of sutureless and rapid deployment valves in aortic valve replacement were given with special respect as an alternative to stented valves. METHODS: Thirty-one international experts in both sutureless, rapid deployment valves and stented bioprostheses constituted the panel. After a thorough literature review, evidence-based recommendations were rated in a three-step modified Delphi approach by the experts. RESULTS: Literature research could identify 67 clinical trials, 4 guidelines and 10 systematic reviews for detailed text analysis to obtain a total of 28 recommendations. After rating by the experts, 12 recommendations were identified and degree of consensus for each was determined. Proctoring and education are necessary for the introduction of sutureless valves on an institutional basis as well as for the individual training of surgeons. Sutureless and rapid deployment should be considered as the valve prosthesis of first choice for isolated procedures in patients with comorbidities, old age, delicate aortic wall conditions such as calcified root, porcelain aorta or prior implantation of aortic homograft and stentless valves as well as for concomitant procedures and small aortic roots to reduce cross-clamp time. Intraoperative transoesophageal echocardiography is highly recommended, and in case of right anterior thoracotomy, preoperative computer tomography is strongly recommended. Suitable annular sizes are 19-27 mm. There is a contraindication for bicuspid valves only for Type 0 and for annular abscess or destruction due to infective endocarditis. Careful but complete decalcification of the aortic root is recommended to avoid paravalvular leakage; extensive decalcification should be avoided not to create annular defects. Proximal anastomoses of concomitant coronary artery bypass grafting should be placed during a single aortic cross-clamp period or alternatively with careful side clamping. Available evidence suggests that the use of sutureless and rapid deployment valve is associated with (can translate into) reduced early complications such as prolonged ventilation, blood transfusion, atrial fibrillation, pleural effusions and renal replacement therapy, respectively, and may result in reduced intensive care unit and hospital stay in comparison with traditional valves. CONCLUSION: The international experts recommend various benefits of sutureless and rapid deployment technology, which may represent a helpful tool in aortic valve replacement for patients requiring a biological valve. However, further evidence will be needed to reaffirm the benefit of sutureless and rapid deployment valves.

Palliative care in cardiopulmonary transplantation.

Cardiopulmonary transplantation is a life-prolonging therapy available to a select population of patients with cardiac or respiratory failure. Transplantation is associated with significant morbidity, mortality and unmet palliative care need. Despite recommendations that palliative care should be a core component of the heart and lung transplant process, collaboration within clinical practice is extremely rare. A key reason for this is the misperception among patients, their families and transplant clinicians, that palliative care is analogous with end of life care. Other challenges include prognostication, communication, and the balance of hope and reality. We suggest a change in clinical practice within cardiopulmonary transplantation, whereby palliative care takes place alongside active management. Greater partnership working will demonstrate clinical credibility and highlight the impact of palliative care interventions. Education is required to address current misperceptions and further research should explore the effect of initiatives to improve palliative care provision for this patient group.

Unusual cause of hypoxemia after automatic implantable cardioverter-defibrillatorleads extraction.

The indication of pacemaker/AICD removal are numerous. Serious complication can occur during their removal, severe tricuspid regurgitation is one of the complication. The occurrence of PFO is not uncommon among adult population. Shunting across PFO in most circumstance is negligible, but in some necessitates closure due to hypoxemia. We report a case of 62 year old man, while undergoing AICD removal, had an emergency sternotomy for cardiac tamponade. Postoperatively, he experienced profound hypoxemia refractory to oxygen therapy. Transthoracic Echocardiogram was performed to rule out intracardiac shunts at an early stage, but it was difficult to obtain an good imaging windows poststernotomy. A small pulmonary emboli was noted on CTPA, but was not sufficient to account for the level of hypoxemia and did not resolve with anticoagulation. Transesophageal echocardiogram showed flail septal tricuspid valve with severe TR and bidirectional shunt through large PFO. Patient was posted for surgery, tricuspid valve was replaced and PFO surgically closed. Subsequently, patient recovered well ad was discharged to home. Cause of hypoxemia might be due to respiratory or cardiac dysfunction. But for hypoxemia refractory to oxygen therapy, transoesophageal echocardiogram should be always considered and performed early as an diagnostic tool in post cardiac surgical patients.

Pentoxifylline is as effective as leukocyte depletion for modulating pulmonary reperfusion injury.

OBJECTIVE: Previous studies have suggested the amelioration of lung reperfusion injury when initial reperfusion is undertaken with leukocyte-depleted blood. Pharmacologic agents, such as pentoxifylline, are also effective, but no previous studies have demonstrated which is superior. We investigated these agents in a porcine model of left single-lung transplantation. METHODS: Donor lungs were preserved with modified Euro-Collins solution for a mean ischemic time of 18.6 hours. Gas exchange, pulmonary vascular resistance, neutrophil elastase level, and free radical release (measured on the basis of malonaldehyde levels) were assessed over a 12-hour period. Group A (n = 5) was a control group with no interventions added. Group B was reperfused through an extracorporeal circuit incorporating a leukocyte-depleting filter for 30 minutes before conventional blood flow was restored. Group C was reperfused with the addition of intravenous pentoxifylline (2 mg x kg(-1) x h(-1)). RESULTS: Groups B and C were similar in terms of oxygenation, pulmonary vascular resistance, and free radical release. Group B displayed increased levels of neutrophil elastase. Both groups were superior with regard to these outcome measures compared with control group A. CONCLUSIONS: Pentoxifylline, when administered to recipient animals, attenuates reperfusion injury to a degree similar to that seen with leukocyte-depleted reperfusion. This technique is simple, safe, and as effective as using a more complex extracorporeal circuit incorporating a leukocyte-depleting filter to ameliorate acute lung injury.

Clinical and hemodynamic evaluation of small Perimount aortic valves in patients aged 75 years or older.

BACKGROUND: There is the potential for iatrogenic aortic stenosis and poor quality of life when small aortic valve bioprostheses are used in elderly patients. The alternative is enlarging the aortic annulus to accommodate larger size prostheses, increasing operative mortality. It was hoped that bovine pericardial valves would improve hemodynamic performance in the smaller valve sizes. METHODS: To determine long-term results and in vivo hemodynamic performance of small-size aortic Carpentier-Edwards bovine pericardial valves (Perimount) in elderly patients, we analyzed our follow-up and echocardiographic data from patients 75 years of age or older receiving isolated 19-mm and 21-mm Perimount valves. Ninety-four patients with a mean age of 77 +/- 2.2 years were followed for 12 years. Seventeen patients with 19-mm and 25 patients with 21-mm Perimount valves underwent transthoracic echocardiograms. RESULTS: Operative mortality was 6.3% (6 of 94). Twelve-year survival was 82.7%. Freedom from thromboembolism was 86.9% at 12 years. Two patients had anticoagulation-related bleeding. Overall New York Heart Association class decreased from 3 +/- 1 to 1.6 +/- 0.7 at the end of follow-up. Hemodynamic performances were satisfactory in both 19-mm and 21-mm Perimount valves, with low peak and mean transvalvular gradients and good effective orifice areas, orifice area indices, and performance indices. CONCLUSIONS: Perimount aortic valve in the small aortic annulus has yielded excellent long-term results and hemodynamic performances. Perimount is a very satisfactory option in elderly patients. Implantation of a Perimount bioprosthesis avoids enlargement of the small aortic annulus, reducing mortality and morbidity associated with this procedure.

Improvements in lung compliance after pulmonary transplantation: correlation with interleukin 8 expression.

OBJECTIVE: Previous studies have suggested reductions in lung reperfusion injury when initial reperfusion is undertaken with the addition of pharmacological modulators. We investigated three pharmacological agents in a porcine model of left single lung transplantation to determine the effect on lung compliance and its relationship with the expression of the cytokine, interleukin-8 (IL-8). METHODS: Donor lungs were preserved with modified Euro-Collins for a mean ischaemic time of 18.6 h. Pulmonary venous oxygenation, lung compliance and IL-8 expression were assessed over a 12-h period. Group A (n=5) was a control group with no interventions added, Group B was reperfused with the addition of intravenous inositol hexakisphosphate (InSP6) (0.02 mg/kg per min), Group C received the nitric oxide donor, 3-morpholinosydnonimine (SIN-1) (0.02 mg/kg per min) and Group D received intravenous Pentoxifylline (2 mg/kg per h). All interventions were administered at a pulmonary artery pressure of 20 mmHg. RESULTS: Group D yielded the best oxygenation (P=0.0041) while Groups B and C were similar. All were superior to Group A (P<0.001). Lung compliance was significantly improved in Groups B, C and D compared to group A. In Group D, the greatest improvements in lung compliance were observed (P<0.0001). Similar observations were seen with regard to pulmonary vascular resistance. IL-8 expression was delayed until after 30 min of reperfusion in Group D, but was evident after 10 min in all the other groups. This correlates with the compliance and oxygenation data. CONCLUSIONS: The addition of InSP6 or SIN-1 at reperfusion significantly attenuates reperfusion injury compared with controls and improves lung compliance. The unique comparison with Pentoxifylline afforded by this study indicates that at the doses studied Pentoxifylline appears to be superior, correlating with a greater inhibition of IL-8 expression.

First report of no-react bovine internal mammary artery performance and patency.

BACKGROUND: No-React treatment is known to render tissues resistant to calcific degeneration and to reduce early inflammatory response. No-React bovine internal mammary artery (NR-IMA) is available for restricted use in Europe. In this first study, our aim was to use magnetic resonance imaging (MRI) to investigate the clinical performance and patency rates of this conduit. METHODS: Seven patients received 8 grafts with NR-IMA. Approval from the Medical Devices Agency of the United Kingdom was obtained for use of this material. One patient needed salvage coronary artery bypass grafting (CABG). Graft patency was investigated with cardiac MRI. One patient was excluded from the MRI study because of the presence of intracerebral metal clips. The mean follow-up period was 2.5 years with a range of 1 to 4.5 years. RESULTS: There was no mortality in this group. After treatment 6 patients were asymptomatic, and 1 patient had class II anginal symptoms. Four (57%) of the 7 NR-IMA grafts remained patent. The longest patency was 4.5 years in a patient who underwent salvage CABG. Other associated grafts in this cohort of patients were 5 left internal mammary arteries (all patent), 1 radial artery graft (patent), and 7 saphenous vein grafts (4 [57%] of 7 patent). There were no occluded NR-IMA grafts in a patient with patent vein grafts. CONCLUSION: We concluded that at 2.5 year follow-up, NR-IMA had a patency rate of 57% (4 of 7 cases). This rate matched the vein graft patency rate in this cohort of patients. With the longest patency of 4.5 years, use of NR-IMA seems to hold promise for the future.

The effect of ex vivo lung perfusion on microbial load in human donor lungs.

BACKGROUND: Ex vivo lung perfusion (EVLP) has emerged as a technique to potentially recondition unusable donor lungs for transplantation. Beneficial effects of EVLP on physiologic function have been reported, but little is known about the effect of normothermic perfusion on the infectious burden of the donor lung. In this study, we investigated the effect of EVLP on the microbial load of human donor lungs. METHODS: Lungs from 18 human donors considered unusable for transplantation underwent EVLP with a perfusate containing high-dose, empirical, broad-spectrum anti-microbial agents. Quantitative cultures of bacteria and fungi were performed on bronchoalveolar lavage fluid from the donor lung before and after 3 to 6 hours of perfusion. The identification of any organisms and changes in number of colony forming units before and after EVLP were assessed and anti-microbial susceptibilities identified. RESULTS: Thirteen out of 18 lungs had positive cultures, with bacterial loads significantly decreasing after EVLP. Yeast loads increased when no anti-fungal treatment was given, but were reduced when prophylactic anti-fungal treatment was added to the circuit. Six lungs were ultimately transplanted into patients, all of whom survived to hospital discharge. There was 1 death at 11 months. CONCLUSIONS: Our study shows that EVLP with high-dose, empirical anti-microbial agents in the perfusate is associated with an effective reduction in the microbial burden of the donor lung, a benefit that has not previously been demonstrated.

Vascular anastomotic complications in lung transplantation: a single institution's experience.

OBJECTIVES: Lung transplant recipients were reviewed to compare our early and current experience of vascular complications. Since 1995, we have had a policy of early identification and intervention. METHODS: We undertook a retrospective review of all adult lung transplants performed at our centre. Patients with pulmonary vascular complications before and after 1995 were identified and reviewed to determine changes in management and outcome. RESULTS: We identified a total of 13 patients with either pulmonary artery or venous obstruction out of a total of 720 adult lung transplants (1.8%). There were 9 females and 4 males with an age range of 25-64 years. Complications were more common in patients with fibrotic lung disease and involved 15 vascular anastomoses, most commonly the pulmonary arterial anastomosis. Prior to 1995, 5 cases were identified, all postoperatively. In this group, the mean time for identification of the complication was 9.4 (range 4-14) days. Only 1 patient survived to discharge. After 1995, vascular complications were identified intraoperatively in 4 cases and corrected immediately. Four cases were identified postoperatively (at <1-17 days) by a computed tomography pulmonary angiogram. Three were treated surgically within 24 h of diagnosis (using cardiopulmonary bypass with cold preservation). One patient was managed conservatively. Among patients identified after 1995, 5 survived to discharge. CONCLUSIONS: Though rare, pulmonary vascular complications after lung transplantation carry high mortality. In our opinion, early identification and intervention improves outcome. Intraoperative assessment by pressure gradient measurement and transoesophageal echocardiography is recommended. Despite this, mortality remains high and prevention is better than cure.