Per Wierup

Transplantation of lungs from non–heart-beating donors after functional assessment ex vivo

BACKGROUND If lungs from patients dying of heart attacks are to serve as donor organs in a safe way, their function should be properly assessed before transplantation. The aim of this study was to investigate donor lung function evaluation in a realistic large animal model. METHODS Twelve 60-kg pigs were used. Five minutes after ventricular fibrillation was induced, cardiopulmonary resuscitation was initiated and maintained for 20 minutes. After a 10-min hands-off period, heparin was administered through a central venous catheter followed by 20 chest compressions. Intrapleural cooling was initiated after 65 minutes of warm ischemia. Cooling proceeded for 6 hours within the cadaver, after which lung function was assessed ex vivo. Recipient pigs underwent left lung transplantation followed by right pneumonectomy, thus making these animals 100% dependent for their survival on the function of the donor lungs. RESULTS The assessment showed that all lungs had adequate function to serve as donor lungs. All recipient animals were in good condition during the 24-hour observation period after the operation. The blood gas function did not differ significantly from that in the healthy donor animals before induction of ventricular fibrillation; pulmonary vascular resistance was within normal range. CONCLUSIONS Lungs from non-heart-beating donors topically cooled in situ for 6 hours after 65 minutes of warm ischemia were assessed ex vivo and found to have normal function. They were then transplanted and retained normal function during a 24-hour observation period.

Ventricular Septal Rupture Complicating Acute Myocardial Infarction: Clinical Characteristics and Contemporary Outcome

BACKGROUND The objective of this paper was to study the patient characteristics and contemporary short- and long-term outcome in patients with postinfarct ventricular septal rupture. METHODS Based on patient files and register data we performed a review of 64 consecutive patients with ventricular septal rupture complicating acute myocardial infarction, admitted to our tertiary center. RESULTS The mean age of the patients was 70 +/- 7. The median time was five days from onset of symptoms to the diagnosis of the ventricular septal rupture. The overall 30-day, one-, and five- year mortalities were 62%, 72%, and 95%, respectively. Medical treated patients (n = 19) had a 30-day mortality of 100%. Among surgically treated patients (n = 45) the survival at one month, one and five years was 71%, 48%, and 32%, respectively. History of hypertension, complicating congestive heart failure, and age were associated with poor outcome. CONCLUSIONS Despite improvements in medical and interventional techniques the early as well as the long-term prognosis remains poor in this contemporary series.

Comparative outcome of double lung transplantation using conventional donor lungs and non-acceptable donor lungs reconditioned ex vivo

A method to evaluate and recondition lungs ex vivo has been tested on donor lungs that have been rejected for transplantation. In the present paper, we compare early postoperative course between the six patients who received reconditioned lungs and the patients who received conventional donor lungs during the same period of time. During 2006 and 2007, a total of 21 patients underwent double sequential lung transplantation at the University Hospital of Lund. Six of those patients received reconditioned lungs. The other 15 patients received conventional donor lungs for transplantation without reconditioning ex vivo. The results are presented as median and interquartile range. Time in intensive care unit (days) between recipients of reconditioned lungs [13 (5-24) days], and recipients of conventional donor lungs [7 (5-12) days], P=0.44. Total hospital stay after transplantation (days) between recipients of reconditioned lungs [52 (47-60) days] and recipients of conventional donor lungs [44 (37-48) days], P=0.9. Ex vivo lung evaluation and reconditioning might not prolong early postoperative course in double lung transplantation. However, given the small number of patients, there might be a failure to detect a difference between the two groups.

Cardiac surgery in patients with haemophilia.

Abstract.  Today the populations of haemophilia patients in many countries have a higher life expectancy than previously known, and age‐related disorders such as arterial disease are expected to become more prevalent, calling for surgical intervention. Cardiac surgery constitutes a major haemostatic challenge because of sternotomy, the need of total heparinization, extracorporal circulation, mild hypothermia and cardiac arrest. To evaluate our current experience and results with cardiac surgery in patients with haemophilia the present case series report on six patients with haemophilia A (Severe = 1, Moderate = 1, Mild = 4) undergoing cardiac surgery (coronary artery bypass grafting; CABG = 2, aortic valve replacement = 1, CABG + aortic valve replacement = 2, ventricular resection + mitral valve reconstruction = 1). The present paper provides detailed information on the haemostatic treatment regimens adopted (factor concentrate dosages, timing and duration) and postoperative thromboprophylaxis (dosing and duration of low molecular weight heparin). Moreover, we present data on concomitant disorders (hypertension, hypercholesterolaemia, atrial fibrillation and diabetes), left ventricle ejection fraction (30–60%), type of anaesthesia, total amount of heparin (34 500–53 500 IU) and duration of extracorporeal circulation (80–115 min). Clinical outcomes included: re‐operation because of bleeding (none), transfusion requirements, peri‐ and postoperative blood loss and complications and postoperative development of inhibitors (none). Clinical outcomes were compared with a control group of patients (n = 5993) without haemophilia and we found no difference in postoperative morbidity. Adopting meticulously supervised haemostatic treatment regimens, we have successfully performed major cardiac surgery in patients with haemophilia A. The clinical outcome as well as the severity and incidence of postoperative complications were similar to patients without haemophilia.

Is anterior leaflet repair always necessary in repair of bileaflet mitral valve prolapse

BACKGROUND Traditionally, bileaflet prolapse has been treated by posterior leaflet resection combined with one of a number of procedures designed to support the anterior leaflet. However, most patients with bileaflet prolapse do not have important anterior chordal pathology. This study was undertaken to evaluate the effectiveness of a strategy of posterior leaflet resection and annuloplasty alone for patients with bileaflet prolapse and no anterior chordal rupture or severe anterior chordal elongation. METHODS From 1993 to 1997, 93 patients with transesophageal echocardiography (TEE) demonstrated bileaflet prolapse and without anterior chordal rupture or important anterior chordal elongation had primary isolated mitral valve repair consisting only of posterior leaflet resection (quadrangular in 28 and sliding in 65) and annuloplasty (Cosgrove-Edwards in 83, pericardial in 9, and Carpentier-Edwards in 1). All patients had severe mitral regurgitation documented by intraoperative TEE. Mean age was 55+/-13 years; 60% were men. RESULTS Postrepair, mitral regurgitation was 0 to trace in 93% and 1+ in 7%. There were no operative deaths. Late follow-up was available in all patients, with 277 patient-years of follow-up available for analysis. Five-year actuarial survival was 95%. At a mean interval of 2.3+/-1.3 (SD) years, echocardiography demonstrated no or trace mitral regurgitation in 65%, 1+ in 28%, and 2+ in 7%. No correlates of late mitral regurgitation were identified by multivariable analysis. No patient has required reoperation. CONCLUSIONS In the absence of significant anterior chordal pathology, a strategy of posterior leaflet resection and annuloplasty corrects anterior leaflet prolapse and mitral regurgitation, and provides a durable repair without the necessity of additional procedures on the anterior leaflet.

How to Recondition Ex Vivo Initially Rejected Donor Lungs for Clinical Transplantation: Clinical Experience from Lund University Hospital

A major problem in clinical lung transplantation is the shortage of donor lungs. Only about 20% of donor lungs are accepted for transplantation. We have recently reported the results of the first six double lung transplantations performed with donor lungs reconditioned ex vivo that had been deemed unsuitable for transplantation by the Scandiatransplant, Eurotransplant, and UK Transplant organizations because the arterial oxygen pressure was less than 40 kPa. The three-month survival of patients undergoing transplant with these lungs was 100%. One patient died due to sepsis after 95 days, and one due to rejection after 9 months. Four recipients are still alive and well 24 months after transplantation, with no signs of bronchiolitis obliterans syndrome. The donor lungs were reconditioned ex vivo in an extracorporeal membrane oxygenation circuit using STEEN solution mixed with erythrocytes, to dehydrate edematous lung tissue. Functional evaluation was performed with deoxygenated perfusate at different inspired fractions of oxygen. The arterial oxygen pressure was significantly improved in this model. This ex vivo evaluation model is thus a valuable addition to the armamentarium in increasing the number of acceptable lungs in a donor population with inferior arterial oxygen pressure values, thereby, increasing the lung donor pool for transplantation. In the following paper we present our clinical experience from the first six patients in the world. We also present the technique we used in detail with flowchart.

Bronchial healing, lung parenchymal histology, and blood gases one month after transplantation of lungs topically cooled for 2 hours in the non-heart-beating cadaver

BACKGROUND The aim of this study was to investigate, in an experimental survival model, the functional and morphologic results of lung transplantation using lungs from non-heart-beating donors. METHODS Left lungs, topically cooled to 25 degrees C for 2 hours in situ after 5 minutes of circulatory arrest followed by 26 minutes of unsuccessful cardiopulmonary resuscitation, were transplanted into syngeneic rats. Five weeks after the transplantation, right pneumonectomy was performed and blood gases measured after 60 minutes. In a control group, fresh donor lungs were used for transplantation and comparison was made with the cadaver group and a group of normal rats after right pneumonectomy. Morphologic changes were evaluated by semiquantitative scoring of 13 different parameters to obtain a total histologic index for each rat. RESULTS Computerized tomography scans of the chest made during the third post-operative week showed normal lung parenchyma in both groups, and at 5 weeks there were no significant differences in blood gases. The bronchial anastomoses showed normal healing in all cases. The histologic changes in the lung parenchyma were generally mild and focal, primarily consisting of interstitial and perivascular mononuclear inflammation, bronchial inflammation and athelectasis. Surprisingly, the transplanted controls demonstrated the most pronounced changes, although only the difference in total histologic index between groups was significant. CONCLUSIONS Lungs from non-heart-beating donors, topically cooled in the cadaver for two hours after failed resuscitation, showed normal bronchial healing and favorable parenchymal histology compared to transplanted control lungs 5 weeks after transplantation.

Gas exchange function one month after transplantation of lungs topically cooled for 2 hours in the non-heart-beating cadaver after failed resuscitation

BACKGROUND If lungs from subjects dying of heart attacks could be used for transplantation, the lung donor shortage could be radically reduced. The aim of this study was to investigate, in an experimental survival model, the results of lung transplantation using lungs from non-heart-beating donors. METHODS The left lung, topically cooled to 25 degrees C for 2 hours in situ after 5 minutes of circulatory arrest and 26 minutes of unsuccessful cardiopulmonary resuscitation, was transplanted into a syngeneic rat. Five weeks after the transplantation, right pneumonectomy was performed and blood gases measured every 10 minutes for 1 hour. Comparison were made with two control groups, one where fresh donor lungs were transplanted and another where only right pneumonectomy was done. RESULTS All animals survived and were in good condition at the end of the observation period. There was no statistically significant difference in arterial oxygen or carbon dioxide tension between the groups. The bronchial anastomoses showed normal healing in all cases. CONCLUSION Lungs from non-heart-beating donors topically cooled in situ to 25 degrees C for 2 hours before being harvested showed excellent gas exchange and bronchial healing 5 weeks after transplantation.

Impact of papillary muscle relocation as adjunct procedure to mitral ring annuloplasty in functional ischemic mitral regurgitation.

Background— The optimal surgical treatment in functional ischemic mitral regurgitation (FIMR) remains controversial. Recently, a posterior papillary muscle relocation (PMR) technique as adjunct procedure to ring annuloplasty has been proposed to prevent recurrent FIMR. In the present study, we used 3D cardiac MRI to assess the impact of relocating both papillary muscles as adjunct procedure to downsized ring annuloplasty on mitral leaflet coaptation geometry in FIMR pigs. Methods and Results— Eleven FIMR pigs were randomized to downsized ring annuloplasty (RA; n=6) or RA combined with PMR (RA+PMR, n=5). In the RA+PMR group, a 2–0 Gore-Tex suture was attached to each trigone, exteriorized through the corresponding papillary muscle, mounted on an epicardial pad, and tightened to relocate the myocardium adjacent to the anterior and posterior papillary muscles 5 and 15 mm, respectively. Using 3D MRI, the impact from these interventions on leaflet geometry was assessed. The distance from the posterior papillary muscle to the anterior trigone was reduced significantly more (median values) in the RA+PMR compared with RA animals at end-diastole (−7.9% versus 3.8%, P<0.01) and end-systole (−9.7% versus 2.5%, P=0.02). Accordingly, lateral tethering of the coaptation point (median values) was reduced significantly more in RA+PMR compared with RA animals (−42.8% versus −29.1%, P<0.01). Conclusions— Adding papillary muscle relocation to downsized ring annuloplasty reduced lateral leaflet tethering in a porcine experimental model of FIMR. Therefore, this technique holds promise for reducing persistent and recurrent FIMR in patients.

Procalcitonin in 759 patients clinically suspected of infective endocarditis.

BACKGROUND diagnostic delay contributes to high morbidity and mortality in infective endocarditis. A readily available diagnostic marker of infective endocarditis is desirable. S-procalcitonin has been proposed as a candidate, but data on its yield are conflicting. We tested its diagnostic value in a large population of patients seen in a tertiary center. METHODS this prospective study included 759 consecutive patients referred for echocardiographic examination on clinical suspicion of infective endocarditis. Transthoracic echocardiography was followed by immediate transesophageal examination, and a blood sample was obtained for procalcitonin analysis. Infective endocarditis was diagnosed by an interdisciplinary team and confirmed according to the Duke criteria. The team was unaware of the results of procalcitonin analyses. RESULTS infective endocarditis was present in 147 patients (19%). Procalcitonin was higher in these patients than in those in whom infective endocarditis was rejected (median, 0.21 ng/mL vs. 0.13 ng/mL; P <.0005). Multivariate analysis identified significant independent determinants of high procalcitonin: blood culture with endocarditis-typical microorganisms (odds ratio [OR], 2.81), temperature ≥ 38°C (OR, 2.61), symptoms ≤ 5 days (OR, 2.39), immunocompromised status (OR, 1.74), and male gender (OR, 1.61). Tests at various procalcitonin thresholds yielded an acceptable sensitivity of 95% at 0.04 ng/mL, but specificity was only 14%. Only 12% had procalcitonin below this threshold, which might justify postponement of further examinations for infective endocarditis. CONCLUSIONS procalcitonin was significantly higher in patients with infective endocarditis than in patients without infective endocarditis and bacteremia with endocarditis-typical organisms was the strongest independent determinant of high procalcitonin. The clinical importance of this is questionable, because a suitable procalcitonin threshold for diagnosing or excluding infective endocarditis was not established.