Bronchial arterial devascularization. An experimental study in pigs.

OBJECTIVE: The lungs have dual blood supply: The bronchial and the pulmonary circulation. The importance of bronchial circulation is disputed. The purpose of this study was to establish an experimental model to examine the importance of the bronchial artery. DESIGN: Comparative porcine experimental study. The surgical technique was evaluated in group A (n = 9). Group B (n = 8) underwent left bronchial arterial devascularization. In group C (n = 9) the left principal bronchus was devascularized, transsected, and reanastomosed. In groups B and C bronchial mucosal blood flow was studied with laser-Doppler velocimetry. Devascularization was controlled by angiography at section, and specimens were examined with conventional histology and scanning electron microscopy. The right bronchus served as control. RESULTS: In group B devascularization caused considerable, yet insignificant reduction in bronchial mucosal blood flow index (p = 0.1282) postoperatively, and after 1 week (p = 0.0678), insignificant histologic (p > 0.2) changes, and no scanning electron microscopy differences. In group C devascularization with bronchial transsection caused significant reduction in mucosal blood flow index (p = 0.0277) postoperatively and after 1 week (p = 0.0277), significant histologic changes (p = 0.0277), and insignificant (p = 0.069) changes in scanning electron microscopy. CONCLUSION: Bronchial arterial devascularization with transsection caused significant physiologic and morphologic changes, and a model with bronchial devascularization should include transsection.

Bronchial transsection and reanastomosis in pigs with and without bronchial arterial circulation.

BACKGROUND: The bronchial artery may be vital to the bronchi and lung parenchyma, but results of lung transplantation have raised doubts. This study was performed to examine the effect of bronchial arterial devascularization on bronchial morphology after bronchial transsection and reanastomosis. METHODS: In 6 pigs (study group), the left main bronchus was transsected, reanastomosed, and devascularized. Six control pigs had the same operation without devascularization. After 1 week, bronchial arterial angiography was performed, and specimens were examined with conventional histology and scanning electron microscopy. RESULTS: Histology showed significant changes (inflammation, edema, and fibrosis) in bronchi and lung parenchyma of the study group compared with the unoperated side (p = 0.028) and with the control group (p = 0.050). Scanning electron microscopy showed significant ciliary denudation in the study group's left bronchus compared with the unoperated side (p = 0.043) and with the control group (p = 0.0071). CONCLUSIONS: The loss of cilia of the bronchial epithelium and the occurrence of inflammation, edema, and fibrosis in bronchi and lung parenchyma 1 week postoperatively were significantly related to the absence of the bronchial arterial circulation.

[Circulatory support with the mechanical heart, "HeartMate"]. / Cirkulationsstøtte med Det mekaniske hjerte, "HeartMate".

Treatment with the mechanical heart, HeartMate, has been introduced in Denmark. Short-term circulatory support can be obtained by intraaortic balloon counterpulsation, an external centrifugal pump and the total artificial heart. Long-term circulatory support can be established by treatment with the HeartMate. The principle of the mechanical heart is simple--a pump is implanted in parallel to the existing heart and connected to external, portable batteries. The patient quickly improves and is brought in an optimal state for transplantation. A few patients have been able to omit the subsequent heart transplantation. The patient's own heart improved during the treatment and the native heart functioned again after the system was explanted. The main complications during treatment are bleeding, infection, thromboembolic events and systemic failure. Permanent, fully implantable mechanical circulatory pumps are under development--which may herald the beginning of a whole new era for treatment of cardiac failure.

[Economic aspects of implementation of the mechanical heart, "HeartMate"]. / Okonomiske betragtninger ved implementering af det mekaniske hjerte, "HeartMate".

This economic evaluation was performed to assess the economic consequences for society and for the Danish health care sector of replacing the traditional treatment with Biomedicus assist device with The Mechanical Heart, HeartMate, as a bridge to transplantation for patients with severe cardiac failure. A cost-effectiveness analysis showed that the use of HeartMate is more cost-effective than the use of Biomedicus assist device. Using HeartMate one life-year gained costs DKK 225,000. Using Biomedicus one life-year gained costs DKK 270,000. The use of HeartMate results in an additional expenditure of DKK 615,000 per patient. By this additional expenditure the patients gain 3.6 extra life-years on average. The marginal expenditure by replacing the Biomedicus treatment with HeartMate is DKK 170,000 per extra life-year gained.

Primary closure of deep sternal wound infection following open heart surgery: a safe operation?

BACKGROUND: Deep median sternotomy wound infection is a significant source of morbidity and mortality after cardiac operations. Management of an infected median sternotomy incision is a subject of controversy. The aim of this study was to assess our experience with primary closure without any irrigation system for infected deep median sternotomy wound. METHODS: Between January 1994 and December 1997, 4,227 consecutive open heart procedures via a median sternotomy under cardiopulmonary bypass were performed in our department. A total of 27 (0.64%) consecutive patients with deep sternotomy wound infection were identified. The mean age of the patients was 45 years. Six were female and 21 were male. RESULTS: The incidence of deep sternal wound infection was therefore 0.64%. The mean duration between the primary operation and the onset of deep sternal wound infection was 2.5 weeks. Staphylococcus aureus and Staphylococcus epidermidis were the most common pathogen causing postoperative mediastinal infection. Out of the 27 cases, 17 were successfully treated, 8 (30%) died and 2 had a persistent fistula. The mean follow-up time was 18 months (range 4 to 52 months). The mortality in the pediatric group was 4/8 (50%) and 4/19 (21%) in the adult group. The mortality for mediastinitis presenting before one week or after 4 weeks after operation was 63%. In contrast, the mortality for mediastinitis presenting after one week but before 4 weeks after operation was 17%. CONCLUSIONS: Mediastinitis after cardiac surgical procedures remains a devastating complication. Primary closure without irrigation-suction system should only be considered in selected patients.

Apoptosis and formation of peroxynitrite in the lungs of patients with obliterative bronchiolitis.

BACKGROUND: Obliterative bronchiolitis (OB) is the principal long-term complication of lung and heart-lung transplantation. OB is characterized histologically by inflammation, epithelial cell loss, fibrosis, and obliteration of the terminal airways. The contribution of apoptosis and peroxynitrite formation in OB was examined and assessed whether immunohistochemical markers of these reactions in transbronchial biopsy specimens were predictive of OB development. METHODS: Pulmonary tissue samples from lung transplant recipients with OB (n = 5) or without OB (control group; n = 7) were investigated by in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and nitrotyrosine immunohistochemistry. Furthermore, TUNEL and nitrotyrosine expression was compared between matched transbronchial biopsy specimens from the two patient groups. RESULTS: Sections with active OB displayed a significantly increased number of TUNEL-positive epithelial cells and macrophages compared with very little TUNEL in control specimens. TUNEL was almost absent in inactive OB. Nitrotyrosine was detected in all samples of pulmonary tissue, but nitrotyrosine expression was more intense in patients with active OB. There was no apparent temporospatial correlation of TUNEL and nitrotyrosine expression, and in matched transbronchial specimens, these immunohistochemical markers failed to identify patients with imminent risk of developing OB. CONCLUSIONS: Apoptosis contributes to the pathophysiology of active OB but is apparently not directly paralleled by tissue peroxynitrite formation. In transbronchial biopsy specimens, markers of apoptosis and peroxynitrite formation are not valid predictors of OB and more studies are required to deliniate the role of these mechanisms in pulmonary allograft rejection.

The porcine bronchial artery. Anastomoses with oesophageal, coronary and intercostal arteries.

Information about the existence and anatomy of arterial anastomoses with the porcine bronchial artery is lacking in the literature. Prior to basic physiological investigations in a porcine model related to lung transplantation with bronchial artery revascularisation, this study was designed to examine the anatomy of systemic arterial anastomoses with the bronchial artery system. Twenty pigs were studied in 3 groups. In 2 groups the heart-lung block was removed with all mediastinal structures. One group served for investigation of coronary-bronchial artery anastomoses and one for investigation of oesophageal-bronchial artery anastomoses. The systemic arteries to be examined were cannulated. The inflated heart-lung block was examined macroscopically with Evans blue, and radiographically after contrast injection. In the 3rd group intercostobronchial artery anastomoses were studied radiographically with the heart-lung block in situ. Coronary-bronchial artery anastomoses were demonstrated in 3 of the 5 pigs with an aortic 'pouch' technique, but contrast was very limited in 2 of these 3. Oesophageal arterial anastomoses with bronchial arterial branches and/or the pulmonary veins were demonstrated in 6 of the 7 pigs and more markedly than the coronary-bronchial anastomoses. Intercostobronchial artery anastomoses could not be demonstrated angiographically. It was concluded that the existence of coronary-bronchial and oesophageal-bronchial artery anastomoses in the pig appear to establish an arterial net between the base of the heart and the distal oesophagus. The resemblance to human oesophageal-bronchial artery anastomoses supports use of a porcine model for experimental studies.

The porcine bronchial artery: surgical and angiographic anatomy.

The pig is often used in experimental studies on the significance of bronchial artery circulation, but the anatomy of this artery is only poorly described. The purpose of this study was to improve the anatomical basis for experimental studies on the porcine bronchial artery circulation. The origin of the artery from the aorta is described in 32 pigs. Heart-lung blocks were perfused with saline and removed in 16 pigs, and the broncho-oesophageal orifice was identified and cannulated. In these 16 specimens the intrapulmonary ramification was studied by angiography, and the extrapulmonary distribution and supply area by injection of Evans Blue. The broncho-oesophageal artery originated from the aorta as a single trunk in 91%. Angiography showed that each principal bronchus was accompanied by 2 bronchial artery branches far into the lung parenchyma. The central branching pattern of the artery between the aorta and the principal bronchi was divided into 3 subtypes. Evans Blue showed communication with the whole mediastinum. The anatomical relations are described. It is concluded that the broncho-oesophageal artery divides to follow each bronchus with 2 bronchial branches. A nomenclature for these branches is suggested. The pig anatomy is suited for experimental investigations on the bronchial circulation.

Apoptosis in acute pulmonary allograft rejection and cytomegalovirus infection.

Apoptosis is a form of programmed cell death, characterized by activation of endonucleases that cleave DNA into oligonucleosomal fragments, which can be identified by in situ terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling (TUNEL). This process has recently been implicated in cardiac and hepatic allograft rejection, and we investigated its contribution to acute pulmonary allograft rejection and cytomegalovirus (CMV) pneumonitis by in situ TUNEL of transbronchial biopsy specimens. In situ TUNEL was performed on 70 transbronchial biopsy samples collected from 25 pulmonary allograft recipients for diagnosis of acute rejection or CMV pneumonitis, and the number of apoptotic nuclei/mm2 was correlated with the rejection grade (International Society of Heart and Lung Transplantation classification). During acute pulmonary allograft rejection, apoptotic nuclei were demonstrated in pulmonary parenchymal cells and mononuclear infiltrating cells, and the number of apoptotic cells was positively correlated with the rejection grade. In addition, a marked increase in the density of apoptotic cells was found in pulmonary allografts with CMV pneumonitis. We conclude that apoptosis contributes to cell death during acute pulmonary allograft rejection and CMV infection.

[Primary pulmonary hypertension]. / Primaer pulmonal hypertension.

Primary pulmonary hypertension (PPH) is defined as continuing increase of the blood pressure in the pulmonary arteries without any known reason. The expected incidence in Western Europe is one to two per one million inhabitants, which in Denmark is around five to ten new cases each year. The diagnosis PPH is established by excluding other known reasons for secondary pulmonary hypertension. Primary pulmonary hypertension is a progressive and incurable disease. The treatment of PPH is with vasodilatory agents and anti-coagulants with supplementary diuretics, digoxin and oxygen as second-line of treatment. The most important vasodilators are calcium-antagonist and Epoprostenol (prostacyclin PGI2). Lung transplantation or combined heart and lung transplantation is at the moment the only possible treatment for progressive PPH disease in Denmark. The one year survival after lung- or heart and lung transplantation for PPH are not as good as the survival among other patients who are heart and lung transplanted.

[Lung volume reduction surgery. A new surgical therapeutic possibility for patients with emphysema]. / Lungevolumenreducerende kirurgi. Et nyt kirurgisk behandlingstilbud til patienter med emfysem.

Lung volume reduction surgery is a new surgical procedure for treatment of patients with pulmonary emphysema. At the operation the most peripheral parts of the lung are resected. Only 15-20% of the patients admitted for lung volume reduction surgery are suitable for operation. The preliminary results have demonstrated improvement in lung function in the majority of the patients. Most of the reports comprise small numbers of patients and have a short time of observation. The longest reported period of observation for a larger number of patients is 24 months and shows a continuing improvement in lung function, dyspnoea and six minute walk test. Because of the high incidence of emphysema, lung volume reduction is a procedure that could reach large extension in the future. However, better definition of criteria of inclusion and better evaluation of the operative procedures are needed.

[Clinical results after en block double lung transplantation with direct bronchial revascularization. The first three and a half years' experience in Denmark]. / Kliniske resultater efter en bloc dobbeltlungetransplantation med direkte bronkial revaskularisering. De første tre et halvt års erfaring i Danmark.

En-bloc double lung transplantation with tracheal anastomosis and direct revascularization of the bronchial arteries to the left internal mammary artery has been carried out in Denmark since June 1992. Forty-seven patients (32 with alfa-1 antitrypsin deficiency, 11 with chronic obstructive pulmonary disease, two with cystic fibrosis and two with primary pulmonary hypertension), 25 men and 22 women, average age 39 years (17-64 years), have received their first double-lung transplant with bronchial artery revascularization. Arteriography of the internal mammary artery and bronchial arteries was performed in 42 (89%) of the patients from 1-150 days after the operation. Successful bronchial artery revascularization was demonstrated arteriographically in 40 patients, in two patients the arteriography failed to show bronchial artery revascularization. Arteriography was not performed in five patients due to early complications and death. Bronchoscopy showed rapid, uncomplicated airway healing in 42 patients. Mucosal necrosis under the tracheal anastomosis was found in three patients, and severe obstructive endobronchial growth of the fungus Aspergillus fumigatus was diagnosed in the last two patients. The one- and two-year survival is 83% (Kaplan-Meier). Eleven patients are dead, five due to pulmonary causes and six due to extra-pulmonary causes. Pulmonary function became normal in nearly all surviving patients between three to six months after the transplantation. In conclusion, en-bloc double-lung transplantation with bronchial artery vascularization has shown good short-term results, and the one- and two-year survival gives hope that a successful bronchial artery revascularization will improve the long-term survival following lung transplantation.

Re-mediastinoscopy in the assessment of resectability of lung cancer.

OBJECTIVE: Thirty-one patients underwent re-mediastinoscopy in the diagnostic assessment of lung cancer. The reason for a repeat mediastinoscopy was either a negative result at the first operation in spite of CT indication of enlarged nodes or an incomplete first mediastinoscopy. METHODS: All patients underwent a conventional mediastinoscopy. RESULTS: In 22 patients with enlarged mediastinal lymph nodes at computed tomography, 10 had a positive lymph node histology at re-mediastinoscopy, while 12 were negative. In 9 patients with no enlarged mediastinal nodes at CT scan, but incomplete biopsies at the first mediastinoscopy, 1 patient had lymph node metastases. The median duration from the first to the second mediastinoscopy was 43 days. No major complications occurred. The staging of the patients was greatly affected by the re-mediastinoscopy. Of 31 patients judged as operable according to the initial mediastinoscopy only 60% were found to be operable following the second mediastinoscopy. CONCLUSION: This study has demonstrated the value of re-mediastinoscopy in assessment of resectability of lung cancer.

Surgical and arteriographic results of bronchial artery revascularization in lung and heart lung transplantation.

BACKGROUND: On the basis of our experience with bronchial artery revascularization (BAR) in lung transplantation since its introduction in Copenhagen in 1992, a description of the surgical anatomy of the bronchial arteries and the results of attempted BAR in these patients will be presented. METHODS: Since June 1992, BAR was performed in 50 en bloc double lung, six single lung, and nine heart-lung transplantations. The location, number, type, and size of each bronchial artery identified and revascularized were recorded. Our choice of conduit for BAR was the internal mammary artery. Routine internal mammary-bronchial arteriography was performed early after the transplantation to evaluate the result of BAR. All arteriograms were carefully studied together with the surgical records. The arteriographic results after attempted BAR were classified as complete, incomplete (bilateral, hemilateral, or poor), or failed. The surgical and arteriographic anatomy of the bronchial arteries has been described, and nomenclature for the as yet unnamed bronchial arteries has been developed. RESULTS: During surgery 128 bronchial arteries were identified in the descending aorta of the 64 donor lung blocs. Internal mammary-bronchial arteriography was performed in 53 patients. BAR was complete in 32, incomplete in 18, and failed in 3. The number of bronchial arteries identified and revascularized in each case increased with experience. The central and intrapulmonary bronchial artery anatomy was described, and different patterns have been identified. CONCLUSIONS: Bronchial artery identification is reliable, but a learning process is involved. BAR is possible with a high success rate. Complete BAR is an obtainable goal in most cases.

[Coronary bypass surgery at the Rigshospitalet 1993-1995. Results after 1.000 consecutive operations]. / Koronar bypass-kirurgi på Rigshospitalet 1993-1995. Resultater efter 1.000 konsekutive operationer.

During 1993-95 1000 consecutive patients were admitted for coronary bypass surgery. The total 30-day mortality of 1.9% was 0.9% for elective cases, 0.8% for reoperations and 0.2% for urgent cases. Perioperative myocardial infarction occurred in 44 patients of whom 25% had infarction at the start of the operation. Respiratory insufficiency occurred in 1.4% of the patients, 3.6% developed renal insufficiency and 1.8% had neurological defects postoperatively. Reoperation for bleeding occurred in 6%, and 0.2% developed sternal or mediastinal infection. This study demonstrates that the results of coronary bypass surgery at Rigshospitalet, Copenhagen are fully comparable to similar results in our neighbouring countries. The results can probably be further improved by more intensive treatment of perioperative ischaemia, especially in reoperations and urgent cases.

A rat model with an isolated bladder in situ.

This paper describes our method for producing a rat model with an isolated bladder in situ in which the bladder makes no contact with urine. First, the right kidney was removed, then an external catheter was placed in the right ureter for bladder infusions, and next the left ureter was anatomosed to the proximal part of the descending colon. The animals were treated with antibiotics, and saline was infused daily into the bladder in order to prevent atrophy. This in situ model is considered to be useful in studies investigating the influence of specific compounds, such as carcinogens, on the bladder and its urothelium.

Revascularization of the bronchial arteries in lung transplantation: an overview.

Development of the surgical technique has minimized the incidence of airway problems associated with single as well as sequential bilateral lung transplantation. Although early results are good, long-term results remain unsatisfactory. The main problems after lung transplantation are pulmonary infections and the bronchiolitis obliterans syndrome. The bronchiolitis obliterans syndrome is usually considered to be chronic rejection, but a multifactorial genesis including airway ischemia has been suggested. We reviewed the literature relevant to direct bronchial artery revascularization during lung transplantation. Although information is limited, there are good reasons to believe that reestablishment of the dual blood supply to the transplanted lung is beneficial not only for healing of the airway anastomoses, but also for the airway and the lung responses to pathologic conditions. In small series, methods of bronchial artery revascularization have proved successful and have been associated with good early results. We believe it is justified to test the impact of direct bronchial artery revascularization on outcome after lung transplantation in large clinical series.