John Wallwork

Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension

The acute effects of inhaled nitric oxide (NO) (40 ppm in air) on pulmonary (PVR) and systemic (SVR) vascular resistance were compared with those of an intravenous infusion of prostacyclin (24 micrograms/h) in 8 patients with severe pulmonary hypertension and 10 cardiac patients with normal values of PVR. 10 healthy volunteers were studied non-invasively. In the patients with pulmonary hypertension, PVR fell significantly after inhaled NO and after prostacyclin. PVR also fell significantly in the cardiac patients after inhaled NO. Although SVR fell substantially after prostacyclin in patients with pulmonary hypertension, inhaled NO had no effect on SVR in any patient or volunteer. Inhaled NO therefore seems to be both a selective and effective pulmonary vasodilator.

Long-term treatment of primary pulmonary hypertension with continuous intravenous epoprostenol (prostacyclin).

A young woman, bedbound with severe pulmonary hypertension, responded to intravenous epoprostenol with a fall in pulmonary vascular resistance, improved oxygenation, and a rise in exercise tolerance. For thirteen months, continuous infusion of epoprostenol has enabled her to live independently at home.

Transmyocardial laser revascularisation in patients with refractory angina: a randomised controlled trial

BACKGROUND Transmyocardial laser revascularisation (TMLR) is used to treat patients with refractory angina due to severe coronary artery disease, not suitable for conventional revascularisation. We aimed in a randomised controlled trial to assess the effectiveness of TMLR compared with medical management. METHODS 188 patients with refractory angina were randomly assigned TMLR plus normal medication or medical management alone. At 3 months, 6 months, and 12 months after surgery (TMLR) or initial assessment (medical management) we assessed exercise capacity with the treadmill test and the 12 min walk. FINDINGS Mean treadmill exercise time, adjusted for baseline values, was 40 s (95% CI -15 to 94) longer in the TMLR group than in the medical-management group at 12 months (p=0.152). Mean 12 min walk distance was 33 m (-7 to 74) further in TMLR patients than medical-management patients (p=0.108) at 12 months. The differences were not significant or clinically important. Perioperative mortality was 5%. Survival at 12 months was 89% (83-96) in the TMLR group and 96% (92-100) in the medical-management group (p=0.14). Canadian Cardiovascular Society score for angina had decreased by at least two classes in 25% of TMLR and 4% of medical-management patients at 12 months (p<0.001). INTERPRETATION Our findings show that the adoption of TMLR cannot be advocated. Further research may be appropriate to assess any potential benefit for sicker patients.

Airway complications after lung transplantation: treatment and long-term outcome

BACKGROUND Airway complications are a significant cause of morbidity after lung transplantation. Effective treatment reduces the impact of these complications. METHODS Data from 123 lung (99 single, 24 bilateral) transplants were reviewed. Potential risk factors for airway complications were analyzed. Stenoses were treated with expanding metal (Gianturco) stents. RESULTS Mean follow-up was 749 days. Thirty-five complications developed in 28 recipients (complication rate: 23.8%/anastomosis). Mean time to diagnosis was 47 days. Only Aspergillus infection and airway necrosis were significantly associated with development of complications (p < 0.00001 and p < 0.03, respectively). Stenosis was diagnosed an average of 42 days posttransplant. Average decline in forced expiratory volume in 1 second (FEV1) was 39%. Eighteen patients (13 single and 5 bilateral) required stent insertion. Mean increase in FEV1 poststenting was 87%. Two stent patients died from infectious complications. Six patients required further intervention. Long-term survival and FEV1 did not differ from nonstented patients. CONCLUSIONS Aspergillus and airway necrosis are associated with the development of airway complications. Expanding metal stents are an effective long-term treatment.

Prostacyclin (epoprostenol) and heart-lung transplantation as treatments for severe pulmonary hypertension

OBJECTIVE--To determine whether epoprostenol (prostacyclin, PGI2) or heart-lung transplantation (HLT), or both improves survival of patients with severe pulmonary hypertension. DESIGN--This was a prospective study where the effects of epoprostenol were compared with conventional treatment. Also, the benefits of epoprostenol and HLT were assessed by comparing survival in this group with that of 120 patients at the Mayo Clinic before HLT and epoprostenol treatment became available. PATIENTS AND INTERVENTIONS--Forty four patients were studied; 25 received continuous epoprostenol over a four year period (mean (SD) cardiac index 1.8 (0.4) 1 min-1 m-2 and mean (SD) pulmonary artery pressure (PAP) 70 (16) mm Hg) and 19 did not (cardiac index 2.1 (0.6) 1 min-1 m-2 and PAP 64 (13) mm Hg). Ten patients underwent HLT: seven had received epoprostenol, and three had not. RESULTS--The therapeutic intervention with epoprostenol, or HLT, or both improved survival compared with the Mayo clinic patients (p = 0.05). Most of the benefit was conferred by epoprostenol, which prolonged survival twofold from a median time of eight to 17 months and doubled the changes of successful HLT. The improved survival with epoprostenol was not related to its immediate capacity to cause pulmonary vasodilation. Those patients who had limited acute pulmonary vasodilation when treated with epoprostenol showed the greatest improvement in survival. CONCLUSIONS--These preliminary results indicate that those pulmonary hypertensive patients with the poorest chance of survival can be helped by epoprostenol and by HLT.

Life supporting function for over one month of a transgenic porcine heart in a baboon

BACKGROUND Inhibition of hyperacute rejection (HAR) and sustained graft survival have been demonstrated in a pig-to-primate model of heterotopic cardiac xenotransplantation using pigs transgenic for human Decay Accelerating Factor (hDAF). Building on this work, an orthotopic model has been developed. This case records 39-day cardiac xenograft function in a life-supporting capacity with clinically applicable immunosuppression. METHODS Using a heart from an hDAF transgenic pig, an orthotopic cardiac transplant was performed on an adult baboon. The immunosuppressive regimen consisted of induction with a short course of cyclophosphamide, followed by maintenance therapy with cyclosporine A, mycophenolate mofetil and a tapering course of corticosteroids. Post-operative monitoring included daily anti-pig hemolytic antibody titer surveillance and endomyocardial biopsy. RESULTS The animal survived 39 days and was active and energetic throughout its postoperative course, remaining free of signs of cardiopulmonary failure. Endomyocardial biopsy performed on post-operative Day 36 revealed only patches of sub-endocardial fibrosis with no signs of active rejection. The baboon succumbed to an acute cardiopulmonary decompensation immediately following administration of medication via oral gavage. Post-mortem histopathology demonstrated well-preserved myocardial architecture with small foci of mild humoral rejection. CONCLUSIONS This case documents the longest survival recorded to date of a discordant orthotopic cardiac xenograft and illustrates that the hDAF transgene combined with a clinically acceptable maintenance immunosuppressive regimen enables sustained, life-supporting function of porcine cardiac xenografts in non-human primates. The inhibition of hyperacute rejection and the subsequent control of humoral and cellular rejection for over 1 month demonstrated in this experiment represent significant progress in the development of a viable strategy for clinical xenotransplantation.

The Effect of Surgery with Cardiopulmonary Bypass on Alveolar-Capillary Barrier Function in Human Beings

We measured the rate of clearance of technetium 99m-labeled diethylenetriamine pentaacetate (99mTcDTPA) (molecular weight, 492 daltons) from the lung into the blood (T1/2LB) in 9 patients before and after operation with cardiopulmonary bypass (CPB). Two hours postoperatively, T1/2LB fell from 49.3 +/- 13.6 minutes (mean +/- standard deviation) to 24.0 +/- 12.8 minutes (p less than 0.001). In addition, alveolar-arterial oxygen tension difference P(A-a)O2 had increased from 73 +/- 28 mm Hg to 164 +/- 37 mm Hg (p less than 0.001). The rates of clearance of 99mTcDTPA had returned to preoperative times by 7 days after operation, although there was still a significant (p less than 0.05) elevation in P(A-a)O2. Postoperative respiratory failure developed in 1 patient. The only abnormality of lung function detected preoperatively was an increased clearance rate for 99mTcDTPA (T1/2LB, 18 minutes). This study has shown an increased clearance from the lung of a low-molecular-weight molecule following operation with CPB. This finding should allow a more rational approach to elucidating the mechanisms of injury to the gas-blood interface in the lung following this type of operation.

HEART-LUNG TRANSPLANTATION FOR CYSTIC FIBROSIS

Abstract 13 patients with severe lung disease and cor pulmonale from cystic fibrosis were accepted for heart-lung transplantation (HLT). 6 have had the operation, of whom 5 are well, with normal lung function, 3-29 months after operation. 1 patient died from adult respiratory distress syndrome after reoperation to control persistent chest-wall bleeding: at necropsy, this patient proved to have cirrhosis. Respiratory tract infections and acute lung rejection after HLT for cystic fibrosis were no more common than in other HLT patients. Of the 7 patients for whom suitable donor organs were not found, 3 died within 3 months of assessment. Initial severity of disease had been similar to that in the transplant group. The cost of assessment, operation, and 1 years treatment after HLT is similar to that of medical treatment for such patients.

Transplantation of liver, heart, and lungs for primary biliary cirrhosis and primary pulmonary hypertension.

Liver, heart, and lung replacement was performed in a woman with severe pulmonary hypertension, cardiorespiratory failure, and end-stage primary biliary cirrhosis. The main surgical considerations were the staging of the various parts of the operation in relation to cardiopulmonary bypass and performing the recipient procedures as expeditiously as possible to reduce the bypass time to a minimum. The patient was able to leave hospital on the 46th postoperative day on low doses of immunosuppressive agents, with excellent liver and cardiopulmonary function. This early satisfactory outcome shows the feasibility and potential of the procedure: such combined allografting may be a suitable treatment in carefully selected cases of advanced liver and lung disease from other causes.

Heart-lung transplantation: Better use of resources

PURPOSE Our goal was to review the experience at Papworth Hospital, Cambridgeshire, England, with combined heart-lung transplantation. PATIENTS AND METHODS Since April 1984, 31 patients have undergone heart-lung transplantation. Donors and recipients are carefully matched with regards to serology, morphology, and cytomegalovirus compatibility. A pulmonary preservation fluid has been developed that allows distant organ procurement with a single pulmonary artery flush technique. RESULTS Acute cardiac rejection has not occurred in these patients. Twenty-three patients are alive between two months and over three years following transplantation. The actuarial survival rate at one year is 78 percent, and 70 percent at two years. Three patients died as a result of cytomegalovirus pneumonitis; in two patients, obliterative bronchiolitis developed, and both died, one after an opportunistic infection developed. Three patients died from other causes. The use of transbronchial biopsy of the lung has provided accurate, early, and safe diagnosis of pulmonary rejection. CONCLUSION Developments in organ preservation and patient management, as well as careful selection of recipients and donors, have led to the effective use of resources and thereby to these good results. In particular, the incidence of obliterative bronchiolitis has been low, which is attributed to the early treatment of pulmonary rejection following diagnosis by transbronchial biopsy.