Conor M. Burke

Pathologic pulmonary alterations in long-term human heart-lung transplantation

Twenty-one patients with end-stage pulmonary hypertension underwent combined allograft heart-lung transplantation after 1980. Almost 80 per cent of these patients survived beyond the immediate postoperative period, with the longest survival period more than 3 1/2 years at the time of this report. Five patients died in the perioperative or immediate postoperative period, and 11 returned to normal lives with essentially normal pulmonary function. In the remaining five allograft recipients recurrent respiratory infections and progressive obstructive airway disease developed, with superimposed restrictive deficits in three of them. Two open lung biopsies, two autopsies, and one retransplantation were performed in these recipients. Morphologically, these allograft recipients showed extensive bronchiolitis obliterans, interstitial and pleural fibrosis, and accelerated arterial and venous arteriosclerosis. Bronchiolitis obliterans may prove to be a significant complication of heart-lung transplantation.

Obliterative Bronchiolitis After Heart-Lung Transplantation: Apparent Arrest by Augmented Immunosuppression

Obliterative bronchiolitis has been the major complication in long-term survivors of human heart-lung transplantation at our institution. We have assessed the effect of the introduction of a third immunosuppressive agent, azathioprine, on the rate of decline in airflow variables in eight heart-lung transplant recipients with obliterative bronchiolitis, and have compared this rate with that in five patients who did not receive augmented immunosuppressive therapy. Specifically, the rate of decline in forced expiratory flow rate between 25% and 75% of vital capacity improved considerably after institution of this therapy (-5.25 +/- 2.85 compared with -0.27 +/- 0.66 [mean +/- SD]; p less than 0.005), whereas the effect on the ratio of forced expiratory volume in one second to forced vital capacity was more modest (-3.61 +/- 1.52 compared with -0.54 +/- 0.93; p less than 0.005). The rate of decline in airflow variables was similar in both groups before the institution of therapy with azathioprine. These results show that augmented immunosuppressive therapy is capable of slowing the rate of progression of obliterative bronchiolitis in this population; they also suggest that the obliterative bronchiolitis may represent a form of chronic pulmonary allograft rejection.

Pulmonary function in advanced pulmonary hypertension.

Pulmonary mechanical function and gas exchange were studied in 33 patients with advanced pulmonary vascular disease, resulting from primary pulmonary hypertension in 18 cases and from Eisenmenger physiology in 15 cases. Evidence of airway obstruction was found in most patients. In addition, mean total lung capacity (TLC) was only 81.5% of predicted and 27% of our subjects had values of TLC less than one standard deviation below the mean predicted value. The mean value for transfer factor (TLCO) was 71.8% of predicted and appreciable arterial hypoxaemia was present, which was disproportionate to the mild derangements in pulmonary mechanics. Patients with Eisenmenger physiology had significantly lower values of arterial oxygen tension (PaO2) (p less than 0.05) and of maximum mid expiratory flow (p less than 0.05) and significantly higher pulmonary arterial pressure (p less than 0.05) than those with primary pulmonary hypertension, but no other variables were significantly different between the two subpopulations. It is concluded that advanced pulmonary vascular disease in patients with primary pulmonary hypertension and Eisenmenger physiology is associated not only with severe hypoxaemia but also with altered pulmonary mechanical function.

Long-term results, hemodynamics, and complications after combined heart and lung transplantation.

During the first 31/2 years of the Stanford heart-lung transplant program, 23 transplants have been carried out in 22 patients with severe pulmonary vascular disease. Actuarial survival curves predict 1 and 2 year survival rates of 71% and 57%, respectively, for all patients. As a result of increasing experience, the early mortality of 26% has been reduced, with only one early death occurring in the last eight patients; prior cardiac surgery was a contributing factor in three of the six patients suffering early deaths. Two late deaths occurred in the series 14 and 15 months after operation. One patient died suddenly as a result of an acute myocardial infarct and the other patient died because of respiratory failure. At autopsy, both patients had severe proliferative coronary atherosclerosis with obliterative bronchiolitis affecting the lungs. An additional patient required a retransplant for obliterative bronchiolitis 37 months after the initial procedure, and he too was found to have severe coronary artery disease. Hemodynamics and left ventricular function were normal in patients studied 1 and 2 years after undergoing the transplantation procedure. Thus, the early mortality and morbidity of combined heart and lung transplantation has been significantly reduced, but the long-term complications, particularly graft atherosclerosis and obliterative bronchiolitis, are yet to be fully controlled.

Indiscretion enteritis. A rabelaisian syndrome

A 76-year-old man had small bowel obstruction and organic small bowel disease following a series of bizarre massive gustatory insults that involved food, medications, and mega-mineral-vitamin supplements. Intestinal obstruction required partial small bowel resection. The dietary indiscretions resulted in severe enteritis (indiscretion enteritis). The sequence has been termed a Rabelaisian syndrome after the great French writer and physician, Francois Rabelais, who vividly described bizarre gustatory habits. Gut injury may result from unwise oral intake of various foods and mineral supplements.