Wrapping the anastomosis with omentum or an internal mammary artery pedicle does not improve bronchial healing after single lung transplantation: results of a randomized clinical trial.

Between May 1989 and March 1990, 36 patients undergoing a first single lung transplantation were randomized to three groups. In the omentum group the bronchial anastomosis was wrapped with an omental pedicle. In the internal mammary artery group, the anastomosis was wrapped in a pedicle of tissue surrounding the internal mammary artery. In the no wrap group, no attempt was made to revascularize the anastomosis. No significant differences were found in the indications for transplantation, recipient age, organ ischemic time, or preoperative steroid use in the three groups. There were two early deaths: one in the omentum group as a result of infection and one in the internal mammary artery group as a result of multiorgan failure. During a mean follow-up period of 21 months (range 9 to 32), there were two additional deaths in the no wrap group and four in the omentum group, one of which involved an anastomotic complication. Actuarial survival at 1 year was 75%, 92%, and 80% in the omentum, internal mammary artery, and no wrap groups, respectively (p = 0.25). Granulation tissue at the site of the anastomosis requiring cryotherapy or bronchial dilatation occurred in two patients in the omentum group, three in the internal mammary artery group, and three in the no wrap group. Bronchial stents were required in one patient in the omentum group and one in the internal mammary artery group. Actuarial survival free of anastomotic complications was similar in the three groups. The incidence of bronchial anastomotic complications after single lung transplantation is not affected by wrapping the anastomosis with either omentum or an internal mammary artery pedicle.

The use of unstented homograft valves for aortic valve reoperations. Review of a twenty-three-year experience.

Unstented homograft valves offer several theoretical advantages when used for patients who have had previous operations on the aortic valve. Between January 1970 and February 1993, 177 patients received unstented homograft valves after previous aortic valve operations. One hundred thirty-four patients had previous aortic valve replacement in the form of homografts (101 patients), mechanical prostheses (24 patients), and bioprostheses (9 patients), and 43 had previous valve repair. The indication for reoperation was deterioration of a noninfected valve (124 patients), infective endocarditis (40 patients), and failure of a noninfected mechanical valve (12 patients). Fresh homograft valves were implanted in 60 patients, homografts preserved in antibiotics were used in 111 patients, and 6 patients received cryopreserved valves. Aortic valve and root replacement was performed in 60 patients, and in 117 the homograft was inserted freehand in the subcoronary position. The early mortality was 5.1%. The actuarial survival at 10 years was 71%. Multivariate analysis demonstrated that patients with previous homograft replacement have a better long-term survival than patients who had previous mechanical valves (p = 0.017). The freedom from valve-related death and reoperation was 70% at 10 years. Fresh homografts faired better than antibiotic-sterilized homografts (p = 0.007). None of the patients had recurrence of endocarditis at 6 months, although 1 patient died of uncontrolled infection despite valve replacement. The freedom from recurrent endocarditis was 88% at 10 years. We conclude that unstented aortic homografts provide good early and long-term results for aortic valve reoperations, particularly in patients with previous homograft replacement. Recurrent endocarditis is uncommon even in patients operated on for prosthetic valve infections.

Role of catalase and heat shock protein on recovery of cardiac endothelial and mechanical function after ischemia.

The aim of this study was to investigate the roles of heat shock proteins and catalase after heat shock stress in the recovery of cardiac mechanical and endothelial function following a prolonged ischemic, cardioplegic arrest. Isolated working rat hearts were subjected to an ischemic cardioplegic arrest for 4 hours at 4 degrees C. Six groups, each of 6 hearts, were studied: control; control treated with 3-aminotriazole, an inhibitor of catalase; sham; sham + 3-aminotriazole; heat-shocked rats; heat shocked rats + 3-aminotriazole. Postischemic recovery of cardiac output and endothelial function (as % of preischemic control values) were respectively 54.6 +/- 1.9 and 21.2 +/- 3.0 in the control group; 52.3 +/- 2.9 and 19.1 +/- 3.9 in the control + 3-aminotriazole group; 72.2 +/- 2.7 and 54.2 +/- 7.6 in the heat shocked group; and 68.0 +/- 4.0 and 21.0 +/- 5.8 in the heat shocked + 3-aminotriazole group. SDS PAGE and western blotting showed induction of heat shock proteins in the heat stressed animals. Measurement of catalase activity showed significant inhibition in the 3-aminotriazole treated groups. It is concluded that, following heat shock stress, the enhanced endothelial recovery after prolonged ischemic cardioplegic arrest is dependent on catalase activity but that this does not apply to the recovery of mechanical functional.

Preserved left ventricular function during supine exercise in patients after orthotopic cardiac transplantation.

Cardiac denervation may affect cardiovascular responses during exercise in patients after orthotopic cardiac transplantation. In 17 such patients, haemodynamic responses and left ventricular function were examined by radionuclide ventriculography during and after supine exercise, at an average of 17.1 +/- 2.6 months after surgery. Data were also obtained during 'volume loading' brought about by leg elevation before exercise. Results were compared with those of six normal controls. At rest, heart rate was significantly faster among transplant patients than among controls (P less than 0.0003). No significant inter-group differences in changes in cardiovascular parameters were found between the two groups during leg elevation. During exercise, heart rate in transplant patients rose at a significantly slower rate than controls (P = 0.0001), but similar increases in ejection fraction, stroke volume and cardiac output were observed among transplant patients and controls. Decline in heart rate (P = 0.0001), ejection fraction (P = 0.0007) and cardiac output (P = 0.0001) was significantly slower in transplant patients during recovery. Although there were differences in rates of increases in heart rate between transplant patients and controls during supine exercise, there were no inter-group differences in increases in cardiac output and ejection fraction and changes in haemodynamic responses and left ventricular volumes.

Magnetic resonance characterization of pulmonary arterial blood flow after single lung transplantation.

Magnetic resonance imaging has been used to study pulmonary arterial anatomy and to measure pulmonary arterial blood flow in patients with single lung transplantation. Nine patients and nine control subjects matched for age and sex were studied. The anatomy of the main pulmonary artery and its main branches, as well as the site of arterial anastomoses, was identified and measurements of their diameters were taken. There were no significant differences in diameters of these vessels between the patients and the control subjects. Arterial blood flows to the transplanted lung were 2.07 +/- 0.45 L/min/m2 in the group with right lung transplantation and 2.43 +/- 0.60 L/min/m2 in those with left lung transplantation compared with 1.22 +/- 0.22 L/min/m2 and 1.27 +/- 0.41 L/min/m2 in the control group, respectively. The ratio of blood flow in the transplanted and the native lungs in all patients studied was 2.8 +/- 0.83:1. The flow profile in the artery of the transplanted lung showed a wide forward flow during systole and most of diastole, whereas that of the native lung showed a narrow early systolic peak and a reverse flow in most of diastole. These differences in the volume and pattern of flow in the transplanted lung are most likely related to the relative resistance in the native and the transplanted lung and could constitute an additional index for monitoring the condition of patients with lung transplantation and help in the understanding of the physiology of the denervated pulmonary vascular bed.

Medium-term results of combined heart and lung transplantation for emphysema.

Between December 1983 and April 1989, 222 combined heart and lung transplant operations were performed for treatment of pulmonary vascular disease and parenchymal lung disease at Harefield Hospital. Seventeen of these patients had emphysema, and 11 of them were followed up for a minimum of 1 year. There were nine male and two female patients. Their mean age was 39 (range, 32 to 54) years. Seven had alpha 1-antitrypsin deficiency. Six patients were receiving continuous oxygen therapy, and two patients were dependent on a ventilator. Postoperatively, the patients' lungs were ventilated for a median of 3 days (range, 24 hours to 2 weeks). Two patients subsequently required further periods of ventilation. Immunosuppression consisted of azathioprine and cyclosporine. Three patients also received low-dose oral steroids. There was one early death, which occurred on the second postoperative day. The remaining patients were followed up for 12 to 53 (mean, 22) months. One patient had cytomegalovirus pneumonitis 6 weeks postoperatively that responded to treatment. There was one late death at 14 months after reoperation for treatment of obliterative bronchiolitis. The overall survival was 91% at 1 year. All survivors achieved an excellent level of rehabilitation. It is concluded that the medium-term results of heart and lung transplantation for treatment of emphysema are good and that patients with alpha 1-antitrypsin deficiency may undergo transplant procedures without substitution therapy.

Gianturco self-expanding metallic stents in treatment of tracheobronchial stenosis after single lung and heart and lung transplantation.

Three patients with recurrent bronchial stenosis following single lung transplant (SLTx), and one patient with tracheal stenosis following heart-lung transplantation (HLTx), not responding to repeated dilatations (3 patients) and prolonged use of silastic stents (patient with tracheal stenosis), have been treated by the endoscopic insertion of Gianturco self-expanding metallic stents under fluoroscopic control. The stent resulted in immediate improvement in respiratory function in all four patients. One patient (SLTx) had early bronchial re-stenosis due to growth of granulation tissue within the stent which was successfully treated by cryotherapy. In one patient (HLTx), a left lower lobe bronchial stenosis developed 14 months after tracheal stenting. The metallic stent appears to be a promising device in the management of recurrent or resistant bronchial stenosis following SLTx or tracheal stenosis after HLTx.

Autoradiographic localization of [125I]endothelin binding sites in human blood vessels and coronary tissue: functional correlates.

The distribution of endothelin-1 (ET-1) receptors on human vascular tissue has been studied. High- and low-resolution autoradiography was used to determine the distribution of [125]ET binding sites in human blood vessels and ventricular myocardium. Dense, displaceable [125I]ET binding was associated with cardiac myocytes and the smooth muscle layer of all vessels were examined. There was also dense binding to vasa vasora. There was increased [125I]ET binding to atheromatous coronary arteries and vein graft, which was associated with the tunica media and vasa vasora or regions of neovascularization. Vasoconstrictor and positive inotropic activity of ET-1 has been established in vitro. The vasoconstrictor effect of ET-1 is likely to be mediated via the binding sites identified on vascular smooth muscle. The striking perivascular [125I]ET-1 binding suggests that ET-1 may also have constrictor activity on vasa vasora. There is experimental evidence that ET-1 has mitogenic activity on vascular smooth muscle cells in culture. The increased binding to both smooth muscle and regions of neovascularization in atheromatous vessels suggests that ET-1 may play a role in atherosclerosis.

Identification of [(125)I]endothelin binding sites in human coronary tissue.

In vitro receptor autoradiography has been used to study the distribution of [(125)I]endothelin binding sites in human coronary tissue from patients undergoing cardiac transplantation. Dense binding of [(125)I]endothelin was associated with the smooth muscle of epicardial coronary arteries as well as to perivascular regions of these vessels. Binding was also associated with the ventricular myocardium. There was an increased binding of [(125)I]endothelin to atheromatous tissue, both coronary arteries and vein graft. The [(125)I]endothelin binding sites identified using in vitro autoradiography are likely to be functionally relevant since endothelin causes a concentration-dependent contraction of segments of human epicardial coronary arteries in vitro and also has positive inotropic activity on isolated human cardiomyocytes. The presence of specific binding sites for [(125)I]endothelin on coronary tissue and the increased binding in atheromatous tissue suggest that endothelin is a peptide which may play a role in the maintenance of vascular tone and/or the pathogenesis of ischaemic heart disease.

Influence of beta blockade on exercise capacity and heart rate response after human orthotopic and heterotopic cardiac transplantation.

It has been reported that use of beta blockers may not be safe after cardiac transplantation because the denervated hearts may be largely dependent on circulating catecholamines to increase cardiac output. Therefore, the effects of intravenous propranolol were studied during maximal treadmill exercise in 7 patients with heterotopic and 6 with orthotopic cardiac transplantations. An average decrease of about 15% in exercise duration (p less than 0.001), a 34% reduction in systolic blood pressure increase (p less than 0.05) and a 40% attenuation in heart rate increase (p less than 0.001) were observed after beta blockade. In patients with heterotopic transplantation, beta blockade produced similar effects on heart rate in the denervated donor hearts and the innervated recipient hearts during and after mild exercise. During peak exercise, beta blockade attenuated the rate to a greater extent in the donor hearts. Although the denervated donor heart is more sensitive to beta blockade than the innervated recipient heart during exercise, no adverse effects were observed. Beta-blocker therapy should be considered for cardiac transplant patients if longer-term studies confirm their safe use in these patients.

Increased sensitivity of the denervated transplanted human heart to isoprenaline both before and after beta-adrenergic blockade.

It is not known whether surgical denervation leads to increased beta-receptor sensitivity after human cardiac transplantation. We assessed cardiac beta-receptor sensitivity by studying the heart rate response to isoprenaline of the denervated donor heart as compared with the innervated recipient heart in eight patients who underwent heterotopic cardiac transplantation and in six patients with orthotopic transplantation. Changes in the donor and recipient hearts seen in these 14 patients were further compared with those seen in 10 normal volunteers. Incremental intravenous infusion of isoprenaline (5, 10, and 15 ng/kg/min) raised heart rate to a greater extent in the donor compared with the recipient hearts in the eight patients who had heterotopic grafts (slopes [beats/min/ng/kg]: donor = +2.26, recipient = +1.59; p less than .01). In addition, the donor hearts of the transplant patients were more sensitive than hearts of the normal volunteers (slopes: donor = +2.26, normal = +0.94; p less than .01). The changes in the two groups of donor hearts were similar (slopes: orthotopic = +2.24, heterotopic = +2.27; NS). The recipient hearts in the patients with heterotopic transplants were more sensitive than the hearts of the normal volunteers (p less than .05), suggesting that the observed differences in isoprenaline sensitivity in the patients with heterotopic grafts were not caused by a decreased sensitivity of the recipient heart. After beta-blockade, the heart rate responses to isoprenaline were attenuated to the same extent in denervated and innervated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of betablockade on dynamic exercise in human heart transplant recipients.

We evaluated the tolerance of heart transplant recipients to acute betablockade during maximal dynamic exercise. Although the increase in rate and systolic blood pressure were attenuated, exercise tolerance was reduced by only about 15%, which is similar to that previously reported in normal individuals. Betablockade attenuated the increases in heart rate of the denervated donor hearts to a greater extent compared to the increases in the innervated recipient hearts in patients with heterotopic heart transplantation. Therefore, betablockers may be safely used in heart transplantation for appropriate indications such as hypertension.