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The purpose of this work was to investigate whether endothelin-1 (ET-1) was able to induce the release of an inhibitory factor from the airway epithelium in isolated human bronchi and to identify this mediator as well as the endothelin receptor involved in this phenomenon. In intact bronchi, ET-1 induced a concentration-dependent contraction (−logEC50=7.92±0.09, n=18) which was potentiated by epithelium removal (−logEC50=8.65±0.11, n=17). BQ-123, an ETA receptor antagonist, induced a significant leftward shift of the ET-1 concentration-response curve (CRC). This leftward shift was abolished after epithelium removal. L-NAME (3×10−3M), an inhibitor of nitric oxide (NO) synthase, induced a significant leftward shift of the ET-1 CRC, and abolished the potentiation by BQ-123 (10−8 M) of ET-1-induced contraction. In intact preparations, the ETB receptor antagonist BQ-788 induced only at 10−5 M a slight rightward shift of the ET-1 CRC. In contrast, in epithelium-denuded bronchi or in intact preparations in the presence of L-NAME, BQ-788 displayed a non-competitive antagonism toward ET-1-induced contraction. IRL 1620, a selective ETB receptor agonist, induced a contraction of the isolated bronchus (−logEC50=7.94±0.11, n=19). This effect was not modified by epithelium removal or by BQ-123. BQ-788 exerted a competitive antagonism against IRL 1620 which was similar in the presence or absence of epithelium. These results show that ET-1 exerts two opposite effects on the human airway smooth muscle. One is contractile via ETB-receptor activation, the other is inhibitory and responsible of NO release which counteracts via ETA-receptor activation the contraction. British Journal of Pharmacology (1999) 126, 529–535; doi:10.1038/sj.bjp.0702327

The present case describes an acute respiratory-related hemodynamic failure during a single left lung transplantation in a 32-year-old woman suffering from end-stage pulmonary lymphangiomyomatosis. During the first 5 min of single right lung ventilation, a progressive increase in airway pressure and decrease in tidal volume associated with a decrease in arterial pressure and Spo2 occurred that were successfully countered by reventilation of the left lung. Proper positioning of the double-lumen tube was confirmed with a fiberoptic bronchoscope. Despite deliberate hypoventilation, within a few respiratory cycles, each further attempt at single lung ventilation was followed by abrupt hypotension, increase in pulmonary artery pressure, while airway pressure rose and tidal volume collapsed. The surgical team saw no signs of right pneumothorax. In these circumstances, cardiopulmonary bypass was required to perform pneumonectomy and grafting. Postoperatively a right anterior pneumothorax remained undiscovered on standard radiograph but was later revealed on soft radiograph. This acute intraoperative respiratory failure could equally well have been related to air trapping, in which case, however, deliberate hypoventilation would have been effective. In addition, the striking difference between the progressive onset of the first episode of hemodynamic failure and the immediate onset of the others argues in favor of a pneumothorax being at cause. Patients with pulmonary lymphangiomyomatosis are at high risk for intraoperative pneumothorax, but in our case, it could not be confirmed and treated during the surgical procedure without putting the patient at high risk for lung injury because of pleurodesis due to earlier pleural abrasion. This case again clearly shows the need to have cardiopulmonary bypass whenever single lung transplantation is performed.

Since 1975 200 tracheal sleeve resections for iatrogenic tracheal and subglottic laryngeal stenoses have been performed in our institution. Preoperative Nd:YAG laser is of paramount help in opening the stenoses. Tracheography is usually performed to specify the length of the stenosis and the distance from the vocal cords. Operative procedures are described. One hundred seventy five (87.5%) patients are definitely cured, but in this group 16 patients required a Montgomery tube for 6 months to 1 year to recover a normal tracheal diameter. Two patients needed a second tracheal sleeve resection. Nine (4.5%) patients died, and 16 (8%) had recurrent stenoses. Stenoses in these patients were treated with use of a tracheostomy tube, a permanent Montgomery tube, or an endotracheal stent. Partial anterior cricoid resections performed in 21 patients have had the same results as those of the whole series. Twenty one laryngeal releases were performed and proved to be efficient and safe. In our experience complications can be avoided by good selection and preparation of the patients, accurate identification of the level and length of the stenosis, and meticulous technique. (J T horac C ardiovasc S urg 1992;104:882-7)

Objective: The use of cardiopulmonary bypass (CPB) for lung transplantation (LTx) has been reported previously. This study reports the authors’ experience of planned and unplanned use of cardiopulmonary bypass for LTx. Design: Case series. Setting: A university teaching hospital. Participants: Patients undergoing LTx. Interventions: A retrospective analysis of the charts of all patients having undergone LTx over the last 10 years. Measurements and Main Results: Among 140 LTx, 23 (16%) were performed with the use of CPB. CPB was planned in 11 cases and unplanned in the 12 other cases. The use of CPB is associated with a longer period of postoperative mechanical ventilation, more pulmonary edema, more blood transfusion requirement, and an increase in postoperative mortality at 48 hours and 1 month. Surgical difficulties related to the dissection of the native left lung and acute right ventricular failure are the main reasons for unscheduled use of CPB. Conclusion: Scheduled and unscheduled CPB for LTx are associated with an increased mortality at 1 month and 1 year.

The aim of this study was to assess the influence of preservation solution type and extra- or intracellular composition on the occurrence of early graft dysfunction after clinical lung transplantation. For 170 patients who underwent a single (n = 124) or bilateral (n = 46) lung transplantation in two centers in Paris between 1988 and 1999, the preservation technique applied to the donor lung was single-flush perfusion of the pulmonary artery with one of several solutions of intracellular (Euro-Collins, n = 61; University of Wisconsin, n = 24) or extracellular composition (Cambridge, n = 64; Celsior, n = 21). The early postoperative outcome of these patients was reviewed. Reimplantation edema occurred in 48% of all patients, and the overall 1-mo survival rate was 84%. No significant difference in the incidence of edema, duration of mechanical ventilation, and 1-mo survival rate was observed between the four groups or between intra- and extracellular groups. After adjustment for graft ischemic time by means of multivariate analysis, the use of extracellular preservation fluid was associated with a lower incidence of reimplantation edema without effect on 1-mo mortality. Graft ischemic time was associated with both edema occurrence and 1-mo survival rate (p = 0.02 and p = 0.01, respectively). We conclude that extracellular-type solutions are associated with better lung preservation than intracellular-type solutions in clinical transplantation.

BACKGROUND: Nebulized cyclosporine (CsA) has been shown to limit lung allograft rejection as well as intramuscular (IM) CsA, with limited blood diffusion. The present study determined the pharmacokinetic parameters of nebulized CsA, by the assessment of regional lung deposition and extrapulmonary diffusion of CsA. METHODS: CsA was given either by IM injection (10 mg/kg) or by aerosol (at 10 and 25 mg/kg doses); 70 rats were killed at 25 and 50 min, and at 2, 4, 6, 8, 12, 24, or 48 hr after CsA administration. CsA levels were measured in the whole lung, in central and peripheral parts of the lung, in whole blood, kidney, and heart. The areas under the concentration time curves (AUCs) were determined. RESULTS: In blood, kidney, and heart, CsA levels were significantly higher for IM than for aerosol administrations at 10 and 25 mg/kg doses. In the whole lung, the AUC was greater for the aerosol route at 25 mg/kg doses (588 ng x hr/mg) than for the low-dose (200 ng x hr/mg) or IM administration (200 ng x hr/mg). The central to peripheral index of CsA (ratio of AUC central/peripheral part of the lung) was not significantly different for both aerosol administrations (0.63 and 0.69, respectively) and for the IM route (0.81). CONCLUSIONS: Nebulized CsA allows better pulmonary concentration than IM administration, with equivalent central and peripheral deposition whatever the mode of administration, and results in lower levels in blood, kidney, and heart.

It is difficult to find lungs of appropriate size for double-lung transplantation in teenagers and small adults. Nevertheless, many young patients suffering from cystic fibrosis are waiting for lung transplantation. We have performed two bilateral lobar transplantations (left lower lobe plus right middle and lower lobe) with good recovery. Details of the technique are described.

Bilateral lung transplantation (BLT) is a recently described procedure based on two sequential single-lung transplantations (SLT), which are performed by a transverse sternobithoracotomy. It does not require either cardiac arrest or routine use of cardiopulmonary bypass (CPB). The intraoperative management of 10 patients suffering from end-stage pulmonary disease is reported. Implantation of the first graft is quite similar to a SLT. Problems encountered during this procedure (ie, hypoxemia, hypercapnia, or low cardiac output) were due to restricted pulmonary and cardiac reserve. Preoperative and intraoperative assessment of the recipient's respiratory and cardiac status was, therefore, of prime importance. Mild preoperative pulmonary hypertension, well-preserved right ventricular function, and removal of the less well-perfused lung limited these difficulties; no patient required partial CPB at this stage. During the second lung implantation, gas exchange was provided by the first grafted lung. Measurements of pulmonary vascular resistance (PVR), venous admixture (Qva/Qt), and dead space (VD/VT) assessed with the arterial-to-end-tidal CO2 difference were used to confirm the adequacy of perfusion and V/Q matching. In one patient, partial CPB was instituted because of surgical difficulty related to inadequate size matching of the lungs. In the other patients, first graft function was satisfactory and the second graft was implanted without CPB. With chest closure, PVR returned to nearly normal values (range, 57-293, mean 167 dynes.s.cm-5) and Qva/Qt increased (range, 3 to 36, mean 20%). This limited series demonstrates that CPB is optional during this procedure. Good selection of recipients and donors, good lung preservation methods, and a short duration of cold ischemia are essential to success.