[Surgical treatment of chronic thromboembolic pulmonary hypertension]. / Traitement chirurgical de la maladie thromboembolique pulmonaire chronique.

Chronic thromboembolic pulmonary hypertension is a condition that has long remained in the shadows, a kind of orphan disease, because of the lack of any curative treatment. The renewal of interest by pulmonary specialists, cardiologists and thoracic surgeon is due to the development over the past 20 years of major new treatments: lung transplantation, continuous prostacyclin infusion, and pulmonary endarterectomy, in chronological order. Most patients with postembolic pulmonary arterial hypertension (PEPAH) in a sufficiently proximal location can benefit from curative surgical treatment by bilateral endarterectomy of the pulmonary arteries. This complex surgery, performed under deep hypothermic circulatory arrest, clears out the pulmonary vascular bed down through its subsegmental branches and results in a frank reduction in pulmonary vascular resistance and normalization of cardiopulmonary function. It is a curative procedure with a perioperative mortality rate less than 7% and a definitive result, unlike pulmonary and cardiopulmonary transplantation, which have a postoperative mortality rate of 20% and a 5-year survival rate of 50%. It is difficult to recognize the postembolic nature of pulmonary hypertension because there is no known history of venous thrombosis or embolic phenomena in more than 50% of cases. Diagnosis is based on the presence of mismatched segmental defects in the radioisotopic ventilation-perfusion scanning. To be accessible to endarterectomy, lesions must involve the main, lobar, or segmental arteries. When conducted by experienced operators according to specific protocols, pulmonary (frontal and lateral views of each lung) and multislice CT angiography optimize assessment of the lesion site. When the pulmonary vascular resistance evaluated by catheterization is correlated with the anatomical obstruction visible on the images, pulmonary endarterectomy has a mortality rate below 4% and offers the patient a substantial chance to regain normal cardiorespiratory function. In cases of pulmonary arterial hypertension due to older embolisms, major arteriolitis occurs in the nonobstructed areas and aggravates the pulmonary hypertension, which may become suprasystemic. The endarterectomy mortality rate is then higher, and in specific cases justifies preoperative medical treatment. Pulmonary or cardiopulmonary transplantation is indicated in this disease only when the lesions are too distal and thus inaccessible to endarterectomy.

[Surgical treatment of post-embolism pulmonary hypertension]. / Traitement chirurgical de l'hypertension artérielle pulmonaire post-embolique.

Pulmonary hypertension is a serous condition which, after a long history as an orphan disease, has raised renewed interest due to the development of efficacious therapeutic options including lung transplantation and continuous infusion of prostacycline. Bilateral endarteriectomy of the pulmonary arteries is another possibility for post-embolism pulmonary hypertension. The procedure is complex and must be performed in conditions of cardiac arrest and deep hypothermia but, unlike transplantation, provides definitive cure. Recognizing the post-embolic nature of pulmonary hypertension is not simple because old episodes of venous thrombosis or embolus migration are not found in 50% of patients. Segmentary defects on the perfusion scintigraphy contrasting with the homogeneous respiratory scintigraphy is the primary diagnostic feature. Lesions must be located in a main trunk or at the origin of lobular or segmentary branches to be accessible to endarteriectomy. An antero-posterior and lateral angiogram of each lung and a multiple-array helicoidal angioscan performed with a precise protocol by an experienced team are needed to identify the localization of the lesions. If the pulmonary resistance determined at right catheterism is correlated with anatomic obstruction, the risk of mortality of pulmonary endarteriectomy is low, offering patients a significant chance for normal or nearly normal cardiorespiratory function.

Chronic thromboembolic pulmonary hypertension.

Pulmonary arterial hypertension is a severe disease that has been ignored for a long time. However, over the past 20 yrs chest physicians, cardiologists and thoracic surgeons have shown increasing interest in this disease because of the development of new therapies, that have improved both the outcome and quality of life of patients, including pulmonary transplantation and prostacyclin therapy. Chronic thromboembolic pulmonary arterial hypertension (CTEPH) can be cured surgically through a complex surgical procedure: the pulmonary thromboendarterectomy. Pulmonary thromboendarterectomy is performed under hypothermia and total circulatory arrest. Due to clinically evident acute-pulmonary embolism episodes being absent in > 50% of patients, the diagnosis of CTEPH can be difficult. Lung scintiscan showing segmental mismatched perfusion defects is the best diagnostic tool to detect CTEPH. Pulmonary angiography confirms the diagnosis and determines the feasibility of endarterectomy according to the location of the disease, proximal versus distal. The technique of angiography must be perfect with the whole arterial tree captured on the same picture for each lung. The lesions must start at the level of the pulmonary artery trunk, or at the level of the lobar arteries, in order to find a plan for the endarterectomy. When the haemodynamic gravity corresponds to the degree of obliteration, pulmonary thromboendarterectomy can be performed with minimal perioperative mortality, providing definitive, excellent functional results in almost all cases.

Noninvasive ventilation reduces mortality in acute respiratory failure following lung resection.

When treated with invasive endotracheal mechanical ventilation (ETMV), acute respiratory insufficiency after lung resection is fatal in up to 80% of cases. Noninvasive positive-pressure ventilation (NPPV) may reduce the need for ETMV, thereby improving survival. We conducted a randomized prospective trial to compare standard therapy with and without nasal-mask NPPV in patients with acute hypoxemic respiratory insufficiency after lung resection. The primary outcome variable was the need for ETMV and the secondary outcome variables were in-hospital and 120-d mortality rates, duration of stay in the intensive care unit, and duration of in-hospital stay. Twelve of the 24 patients (50%) randomly assigned to the no-NPPV group required ETMV, versus only five of the 24 patients (20.8%) in the NPPV group (p = 0.035). Nine patients in the no-NPPV group died (37.5%), and three (12.5 %) patients in the NPPV group died (p = 0.045). The other secondary outcomes were similar in the two groups. NPPV is safe and effective in reducing the need for ETMV and improving survival after lung resection.

Factors affecting long-term survival after en-bloc resection of lung cancer invading the chest wall.

OBJECTIVE: Several reports emphasize the importance of en-bloc resection as the optimal surgical treatment of lung cancer with chest wall invasion. We investigated possible factors which could affect long-term survival following radical resection of these tumors. METHODS: Between 1981 and 1998, 100 patients (90 male; ten female), with a median age of 60 years (36-84), underwent radical en-bloc resection of non-small cell lung cancer (NSCLC) with chest wall involvement. Patients with superior sulcus tumors invading the thoracic inlet were excluded from this series. There were 43 squamous and 57 non-squamous tumors. The median number of resected ribs was three (1-5). Lung resection included 73 lobectomies, two bilobectomies, 18 pneumonectomies and seven segmentectomies. Chest wall resection also extended to the sternum in one patient, the transverse process in one, the costotransverse foramen and hemivertebrae in two. All patients had a complete resection. Sixty-three patients received postoperative radiotherapy and 12 received chemotherapy. Histological data, including differentiation and depth of chest wall invasion, were carefully reviewed. The effect of various factors on survival were studied. RESULTS: There were four in-hospital deaths. Lymph node involvement was negative on surgical specimens in 65 patients, and 28 patients had positive N1 nodes; the final histology revealed seven N2 diseases. Chest wall invasion was limited to the parietal pleura in 29 patients and included intercostal muscles, bones and extrathoracic muscles in 67, 24 and seven cases, respectively. The overall 2-year survival rate was 41%. The 5-year survival for patients with N0, N1 and N2 disease was 22, 9 and 0%, respectively. A local recurrence occurred in 13 patients, with four having a new resection and 45 patients developing systemic metastases. The nodal status (N0-1 vs. N2; P=0. 026) and the number of resected ribs(<2 vs. >2; P=0.03) were survival predictors in univariate analysis. By multivariate analysis, the two independent factors affecting long-term survival were the histological differentiation (well vs. poorly differentiated; P=0. 01) and the depth of chest wall invasion (parietal pleura vs. others; P=0.024). CONCLUSIONS: Histological differentiation and depth of chest wall involvement were the main factors affecting long-term survival in this series. The role of induction chemotherapy for tumors with poor prognosis should be investigated.

Angioscopic video-assisted pulmonary endarterectomy for post-embolic pulmonary hypertension.

OBJECTIVES: To assess whether the use of video-assisted angioscopy would increase the outcome of pulmonary thromboendarterectomy (PTE). METHODS: PTE included a median sternotomy, intrapericardial dissection of the superior vena cava, institution of cardiopulmonary bypass, deep hypothermia and sequential circulatory arrest periods. It was always performed through two separate arteriotomies on both main intrapericardial pulmonary arteries, into which a rigid 5 mm angioscope connected to a video camera was introduced to increase the visibility and endarterectomies. RESULTS: From January 1996 to July 1998, 68 consecutive patients (35 males and 33 females) aged 54.3 +/- 13.5 years underwent PTE. Patients were in New York Heart Association (NYHA) class II (n = 2), III (n = 43) or IV (n = 23) with the following hemodynamics: mean pulmonary arterial pressure (PAP) 54 +/- 13 mmHg; cardiac output (CO): 3.8 +/- 0.8 l/min, and total pulmonary resistance (TPR): 1207 +/- 416 dyne x s x cm(-5). The cumulated circulatory arrest time was 23 +/- 12 min and postoperative length of ventilatory support 10 +/- 12 days. Nine patients died, for an overall in-hospital mortality of 13.2%. The functional outcome in surviving patients was significantly improved (P < 0.0001) both clinically (NYHA class 3.2 +/- 0.5 vs. 1.3 +/- 0.6) and hemodynamically (PAP (mmHg) 53.1 +/- 13 vs. 30.2 +/- 11.8, CI (l/min per m2) 2.1 +/- 0.5 vs. 2.8 +/- 0.6, TPR (dyne x s x cm(-5)) 1174 +/- 416 vs. 519 +/- 250). CONCLUSIONS: Video-assisted angioscopy improves the quality and degree of pulmonary endarterectomy expanding the indications to include patients with previously inaccessible distal disease.

Clamshell or sternotomy for double lung or heart-lung transplantation?

OBJECTIVE: To evaluate the influence of either incision on the lungs and chest wall. METHODS: Ninety-two double lung (DLT) or heart-lung (HLT) transplantations were done since January 1990. There were 22 (24%) hospital deaths, leaving 70 patients with complete data for evaluation. We did 38 DLT and 32 HLT for end-stage chronic respiratory failure (n = 22) and primary (n = 34) or secondary (n = 14) pulmonary hypertension, using 37 fourth or fifth interspace clamshell incisions and 33 median sternotomies. RESULTS: The clamshell group included a higher percentage of DLTs (73 vs. 33%, P = 0.001) but recipient age, gender, preoperative diagnosis, bronchial anastomotic complications, number of cytomegalovirus infection, episode of acute rejection per patient-months and incidence of bronchiolitis obliterans were not statistically different between the two groups. At a follow-up time of 3.7 +/- 2 years, the overall 5-year survival of 57% was not influenced by the type of incision. The clamshell incision caused sternal over-riding in 12 (32%) patients, and eight surgical clamshell revision were necessary as compared with one median sternotomy (P = 0.02). The clamshell incision was associated with a significantly higher incidence of postoperative chronic pain (27 vs. 6%, P = 0.02). Postoperative mechanical properties of the chest wall were significantly (P < 0.0001) worse in the clamshell-group patients while the intrinsic properties of the airways were not different. CONCLUSIONS: The clamshell incision results in more postoperative deformity, chronic pain, and impaired function as compared with median sternotomy. A bilateral anterolateral thoracotomy without division of the sternum is proposed for the sequential bilateral lung transplantation technique.

Subclavian artery resection and reconstruction for thoracic inlet cancers.

PURPOSE: We previously described an original transcervical approach to resect primary or secondary malignant diseases that invade the thoracic inlet (TI). The purpose of this study was to evaluate the technical aspects and long-term results of the resection and revascularization of the subclavian artery (SA). METHODS: Between 1986 and 1998, 34 patients (mean age, 49 years) underwent en bloc resection of TI cancer that had invaded the SA. The surgical approach was an L-shaped transclavicular cervicotomy in 33 patients. In 14 of these patients, this approach was associated with a posterolateral thoracotomy (n = 10) or a posterior midline approach (n = 4). In one patient, the procedure was achieved with a single posterolateral thoracotomy approach. An end-to-end anastomosis was performed in 16 patients. In one patient, a subclavian-left common carotid artery transposition was performed. In one other patient, an end-to-end anastomosis was performed between the proximal innominate artery and the SA. The right carotid artery was transposed into the SA in an end-to-side fashion. In 16 patients, prosthetic revascularization with a polytetrafluoroethylene graft was performed. Thirty-three patients underwent postoperative radiation therapy. RESULTS: There were no cases of perioperative death, neurologic sequelae, graft infections or occlusions, or limb ischemia. There were two delayed asymptomatic polytetrafluoroethylene graft occlusions at 12 and 31 months. The 5-year patency rate was 85%. During this study, 20 patients died: 18 died of tumor recurrence (5 local and systemic and 13 systemic), one of respiratory failure, and one of an unknown cause at 74 months. The overall 5-year survival rate was 36%, and the 5-year disease-free survival rate was 18%. CONCLUSION: Tumor arterial invasion per se should not be a contraindication to TI cancer resection. This study shows that cancers that invade the SA can be resected through an L-shaped transclavicular cervicotomy, with good results with a concomitant revascularization of the SA.

Expression and modulation of ICAM-1, TNF-alpha and RANTES in human alveolar macrophages from lung-transplant recipients in vitro.

Alveolar macrophages (AMs) play a central role in pulmonary inflammation in response to local stimuli. As a model for investigating anti-inflammatory drugs, we studied the effects of the cyclohexadepsipeptide antibiotic, fusafungine, and that of the glucocorticoid dexamethasone on the expression of ICAM-1, TNF-alpha and RANTES, induced in vitro by rIFN-gamma in human AMs freshly isolated from bronchoalveolar lavage fluid (BAL) obtained in lung-transplanted patients. ICAM-1 antigen expression, induced on AMs after 24 h of culture, was significantly inhibited by fusafungine in a concentration-dependent manner, as measured by flow cytometry analysis using an anti-CD54 monoclonal antibody. TNF-alpha production, but not RANTES release (measured by ELISA), was significantly inhibited. mRNA studies, by means of polymerase chain reaction amplification of complementary deoxyribonucleic acids (RT-PCR), showed no significant modification of mRNA levels, suggesting that fusafungine acts mainly at a post-transcriptional level. In the same conditions, dexamethasone significantly inhibited the release both of TNF-alpha and RANTES by AMs, mainly acting at the mRNA level, but had no effect on ICAM-1 expression. Assessment of the cellular and molecular targets of anti-inflammatory drugs in this model of human AM activation should lead to more appropriate treatment of inflammatory process of the respiratory tract. By virtue of its anti-inflammatory effects on alveolar macrophages, combined with its antibacterial properties, fusafungine should prove particularly suitable for local treatment of bacterial infections of the respiratory tract.

[Pulmonary thromboendarterectomy with video-angioscopy and circulatory arrest: an alternative to cardiopulmonary transplantation and post-embolism pulmonary artery hypertension]. / Thrombo-endartériectomie pulmonaire sous vidéo-angioscopie et arrêt circulatoire: une alternative à la transplantation cardiopulmonaire dans l'hypertension artérielle pulmonaire postembolique.

The best predictor of poor or suboptimum outcome from pulmonary thromboendarterectomy (PTE) is insufficient relief of obstruction, especially in the lower lobes. The aim of this study is to emphasize that the use of video-assisted angioscopy may increase the quality of PTE and thus improve outcome. PTE included a median sternotomy, intrapericardial dissection limited to the superior vena cava, institution of cardiopulmonary bypass, deep hypothermia and sequential circulatory arrest periods. PTE was always bilateral and performed through two separate arteriotomies of both main intrapericardial pulmonary arteries. A rigid 5 mm angioscope connected to a video camera was introduced through the arteriotomy into the lumen to increase the visibility and perform the video-assisted endarterectomies of all obstructed segmental branches, including normally inaccessible anterior segmental branches. Between January 1996 and December 1997, 48 patients with severe postembolic pulmonary hypertension had PTE. Patients were in New York Heart Association (NYHA) class II (n = 2), III (n = 28) or IV (n = 18) with the following hemodynamics: mean pulmonary arterial pressure (PAP) 53 +/- 13 mmHg, cardiac index 2.16 +/- 0.5 L/min/m2, pulmonary vascular resistances (PVR): 1,152 +/- 414 dyne.s-1.cm-5. Six patients died from alveolar hemorrhage (n = 1), high residual pulmonary pressure and rethrombosis (n = 4) and hypoxic cardiac arrest (n = 1). The functional outcome in surviving patients was as follows: (NYHA) class I (n = 24), II (n = 16) or III (n = 2) with improved hemodynamics: mean pulmonary arterial pressure: 30 +/- 9 mmHg, cardiac index: 2.78 +/- 0.5 L/min/m2, pulmonary vascular resistances (PVR): 484 +/- 159 dynes.s-1.cm-5. Video-assisted angioscopy allows much improved quality and degree of pulmonary endarterectomy. This expands the indications to include patients with previously inaccessible distal disease and candidates for heart-lung transplantation.

Prognostic value of pulmonary hypertension in patients with chronic interstitial lung disease referred for lung or heart-lung transplantation.

BACKGROUND: The purpose of this study was to identify precise and reliable prognostic parameters in patients affected by serious chronic interstitial lung disease, who were undergoing screening for lung or heart-lung transplantation. METHODS: Hemodynamic and respiratory function parameters of 67 patients (43 with idiopathic pulmonary fibrosis, 18 with histiocytosis X, and 6 with lymphangioleiomyomatosis) undergoing clinical screening for lung transplantation. RESULTS: Statistical analysis showed that hemodynamic and respiratory function parameters in patients affected by histiocytosis X and idiopathic pulmonary fibrosis were not related to survival time. Moreover, the degree of pulmonary hypertension showed no correlation between respiratory function parameters in all the groups of diseases examined. Patients affected with histiocytosis X, even with higher degrees of pulmonary hypertension, had a better survival rate (p < 0.0005) compared with patients with idiopathic pulmonary fibrosis. CONCLUSIONS: Hemodynamic and respiratory parameters obtained during the clinical screening for lung transplantation do not predict survival and cannot be used as prognostic indicators.

Aspergillus osteomyelitis after heart-lung transplantation.

Aspergillus osteomyelitis is a severe complication of invasive aspergillosis. Fewer than 15 cases have been observed after solid organ transplantation. We describe a case of Aspergillus osteomyelitis of the ilium after heart-lung transplantation with favorable outcome after medical treatment.

Respiratory sensation related to resistive loads in lung transplant recipients.

In order to assess the contribution of pulmonary afferent nerves to the processing of respiratory sensation, we compared sensation related to inspiratory resistive loaded breathing in 14 lung transplant recipients with normal lung function with that in 14 matched healthy control subjects. Respiratory sensation was characterized for each subject by the correlation coefficient and slope of the linear relationship between the intensity of sensation (expressed as Borg scores [BSc]) and peak inspiratory mouth pressure (peak Pm), which was considered the main physical stimulus of the sensation. Individual correlation coefficients were very high and did not differ between lung transplant recipients and controls. In contrast, individual slopes of BSc as a function of peak Pm (BSc/peak Pm slopes) were significantly lower in lung transplant recipients than in controls (0.63 versus 1.26; p < 0.01). Furthermore, ventilatory responses to external loads differed significantly between lung transplant recipients and controls in terms of higher values and ranges of generated peak Pm and peak inspiratory flow in lung transplant recipients than in controls (all p < 0.05). These results suggest that pulmonary afferent nerves may contribute to ventilatory and sensory responses to external loads. However, as suggested by the inverse relation between BSc/peak Pm slopes and peak Pm ranges, higher stimulus ranges in lung transplant recipients may also have contributed to intergroup differences in respiratory sensation related to loaded breathing.

Intrapulmonary production of RANTES during rejection and CMV pneumonitis after lung transplantation.

RANTES (regulated upon activation, normally T expressed and secreted) is a chemoattractant for macrophages, memory T lymphocytes, and eosinophils. We investigated whether intrapulmonary production of the chemokine RANTES contributes to the recruitment of immune cells during lung transplantation complications. RANTES concentration was measured in bronchoalveolar lavage (BAL) fluids using an ELISA assay. It was significantly higher during CMV pneumonitis (36.2 +/- l6 pg/ml, n=12, P=0.031) and allograft rejection (31.1 +/- 8.5 pg/ml, n=27, P=0.013) than in patients without complications (9.1 +/- 2.3 pg/ml, n=22). At least some of the RANTES was produced by lung macrophages: BAL macrophages cultured for 24 hr spontaneously released larger amount of RANTES during CMV pneumonitis (140 +/- 53 pg/ml, n=8, P=0.002) and allograft rejection (84 +/- 44 pg/ml, n=11, P=0.037) than in control patients (15.2 +/- 6.5 pg/ml, n=21). Moreover, macrophages in transbronchial biopsies were labeled by an anti-RANTES mAb. RANTES production by BAL macrophages was followed in 2 patients with CMV pneumonitis. It remained high as long as CMV-induced cytopathic effects or clinical symptoms were present, but it returned to baseline as the infection was controlled. These results suggest that the intrapulmonary production of the chemokine RANTES by activated macrophages contributes to the intrapulmonary accumulation of immune cells during complications of lung transplantation.

Modulation of ICAM-1 expression in human alveolar macrophages in vitro.

Modulation of intercellular adhesion molecule-1 (ICAM-1) expression may be a basic mechanism by which alveolar macrophages (AMs) regulate the inflammatory process in the lung in response to local stimuli. As a model for studying the anti-inflammatory activity of drugs on human AMs, we investigated the effects of fusafungine, an antibiotic for local use by aerosol with anti-inflammatory properties, and that of the glucocorticoid dexamethasone, on ICAM-1 expression induced in vitro by recombinant interferon-gamma (rIFN-gamma). ICAM-1 protein expression was studied on AMs by means of flow cytometry with an anti-CD54 monoclonal antibody; messenger ribonucleic acid (mRNA) levels were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). ICAM-1 was expressed before culture on 21% of bronchoalveolar lavage (BAL) cells, with low intensity. Culture for 24 h with rIFN-gamma resulted in a significant increase in ICAM-1 protein expression (82% of cells were strongly positive). Fusafungine significantly inhibited rIFN-gamma-induced ICAM-1-protein expression on AMs in a concentration-dependent fashion. The mechanism of ICAM-1 downregulation was mainly post-transcriptional, but also partly transcriptional. By contrast, dexamethasone did not influence rIFN-gamma-induced ICAM-1 expression. This in vitro model using human AMs should prove useful for investigating the cellular and molecular targets of anti-inflammatory drugs.

Successful chemotherapy including epirubicin in a pregnant non-Hodgkin's lymphoma patient.

We report a case of non-Hodgkin's lymphoma (NHL) successfully treated with combination chemotherapy during pregnancy. The histological diagnosis was large-cell B-type NHL. Four courses of chemotherapy with epirubicin, vincristine and prednisolone were given before delivery. The patient is in complete remission and her baby, now four years old, has developed normally. To our knowledge, this is the first reported case of epirubicin administration during pregnancy and in which chemotherapy was given safely to NHL patients during the second and third trimester of pregnancy.

Vascular ring causing symptomatic tracheal compression in adulthood.

A 32-year-old woman was referred for evaluation of a 3-year history of exertion dyspnea. An anomalous vascular ring created by a right aortic arch with mirror-image branching, left descending aorta, and aortic diverticulum narrowed the trachea circumferentially. This feature was surgically approached through a right posterolateral thoracotomy, and simple amputation of the aortic diverticulum resulted in immediate symptomatic relief.

Increased plasma serotonin in primary pulmonary hypertension.

PURPOSE: Pulmonary hypertension can occur in patients who have disorders associated with altered platelet serotonin storage, including collagen vascular disease and platelet storage pool disease. We tested the hypothesis that primary pulmonary hypertension (PPH) may be also associated with impaired handling of serotonin by platelets, resulting in increased plasma serotonin levels. PATIENTS AND METHODS: We used radioenzymatic assays to measure serotonin in platelets and plasma and serotonin released during in vitro platelet aggregation in 16 patients with PPH, and in 16 normal controls matched for age and sex. Six patients were restudied after heart-lung transplantation to determine whether serotonin abnormalities persisted after pulmonary arterial pressure returned to normal. RESULTS: Patients had decreased platelet serotonin concentration (1.8 +/- 0.6 x 10(-18) mol/platelet versus 3.2 +/- 0.2 x 10(-18) mol/platelet in controls; P < 0.01) and increased plasma serotonin concentration (30.1 +/- 9.2 x 10(-9) mol/L versus 0.6 +/- 0.1 x 10(-9) mol/L in controls; P < 0.001). Serotonin released during in vitro platelet aggregation was higher in patients than in controls. After heart-lung transplantation, platelet serotonin concentrations remained decreased and plasma levels remained increased. CONCLUSIONS: Abnormal handling of serotonin by platelets leading to an increase in plasma serotonin occurs in PPH. The persistent decrease in platelet storage of serotonin after heart-lung transplantation suggests that this platelet abnormality is not secondary to PPH.

[Expression of intercellular adhesion molecule 1 (ICAM-1) on human alveolar macrophages]. / Expression de la molécule d'adhésion intercellulaire 1 (ICAM-1) sur les macrophages alvéolaires humains.

Modulation of intercellular adhesion molecule 1 (ICAM-1) expression on alveolar macrophages (AM) may be one of the the basic mechanisms by which AM regulate the course of inflammatory response during pulmonary allograft rejection and infectious processes by mediating macrophage-lymphocyte interactions. As a model for studying anti-inflammatory activity of drugs on AM, we have investigated the effect of fusafungine, a local antibiotic which displays also anti-inflammatory properties, on the regulation of ICAM-1 membrane expression induced in vitro by stimulating AM from lung-transplant recipients. We have studied ICAM-1 membrane expression by immunocytofluorometric analysis using the anti-CD54 monoclonal antibody. The ICAM-1 molecule was expressed on 10 to 47% of freshly isolated AM, depending on the clinical status of the patients. After 24 hr cultivation with 250 U/ml gamma-IFN, the percentage of ICAM-1+ AM s increased to more than 90%. When added with the stimulating agent, fusafungine could inhibit the induction of ICAM-1 membrane expression, up to 90% of inhibition at 8 microgram/ml. However, once ICAM-1 was induced after 24 hr cultivation upon stimulation, fusafungine could not afford any reversion. On going investigations on mRNA for ICAM-1 should indicate whether fusafungine acts at the transcriptional level. These results clearly demonstrate the capacity of fusafungine to down-regulate ICAM-1 expression on AM upon activation. This approach could represent a useful tool for in vitro study of drug efficacy upon inflammatory processes of the respiratory mucasa.