Search

To explore possible mechanisms responsible for the absence of cell re-colonization of mural thrombi in aneurysms, we analyzed the release and storage of leukocyte proteases in the most luminal layer versus intermediate and abluminal layers of 10 mural thrombi of human abdominal aortic aneurysms. The luminal layer contained many polymorphonuclear leukocytes (PMNs), which released pro-matrix metalloproteinase (MMP)-9 and MMP-8. Leukocyte elastase was also stored and released by the luminal layer (immunohistochemistry, activity on synthetic substrates, and casein zymography). Acid buffer allowed extraction of leukocyte elastase from the luminal layer, which was inhibited by elastase inhibitors. Casein zymography of luminal extracts and conditioned medium from formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMNs exhibited a similar lysis pattern, corresponding to elastase activity. Smooth muscle cell (SMC) seeding resulted in colonization of the intermediate thrombus layer ex vivo but not of the luminal layer. Extracts of the luminal layer induced loss of anchorage of both cultured human smooth muscle cells and stromal cells of bone marrow origin (anoikis). This anoikis was prevented by preincubation of the extracts with serine protease inhibitors. Moreover, adhesion of human SMCs and stromal bone marrow cells on fibrin gels was strongly inhibited when the gel was preincubated with pure elastase, medium of fMLP-stimulated PMNs, or extracts of luminal layers of mural thrombi. This loss of cell anchorage was prevented by the preincubation of the medium or extracts with alpha(1)-antitrypsin, but not when alpha(1)-antitrypsin was added after binding of elastase to the fibrin gel. In conclusion, elastase released by PMNs trapped within the mural thrombus impairs the spontaneous anchorage of mesenchymal cells to a fibrin matrix. This phenomenon could be one mechanism by which cellular healing of the mural thrombus in aneurysms is prevented.

In lung or heart-lung recipients, an irreversible graft-failure may develop in connection with chronic rejection, infection or bronchial complications. A limited number of transplant-recipients have undergone a retransplantation procedure in several centres. First results are discouraging, especially in the case of early retransplantation. We decided, 3 yrs ago, to evaluate the feasibility and benefits of single-lung retransplantation in lung-transplant recipients with late graft-failure. Eight consecutive single-lung retransplantations were performed in patients with previous single-lung (n = 7), or double-lung (n = 1) transplant. Primary graft and native lung were removed in 5 and 3 patients, respectively. The delay between the two surgical procedures was 16 +/- 10 months (range 6-37 months). Three patients died within 3 months. Long-term survivors experienced stable and satisfactory functional results (forced expiratory volume in one second (FEV1 63 +/- 21% predicted; range 40-103% predicted), with survival values ranging 8-20 months. One patient died of septic shock 16.5 months after retransplantation. The remaining four patients are alive. These data suggest that the retransplantation option could be considered in selected patients with late graft-failure. The final decision for retransplantation, however, is largely influenced by the current shortage of donor lungs.

A study was carried out in patients with intermittent claudication (Fontaine's stage II). The atheromatous origin of the disease was confirmed and localized by angiography or Doppler. One hundred eight-three patients were selected initially (day -30) with a pain-free walking distance on a treadmill (at a speed of 3 km/h and a slope of 10%) ranging from 150 to 300 m. During the first month (washout period) all patients received two placebo tablets daily. At the end of this run-in period (day -30; day 0) and after checking walking distance stability (allowed variation: 20% between the two measurements), patients were included in the study. According to this criterion, 112 patients were selected and 94 remained during the whole study. The study was designed in double-blind, using two parallel, randomly selected groups. Fifty-two patients received naftidrofuryl (2 x 316.5 mg tablets daily with meals) for 6 months; 42 patients received placebo under the same conditions. During this period, clinical and paraclinical examinations were carried out every quarter (day 90 and day 180). After checking the initial homogeneity of the naftidrofuryl and placebo groups, the comparison between the two groups indicates a significant improvement in the naftidrofuryl group after 3 months and 6 months of treatment, for the pain-free walking distance. For the maximal walking distance, a significant improvement was found at day 180. Nonparametric analysis (chi 2 test) also indicated a significant improvement for the naftidrofuryl group. These results confirm that naftidrofuryl is beneficial in the treatment of patients with chronic arterial disease.