We read with interest the review of JANSSENS et al. [1] entitled "Physiological changes in respiratory function associated with ageing", more specifically the subheading devoted to changes in arterial oxygenation and ventilation-perfusion (V ©/Q ©) relationships. Although the seminal study of WAGNER et al.[2] was addressed in full, it was a shame that they did not discuss the more recent comprehensive work of our group in this field [3]. We extensively investigated the distributions of V ©/Q © ratios in 64 healthy individuals aged 18±71 yrs. The principal findings of that study were: 1) that V ©/Q © imbalance, but not increased intrapulmonary shunting, did increase with age as previously expected; 2) that the increase over the span of~50 yrs was physiologically very small; 3) that most of the variance in V ©/Q © mismatch in this cohort of subjects was not due to ageing and remained unsettled; and 4) that the fall in arterial partial pressure of oxygen (PO 2 ) with age was also quite small but was internally consistent with the V ©/Q © changes measured independently.V ©/Q © relationships were characterized in most of these healthy individuals by narrow distributions that widened slightly with age together with a trivial shunt of <1% of the cardiac output in 90% of cases. Both the second moments (dispersions) of pulmonary blood flow (Log SDQ) and of alveolar ventilation (Log SDV) increased by~0.1 between 20±70 yrs. Accordingly, the dispersion of pulmonary perfusion (Log SDQ) increased from 0.36±0.47, akin to a decrease of oxygen tension in arterial blood (Pa,O 2 ) of only~6 mmHg. Only 10% of the total variance was attributed to age. A similar amount was due to intrasubject variability, but none was due to variations in other factors, such as forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC) ratio, weight or height. We did not measure closing volume and it is therefore likely that age could disturb V ©/Q © matching as a result of increases in closing volume. However, since the latter mechanism is highly unlikely to influence V ©/ Q © relationships in young healthy individuals [4], and since the variance of the dispersion of pulmonary blood flow was as large amongst the subset of young as that of old individuals, we would postulate that increased closing volume is not a determinant factor of the variance in V ©/Q © homogeneity.

Tumor necrosis factor-alpha (TNF-alpha) activates sodium channels in Type II alveolar epithelial cells, an important mechanism for the reported fluid resorption capacity of the cytokine. Both TNF-alpha receptor-dependent and -independent effects were proposed for this activity in vitro, the latter mechanism mediated by the lectin-like domain of the molecule. In this study, the relative contribution of the receptor-dependent versus receptor-independent activities was investigated in an in situ mouse lung model and an ex vivo rat lung model. Fluid resorption due to murine TNF-alpha (mTNF-alpha) was functional in mice that were genetically deficient in both types of mTNF-alpha receptor, establishing the importance of mTNF-alpha receptor-independent effects in this species. In addition, we assessed the capacity of an mTNF-alpha-derived peptide (mLtip), which activates sodium transport by a receptor-independent mechanism, to reduce lung water content in an isolated, ventilated, autologous blood-perfused rat lung model. The results show that in this model, mLtip, in contrast to mTNF-alpha, produced a progressive recovery of dynamic lung compliance and airway resistance after alveolar flooding. There was also a significant reduction in lung water. These results indicate that the receptor-independent lectin-like domain of mTNF-alpha has a potential physiological role in the resolution of alveolar edema in rats and mice.

Background and Purpose-We sought to quantitatively and qualitatively evaluate the release of atheromatous plaque debris induced by carotid stenting procedures. Methods-Eight patients with severe carotid atheromatous stenoses were treated by stent implantation under distal balloon protection. Blood samplings were obtained after stent deployment in the blood pooled below the inflated protection balloon. The samples were centrifuged and evaluated for plaque debris with the use of light microscopy. The debris release was quantitatively estimated by dividing the total volume of debris obtained by the mean debris size. Five patients without endovascular procedure were used as a control group. Results-The 2 main debris types found were nonrefringent cholesterol crystals (4 to 389 m; 115 to 8697 in number) and lipoid masses (7 to 600 m; 341 to 34 000 in number). There was a statistically significant difference compared with the samples obtained in the control group (Pϭ0.017). Conclusions-Blood

volvement of pulmonary circulation in the mechanical properties was studied in isolated rat lungs. Pulmonary input impedance (ZL) was measured at a mean transpulmonary pressure (Ptp mean) of 2 cmH2O before and after physiological perfusion with either blood or albumin. In these lungs and in a group of unperfused lungs, ZL was also measured at Ptp mean values between 1 and 8 cmH2O. Airway resistance (R aw) and parenchymal damping (G) and elastance (H) were estimated from ZL. End-expiratory lung volume (EELV) was measured by immersion before and after blood perfusion. The orientation of the elastin fibers relative to the basal membrane was assessed in additional unperfused and blood-perfused lungs. Pressurization of the pulmonary capillaries significantly decreased H by 31.5 Ϯ 3.7% and 18.7 Ϯ 2.7% for blood and albumin, respectively. Perfusion had no effect on R aw but markedly altered the Ptpmean dependences of G and H Ͻ4 cmH 2O, with significantly lower values than in the unperfused lungs. At a Ptp mean of 2 cmH2O, EELV increased by 31 Ϯ 11% (P ϭ 0.01) following pressurization of the capillaries, and the elastin fibers became more parallel to the basal membrane. Because the organization of elastin fibers results in smaller H values of the individual alveolus, the higher H in the unperfused lungs is probably due to a partial alveolar collapse leading to a loss in lung volume. We conclude that the physiological pressure in the pulmonary capillaries is an important mechanical factor in the maintenance of the stability of the alveolar architecture. forced oscillations; alveolar wall; elastin; end-expiratory lung volume THE MECHANICAL PROPERTIES of the lungs are significantly influenced by changes in the pulmonary hemodynamic conditions (3,7,9,11,20,21, 27,29,(35)(36)(37)40). Numerous clinical (3,7,9,11,20, 27) and experimental studies (29,36,37) have demonstrated that elevation of the pulmonary blood flow (7,20, 27) and/or pressure (3, 11, 29, 36, 37) leads to a deterioration of the lung function via a decrease in functional residual capacity (FRC) (7) and/or stiffening of the alveolar wall (40). Although the qualitative examinations performed by von Basch (38a) in 1889 suggested that not only congestion, but also pulmonary hypoperfusion, can alter the lung configuration, few data are available concerning the changes in the mechanical conditions of the lungs during hypoperfusion or the complete absence of pulmonary perfusion (21,25,29,35). Mitzner et al. (25) observed a transient increase in the respiratory resistance and a decrease in the compliance after occluding a pulmonary artery in mice, but the explanation of this finding remained unclarified. Furthermore, we recently demonstrated that low pulmonary venous pressures cause an impairment in lung mechanics, manifested in increases in the parenchymal resistive and elastic parameters, while the airway properties remain unaffected (29). However, the mechanisms responsible for the compromised lung mechanics at low vascular pressure or when there is no perfusion ...