The authors could detect regional neutrophil activation in VILI even when end-expiratory derecruitment was prevented and impairment of gas exchange was not evident. Concomitant end-expiratory derecruitment converted this activation into profound inflammation with decreased aeration and regional shunting.
Rationale: Bronchoconstriction in asthma leads to heterogeneous ventilation and the formation of large and contiguous ventilation defects in the lungs. However, the regional adaptations of pulmonary perfusion (Q ) to such ventilation defects have not been well studied. Methods: We used positron emission tomography to assess the intrapulmonary kinetics of intravenously infused tracer nitrogen-13 ( 13 NN), and measured the regional distributions of ventilation and perfusion in 11 patients with mild asthma. For each subject, the regional washout kinetics of 13 NN before and during methacholineinduced bronchoconstriction were analyzed. Two regions of interest (ROIs) were defined: one over a spatially contiguous area of high tracer retention (TR) during bronchoconstriction and a second one covering an area of similar size, showing minimal tracer retention (NR). Results: Both ROIs demonstrated heterogeneous washout kinetics, which could be described by a two-compartment model with fast and slow washout rates. We found a systematic reduction in regional Q to the TR ROI during bronchoconstriction and a variable and nonsignificant change in relative Q for NR regions. The reduction in regional Q was associated with an increase in regional gas content of the TR ROI, but its magnitude was greater than that anticipated solely by the change in regional lung inflation. Conclusion: During methacholine-induced bronchoconstriction, perfusion to ventilation defects are systematically reduced by a relative increase in regional pulmonary vascular resistance.Keywords: emission computed tomography; pulmonary gas exchange; vascular resistance; vasoconstriction; ventilation-perfusion ratio It is well established that severe heterogeneity of regional ventilation contributes significantly to gas exchange impairment in asthma. However, the extent to which regional pulmonary perfusion adapts to match changes in ventilation during an asthma attack is unknown. Evidence for severe heterogeneity of regional ventilation in patients with asthma has come from measurements with external scintillation counters (1, 2), single-photon emission computed tomography (CT) of Technegas (3), nuclear magnetic resonance imaging after a single-breath inhalation of hyperpolarized helium (4), and high-resolution CT (5-10). Most of these studies, however, did not quantify regional ventilation during normal breathing and did not evaluate the effect of bronchoconstriction on regional pulmonary perfusion.Changes in regional perfusion during bronchoconstriction (BC) have been measured using technetium ( 99m Tc)-labeled macroaggregated albumin (11,12). In one study, perfusion defects of segmental or smaller size were reported mainly at the periphery of middle or lower lung zones in children with asthma, despite normal chest X-rays, blood gases, and peak expiratory flows (13). That study, however, did not assess whether these perfusion defects corresponded to defects in ventilation. Another study assessed ventilation with krypton ( 81m Kr) gas and perfusion with 99m Tc ...
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