Worsening of lung perfusion to tissue density distributions during early acute lung injury.

Lung perfusion magnitude and distribution are essential for oxygenation and, potentially, lung inflammation and protection during acute respiratory distress syndrome (ARDS). Yet, perfusion patterns and their relationship to inflammation are unknown pre-ARDS. We aimed to assess perfusion/density ratios and spatial perfusion-density distributions and associate these to lung inflammation, during early lung injury in large animals at different physiological conditions caused by different systemic inflammation and positive end-expiratory pressure (PEEP) levels. Sheep were protectively ventilated (16-24 h) and imaged for lung density, pulmonary capillary perfusion (13Nitrogen-saline), and inflammation (18F-fluorodeoxyglucose) using positron emission and computed tomography. We studied four conditions: permissive atelectasis (PEEP = 0 cmH2O); and ARDSNet low-stretch PEEP-setting strategy with supine moderate or mild endotoxemia, and prone mild endotoxemia. Perfusion/density heterogeneity increased pre-ARDS in all groups. Perfusion redistribution to density depended on ventilation strategy and endotoxemia level, producing more atelectasis in mild than moderate endotoxemia (P = 0.010) with the oxygenation-based PEEP-setting strategy. The spatial distribution of 18F-fluorodeoxyglucose uptake was related to local Q/D (P < 0.001 for Q/D group interaction). Moderate endotoxemia yielded markedly low/zero perfusion in normal-low density lung, with 13Nitrogen-saline perfusion indicating nondependent capillary obliteration. Prone animals' perfusion was remarkably homogeneously distributed with density. Lung perfusion redistributes heterogeneously to density during pre-ARDS protective ventilation in animals. This is associated with increased inflammation, nondependent capillary obliteration, and lung derecruitment susceptibility depending on endotoxemia level and ventilation strategy.NEW & NOTEWORTHY Perfusion redistribution does not follow lung density redistribution in the first 16-24 h of systemic endotoxemia and protective tidal volume mechanical ventilation. The same oxygenation-based positive end-expiratory pressure (PEEP)-setting strategy can lead at different endotoxemia levels to different perfusion redistributions, PEEP values, and lung aerations, worsening lung biomechanical conditions. During early acute lung injury, regional perfusion-to-tissue density ratio is associated with increased neutrophilic inflammation, and susceptibility to nondependent capillary occlusion and lung derecruitment, potentially marking and/or driving lung injury.

Physiological mechanism and spatial distribution of increased alveolar dead-space in early ARDS: An experimental study.

BACKGROUND: We aimed to investigate the physiological mechanism and spatial distribution of increased physiological dead-space, an early marker of ARDS mortality, in the initial stages of ARDS. We hypothesized that: increased dead-space results from the spatial redistribution of pulmonary perfusion, not ventilation; such redistribution is not related to thromboembolism (ie, areas with perfusion = 0 and infinite ventilation-perfusion ratio, V ˙ / Q ˙ ), but rather to moderate shifts of perfusion increasing V ˙ / Q ˙ in non-dependent regions. METHODS: Five healthy anesthetized sheep received protective ventilation for 20 hours, while endotoxin was continuously infused. Maps of voxel-level lung ventilation, perfusion, V ˙ / Q ˙ , CO2 partial pressures, and alveolar dead-space fraction were estimated from positron emission tomography at baseline and 20 hours. RESULTS: Alveolar dead-space fraction increased during the 20 hours (+0.05, P = .031), mainly in non-dependent regions (+0.03, P = .031). This was mediated by perfusion redistribution away from non-dependent regions (-5.9%, P = .031), while the spatial distribution of ventilation did not change, resulting in increased V ˙ / Q ˙ in non-dependent regions. The increased alveolar dead-space derived mostly from areas with intermediate V ˙ / Q ˙ (0.5≤ V ˙ / Q ˙ ≤10), not areas of nearly "complete" dead-space ( V ˙ / Q ˙ >10). CONCLUSIONS: In this early ARDS model, increases in alveolar dead-space occur within 20 hours due to the regional redistribution of perfusion and not ventilation. This moderate redistribution suggests changes in the interplay between active and passive perfusion redistribution mechanisms (including hypoxic vasoconstriction and gravitational effects), not the appearance of thromboembolism. Hence, the association between mortality and increased dead-space possibly arises from the former, reflecting gas-exchange inefficiency due to perfusion heterogeneity. Such heterogeneity results from the injury and exhaustion of compensatory mechanisms for perfusion redistribution.