Noninvasive assessment of alveolar microvascular recruitment in conscious non-sedated rats.

Recruitment of alveolar microvascular reserves, assessed from the relationship between pulmonary diffusing capacity (DLCO) and perfusion (Q˙c), is critical to the maintenance of arterial blood oxygenation. Leptin-resistant ZDF fatty diabetic (fa/fa) rats exhibit restricted cardiopulmonary physiology under anesthesia. To assess alveolar microvascular function in conscious, non-sedated, non-instrumented, and minimally restrained animals, we adapted a rebreathing technique to study fa/fa and control non-diabetic (+/+) rats (4-5 and 7-11mo old) at rest and during mild spontaneous activity. Measurements included O2 uptake, lung volume, Q˙c, DLCO, membrane diffusing capacity (DMCO), capillary blood volume (Vc) and septal tissue-blood volume. In older fa/fa than +/+ animals, DLCO and DMCO at a given Q˙c were lower; Vc was reduced in proportion to Q˙c. Results demonstrate the consequences of alveolar microangiopathy in the metabolic syndrome: lung volume restriction, reduced Q˙c, and elevated membrane resistance to diffusion. At a given Q˙c, DLCO is lower in rats and guinea pigs than dogs or humans, consistent with limited alveolar microvascular reserves in small animals.

Quantifying heterogeneity in emphysema from high-resolution computed tomography: a lung tissue research consortium study.

RATIONALE AND OBJECTIVES: To quantify spatial distribution of emphysema using high-resolution computed tomography (HRCT), we applied semiautomated analysis with internal attenuation calibration to measure regional air volume, tissue volume, and fractional tissue volume (FTV = tissue/[air + tissue] volume) in well-characterized patients studied by the Lung Tissue Research Consortium (LTRC). METHODS: HRCT was obtained at supine end-inspiration and end-expiration, and prone end-inspiration from 31 patients with mild, moderate, severe, or very severe emphysema (stages II-V, forced expiratory volume at 1 second >75%, 51%-75%, 21%-50% and ≤20% predicted, respectively). Control data were from 20 healthy non-smokers (stage I). Each lobe was analyzed separately. Heterogeneity of FTV was assessed from coefficients of variation (CV) within and among lobes, and the kurtosis and skewness of FTV histograms. RESULTS: In emphysema, lobar air volume increased up to 177% above normal except in the right middle lobe. Lobar tissue volume increased up to 107% in mild-moderate stages then normalized in advanced stages. Normally, FTV was up to 82% higher in lower than upper lobes. In mild-moderate emphysema, lobar FTV increased by up to 74% above normal at supine inspiration. In severe emphysema, FTV declined below normal in all lobes and positions in correlation with pulmonary function (P < .05). Markers of FTV heterogeneity increased steadily with disease stage in correlation with pulmonary function (P < .05); the pattern is distinct from that seen in interstitial lung disease (ILD). CONCLUSION: CT-derived biomarkers differentiate the spatial patterns of emphysema distribution and heterogeneity from that in ILD. Early emphysema is associated with elevated tissue volume and FTV, consistent with hyperemia, inflammation or atelectasis.