Topographic basis of bimodal ventilation-perfusion distributions during bronchoconstriction in sheep.

The distribution of ventilation-perfusion (VA/Q) ratios during bronchoconstriction measured with the multiple inert gases elimination technique is frequently bimodal. However, the topographic basis and the cause of that bimodality remain unknown. In this article, regional VA/Q is quantified by three-dimensional positron emission tomography (PET) imaging of methacholine-induced bronchoconstriction in sheep. Regional VA/Q ratios were calculated from the imaged kinetics of intravenously injected 13NN-saline bolus, assembled into global VA/Q distributions, and used to estimate gas exchange. During bronchoconstriction, large regions with impaired tracer washout were observed adjacent to regions of normal ventilation. PET-derived VA/Q distributions during bronchoconstriction were consistently bimodal, with areas of low VA/Q receiving a large fraction of Q. The standard deviation of the VA/Q distribution was 38% lower if small-scale (subresolution) heterogeneity (< 2.2 cm3) was ignored. Arterial blood gases predicted from PET data correlated well with measured values for Pa(O2) (r2= 0.91, p < 0.01) and Pa(CO2) (r2= 0.90, p < 0.01). We conclude that the bimodality of VA/Q distributions in bronchoconstriction reflects the involvement of large contiguous regions of hypoventilation with substantial subresolution intraregional VA/Q heterogeneity. Assessment of the subresolution VA/Q heterogeneity is therefore essential to accurately quantify global gas exchange impairment during bronchoconstriction.

Mechanism by which a sustained inflation can worsen oxygenation in acute lung injury.

BACKGROUND: Sustained lung inflations (recruitment maneuvers [RMs]) are occasionally used during mechanical ventilation of patients with acute lung injury to restore aeration to atelectatic alveoli. However, RMs do not improve, and may even worsen, gas exchange in a fraction of these patients. In this study, the authors sought to determine the mechanism by which an RM can impair gas exchange in acute lung injury. METHODS: The authors selected a model of acute lung injury that was unlikely to exhibit sustained recruitment in response to a lung inflation. In five sheep, lung injury was induced by lavage with 0.2% polysorbate 80 in saline. Positron emission tomography and [13N]nitrogen were used to assess regional lung function in dependent, middle, and nondependent lung regions. Physiologic data and positron emission scans were collected before and 5 min after a sustained inflation (continuous positive airway pressure of 50 cm H2O for 30 s). RESULTS: All animals showed greater loss of aeration and higher perfusion and shunting blood flow in the dependent region. After the RM, Pao2 decreased in all animals by 35 +/- 22 mmHg (P < 0.05). This decrease in Pao2 was associated with redistribution of pulmonary blood flow from the middle, more aerated region to the dependent, less aerated region (P < 0.05) and with an increase in the fraction of pulmonary blood flow that was shunted in the dependent region (P < 0.05). Neither respiratory compliance nor aeration of the dependent region improved after the RM. CONCLUSIONS: When a sustained inflation does not restore aeration to atelectatic regions, it can worsen oxygenation by increasing the fraction of pulmonary blood flow that is shunted in nonaerated regions.

Topographical distribution of pulmonary perfusion and ventilation, assessed by PET in supine and prone humans.

Using positron emission tomography (PET) and intravenously injected (13)N(2), we assessed the topographical distribution of pulmonary perfusion (Q) and ventilation (V) in six healthy, spontaneously breathing subjects in the supine and prone position. In this technique, the intrapulmonary distribution of (13)N(2), measured during a short apnea, is proportional to regional Q. After resumption of breathing, regional specific alveolar V (sVA, ventilation per unit of alveolar gas volume) can be calculated from the tracer washout rate. The PET scanner imaged 15 contiguous, 6-mm-thick, slices of lung. Vertical gradients of Q and sVA were computed by linear regression, and spatial heterogeneity was assessed from the squared coefficient of variation (CV(2)). Both CV and CV were corrected for the estimated contribution of random imaging noise. We found that 1) both Q and V had vertical gradients favoring dependent lung regions, 2) vertical gradients were similar in the supine and prone position and explained, on average, 24% of Q heterogeneity and 8% of V heterogeneity, 3) CV was similar in the supine and prone position, and 4) CV was lower in the prone position. We conclude that, in recumbent, spontaneously breathing humans, 1) vertical gradients favoring dependent lung regions explain a significant fraction of heterogeneity, especially of Q, and 2) although Q does not seem to be systematically more homogeneous in the prone position, differences in individual behaviors may make the prone position advantageous, in terms of V-to-Q matching, in selected subjects.