The distribution of ventilation during bronchoconstriction is patchy and bimodal: A PET imaging study
Introduction
distribution in asthmatics and bronchoconstricted animals has been shown to be bimodal (Rubinfeld et al., 1978, Wagner et al., 1978, Wagner et al., 1987) and regionally patchy (de Siqueira et al., 1997, Horsley et al., 1985, King et al., 1998). In a recent report, we presented PET derived distributions obtained from bronchoconstricted sheep (Vidal Melo et al., 2005). These distributions were bimodal and showed a patchy distribution of regional ventilation (). Further analysis demonstrated a large fraction of the measured heterogeneity in at sub-resolution levels (<2.2 ml) and that sub-resolution heterogeneity contributed significantly to the bimodality in in all animals studied. Although it is expected that the heterogeneity caused by bronchoconstriction should be mostly caused by heterogeneity, our previous analysis did not determine the extent to which the reported heterogeneity and bimodality of the distribution was due to spatial heterogeneity in or , nor the contribution of the observed patchiness in ventilation to global heterogeneity in . It also remained unclear whether regions of reduced ventilation during inhaled methacholine had any recognizable predisposition for bronchoconstriction as compared to the other lung regions. In this paper, we reanalyze the previous experimental data to establish the contribution of heterogeneity to the bimodality in and to characterize the distributions of and inside and outside the regions of hypoventilation. In addition, we test whether the regions of reduced ventilation following methacholine induced bronchoconstriction had different or lung aeration than the rest of the lung prior to the delivery of methacholine.
Section snippets
Methods
We analyze data from six normal sheep weighing 17 kg (range 15–21 kg) with a study protocol described in detail (Vidal Melo et al., 2005). The protocol was approved by the Committee on Animal Care of the MGH. Briefly, the animals were anesthetized, intubated, mechanically ventilated and placed in the prone position. Mechanical ventilation was set at an inspired oxygen fraction () = 0.49 ± 0.02, positive end-expiratory pressure (PEEP) = 5 cmH2O, tidal volume (VT) = 17 ± 2 cm3/kg and inspiratory time of
Results
Significant bronchoconstriction was achieved in all animals. Ppeak during methacholine inhalation was 2.4 ± 04 times that at baseline, as required by protocol design. Also, arterial partial pressure of O2 was significantly reduced and alveolar–arterial gradient () and was significantly increased during bronchoconstriction (Table 1).
PET imaging scans showed nearly complete tracer washout in control conditions and significant amounts of residual tracer remained in the lungs at the
Discussion
In a previous analysis of this set of data, we demonstrated that in this animal model of severe bronchoconstriction the distribution of was clearly bimodal (Vidal Melo et al., 2005). We also showed that the bimodality was in great part the result of heterogeneity in at length scales smaller than the spatial resolution of our imaging instrument (2.2 cm3) and that assessment of such “sub-resolution” heterogeneity was not important in normal lungs but was critical for accurate
Acknowledgments
This work was funded by NIH grant HL068011. T. Schroeder was supported in part by the German Academic Exchange Service (DAAD).
References (14)
- et al.
A new murine model of pulmonary eosinophilic hypersensitivity: contribution to experimental asthma
J. Allergy Clin. Immunol.
(1997) - et al.
The effect of methacholine inhalation challenge on regional residual volume in patients with subclinical asthma
Chest
(1985) - et al.
Airway stability and heterogeneity in the constricted lung
J. Appl. Physiol.
(2001) - et al.
Impedance, gas mixing, and bimodal ventilation in constricted lungs
J. Appl. Physiol.
(2003) - et al.
Time course of the bronchoconstriction induced by inhaled histamine and methacholine
J. Appl. Physiol.
(1983) - et al.
Regional VA, Q, and VA/Q during PLV: effects of nitroprusside and inhaled nitric oxide
J. Appl. Physiol.
(2002) - et al.
Dynamic equilibration of airway smooth muscle contraction during physiological loading
J. Appl. Physiol.
(2002)