Regional lung blood flow and ventilation in upright humans studied with quantitative SPECT
Introduction
The influence of posture and gravity, on the regional distributions of lung blood flow and ventilation has been of longstanding interest to the physiologic community (Martin et al., 1953, Rahn et al., 1956). Early human studies, using methods with a spatial resolution limited to one or two directions, demonstrated greater blood flow and ventilation in dependent regions independent of posture (West and Dollery, 1960, Bryan et al., 1964, Anthonisen and Milic-Emili, 1966, Glazier and DeNardo, 1966, Kaneko et al., 1966, Milic-Emili et al., 1966, Hughes et al., 1968). The non-uniform, but well-matched, distributions of regional lung blood flow and ventilation were therefore explained by the shared influence of gravity. Later animal and human studies demonstrated heterogeneity of blood flow within isogravitational planes (Reed and Wood, 1970, Greenleaf et al., 1974, Beck and Rehder, 1986, Hakim et al., 1987, Lisbona et al., 1987, Hakim et al., 1988a, Hakim et al., 1988b), which led to the conclusion that blood flow heterogeneity must be determined by other factors in addition to gravity. Further animal studies have demonstrated that gravity (posture) has an important, but secondary, influence on the distribution of blood flow (Glenny et al., 1991a, Glenny et al., 1991b, Glenny et al., 1999). No study has previously employed high-resolution imaging methods to simultaneously quantify the effect of gravity on the distribution of both regional lung blood flow and ventilation in upright humans.
In animal studies, regional distributions have been described as per unit lung tissue, i.e. per alveolus. In contrast, most human studies employing high-resolution methods have described the distributions as per unit lung volume. Interpretation of results from these studies is complicated by the non-uniform and posture-dependent distribution of lung tissue. In each posture the amount of lung tissue per unit lung volume varies between regions. Similarly, the amount of lung tissue in a unit volume of the lung, defined by its relationship to anatomical landmarks, varies between postures. Recently we used a novel application of the Single Photon Emission Computed Tomography (SPECT) technique to demonstrate that these phenomena greatly contribute to the differences in blood flow and ventilation distributions imaged in the supine and prone postures (Petersson et al., 2007). With SPECT, regional blood flow and ventilation can be marked using radiotracers that remain fixed in the lung parenchyma after administration. In this study of spontaneously breathing healthy volunteers, we used these radiotracers to mark regional lung blood flow and ventilation in the sitting upright, supine and prone postures. All images of the radiotracer distributions were acquired in the supine posture; regional blood flow and ventilation were therefore observed as per unit volume supine lung. These distributions were further characterized as cranial-to-caudal gradients of relative blood flow and ventilation per unit volume supine lung. The gradients were compared, looking for the effect of subjects having been supine, prone or upright at the time of radiotracer administration, which allowed us to quantify the effect of posture/gravity on the distribution of blood flow and ventilation within the lung parenchyma. We believe that the current work adds to the ongoing debate on the importance of gravity to lung blood flow and ventilation distributions by: (1) studying upright humans, a posture that is not amenable to other modern imaging methods, (2) confirming that gravity is an important determinant of regional lung blood flow and ventilation in upright humans, (3) obtaining simultaneous measurements of regional blood flow and ventilation allowing assessment of regional ventilation-to-perfusion ratios, (4) acquiring measurements during normal breathing as oppose to special breathing manoeuvres, and (5) using a novel approach to exclude the confounding effect of lung tissue distribution when comparing blood flow and ventilation distributions in different postures.
Section snippets
Methods
This study consists of new data from previously reported experiments (Petersson et al., 2004, Petersson et al., 2007). The current study, however, includes no previously published data on the regional distributions of lung blood flow or ventilation.
SPECT
Subjects received 62–105 MBq of 113mIn, corresponding to 270,000–700,000 Lyo-MAA particles. Technegas breathing required 120–387 s. The lowest pulse oximetry reading recorded during Technegas administration was 95%.
Plots of blood flow and ventilation distributions
In the following, dependent, non-dependent and posture always refers to conditions at the time of radiotracer administration. The profiles for the distribution of blood flow and ventilation in the cranial-to-caudal direction are presented in Fig. 1. In upright regional blood flow and
Discussion
The relative effect of gravity on regional lung blood flow and ventilation continues to be debated (Glenny et al., 2007). At least some of this controversy stems from differing results between studies of upright humans and horizontal animals. These studies also differ in the spatial resolution of the employed methodologies. In addition, prior works have also differed in their consideration of lung compression as a confounder of observed blood flow and ventilation distributions (Hopkins et al.,
Acknowledgements
We gratefully acknowledge the dedication of our subjects and the excellent technical support from Ann-Marie Danielsson, Annette Ebberyd, Marie Finnbogason, Gunilla Fyhr, Ingeborg Gottlieb-Inacio and Jan-Olov Thorell.
Grants: This research was supported by the Swedish Medical Research Council grant K2003-74X-10401-11A, the Swedish Heart and Lung Foundation grants 200141470 and 20040689 and Linde Healthcare AGA AB.
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