New evidence suggests that the pulmonary circulation has unexpected forms of regulation, both in the arteries and within capillaries. Videomicroscopy of the pulmonary microvasculature in our laboratory shows that not all capillaries are continually perfused; rather the blood flow continually switches among the capillaries. The switching continues even when vascular pressures and flows are constant. The switching is not random: it follows a subtle, repeating pattern that is fractal in nature and depends on the unique characteristics of each alveolar network. This results in perfusion patterns that are independent among neighboring alveoli, creating a robust system in which failure of one network does not affect the neighbors.
Specific Aim 1. To determine the mechanisms that cause the switching of flow among capillaries in individual capillary networks. The switching could be the result of a particulate fluid flowing through a complex but passive capillary network, or it could be caused by active capillary vasomotion. To differentiate between these causes, we will analyze the perfusion patterns using software we have developed, as well as fractal mathematics to determine the level of repetition of the perfusion patterns. Our first hypothesis is that the capillaries are passive; the switching of blood flow among the capillaries is the result of highly flexible red blood cells traversing dozens of capillary junctions that comprise the network. The second hypothesis is that the capillaries are active; switching of blood flow among the capillaries is determined by active changes of capillary lumenal diameter. We will test these hypotheses by creating a passive state in which the capillary lumenal, diameters are fixed, thereby blocking the ability of the capillaries to alter their lumens. Unaltered switching would show that the network was passive. Altered switching would be direct evidence for capillary vasomotion.
In Specific Aim 2 we will investigate the function of the sympathetic nerves that innervate the pulmonary arteries. Stimulation of the stellate sympathetic ganglion stiffens the pulmonary arterial walls, which increases pulmonary arterial systolic pressure. We hypothesize that when the enhanced systolic pressure wave reaches the capillary bed, the gas exchange surface area will increase through the recruitment of capillaries. Our pilot data strongly suggests this hypothesis is correct. We will complete an extensive test of this hypothesis by studying the changes in capillary perfusion during sympathetic stimulation. Successful completion of these experiments will replace the current idea, that the pulmonary circulation does not do very much, with a new concept that these vessels are capable of potent yet subtle control. After decades of technical development, we are at last in a position to conduct these experiments.
| Baumgartner Jr, William A; Peterson, Amanda J; Presson Jr, Robert G et al. (2004) Blood flow switching among pulmonary capillaries is decreased during high hematocrit. J Appl Physiol 97:522-6 |
| Baumgartner Jr, William A; Jaryszak, Eric M; Peterson, Amanda J et al. (2003) Heterogeneous capillary recruitment among adjoining alveoli. J Appl Physiol 95:469-76 |
| Presson Jr, Robert G; Baumgartner Jr, William A; Peterson, Amanda J et al. (2002) Pulmonary capillaries are recruited during pulsatile flow. J Appl Physiol 92:1183-90 |
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| Hanson, W L; Boggs, D F; Kay, J M et al. (2000) Pulmonary vascular response of the coati to chronic hypoxia. J Appl Physiol 88:981-6 |
| Wagner Jr, W W; Todoran, T M; Tanabe, N et al. (1999) Pulmonary capillary perfusion: intra-alveolar fractal patterns and interalveolar independence. J Appl Physiol 86:825-31 |
| Tanabe, N; Todoran, T M; Zenk, G M et al. (1998) Perfusion heterogeneity in the pulmonary acinus. J Appl Physiol 84:933-8 |
| Presson Jr, R G; Audi, S H; Hanger, C C et al. (1998) Anatomic distribution of pulmonary vascular compliance. J Appl Physiol 84:303-10 |
| Hillier, S C; Graham, J A; Hanger, C C et al. (1997) Hypoxic vasoconstriction in pulmonary arterioles and venules. J Appl Physiol 82:1084-90 |
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