Abnormal Pulmonary Blood-Gas Perfusion at Hypergravity (+G) States

Joshua Leigh (91936070)Alex Klemm (61682084

November 28, 2011

Similarly to a body in a directional Cartesian plane, hypergravity forces, or G-forces can be isolated to a three dimensional model. Within this 3 dimensional model of directionally applied forces, the driving physiological effects vary with the magnitude of the applied acceleration, the duration, the location of impact, and the axis of the force. (Strapp, 1986) Therefore, G-forces can now be defined in a three dimensional analysis consisting of a Gx, Gz, and Gy orientation in attempt to explain regional pulmonary perfusion during increased gravitational stress. For our purposes we will apply this coordinate system to a seated subject as found in an aircraft, roller coaster, human/animal centrifuge, ect. Acceleration in the Gz direction, or caudal direction, pushes the body into the seat, resulting in a drain of blood from the head toward the feet. This increase of gravitational force is also suggested to pull the diaphragm downward causing an emptying of air from the lungs and possible loss of vital capacity. (Alberv, 2004)) Acceleration in the Gx direction, or transverse exposure is often coupled with the often-referenced Gz force. This plane applies a G-force from the ventral to dorsal side of the body and increases pressure on supporting areas of the body such as the spinal column. The body has a much higher tolerance to Gx force than to the previously suggested Gz forces. (Alverv, 2004) However an exposure, even brief, to a +20Gx force can cause significant problems with lung inflation movements. (Strapp, 1986) Due to this increased tolerance to increased force in the transverse plane, until recently, there was no known active redistribution of blood during hypergravity states in this directional space. Finally, acceleration in the Gy plane is possible, however, this transverse directional force is very similar to Gx and is considered identical in our analysis.

Abnormalities in pulmonary perfusion have been identified to occur at hypergravity stress, yet no mechanical mechanism has been supplied to support such a change in perfusion. Therefore, is gravity responsible for this abnormality, and major determinate of pulmonary perfusion? In order to answer this question we must outline a model to describe pulmonary perfusion both at rest, as a control, and at an increasing level of hypergravity stress. John West, Peter Wagner, and Michael Hughes (Figure 4-8) outline a starling resister model where blood flow is the highest at the lower region of the lung due to hydrostatic pressure differences in the blood vessels. While in a standing/upright position, the apex of the lung(zone 1), exhibits a lack of blood flow resulting in alveolar dead space. (West Textbook) This suggests that the lung has a heterogeneous distribution of blood flow increasing from the cranial to caudal direction. Furthermore, John West also suggests that when in the prone position the suggested model of perfusion shifts to a more homogenous distribution when the lung is in a prone position.

Glaister sought to test this simple yet effective model on humans exposed to +1, +2, and +3G states in a human centrifuge. Before exposure he confirmed an increasing gradient of pulmonary perfusion from the cranial to caudal direction with noticeable alveolar dead space at the apex of the lung. As the subjects were exposed to a +2G force the alveolar dead space at the apex of the lung grew causing a caudal shift of pulmonary perfusion. Therefore, he determined that exposing the human lung to increased gravitational force greatly exaggerates the topographical inequality of blood flow such that in the upright human lung at +3G, the upper two-thirds of the lung are unperfused.

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(Glaister, 1977) This supports the model suggested by John West and colleges and supports gravity as the major determinate of pulmonary blood perfusion both at rest and at hypergravity states. However this only provides us with a two-dimensional cranial to caudal model, only accounting for Gz accelerations and therefore failing to explain Gx/Gy forces. In addition, it is argued that the methods used in these studies had relatively low-spatial resolution that could not measure variability of isogravatational perfusion and, hence, could not quantify the relative contribution of gravity to blood flow heterogeneity. (Glenny, 1999)

Previously hypergravity was defined as a three-dimensional force with varying physiological effects depending on not only the magnitude but the location of impact as well. Unfortunately we cannot apply a three-dimensional force model to a two dimensional figure without not accounting for a transverse pulmonary perfusion heterogeneity. A collective based out of the University of Washington led by Glenny has sought to redefine gravity as a secondary determinate of pulmonary blood flow both at rest and at hypergravity states. Fluorescent microspheres were injected into the pulmonary circulation of six pigs. The microspheres had a higher density than the blood allowing them to remain stationary after the test was completed. The pigs were then flown in a KC-135 Aircraft and exposed to up to +1.8G subjecting their pulmonary systems to a variety of postural and gravitational conditions. The lungs were then removed and dried at full vital capacity (FVC). The lungs were then sectioned into 2cm3 pieces and the flow was averaged both in the cranial plane as well as the transverse plane. “Both gravity and the geometry of the pulmonary vascular tree influence regional pulmonary blood flow. However, the structure of the vascular tree is the primary determinant of regional perfusion. Heterogeneitites in vascular resistance can produce a range of zonal conditions within isogravitatational plans rather than vertically stacked in the lung.”(Glenny, 2000) These findings suggest that the lung cannot be just viewed as a simple two-dimensional model ignoring the effects of the transverse plane. Since gravity may not be the major determinant of pulmonary blood flow the isograviatational transverse plane must be averaged against the cranial plane. When this is done the effect of gravity is determined to be minimized and only accounts for one fifth of the overall perfusion inequality.

If the main proponent of pulmonary perfusion is indeed the geometry of the pulmonary vascular tree then there might be discrepancy between animals and or posture. A quadruped such as a pig might have a different vascular structure or lung posture than a biped such as a human or baboon. Thus, the blood perfusion of a biped baboon was measured in a variety of postures with radioactive markers to establish a parallel between the effects of gravity on pig lung perfusion to that of a biped mammal. (Figure Glenny 1999). Similarly to the previous pig studies, the baboons were injected with fluorescent microspheres and subjected to a variety of prone and supine postures. The baboons were then killed, the lungs removed, and the lungs dried at full vital capacity (FVC). After the lungs were sectioned and averaged it was determined that changes in gas exchange with postural changes are identical to those in humans with the same physiological structures as a human lung. The study concluded that pulmonary blood flow is heterogeneously distributed in an upright lung. In addition, gravity plays a greater role in perfusion when

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the animals are upright. This agrees with West et. Al. two-dimensional lung model and also supports the suggestion that there is a difference between prone and supine positions. Relative contribution of gravity is similar in supine/prone primates to similar animals. This conclusion allows us to parallel the pig study with human application and directly challenges the two-dimensional model. It still acknowledges that perfusion might differ between the two positions but is constant between species. Finally, the study reaffirms that gravity might be a secondary determinant of pulmonary perfusion.

In conclusion, this is a dynamic debate that has faults on both sides. The Seattle group has acknowledged that there is a time delay from the +G exposure to the removal of the lungs. In addition, the lungs are dried at full vital capacity (FVC) outside of the chest wall. This creates an increase in volume, as the lungs when dried, are not restricted by the ribs and external musculature. This results in an in vivo actual FVC that is slightly smaller that the one used in the study. The dried lungs also produce the issue of not being actively perfused with blood at the time of measurement. Since blood heavily perfuse lung tissue throughout the lung, in vivo the alveoli at the base of the lung are subjected to some gravitational sag due to the increased weight of the column of fluid. Thus, drying the lung before measurement might greatly dampen the resulting effect of gravity. On the contrary, as was discussed West’s two-dimensional model fails to address the existence of a change in blood perfusion on an isogravitational transverse plane. Although not completely correct, West’s model has been essential to our current understanding of preventative G-force measures and understanding leading to the creation of the anti-gravitational suit.

In addition to the normal pulmonary changes that occur in the human body, tolerance to hypergravity also varies between individuals and can fluctuate day to day for a single person. Factors that will lower a person’s tolerance to a Gz acceleration include general fatigue, sleep deprivation, hangover, illness, heat stress, dehydration, and various types of medication. (Balldin, 2002) Heat stress and dehydration are also major factors in transient hypergravity tolerance. A 3% level of dehydration will significantly reduce tolerance for high acceleration even with the use of anti-G suits and straining maneuvers. (Rohdin et at.,2004) Hyperventilation can also lower tolerance to hypergravity stress through anxiety, mental stress, hypoxia, and pressure breathing. (Balldin, 2002) When an individual beings to reach their tolerance they often experience a tunneling vision, dimmin, grayout, and eventually blackout. If G-force is increased or sustained then G-LOC will occur. With slow onset of acceleration without an anti-G suit initial visual symptoms can occur within the range of +2 to +7G with an average of +4G. Blackout will follow the initial visual symptoms with a further increase of +1G. With a faster onset of acceleration, the visual symptoms will occur at lower acceleration levels. (Rohdin et al., 2004)

In response to the transient and often unpredictable responses to hypergravity stress between subjects the airforce sought to introduce new preventative measure to increase +G tolerance by reducing known abnormal pulmonary behavior. An Anti-G suit is a mechanism “to counteract the circulatory effects of increased G-forces in the head to

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foot direction (+Gz)” through the means of “inflatable bladders that completely cover the lower limbs and the abdomen”. (Gronkvist et al., 2005)

Women exposed to high +G loads are not studied often, but those who are generally experience similar risk to men. Women do require a tailoring of the anti-G suit to properly fit their body type and prevent the abdominal bladder from compressing the lower ribs, causing pain and restricting breating. Women can experience increased menstrual flow or bleeding/spotting between menses during G-stress acceleration. Rarely, oral contraceptives may cause the formtion of thrombosis. (Gillingham et al., 1986) This can become dislodged and advance to the lungs causing possible fatal results. Lower hormone contect of modern oral contraceptives have minimized this risk. Men have a slight risk of discomort and pain to their genitalia, such as scrotal pain and hemorrhage. (Dooley et al., 2001)

In additional to the lack of univeral design of the anti-g suit, there are several known negative effects. Inflation of the anti-G suit causes and increase in alveolar dead space through a provoked significant impairment of gas mixing between and within the most distal airways. Vital decreases noticeably, up to 17%, when the anti_G suit becomes inflated. However, decrements to vital capacity by further acceleration are greatly reduced. (Gronkvist et al., 2005) The extended descent of the diaphragm due to hypergravity is not prevented by the anti-G suit as expected. Although, the descent is less pronounced than when the suit is not inflated at the same level of hypergravity. (Gustafsson, et al., 2001) In addition, a study found that compression of the lower limbs and abdomen by the anti-G suit reduces vital capacity, up to +3 Gz more than when influenced by hypergravity alone. (Gronkvist, 2005) The incidence of atelectasis while breathing oxygen in a hypergavity environment is considerably higher when an anti-G suit is worn. “Atelectasis would rapidly occur if the basal alveoli were oxygen filled and the terminal airways were collapsed.” (Bryan et al., 1965) If there is a minor fit problem of the anti-G suit in any way, in a hypergravity enviorment this will lead to painful pinching, friction, and bruising along with petechiae, edema, and hematoma formation in the unprotected areas below the heart. (Gronkvist et. Al., 2005)

Now that pulmapplied nature of G-force and a knowledge of the resulting pulmonary perfusion abnormalities resulting from an increased stress, is gravity the main determinant of the distribution of pulmonary blood flow? And is this gradient exacerbated when exposed to an increased hypergravity stress?

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Works Cited

Stapp J P (1986) Biodynamics the key to flight, aviation, space, and environmental medicine 5710 Pt 2), A32-6.

Albery, W. B. (2004) “Acceleration in other axes affects +Gz Tolerance: dynamic centrifuge simulation of agile flight,” Aviation, space and environmental Medicine, Vol. 75(1), 1-6.

The effects of inertial load and countermeasures on the distribution of pulmonary blood flow. (study)

(Balldin, 2002; Gronkvist et al., 2005; Rohdin & Linnarsson, 2002)(Balldin, 2002; Browne et al, 1970; Bryan et al, 1966)(Glaister,1977)(West, 2002)(Glenny, 2000)(Glenny, 1999)John West, Peter Wagner, and Michael Hughes:(Balldin, 2002; Rohdin et al., 2004)(Grönkvist et al., 2005).(Balldin, 2002; Dooley et al., 2001; Gillingham et al., 1986)(Gronkvist et al., 2005; Gustafsson, et al., 2001)Gronkvist, M.J., Bergsten, E., Eiken, O., & Gustafsson, P.M. (2005) “Contributions of lower limb and abdominal compression to ventilation inhomogeneity in hypergravity” Respiratory Physiology & Neurobiology 148: 113-123

Bryan, A.C., Milic-Emili, J., & Pengelly, D. (1966). “Effect of gravity on distribution of pulmonary ventilation” Journal of Applied Physiology 21(3): 778-784

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Appendix

Figure 1: Zonal Perfusion of the lung 2D Model

Figure 2: 3D Model of +G Forces

Albery, W. B. (2004) “Acceleration in other axes affects +Gz Tolerance: dynamic centrifuge simulation of agile flight,” Aviation, space and environmental Medicine, Vol. 75(1), 1-6.

Figure 3: 3D Model of +G Forces

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The effects of inertial load and countermeasures on the distribution of pulmonary blood flow. (paper)

Figure 4: (Glaister, 1977)

Figure 5: (Glenny, 2000)

Figure 6: (Glenny, 1999)

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Figure 7:

Figure 8:

Figure 9: Female Tailoring Anti-G suit

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