Difference in blood volume distribution between upright humans and standing quadrupeds.

TO THE EDITOR: After two decades of animal studies on vascular adaptation to microgravity using the rat analog (for review, see Ref. 3), it is gratifying to note the recently published findings on space-flown mice by Sofronova and coworkers (1). They demonstrate that both vasoconstrictor and vasodilator properties are attenuated in basilar arteries (BA) isolated from the mice flown 30 days on a Bion biosatellite. A previous study showed that a 13-day flight on the Space Shuttle diminishes the myogenic vasoconstriction and vascular stiffness and increases distensibility of isolated BA in mice (2). However, it has been well documented that simulated microgravity induces augmented myogenic tone and vasoreactivity, diminished vasodilatory function, and hypertrophic remodeling in cerebral arteries, such as middle cerebral artery (MCA) and BA of rats (3). The principal factor that determines the discrepancy between cerebral vascular adaptation to real and simulated microgravity in small rodents might be attributed to the difference in blood volume distribution between humans and quadrupeds. There is a considerable difference in gravitationally dependent distribution of blood volume: in upright humans, 70% of blood volume is distributed below the heart level, whereas in a standing small quadruped, most of the blood volume is close to heart level along the nearly horizontal axis of the aorta (3). In a 1-G environment, the acceleration vector on standing rats/mice is dorsoventral ( Gx) rather than from head to foot ( Gz). Therefore, microgravity-induced redistribution of transmural pressures and flows along the arterial vasculature and the fluid shifts in small rodents differ widely from that in bipeds. In simulated microgravity rats/mice, cerebral vascular adaptation is induced by G-vector change due to chronic head-down tilt in a 1-G environment, whereas during real microgravity, the speculated increase of transmural pressures along the vasculature due to the loss of hydrostatic pressure gradients should be very small, because the vertical head-to-heart distance is very short in small rodents. Thus microgravity exposure could not induce a significant redistribution of transmural pressures and flows along the vasculature in small rodents. The observed discrepancy does not seem to influence the basic conclusions thus obtained by using the head-down tilt, hindlimb unweighting rat model, which simulates microgravity-induced vascular adaptation in humans by a chronic headdown tilt posture (3). Nevertheless, a new series of sophisticated ground-based and space studies with small rodents are expected to add supplementary explanation to this discrepancy and provide a deeper insight into vascular adaptation to microgravity in humans. It seems that several key issues should be addressed. First, in small rodents, whether the transmural pressure redistribution along arterial vasculature in simulated microgravity differs greatly from that during real microgravity. Second, sufficient data with respect to other environmental factors during spaceflight, such as the CO2 level and radiation, and animal care and inflight monitoring are required to clarify their contribution to the vascular effects. Third, MCA is a proximal resistance artery, whereas BA is a large cerebral artery that contributes importantly to cerebrovascular resistance. The difference between these two kinds of arteries should be considered (3).