Systemic Oxygen Transport with Rest, Exercise, and Hypoxia: A Comparison of Humans, Rats, and Mice

Abstract

The objective of this article is to compare and contrast the known characteristics of the systemic O transport of humans, rats, and mice at rest and during exercise in normoxia and hypoxia. This analysis should help understand when rodent O transport findings can-and cannot-be applied to human responses to similar conditions. The O -transport system was analyzed as composed of four linked conductances: ventilation, alveolo-capillary diffusion, circulatory convection, and tissue capillary-cell diffusion. While the mechanisms of O transport are similar in the three species, the quantitative differences are naturally large. There are abundant data on total O consumption and on ventilatory and pulmonary diffusive conductances under resting conditions in the three species; however, there is much less available information on pulmonary gas exchange, circulatory O convection, and tissue O diffusion in mice. The scarcity of data largely derives from the difficulty of obtaining blood samples in these small animals and highlights the need for additional research in this area. In spite of the large quantitative differences in absolute and mass-specific O flux, available evidence indicates that resting alveolar and arterial and venous blood PO values under normoxia are similar in the three species. Additionally, at least in rats, alveolar and arterial blood PO under hypoxia and exercise remain closer to the resting values than those observed in humans. This is achieved by a greater ventilatory response, coupled with a closer value of arterial to alveolar PO , suggesting a greater efficacy of gas exchange in the rats. © 2018 American Physiological Society. Compr Physiol 8:1537-1573, 2018.

Tumor vascular status controls oxygen delivery facilitated by infused polymerized hemoglobins with varying oxygen affinity

“…The tumor MRO 2 was approximately two times higher in the human model when compared to the mouse model. This is in agreement with the increase in O 2 consumption in humans under hypoxia [31,50,51]. This is likely a result of significantly decreased O 2 release from the mouse Hb in RBCs under hypoxic conditions when compared to trends in the literature [31].…”

“…This is in agreement with the increase in O 2 consumption in humans under hypoxia [31,50,51]. This is likely a result of significantly decreased O 2 release from the mouse Hb in RBCs under hypoxic conditions when compared to trends in the literature [31]. Additionally, the mouse host tissue MRO 2 was significantly greater than human host tissue MRO 2 (Data shown in S4 Appendix).…”

“…Furthermore, commonly used small animal models, such as mice, have distinct physiologic differences in O 2 transport when compared to humans. These differences can be summarized by three alterations in fluid and mass transport when compared to humans: (1) decreased mouse red blood cell (RBC) size [ 30 ], (2) increased metabolic rate of O 2 consumption in the mouse host tissue [ 31 – 33 ], and (3) decreased O 2 affinity of mouse Hb in RBCs [ 34 ]. In mice, the decreased O 2 affinity of Hb in RBCs may result in reduced O 2 release from HBOC species in circulation when compared to HBOC performance in humans.…”

Intermittent Hypoxia Exposure Can Prevent Reductions in Hemoglobin Concentration After Intense Exercise Training in Rats

“…Indeed, our data show that such a simulated altitude was sufficient to prevent low concentrations of hemoglobin in SD rats. However, laboratory animals, such as the rodents used herein, can be more sensitive to hypoxia than humans (Gonzalez and Kuwahira, 2018). Therefore, future experiments should test the efficacy of the simulated altitude and duration of hypoxic exposure from this study in humans with low concentrations of hemoglobin, but given the hypoxia-EPO-hemoglobin machinery is conserved in both humans and rats, similar findings may be expected (Haase, 2013;Viscor et al, 2018) (unpublished data for another manuscript in preparation).…”

Impacts of Changes in Atmospheric O2 on Human Physiology. Is There a Basis for Concern?

“…This study used subjects with of ∼ 66 ml O 2 /kg/min ( Wehrlin and Hallén, 2006 ) compared to a normal value for a healthy individual of ∼40 ml O 2 /kg/min. Other reviews of the literature have found linear decreases in with inspired P O 2 between 150 and 80 mmHg and predict a similar decrease in of less than 1% for the 1.5 mmHg decrease ( Gonzalez and Kuwahira, 2018 ).…”