In vivo blood oxygen binding in hypoxic lesser spear-nosed bats: relationship to control of breathing

Abstract

The hypoxic ventilatory threshold of many mammals correlates with their hemoglobin-oxygen affinity (P₅₀). Yet, in some small mammals ventilation actually declines, rather than increases, with exposure to decreasing Pa_O2; their air convection requirement , however, is elevated in hypoxia. We propose that the threshold of the hypoxic of small mammals coincides with the inflection (‘knee’) of their in vivo O₂ equilibrium curve (O₂EC). In vivo blood gas and pH data were obtained from normoxic and hypoxic lesser-spear nosed bats, Phyllostomus discolor; in vitro blood O₂EC were also generated for normoxic bats at 32 and 37°C and at three P_CO2’s. The hypoxic threshold of P. discolor occurs at Pa_O2=39 Torr; the corresponding in vivo O₂ saturation is 0.70, approximating the inflection of the O₂EC. This animal has a high blood O₂ affinity (P₅₀=27.5 Torr at pH 7.40 and 37°C; P₅₀=30.8 Torr at in vivo pH of 7.31 and Tb of 37.4°C). As Pa_O2 is reduced, a pronounced hypoxia-induced respiratory alkalosis and hypothermia help maintain Sa_O2 near the O₂EC inflection (0.64–0.70 S_O2).

Introduction

The literature on comparative respiratory control suggests a correlation between hypoxic ventilatory response and blood O₂ affinity (P₅₀) in mammals and birds (Boggs, 1995). The functional advantage of this proposed strategy is that ventilation would increase only when the decline in Pa_O2 is sufficient to cause a marked reduction of arterial O₂ saturation (Sa_O2). As Sa_O2 falls below the inflection (‘knee’) of the O₂ equilibrium curve (O₂EC), there is a proportionate decrease in blood O₂ content. A significant reduction of Pa_O2, on the other hand, might result in little or no change in Ca_O2 (e.g. on the O₂EC plateau). Furthermore, it has been hypothesized that the apparent relationship between hypoxic ventilatory response and P₅₀ may be mediated by a heme protein in the transduction mechanism of P_O2 sensitive glomus cells in the carotid body. The O₂ binding characteristics of this heme protein may parallel those of the animal’s hemoglobin (Boggs, 1995).

The initial investigations of comparative ventilatory response focused on correlations between hypoxic ventilatory threshold (HVT; Pa_O2 at which ventilation exceeds normoxic levels by greater than 10%) and blood O₂ affinity (as represented by P₅₀ at pH of 7.4 and 37°C). However, not all species fit this pattern. Some small mammals, like the lesser spear-nosed bat (Phyllostomus discolor), exhibit a decreased ventilatory response to hypoxia (Walsh et al., 1996). Yet, since hypoxia caused a greater reduction in aerobic metabolism than in ventilation, the bat’s air convection requirement () increased. Furthermore, the hypoxic threshold for the response in P. discolor occurred at a lower inspired P_O2 than observed in other small mammals (Walsh et al., 1996), consistent with the bat’s unusually high blood O₂ affinity (Jürgens et al., 1981).

The more important variable in regulating arterial oxygen may therefore be the relationship between ventilation and metabolic rate, or air convection requirement, rather than ventilation per se (Dejours et al., 1970). This may be particularly relevant for smaller mammals which frequently experience significant reductions in body temperature and metabolic rate with hypoxic exposure (Frappell et al., 1992, Mortola and Gautier, 1995). Furthermore, it would seem reasonable to hypothesize that the threshold for the hypoxic convection requirement response should correspond to the inflection of the whole blood O₂EC (i.e. 0.70–0.85 S_O2). However, the determination of O₂ECs at standard conditions of pH and temperature (7.4 and 37°C, respectively), as is frequently reported for oxygen binding studies, may preclude the opportunity to accurately access the in vivo Sa_O2 at the hypoxic threshold. Consequently, a more rigorous test of the hypoxic threshold-blood O₂ affinity hypothesis will require in vivo blood O₂ equilibrium data that can account for observed changes in body temperature and blood pH associated with hypoxic exposure.

Objectives for the present study were therefore to: (1) measure in vivo blood gases and pH in lesser spear-nosed bats breathing normoxic and hypoxic gas mixtures; (2) characterize the O₂ binding properties for P. discolor blood over a range of temperatures and pHs to account for the hypothermia and respiratory alkalosis experienced during hypoxia; and (3) determine whether the hypoxic threshold coincides with the inflection of the bat’s in vivo O₂ equilibrium curve.