Cerebral blood flow and oxygenation in ovine fetus: responses to superimposed hypoxia at both low and high altitude

Abstract

For the fetus, although the roles of arterial blood gases are recognized to be critical in the regulation of cerebral blood flow (CBF) and cerebral oxygenation, the relation of CBF, cortical tissue P(O2) (tP(O2)), sagittal sinus P(O2), and related indices of cerebral oxygenation to arterial blood gases are not well defined. This is particularly true for that fetus subjected to long-term hypoxia (LTH). In an effort to elucidate these interrelations, we tested the hypothesis that in the fetus acclimatized to high altitude, cerebral oxygenation is not compromised relative to that at low altitude. By use of a laser Doppler flowmeter with a fluorescent O2 probe, in near-term fetal sheep at low altitude (n = 8) and those acclimatized to high altitude hypoxia (3801 m for 90 +/- 5 days; n = 6), we measured laser Doppler CBF (LD-CBF), tP(O2), and related variables in response to 40 min superimposed hypoxia. At both altitudes, fetal LD-CBF, cerebral O2 delivery, tP(O2), and several other variables including sagittal sinus P(O2), correlated highly with arterial P(O2) (P(a,O2)). In response to superimposed hypoxia (P(a,O2) = 11 +/- 1 Torr), LD-CBF was significantly blunted at high altitude, as compared with that at low altitude. In the two altitude groups fetal cerebral oxygenation was similar under both control conditions and with superimposed hypoxia, cortical tP(O2) decreasing from 8 +/- 1 and 6 +/- 1 Torr, respectively, to 2 +/- 1 Torr. Also, for these conditions sagittal sinus P(O2) and [HbO2] values were similar. In response to superimposed hypoxia, cerebral metabolic rate for O(2) decreased approximately 50% in each group (P < 0.05). For both the fetus at low altitude and that acclimatized to high altitude LTH, we present the first dose-response data on the relation of LD-CBF, cortical tP(O2), and sagittal sinus blood gas values to P(a,O2). In addition, despite differences in several variables, the fetus at high altitude showed evidence of successful acclimatization, supporting the hypothesis that such fetuses demonstrate no compromise in cerebral oxygenation.

Figure 1. Mean values of laser Doppler cerebral blood flow and cortical tissueP_O2, in both low altitude near-term fetuses (squares) and those acclimatized to high altitude (triangles) in response to superimposed isocapnic hypoxia induced by the ewe breathing 10.5% O₂ in 3–5% CO₂

Following a 40 min control period (maternal P_a,O2 = 100 ± 3 and 60 ± 3 Torr in the two altitude groups, respectively, fetal P_a,O2 = 23 ± 1 and 19 ± 1 Torr, respectively), fetal responses to 40 min of superimposed hypoxia (fetal P_a,O2 = 11 ± 1 Torr) are shown, beginning at time 0 and indicated by the shaded band. This was followed by a 40 min recovery period. A, LD-CBF (percentage baseline control). The difference between LD-CBF values of fetus at high altitude and those at low altitude are significant, as is the overall upper and lower curves during superimposed hypoxia, *P < 0.05. B, cerebral cortical tissue P_O2 (Torr). Values of t P_O2 in fetus at high altitude were not statistically different from those at low altitude. Symbols as in A.

Figure 2. Relation of fetal LD-CBF to arterial oxygen tension, of cortical tissueP_O2toP_a,O2, and of tP_O2to LD-CBF, for near-term fetus acclimatized to high altitude, as compared to those at low altitude

A, fetal LD-CBF as a function of P_a,O2 (Torr); (squares, low altitude controls; triangles, high altitude acclimatized fetuses). The slopes for the two altitude groups were −1.67 ± 0.33 (low altitude) and −2.88 ± 0.32 (high altitude) (r² = 0.28 and 0.47, respectively, P < 0.01). B, fetal cortical tissue O₂ tension (Torr) showed a liner relationship to P_a,O2 for the fetuses in both altitude groups, with no significant difference between groups (r² = 0.69, slope = 0.47 ± 0.04 for low altitude group; r² = 0.56, slope = 0.41 ± 0.05 for high altitude group). C, fetal cortical t P_O2 as a function of LD-CBF in low altitude control and high altitude acclimatized fetuses (symbols as in A). The curves for the two altitude groups were statistically different, P < 0.01.

Figure 3. Sagittal sinus P_O2(Torr) and oxyhaemoglobin saturation as a function of both arterial P_O2 (Torr) and cortical tissue P_O2 (Torr) in fetuses acclimatized to high altitude and those at low altitude

A, sagittal sinus P_O2 showed a linear relationship to P_a,O2 in both altitude groups (r² = 0.68, slope = 0.57 ± 0.07 for low altitude group; r² = 0.88, slope = 0.72 ± 0.04 for high altitude group) with no significant difference between groups (symbols same as Figs 1 and 2). B, sagittal sinus P_O2 (Torr) as a function of cortical tissue P_O2 (Torr) for fetuses in both altitude groups. This curvilinear relationship was not statistically different between the two groups. C, sagittal sinus [HbO₂] as a function of t P_O2 for fetuses at both low and high altitude. Again, this curvilinear relationship did not differ between the two groups. symbols as in Figs 1 and 2.

Figure 4. Relative cerebral oxygen delivery, arterial to sagittal sinus O₂ content difference, fractional O₂ extraction, and cerebral metabolic rate for O₂ (CMR_O2), for near-term high altitude acclimatized fetus, as compared to low altitude controls, in response to superimposed isocapnic hypoxic hypoxia

A, fetal relative O₂ delivery (% baseline) as a function of P_a,O2 (Torr); (r² = 0.86; slope = 4.97 ± 0.25; and r² = 0.60; slope = 4.04 ± 0.30 for low and high altitude groups, respectively). These slopes differed significantly (P < 0.05). B, fetal arterial to sagittal sinus O₂ content difference as function of P_a,O2 (Torr); (r² = 0.65 and 0.76 for low and high altitude groups, respectively). The slopes did not differ significantly. C, fetal fractional O₂ extraction as a function of P_a,O2 (Torr) (r² = 0.08; slope = −0.01 ± 0.01 for low altitude group; r² = 0.01; slope = 0.01 ± 0.01 for high altitude group). VO₂Cont, venous O₂ content; AO₂Cont, arterial O₂ content. The slopes differed significantly, P < 0.05. D, fetal cerebral metabolic rate for O₂ as a function of P_a,O2 (Torr). r² = 0.27; slope = 3.6 ± 0.9 for low altitude group; r² = 0.67; slope = 5.0 ± 0.4 for high altitude group. Symbols as in Figs 1 and 2 above. The slopes differed significantly, P < 0.05.