The contribution of arterial blood gases in cerebral blood flow regulation and fuel utilization in man at high altitude

Abstract

The effects of partial acclimatization to high altitude (HA; 5,050 m) on cerebral metabolism and cerebrovascular function have not been characterized. We hypothesized (1) increased cerebrovascular reactivity (CVR) at HA; and (2) that CO2 would affect cerebral metabolism more than hypoxia. PaO2 and PaCO2 were manipulated at sea level (SL) to simulate HA exposure, and at HA, SL blood gases were simulated; CVR was assessed at both altitudes. Arterial-jugular venous differences were measured to calculate cerebral metabolic rates and cerebral blood flow (CBF). We observed that (1) partial acclimatization yields a steeper CO2-H(+) relation in both arterial and jugular venous blood; yet (2) CVR did not change, despite (3) mean arterial pressure (MAP)-CO2 reactivity being doubled at HA, thus indicating effective cerebral autoregulation. (4) At SL hypoxia increased CBF, and restoration of oxygen at HA reduced CBF, but neither had any effect on cerebral metabolism. Acclimatization resets the cerebrovasculature to chronic hypocapnia.

Figure 1

Percent difference in mean arterial pressure (MAP) from baseline (A) during euoxic changes in PaCO₂ at sea level (SL) (solid squares) and high altitude (HA) (hollow squares), and the individual slopes of this relationship in the hypercapnic range (B). Mean slopes (±s.d.) for this relationship were SL hypercapnic range 1.2±0.7%/mm Hg; HA, hypocapnic range 1.1±0.7%/mm Hg (not-shown); HA, hypercapnic range 2.8±1.0%/mm Hg. *P<0.05.

Figure 2

Individual cerebral blood flow (CBF_total) values during isocapnic changes in PaO₂ at sea level (SL) and high altitude (HA). The top plots (A and B) show data from SL; the bottom plots (C and D) show data from 5,050 m. The left side of each plot depicts CBF while PaO₂ was ~100 mm Hg (except at SL—plot A—where ambient PO₂ yielded a smaller PaO₂), whereas hypoxia is shown on the right side of each plot. The left hand plots (A and C) show isocapnia clamped at ~40 mm Hg at SL and ~35 mm Hg at HA (the lower PaCO₂ values at HA were due to inability of subjects to tolerate higher values; see Results and Discussion). Right side plots (B and D) show isocapnic clamp at ~25 mm Hg. Please see Materials and methods for further details on gas permutations. *P<0.05.

Figure 3

Total cerebral blood flow (CBF_total) during steady-state euxoic changes in PCO₂ at sea level (SL) and high altitude (HA). Hollow squares represent CBF plotted against arterial PCO₂ and solid squares against internal jugular vein PCO₂. CBF was significantly altered from baseline at all levels of PCO₂ at both SL and 5,050 m (P<0.05). Data are mean±s.d.

Figure 4

Individual (circles, gray) and mean (squares, black) cerebrovascular reactivity (CVR) to euoxic changes in arterial (left) and jugular (right) PCO₂ (Top) and [H⁺] (bottom). CVR in the hypocapnic range was lower than in the hypercapnic at both elevations when determined as a function of PaCO₂ or arterial [H⁺] (A and C; P<0.05). P_IJVCO₂ CVR did not differ between hypo- and hypercapnia nor between altitudes (B), whereas [H⁺]_IJV was greater in the hypercapnic range at high altitude (HA) (D); P<0.05. The very high arterial CVR in one individual at HA (11.2%/mm Hg) was more than two standard deviations above the mean (6.8±5.4%/mm Hg); however, removal of this individual did not affect statistical significance. IJV, internal jugular vein. *P<0.05.

Figure 5

Comparison of cerebral blood flow (CBF) versus middle cerebral artery (MCA) velocity (MCAv) reactivities to change in PaCO₂ at sea level (SL) and high altitude (HA). MCAv cerebrovascular reactivity (CVR) was lower than CBF CVR in the hypercapnic range at both altitudes, likely due to dilation of the MCA during increases in CO₂, slowing of MCA blood velocity and consequent underestimation of reactivity to increases in PaCO₂. Data are mean±s.d. *P<0.05.

Figure 6

Relationships between cerebral blood flow (CBF) and ΔMAP at sea level (SL) and high altitude (HA). Plots A and B depict CBF versus the percent change in MAP from baseline at SL (A) and HA (B). Each individual's change in CBF per percent ΔMAP within the hypercapnic range is given in plot C. This CBF-MAP reactivity was observed to decrease in every subject but one, despite a greater MAP-PCO₂ reactivity at HA that elicited greater hypertension than at SL. P<0.0001 for the linear fit of all regression equations. MAP, mean arterial pressure. *P<0.05.

Figure 7

Proton concentration in arterial (A) and internal jugular venous blood (B) at sea level (SL) and high altitude (HA) during acute euoxic changes in PETCO₂. Slopes of the regression were significantly less at SL than at HA for both arterial and internal jugular venous blood (P<0.05). P<0.0001 for the linear fit of all regression equations.