Differences in the control of breathing between Andean highlanders and lowlanders after 10 days acclimatization at 3850 m

Abstract

We used Duffin's isoxic hyperoxic ( mmHg) and hypoxic ( mmHg) rebreathing tests to compare the control of breathing in eight (7 male) Andean highlanders and six (4 male) acclimatizing Caucasian lowlanders after 10 days at 3850 m. Compared to lowlanders, highlanders had an increased non-chemoreflex drive to breathe, characterized by higher basal ventilation at both hyperoxia (10.5 +/- 0.7 vs. 4.9 +/- 0.5 l min(1), P = 0.002) and hypoxia (13.8 +/- 1.4 vs. 5.7 +/- 0.9 l min(1), P < 0.001). Highlanders had a single ventilatory sensitivity to CO(2) that was lower than that of the lowlanders (P < 0.001), whose response was characterized by two ventilatory sensitivities (VeS1 and VeS2) separated by a patterning threshold. There was no difference in ventilatory recruitment thresholds (VRTs) between populations (P = 0.209). Hypoxia decreased VRT within both populations (highlanders: 36.4 +/- 1.3 to 31.7 +/- 0.7 mmHg, P < 0.001; lowlanders: 35.3 +/- 1.3 to 28.8 +/- 0.9 mmHg, P < 0.001), but it had no effect on basal ventilation (P = 0.12) or on ventilatory sensitivities in either population (P = 0.684). Within lowlanders, VeS2 was substantially greater than VeS1 at both isoxic tensions (hyperoxic: 9.9 +/- 1.7 vs. 2.8 +/- 0.2, P = 0.005; hypoxic: 13.2 +/- 1.9 vs. 2.8 +/- 0.5, P < 0.001), although hypoxia had no effect on either of the sensitivities (P = 0.192). We conclude that the control of breathing in Andean highlanders is different from that in acclimatizing lowlanders, although there are some similarities. Specifically, acclimatizing lowlanders have relatively lower non-chemoreflex drives to breathe, increased ventilatory sensitivities to CO(2), and an altered pattern of ventilatory response to CO(2) with two ventilatory sensitivities separated by a patterning threshold. Similar to highlanders and unlike lowlanders at sea-level, acclimatizing lowlanders respond to hypobaric hypoxia by decreasing their VRT instead of changing their ventilatory sensitivity to CO(2).

Figure 1. The control of breathing model (Lloyd & Cunningham, 1963)

The total ventilatory drive is the sum of chemoreflex and non-chemoreflex drives to breathe, which are integrated in the respiratory centre. The ventilatory drive exerts its action on the respiratory muscles that affect pulmonary ventilation and result in changes in arterial and . Arterial [H⁺] is ‘sampled’ by the peripheral chemoreceptors located in the carotid bodies, where it determines the peripheral chemoreflex drive. Hypoxia exerts its effect on ventilation via peripheral chemoreceptors, where it acts indirectly via increasing the ventilatory sensitivity to [H⁺] in most individuals but may also act directly by increasing the overall activity of the receptor. Central chemoreceptors respond to changes in the local [H⁺] environment, which is affected by brain tissue . Brain tissue is a function of both arterial and cerebral blood flow, which acts to decrease the brain tissue at a higher flow (Berkenbosch et al. 1989; Mohan et al. 1999). The central and peripheral chemoreflex drives add together to form a total chemoreflex drive to breathe.

Figure 2. Breath-by-breath ventilation vs. end-tidal during a representative Duffin's rebreathing test for one highlander (A) and one lowlander (B) illustrating fitting of the plots

In highlanders (A), the plots were fitted by dividing them into 2 segments, separated by a breakpoint corresponding to the ventilatory recruitment threshold (VRT). In lowlander subjects (B), the plots were fitted by dividing them into 3 segments, separated by two breakpoints, VRT and T2. T2 was defined as the at which there was a change in the slope of the ventilatory response to CO₂ above VRT. In both populations, the first segment was fitted with either an exponential decline to a final value, or a mean, and measured sub-VRT ventilation (VeB) that represents non-chemoreflex ventilation drive. In highlanders, the second segment was fitted with a straight line where the slope measured the sensitivity (VeS). In lowlanders, the second and third segments were also fitted with straight lines where the slopes measured the first (VeS1) and second (VeS2) ventilatory sensitivities to CO₂.

Figure 3. Mean breath-by-breath ventilation vs. during isoxic hyperoxic and hypoxic Duffin's rebreathing tests for all Andean highlander (continuous lines) and lowlander (dashed lines) subjects

Note the presence of two ventilatory sensitivity slopes, VeS1 and VeS2, in acclimatized lowlanders, while highlander responses have only one slope.

Figure 5. Patterns of ventilatory response to hypoxic and hyperoxic rebreathing from all lowlander subjects illustrating the patterning thresholds

Note that only Lowlander 1 displayed the classic patterning threshold with tidal volume reaching a maximum so that a further increase in ventilation was driven by an increase in respiratory rate alone. The rest of lowlanders increased both their tidal volume and respiratory rate at T2.

Figure 4. Two types of patterning threshold (T2) were identified in acclimatizing lowlanders

Pattern A has been previously seen in lowlanders at sea-level (Duffin & Mahamed, 2003) and is characterized by a decrease in the rate of rise of tidal volume (V_T) and an increase in the rate of rise in respiratory rate (RR), leading to overall increase in ventilatory sensitivity to CO₂ above T2. Pattern B is characterized by an increased rate of rise of both V_T and RR above T2, leading to an overall increase in ventilatory sensitivity to CO₂ above T2. Most of the acclimatizing lowlander subjects (5 out of 6) displayed pattern B.

Figure 6. Hypoxic and hyperoxic rebreathing responses from all highlander subjects

Note the different patterns of responses between hypoxic and hyperoxic rebreathing (see text for more detailed discussion).