Mechanisms of the cerebrovascular response to apnoea in humans

Abstract

We measured ventilation, arterial O2 saturation, end-tidal CO2 (PET,CO2), blood pressure (intra-arterial catheter or photoelectric plethysmograph), and flow velocity in the middle cerebral artery (CFV) (pulsed Doppler ultrasound) in 17 healthy awake subjects while they performed 20 s breath holds under control conditions and during ganglionic blockade (intravenous trimethaphan, 4.4 +/- 1.1 mg min-1 (mean +/- S.D.)). Under control conditions, breath holding caused increases in PET,CO2 (7 +/- 1 mmHg) and in mean arterial pressure (MAP) (15 +/- 2 mmHg). A transient hyperventilation (PET,CO2 -7 +/- 1 mmHg vs. baseline) occurred post-apnoea. CFV increased during apnoeas (by 42 +/- 3 %) and decreased below baseline (by 20 +/- 2 %) during post-apnoea hyperventilation. In the post-apnoea recovery period, CFV returned to baseline in 45 +/- 4 s. The post-apnoea decrease in CFV did not occur when hyperventilation was prevented. During ganglionic blockade, which abolished the increase in MAP, apnoea-induced increases in CFV were partially attenuated (by 26 +/- 2 %). Increases in PET,CO2 and decreases in oxyhaemoglobin saturation (Sa,O2) (by 2 +/- 1 %) during breath holds were identical in the intact and blocked conditions. Ganglionic blockade had no effect on the slope of the CFV response to hypocapnia but it reduced the CFV response to hypercapnia (by 17 +/- 5 %). We attribute this effect to abolition of the hypercapnia-induced increase in MAP. Peak increases in CFV during 20 s Mueller manoeuvres (40 +/- 3 %) were the same as control breath holds, despite a 15 mmHg initial, transient decrease in MAP. Hyperoxia also had no effect on the apnoea-induced increase in CFV (40 +/- 4 %). We conclude that apnoea-induced fluctuations in CFV were caused primarily by increases and decreases in arterial partial pressure of CO2 (Pa,CO2) and that sympathetic nervous system activity was not required for either the initiation or the maintenance of the cerebrovascular response to hyper- and hypocapnia. Increased MAP or other unknown influences of autonomic activation on the cerebral circulation played a smaller but significant role in the apnoea-induced increase in CFV; however, negative intrathoracic pressure and the small amount of oxyhaemoglobin desaturation caused by 20 s apnoea did not affect CFV.

Figure 1. Original record showing typical cardiovascular and ventilatory responses to a 20 s breath hold in the intact condition

The P_ET,CO2 of the first post-apnoeic exhalation fails to reflect CO₂ accumulation caused by the apnoea because the subject spontaneously inspired upon apnoea termination, thereby diluting the alveolar gas. The values for post-apnoeic P_ET,CO2 shown in subsequent figures were determined in separate trials in which subjects exhaled immediately at apnoea termination (see Methods). V_T, tidal volume.

Figure 2. Cerebrovascular responses to 20 s breath holds with hyperpnoeic recovery periods in the intact condition (•) and during ganglionic blockade (▵) (n = 8)

The dashed vertical lines indicate the duration of the apnoeas and the continuous vertical lines indicate standard errors of the mean (s.e.m.). CFV, cerebral blood flow velocity; MAP, mean arterial pressure. Baseline values for CFV: 65.0 ± 3.6 cm s⁻¹ (intact condition) and 64.0 ± 3.7 cm s⁻¹ (ganglionic blockade). The P_ET,CO2 values noted at apnoea termination were determined in separate trials (see Fig. 1 legend).

Figure 3. Cerebrovascular responses to 20 s breath holds with hyperpnoeic (▴) and controlled (□) recovery periods in the intact condition (n = 8)

The dashed vertical lines indicate the duration of the apnoeas and the continuous vertical lines indicate s.e.m. values. Abbreviations as in Fig. 2. Baseline values for CFV: 65.0 ± 3.6 cm s⁻¹ (hyperpnoeic recovery) and 64.9 ± 3.7 cm s⁻¹ (controlled recovery).

Figure 4. Cerebrovascular responses to 20 s breath holds performed in normoxia (•), hyperoxia (▵), and with sustained negative intrathoracic pressure (Mueller manoeuvres, ⋄)

All breath holds were followed by controlled recovery periods (n = 7). The dashed vertical lines indicate the duration of the apnoeas and the continuous vertical lines indicate standard errors of the mean. Abbreviations as in Fig. 2. Apnoea-induced increases in P_ET,CO2, measured during normoxic breath holds, were presumed to be the same during Mueller manoeuvres and hyperoxic breath holds. Baseline values for CFV: 34.5 ± 2.4 cm s⁻¹ (normoxic breath holds), 33.8 ± 2.7 cm s⁻¹ (hyperoxic breath holds) and 34.4 ± 2.5 cm s⁻¹ (Mueller manoeuvres).

Figure 5. Relationships between P_ET,CO2 and cerebral blood flow velocity (CFV) and mean arterial pressure (MAP) in the intact condition (•) and during ganglionic blockade (▵) (n = 9)

Data shown are means ±s.e.m. Asterisks indicate that the slopes of the CFV and MAP responses to hypercapnia were greater in the intact versus the ganglionic blockade condition (P < 0.05).

Figure 6. Time courses of cerebrovascular responses to hyper- and hypocapnia in the intact condition (•) and during ganglionic blockade (▵)

CFV, cerebral blood flow velocity; P_ET,CO2, end-tidal CO₂ tension. All points represent the mean values from 9 subjects.