Cerebral blood flow and oxygenation at maximal exercise: the effect of clamping carbon dioxide

During exercise, as end-tidal carbon dioxide (P_ETCO2$P_{\text{E}{\text{T}}_{\text{C}{\text{O}}_2}}$) drops after the respiratory compensation point (RCP), so does cerebral blood flow velocity (CBFv) and cerebral oxygenation. This low-flow, low-oxygenation state may limit work capacity. We hypothesized that by preventing the fall in P_ETCO2$P_{\text{E}{\text{T}}_{\text{C}{\text{O}}_2}}$ at peak work capacity (W_max) with a newly designed high-flow, low-resistance rebreathing circuit, we would improve CBFv, cerebral oxygenation, and W_max. Ten cyclists performed two incremental exercise tests, one as control and one with P_ETCO2$P_{\text{E}{\text{T}}_{\text{C}{\text{O}}_2}}$ constant (clamped) after the RCP. We analyzed , middle cerebral artery CBFv, cerebral oxygenation, and cardiopulmonary measures. At W_max, when we clamped P_ETCO2$P_{\text{E}{\text{T}}_{\text{C}{\text{O}}_2}}$ (39.7 ± 5.2 mmHg vs. 29.6 ± 4.7 mmHg, P < 0.001), CBFv increased (92.6 ± 15.9 cm/s vs. 73.6 ± 12.5 cm/s, P < 0.001). However, cerebral oxygenation was unchanged (ΔTSI −21.3 ± 13.1% vs. −24.3 ± 8.1%, P = 0.33), and W_max decreased (380.9 ± 20.4 W vs. 405.7 ± 26.8 W, P < 0.001). At W_max, clamping P_ETCO2$P_{\text{E}{\text{T}}_{\text{C}{\text{O}}_2}}$ increases CBFv, but this does not appear to improve W_max.     

Hypoxia induced changes in lung fluid balance in humans is associated with beta-2 adrenergic receptor density on lymphocytes

Background

Previous studies have demonstrated an important role for beta-2 adrenergic receptors (β₂AR) in lung fluid clearance. The purpose of this investigation was to examine the relationship between β₂AR density on lymphocytes and indices of lung water in healthy humans exposed to ∼17 h of hypoxia (F_IO2=12.5%$F_{{\text{IO}}_2}=12.5\%$ in a hypoxia tent).

Methods

Thirteen adults (mean ± SEM; age = 31 ± 3 years, BMI = 24 ± 1 kg/m², V_O2 Peak=40±2 ml/kg/min$V_{{\text{O}}_{2\text{Peak}}}=40\pm 2\text{ml}/\text{kg}/\text{min}$) participated. Pulmonary function, CT derived lung tissue volume (V_tis-tissue, blood and water), lung diffusing capacity for carbon monoxide (D_CO) and nitric oxide (D_NO), alveolar-capillary conductance (D_M), pulmonary capillary blood volume (V_c) and lung water (CT V_tis − V_c) were assessed before and after ∼17 h normobaric hypoxia (F_IO2=12.5%$F_{{\text{IO}}_2}=12.5\%$). β₂AR density on lymphocytes was measured via radioligand binding. Arterial oxygen saturation (Sa_O2${\text{Sa}}_{{\text{O}}_2}$), cardiac output (Q), right ventricular systolic pressure (RVSP) and blood pressure (BP) were also assessed.

Results

After 17 h hypoxia, Sa_O2${\text{Sa}}_{{\text{O}}_2}$ decreased from 97 ± 1 (normoxia) to 82 ± 4% and RVSP increased from 14 ± 3 (normoxia) to 29 ± 2 mmHg (p < 0.05) with little change in Q or BP. V_c and D_M both increased with hypoxia with a small increase in D_M/V_c ratio (p > 0.05). CT V_tis decreased and lung water was estimated to decline 7 ± 13%, respectively. β₂AR density averaged 1497 ± 187 receptors/lymphocyte and increased 21 ± 34% with hypoxia (range −31 to +86%). The post-hypoxia increase in β₂AR density was significantly related to the reduction in lung water (r = −0.64, p < 0.05), with the subjects with the greatest increase in density demonstrating the largest decline in lung water.

Conclusions

Lung water decreases with 17 h normobaric hypoxia are associated with changes in beta adrenergic receptor density on lymphocytes in healthy adults.     

The influence of varying inspired fractions of O₂ and CO₂ on the development of involuntary breathing movements during maximal apnoea

The growing urge to breathe that occurs during breath-holding results in development of involuntary breathing movements (IBMs). The present study determined whether IBMs are initiated at critical levels of hypercapnia and/or hypoxia during maximal apnoea. Arterial blood gasses at the onset of IBM were monitored during maximal voluntary breath-holds. Eleven healthy men performed breath holds after breathing air, hyperoxic–normocapnia, hypoxic–normocapnia, and normoxic–hypercapnia. Pre-breathing of the gas mixtures facilitated the IBM onset, reducing the time-to-onset for ∼46% (hyperoxic condition) and for ∼80% (hypoxic condition) compared to the normoxic air breathing time. A strong correlation (R = 0.83, P = 0.002) between arterial partial pressure of CO₂ (Pa_CO2${\text{Pa}}_{{\text{CO}}_2}$) at IBM onset after pre-breathing hyperoxic and hypercapnic gas mixtures was observed, suggesting the existence of a possible IBM Pa_CO2${\text{Pa}}_{{\text{CO}}_2}$ threshold level of ∼6.5 ± 0.5 kPa. No clear “threshold” was observed for partial pressure of arterial O₂ (Pa_O2${\text{Pa}}_{{\text{O}}_2}$). However, we observed that IBM onset was influenced, in part, by an interaction between Pa_O2${\text{Pa}}_{{\text{O}}_2}$ and Pa_CO2${\text{Pa}}_{{\text{CO}}_2}$ levels during maximal apnoea. This study demonstrated the complex interaction between arterial blood-gases and the physiological response to maximal breath holding.     

Bronchoconstriction during alveolar hypocapnia and systemic hypercapnia in dogs with a cardiopulmonary bypass

The roles of the alveolar and systemic CO₂ on the lung mechanics were investigated in dogs subjected to cardiopulmonary bypass. Low-frequency pulmonary impedance data (Z_L) were collected in open-chest dogs with an alveolar CO₂ level (FA_CO2)$(\text{F}{\text{A}}_{\text{C}{\text{O}}_2})$ of 0.2–7% and during systemic hypercapnia before and after elimination of the vagal tone. Airway resistance (R_aw), inertance (I_aw), parenchymal damping (G) and elastance (H) were estimated from the Z_L. The highest R_aw observed at 0.2% FA_CO2$\text{F}{\text{A}}_{\text{C}{\text{O}}_2}$, which decreased markedly up to a FA_CO2$\text{F}{\text{A}}_{\text{C}{\text{O}}_2}$ of 2% (212 ± 24%), and remained unchanged under normo- and hypercapnia (FA_CO2$\text{F}{\text{A}}_{\text{C}{\text{O}}_2}$ 2–7%). These changes were associated with smaller decreases in I_aw (−16.6 ± 3.7%), mild elevations in G (25.7 ± 4.7%), and no change in H. Significant increases in all mechanical parameters were observed following systemic hypercapnia; atropine counteracted the R_aw rises. We conclude that severe alveolar hypocapnia may contribute to minimization of the ventilation–perfusion mismatch by constricting the airways in poorly perfused lung regions. The constrictor potential of systemic hypercapnia is mediated by vagal reflexes.     

Respiratory responses to hypoxia or hypercapnia in goldfish (Carassius auratus) experiencing gill remodelling

The presence of an interlamellar cell mass (ILCM) on the gills of goldfish significantly decreases the functional lamellar surface area and increases the diffusion distance for gas transfer and thus may impose a serious challenge for the transfer of respiratory gases (O₂ and CO₂). Here we tested the hypothesis that the presence of the ILCM in goldfish acclimated to 7 °C impedes the uptake of O2 and excretion of CO₂. While Pa_O2$\text{P}{\text{a}}_{{\text{O}}_2}$ remained unaltered, the baseline values of Pa_CO2$\text{P}{\text{a}}_{\text{C}{\text{O}}_2}$ were significantly higher in goldfish at 7 °C with ILCM present (5.55 ± 0.54 mmHg; mean ± SEM) than in goldfish at 25 °C without the ILCM (3.98 ± 0.18 mmHg). Carbonic anhydrase (CA) injections relieved the apparent diffusion limitation imposed by the presence of the ILCM on CO₂ excretion (Pw_CO2$\text{P}{\text{w}}_{\text{C}{\text{O}}_2}$ levels dropped to 3.07 ± 0.32 mmHg). Interestingly, the exposure of fish to acute hypoxia evoked similar changes in Pa_O2$\text{P}{\text{a}}_{{\text{O}}_2}$ at the two acclimation temperatures. Ethanol (EtOH) exposure was also used as a tool to further investigate the potential effects of the ILCM on branchial solute transfer. The results showed that the ILCM does not impede EtOH uptake in 7 °C goldfish. Overall, the results of this study demonstrate that the remodelling of the goldfish gill associated with acclimation to 7 °C water, while increasing Pa_CO2$\text{P}{\text{a}}_{\text{C}{\text{O}}_2}$, has minimal impact on branchial O2 transfer.     

Blood gases and cardiovascular shunt in the South American lungfish (Lepidosiren paradoxa) during normoxia and hyperoxia

The South American lungfish (Lepidosiren paradoxa  ) has an arterial P_O2${\text{P}}_{{\text{O}}_2}$ (Pa_O2$\text{P}{\text{a}}_{{\text{O}}_2}$) as high as 70–100 mm Hg, corresponding to Hb–O₂ saturations from 90% to 95%, which indicates a moderate cardiovascular right to left (R–L) shunt. In hyperoxia (50% O₂), we studied animals in: (1) aerated water combined with aerial hyperoxia, which increased Pa_O2$\text{P}{\text{a}}_{{\text{O}}_2}$ from 78 ± 2 to 114 ± 3 mm Hg and (2) and aquatic hyperoxia (50% O₂) combined room air, which gradually increased Pa_O2$\text{P}{\text{a}}_{{\text{O}}_2}$ from 75 ± 4 mm Hg to as much as 146 ± 10 mm Hg. Further, the hyperoxia (50%) depressed pulmonary ventilation from 58 ± 13 to 5.5 ± 3.0 mL BTPS kg h⁻¹, and Pa_CO2$\text{P}{\text{a}}_{\text{C}{\text{O}}_2}$ increased from 20 ± 2 to 31 ± 4 mm Hg, while pHa became reduced from 7.56 ± 0.03 to 7.31 ± 0.09. At the same time, venous P_O2${\text{P}}_{{\text{O}}_2}$ (Pv_O2$\text{P}{\text{v}}_{{\text{O}}_2}$) rose from 40.0 ± 2.3 to 46.4 ± 1.2 mm Hg and, concomitantly, Pv_CO2$\text{P}{\text{v}}_{\text{C}{\text{O}}_2}$ increased from 23.2 ± 1.1 to 32.2 ± 0.5 mm Hg. R–L shunts were estimated to about 19%, which is moderate when compared to most amphibians.     

Sleep-disordered breathing and oxidative stress in preclinical chronic mountain sickness (excessive erythrocytosis)

Chronic mountain sickness (CMS) is considered to be a loss of ventilatory acclimatization to high altitude (>2500 m) resulting in marked arterial hypoxemia and polycythemia. This case–control study explores the possibility that sleep-disordered breathing (SDB) and associated oxidative stress contribute to the etiology of CMS. Nocturnal respiratory and Sa_O2${\text{Sa}}_{{\text{O}}_2}$ patterns were measured using standard polysomnography techniques and compared between male high-altitude residents (aged 18–25) with preclinical CMS (excessive erythrocytosis (EE), n = 20) and controls (n = 19). Measures of oxidative stress and antioxidant status included isoprostanes (8-iso-PGF2_alpha), superoxide dismutase and ascorbic acid. EE cases had a greater apnea–hypopnea index, a higher frequency of apneas (central and obstructive) and hypopneas during REM sleep, and lower nocturnal Sa_O2${\text{Sa}}_{{\text{O}}_2}$ compared to controls. 8-iso-PGF2_alpha was greater in EE than controls, negatively associated with nocturnal Sa_O2${\text{Sa}}_{{\text{O}}_2}$, and positively associated with hemoglobin concentration. Mild sleep-disordered breathing and oxidative stress are evident in preclinical CMS, suggesting that the resolution of nocturnal hypoxemia or antioxidant treatment may prevent disease progression.     

Assessment of pulmonary oxygen toxicity: Relevance to professional diving; a review

When breathing oxygen with partial oxygen pressures (P_O2)$(P_{{\text{O}}_2})$ of between 50 and 300 kPa pathological pulmonary changes develop after 3–24 h depending on the P_O2$P_{{\text{O}}_2}$. This kind of injury (known as pulmonary oxygen toxicity) is not only observed in ventilated patients but is also considered an occupational hazard in oxygen divers or mixed gas divers. To prevent these latter groups from sustaining irreversible lesions adequate prevention is required.     

High CO2/H dialysis in the caudal ventrolateral medulla (Loeschcke's area) increases ventilation in wakefulness

Central chemoreception, the detection of CO₂/H⁺ within the brain and the resultant effect on ventilation, was initially localized at two areas on the ventrolateral medulla, one rostral (rVLM-Mitchell's) the other caudal (cVLM-Loeschcke's), by surface application of acidic solutions in anesthetized animals. Focal dialysis of a high CO₂/H⁺ artificial cerebrospinal fluid (aCSF) that produced a milder local pH change in unanesthetized rats (like that with a ∼6.6 mm Hg increase in arterial P_CO2$P_{\text{C}{\text{O}}_2}$) delineated putative chemoreceptor regions for the rVLM at the retrotrapezoid nucleus and the rostral medullary raphe that function predominantly in wakefulness and sleep, respectively. Here we ask if chemoreception in the cVLM can be detected by mild focal stimulation and if it functions in a state dependent manner. At responsive sites just beneath Loeschcke's area, ventilation was increased by, on average, 17% (P < 0.01) only in wakefulness. These data support our hypothesis that central chemoreception is a distributed property with some sites functioning in a state dependent manner.