Effects Of Chronic Hypercapnia Research Articles

Hypercapnia in COPD: Causes, Consequences, and Therapy.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder that may lead to gas exchange abnormalities, including hypercapnia. Chronic hypercapnia is an independent risk factor of mortality in COPD, leading to epithelial dysfunction and impaired lung immunity. Moreover, chronic hypercapnia affects the cardiovascular physiology, increases the risk of cardiovascular morbidity and mortality, and promotes muscle wasting and musculoskeletal abnormalities. Noninvasive ventilation is a widely used technique to remove carbon dioxide, and several studies have investigated its role in COPD. In the present review, we aim to summarize the causes and effects of chronic hypercapnia in COPD. Furthermore, we discuss the use of domiciliary noninvasive ventilation as a treatment option for hypercapnia while highlighting the controversies within the evidence. Finally, we provide some insightful clinical recommendations and draw attention to possible future research areas.

Acid-base adjustments and first evidence of denticle corrosion caused by ocean acidification conditions in a demersal shark species

Global ocean acidification is expected to chronically lower the pH to 7.3 (>2200 µatm seawater pCO2) by the year 2300. Acute hypercapnia already occurs along the South African west and south coasts due to upwelling- and low-oxygen events, with increasing frequency. In the present project we investigated the impact of hypercapnia on the endemic demersal shark species Haploblepharus edwardsii. Specifically, we experimentally analysed acid-base regulation during acute and chronic hypercapnia, the effects of chronic hypercapnia on growth rates and on denticle structure- and composition. While H. edwardsii are physiologically well adapted to acute and chronic hypercapnia, we observed, for the first time, denticle corrosion as a result of chronic exposure. We conclude that denticle corrosion could increase denticle turnover and compromise hydrodynamics and skin protection.

Effects of chronic hypercapnia on ammonium transport in the mouse kidney.

Hypercapnia and subsequent respiratory acidosis are serious complications in many patients with respiratory disorders. The acute response to hypercapnia is buffering of H+ by hemoglobin and cellular proteins but this effect is limited. The chronic response is renal compensation that increases HCO3 − reabsorption, and stimulates urinary excretion of titratable acids (TA) and NH4 +. However, the main effective pathway is the excretion of NH4 + in the collecting duct. Our hypothesis is that, the renal NH3/NH4 + transporters, Rhbg and Rhcg, in the collecting duct mediate this response. The effect of hypercapnia on these transporters is unknown. We conducted in vivo experiments on mice subjected to chronic hypercapnia. One group breathed 8% CO2 and the other breathed normal air as control (0.04% CO2). After 3 days, the mice were euthanized and kidneys, blood, and urine samples were collected. We used immunohistochemistry and Western blot analysis to determine the effects of high CO2 on localization and expression of the Rh proteins, carbonic anhydrase IV, and pendrin. In hypercapnic animals, there was a significant increase in urinary NH4 + excretion but no change in TA. Western blot analysis showed a significant increase in cortical expression of Rhbg (43%) but not of Rhcg. Expression of CA‐IV was increased but pendrin was reduced. These data suggest that hypercapnia leads to compensatory upregulation of Rhbg that contributes to excretion of NH3/NH4 + in the kidney. These studies are the first to show a link among hypercapnia, NH4 + excretion, and Rh expression.

Effects of chronic hypercapnia and elevated temperature on the immune response of the spiny lobster, Jasus lalandii

The West Coast rock lobster (WCRL), Jasus lalandii, inhabits highly variable environments frequented by upwelling events, episodes of hypercapnia and large temperature variations. Coupled with the predicted threat of ocean acidification and temperature change for the coming centuries, the immune response in this crustacean will most likely be affected. We therefore tested the hypothesis that chronic exposure to hypercapnia and elevated seawater temperature will alter immune function of the WCRL. The chronic effects of four combinations of two stressors (seawater pCO2 and temperature) on the total number of circulating haemocytes (THC) as well as on the lobsters’ ability to clear (inactivate) an injected dose of Vibrio anguillarum from haemolymph circulation were assessed. Juvenile lobsters were held in normocapnic (pH 8.01) or hypercapnic (pH 7.34) conditions at two temperatures (15.6 and 18.9 °C) for 48 weeks (n = 30 lobster per treatment), after which a subsample of lobsters (n = 8/treatment), all at a similar moult stage, were selected from each treatment for the immune challenge. Baseline levels of haemocytes (THC ml−1) and bacteria (CFU ml−1) in their haemolymph were quantified 24 h prior to bacterial challenge. Lobsters were then challenged by injecting 4 × 104V. anguillarum per g body weight directly into the cardiac region of each lobster and circulating haemocyte and culturable bacteria were measured at 20 min post challenge. No significant differences in THC ml−1 (p < 0.05) were observed between any of the treatment groups prior to the bacterial challenge. However lobsters chronically exposed to a combination of hypercapnia and low temperature had significantly higher (p < 0.05) THCs post-challenge in comparison with lobsters chronically exposed to hypercapnia and high temperature. A significant interactive effect was recorded between temperature and pH for the post-challenge THC data (two-way ANOVA, p = 0.0025). Lobster were very efficient at rendering an injected dose of bacteria non-culturable, with more than 83% of the theoretical challenge dose (∼1.7 × 105Vibrio ml−1 haemolymph) inactivated within the first 10 min following injection. Although differences in the inactivation of V. anguillarum were observed between treatment groups, none of these differences were significant. Clearance efficiency was in the following order: Hypercapnia/low temperature > normocapnia/high temperature > normocapnia/low temperature > hypercapnia/high temperature. This study demonstrated that despite chronic exposure to combinations of reduced seawater pH and high temperature, the WCRL was still capable of rapidly rendering an injected dose of bacteria non-culturable.

Glutamate Receptor Plasticity in Brainstem Respiratory Nuclei Following Chronic Hypercapnia in Goats

Patients that retain CO2 with respiratory diseases such as chronic obstructive pulmonary disease (COPD) have worse prognoses and higher mortality rates than those with equal impairment of lung function without hypercapnia. However, little is known about the effects of chronic hypercapnia on the neurochemical mechanisms controlling brainstem respiratory nuclei (BRN). Common mechanisms of neuroplasticity involve changes in glutamate receptor expression/phosphorylation to modulate synaptic strength and network excitability, driven by changes in both AMPA (GluR) and NMDA (GluN) glutamate receptors. Accordingly, herein we tested the hypothesis that changes occur in glutamatergic signaling within the BRN during exposure to chronically elevated inspired CO2 (InCO2) induced hypercapnia. Healthy goats were euthanized after either 24 hours or 30 days of chronic exposure to 6% InCO2 or room air. The brainstems were extracted for western blot analyses to assess GluR and GluN receptor expression and phosphorylation state within the BRN. Compared to room air control goats, the following significant (P&lt;0.05) changes were found after 24 hours of exposure to chronic hypercapnia: 1) AMPA receptor expression was greater, and NMDA receptor expression lower within the rostral solitary complex. 2) NMDA receptor expression/phosphorylation and APMA receptor phosphorylation were lower within the rostral ventrolateral medulla (VLM), while AMPA receptor expression/phosphorylation were greater in the caudal VLM. 3) AMPA receptor expression/phosphorylation were lower within the rostral retrotrapezoid nucleus. And, 4) NMDA receptor expression was greater within the caudal Raphe nucleus. The data indicate that within 24 hours of chronic hypercapnia changes have occurred in four BRN in GluR/GluN signaling which may contribute to an attenuated CO2‐induced hyperpnea and attenuated CO2 chemoreflex between 1 and 24 hours of hypercapnia (J. Physiol. 2018). GluR/GluN changes found at 24 hours of hypercapnia had returned to control levels after 30 days of hypercapnia. However, compared to room air control goats, the following significant (P&lt;0.05) changes were found following 30 days of hypercapnia: 1) NMDA receptor phosphorylation was greater in the caudal ventral respiratory column, and 2) AMPA receptor expression was greater in the caudal RTN. The changes in GluR/GluN signaling between 24 hours and 30 days of chronic InCO2 may contribute to a sustained hyperpnea and normalization of the CO2 chemoreflex at 30 days.Support or Funding Information‐Department of Veteran Affairs ‐NIH Grant 007852This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Massive Scrotal Edema: An Unusual Manifestation of Obstructive Sleep Apnea and Obesity-Hypoventilation Syndrome

Obstructive sleep apnea (OSA) may occur in association with obesity-hypoventilation (Pickwickian) syndrome, a disorder of ventilatory control affecting individuals with morbid obesity. Through the pressor effects of chronic hypercapnia and hypoxemia, this syndrome may result in pulmonary hypertension, right heart failure, and massive peripheral edema. We present a case of severe scrotal edema in a 36-year-old male with OSA and obesity-hypoventilation syndrome. A tracheostomy was performed to relieve hypoxemia and led to dramatic improvement of scrotal edema. No scrotal surgery was necessary. Followup at two months showed complete resolution of scrotal edema, improvement in mental status, and normalization of arterial blood gas measurements. This case demonstrates that OSA and obesity-hypoventilation syndrome may present with massive scrotal edema. Furthermore, if OSA is recognized as the cause of right heart failure, and if the apnea is corrected, the resultant improvement in cardiac function may allow reversal of massive peripheral, including scrotal, edema.

Effects of Chronic Hypercapnia in the Neonatal Mouse Lung and Brain

Permissive hypercapnia is increasingly utilized in the care of premature infants to prevent bronchopulmonary dysplasia. In a previous investigation, we described gene expression changes in the neonatal mouse lung exposed to chronic hypercapnia that might contribute to lung protection and accelerated maturation. However, it is unknown whether chronic hypercapnia increases alveolar formation, nor if it has detrimental effects in other developing organs such as the brain. To determine whether chronic hypercapnia accelerates early alveolar formation and increases neuronal cell injury in the developing mouse lung and brain, respectively. Mouse pups were exposed to 8% CO(2) + 21% O(2) starting at postnatal day (P) 2 until P7. Control animals were maintained in room air. Animals were sacrificed at P4 or P7, and lungs and brains were excised and analyzed. Exposure to 8% CO(2) resulted in an increased expression of alpha-smooth muscle actin (alpha-sma) which localized to the tips of developing alveolar buds, and also an increased number of alveolar buds at P7. Importantly, hypercapnic animals also demonstrated evidence of increased TUNEL-positive cells in the brain. Exposure to chronic hypercapnia may lead to early initiation of alveolar budding in the neonatal mouse, but may also lead to increased TUNEL-positive cells in the developing brain.

Cardioprotective effect of chronic hypoxia is blunted by concomitant hypercapnia

The effect of chronic hypercapnia on cardioprotection induced by chronic hypoxia was investigated in adult male Wistar rats exposed to isobaric hypoxia (10 % O2) for three weeks. In the first experimental group, CO2 in the chamber was fully absorbed; in the second group, its level was increased to 4.1 %. Normoxic controls were kept in atmospheric air. Anesthetized open-chest animals were subjected to 20-min LAD coronary artery occlusion and 3-h reperfusion for infarct size determination (TTC staining). Chronic hypoxia alone reduced body weight and increased hematocrit; these effects were significantly attenuated by hypercapnia. The infarct size was reduced from 61.9 ± 2.2 % of the area at risk in the normoxic controls to 44.5±3.3 % in the hypoxic group (P&lt;0.05). Hypercapnia blunted the infarct size-limiting effect of hypoxia (54.8±2.4 %; P&lt;0.05). It is concluded that increased CO2 levels in the inspired air suppress the development of the chronic hypoxia-induced cardioprotective mechanism, possibly by interacting with ROS signalling pathways.

Effect of chronic hypercapnia on body temperature regulation

Guinea pigs and rats exposed to 15% CO2 for 7 days showed a parallel time course of changes in pH, body temperature (TB), and oxygen consumption (VO2). Between 1 and 6 h of exposure the maximal drop in actual pH occurred in guinea pigs simultaneously with the maximal fall in TB and VO2. During the subsequent period pH TB, VO2 rose again. Skin blood content (heat loss) also exhibited a biphasic pH-dependent time course. Animals showing no partial compensation of respiratory acidosis during 3 days exposure also failed in raising their TB back to normal in this time. The behavior of TB was found to be a good indicator of the acid-base status and adaptive potential of the animals to hypercapnia. Similar results were obtained in rats. Thermo-regulatory processes in the hypothalamus were affected during exposure to 15% CO2. Both guinea pigs and rats showed a decrease in norepinephrine content of the hypothalamus during the first part of exposure reaching a maximal fall at the end of 24 h. The serotonin content increased slightly during this period. During prolonged exposure to 3% CO2 for 7 days, TB showed a transient rise, and VO2 was slightly elevated.

The effects of chronic hypercapnia on blood phosphofructokinase activity and the adenine nucleotide system

Phosphofructokinase activity and adenine nucleotide levels were determined in blood of guinea pigs exposed to 15% CO 2 in 21 % O 2, balance N 2, for varying periods of time up to one week. Acute exposure produced a decrease in enzyme activity while the chronic phase increased activity without attainment of control values. These alterations in blood phosphofructokinase activity strikingly paralleled the biphasic changes in blood pH during acute and chronic hypercapnia. These findings demonstrate that blood phosphofructokinase activity is capable of responding to in vivo fluctuations in blood pH. Arterial ATP, ADP, and AMP concentrations and the energy charge were virtually unchanged during both phases indicating that hypereapnia is characterized by conservation of high-energy phosphates.

The effect of chronic hypercapnia on oxygen affinity and 2,3-diphosphoglycerate

The relationship between oxygen affinity and 2,3-diphosphoglycerate (2,3-DPG) in the red cell has been studied in chronic hypercapnia induced by prolonged exposure of guinea pigs to 15% CO 2 and 21% O 2 in N 2. Red cell pH fell to a minimum after six hours of exposure and subsequently rose without reaching initial values after seven days of exposure. Both oxygen half-saturation pressure (P 50) and the level of 2,3-DPG of the red cells followed the time course of the pH changes. However, both parameters required 24 hours to reach a minimum, following which they increased steadily and were not different from control values after seven days of exposure.

Effect of chronic hypercapnia on gastric secretion in the dog.

Effect of chronic hypercapnia on gastric secretion in the dog.

Effects of chronic hypercapnia on electrolyte and acid-base equilibrium. III. Characteristics of the adaptive and recovery process as evaluated by provision of alkali.

Effects of chronic hypercapnia on electrolyte and acid-base equilibrium. III. Characteristics of the adaptive and recovery process as evaluated by provision of alkali.

Effects of chronic hypercapnia on electrolyte and acid-base equilibrium. I. Adaptation.

Effects of chronic hypercapnia on electrolyte and acid-base equilibrium. I. Adaptation.