OBJECTIVES: To evaluate the base excess response during acute in vivo carbon dioxide changes. DESIGN: Secondary analysis of individual participant data from experimental studies. SETTING: Three experimental studies investigating the effect of acute in vivo respiratory derangements on acid-base variables. SUBJECTS: Eighty-nine (canine and human) carbon dioxide exposures. INTERVENTIONS: Arterial carbon dioxide titration through environmental chambers or mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: For each subject, base excess was calculated using bicarbonate and pH using a fixed buffer power of 16.2. Analyses were performed using linear regression with arterial dioxide (predictor), base excess (outcome), and studies (interaction term). All studies show different baselines and slopes for base excess across carbon dioxide titrations methods. Individual subjects show substantial, and potentially clinically relevant, variations in base excess response across the hypercapnic range. Using a mathematical simulation of 10,000 buffer power coefficients we determined that a coefficient of 12.1 (95% CI, 9.1-15.1) instead of 16.2 facilitates a more conceptually appropriate in vivo base excess equation for general clinical application. CONCLUSIONS: In vivo changes in carbon dioxide leads to changes in base excess that may be clinically relevant for individual patients. A buffer power coefficient of 16.2 may not be appropriate in vivo and needs external validation in a range of clinical settings.

• Keywords
• base deficit, buffer, carbon dioxide, metabolic, respiratory, resuscitation,
• MeSH
• Acid-Base Equilibrium * physiology   MeSH
• Adult MeSH
• Hypercapnia physiopathology   metabolism   MeSH
• Hydrogen-Ion Concentration MeSH
• Humans MeSH
• Carbon Dioxide * metabolism   MeSH
• Acid-Base Imbalance physiopathology   metabolism   MeSH
• Dogs MeSH
• Respiration, Artificial MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Dogs MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Carbon Dioxide * MeSH

This review summarizes the issue of acute hypercapnic respiratory failure. Acute respiratory failure is a condition in which the respiratory system is unable to fulfill its basic function, i.e. enriching the blood with oxygen and excreting carbon dioxide. Chronologically, we divide it into acute and chronic, and according to the manifestation into hypoxemic or hypoxemic with hypercapnia. Multiple factors, such as reduced ventilation and increased dead space, contribute to the development of hypoxemic-hypercapnic (global) respiratory failure. Both the patient's clinical presentation and laboratory examination of blood gases and acid-base balance (preferably from arterial blood) are used for diagnosis. In the absence of contraindications, non-invasive ventilation is used to establish normocapnia.

• Keywords
• Respiratory failure, hypercapnia, non-invasive ventilation, noninvasive ventilation, respiratory insufficiency,
• MeSH
• Pulmonary Disease, Chronic Obstructive * MeSH
• Hypercapnia complications   MeSH
• Humans MeSH
• Lung MeSH
• Respiratory Insufficiency * etiology   therapy   MeSH
• Respiration, Artificial MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The study investigated the role of alpha2-adrenergic receptors of the caudal raphe region in the sympathetic and cardiovascular responses to the acute intermittent hypercapnia (AIHc). Urethane-anesthetized, vagotomized, mechanically ventilated Sprague-Dawley rats (n=38) were exposed to the AIHc protocol (5×3 min, 15 % CO2+50 % O2) in hyperoxic background (50 % O2). alpha2-adrenergic receptor antagonist-yohimbine was applied intravenously (1 mg/kg, n=9) or microinjected into the caudal raphe region (2 mM, n=12) prior to exposure to AIHc. Control groups of animals received saline intravenously (n=7) or into the caudal raphe region (n=10) prior to exposure to AIHc. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were monitored before exposure to the AIHc protocol (T0), during five hypercapnic episodes (THc1-5) and at 15 min following the end of the last hypercapnic episode (T15). Following intravenous administration of yohimbine, RSNA was significantly greater during THc1-5 and at T15 than in the control group (P<0.05). When yohimbine was microinjected into the caudal raphe region, AIHc elicited greater increases in RSNA during THc1-5 when compared to the controls (THc1: 138.0+/-4.0 % vs. 123.7+/-4.8 %, P=0.032; THc2: 137.1+/-5.0 % vs. 124.1+/-4.5 %, P=0.071; THc3: 143.1+/-6.4 % vs. 122.0±4.8 %, P=0.020; THc4: 146.1+/-6.2 % vs. 120.7+/-5.7 %, P=0.007 and THc5: 143.2+/-7.7 % vs. 119.2+/-7.2 %, P=0.038). During THc1-5, significant decreases in HR from T0 were observed in all groups, while changes in MAP were observed in the group that received yohimbine intravenously. These findings suggest that blockade of the alpha2-adrenegic receptors in the caudal raphe region might have an important role in sympathetic responses to AIHc.

• MeSH
• Receptors, Adrenergic MeSH
• Hypercapnia * chemically induced   MeSH
• Blood Pressure physiology   MeSH
• Rats MeSH
• Raphe Nuclei MeSH
• Rats, Sprague-Dawley MeSH
• Heart Rate MeSH
• Sympathetic Nervous System * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Receptors, Adrenergic MeSH

Domiciliary non-invasive ventilation has been an established method of treating chronic hypercapnic respiratory insufficiency for decades. Its effectiveness is based on a number of clinical studies and the prevalence of use worldwide and in the Czech Republic is increasing. The article offers a brief summary of the pathophysiology of hypercapnic respiratory insufficiency and its treatment.

• Keywords
• NIV, domiciliary non-invasive ventilation, hypercapnia, non-invasive ventilation, respiratory insufficiency,
• MeSH
• Pulmonary Disease, Chronic Obstructive * complications   therapy   MeSH
• Hypercapnia therapy   MeSH
• Humans MeSH
• Noninvasive Ventilation * methods   MeSH
• Respiratory Insufficiency * therapy   MeSH
• Respiration, Artificial MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Breathing impairments, such as an alteration in breathing pattern, dyspnoea, and sleep apnoea, are common health deficits recognised in Parkinson's disease (PD). The mechanism that underlies these disturbances, however, remains unclear. We investigated the effect of the unilateral damage to the rat nigrostriatal pathway on the central ventilatory response to hypercapnia, evoked by administering 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB). The respiratory experiments were carried out in conscious animals in the plethysmography chamber. The ventilatory parameters were studied in normocapnic and hyperoxic hypercapnia before and 14 days after the neurotoxin injection. Lesion with the 6-OHDA produced an increased tidal volume during normoxia. The magnified response of tidal volume and a decrease of breathing frequency to hypercapnia were observed in comparison to the pre-lesion and sham controls. Changes in both respiratory parameters resulted in an increase of minute ventilation of the response to CO(2) by 28% in comparison to the pre-lesion state at 60 s. Our results demonstrate that rats with implemented unilateral PD model presented an altered respiratory pattern most often during a ventilatory response to hypercapnia. Preserved noradrenaline and specific changes in dopamine and serotonin characteristic for this model could be responsible for the pattern of breathing observed during hypercapnia.

• MeSH
• Medial Forebrain Bundle drug effects   physiology   MeSH
• Hypercapnia physiopathology   MeSH
• Rats MeSH
• Oxidopamine toxicity   MeSH
• Parkinsonian Disorders chemically induced   physiopathology   MeSH
• Pulmonary Ventilation drug effects   physiology   MeSH
• Rats, Wistar MeSH
• Sympatholytics toxicity   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Oxidopamine MeSH
• Sympatholytics MeSH

The aim of study was to review the status of arterial pH, pO(2) and pCO(2) under general anesthesias in dependence on the light-dark (LD) cycle in spontaneously breathing rats. The experiments were performed using three- to four-month-old pentobarbital(P)-, ketamine/xylazine(K/X)- and zoletil(Z)-anesthetized female Wistar rats after a four-week adaptation to an LD cycle (12 h light:12 h dark). The animals were divided into three experimental groups according to the anesthetic agent used: P (light n=11; dark n=8); K/X (light n=13; dark n=11); and Z (light n=18; dark n=26). pH and blood gases from arterial blood were analyzed. In P anesthesia, LD differences in pH, pO(2), and pCO(2) were eliminated. In K/X anesthesia, parameters showed significant LD differences. In Z anesthesia, LD differences were detected for pH and pO(2) only. Acidosis, hypoxia, and hypercapnia have been reported for all types of anesthesia during the light period. In the dark period, except for P anesthesia, the environment was more stable and values fluctuated within normal ranges. From a chronobiological perspective, P anesthesia was not the most appropriate type of anesthesia in these rat experiments. It eliminated LD differences, and also produced a more acidic environment and more pronounced hypercapnia than K/X and Z anesthesias.

• MeSH
• Blood Gas Analysis methods   MeSH
• Anesthetics, General adverse effects   blood   pharmacology   MeSH
• Anesthesia, General * adverse effects   trends   MeSH
• Chronobiology Phenomena drug effects   physiology   MeSH
• Drug Combinations MeSH
• Hypercapnia blood   chemically induced   MeSH
• Hypoxia blood   chemically induced   MeSH
• Ketamine adverse effects   pharmacology   MeSH
• Rats MeSH
• Pentobarbital adverse effects   pharmacology   MeSH
• Rats, Wistar MeSH
• Tiletamine adverse effects   pharmacology   MeSH
• Zolazepam adverse effects   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anesthetics, General MeSH
• Drug Combinations MeSH
• Ketamine MeSH
• Pentobarbital MeSH
• Tiletamine MeSH
• tiletamine, zolazepam drug combination MeSH Browser
• Zolazepam MeSH

BACKGROUND: Respiratory parameters are important predictors of prognosis in the COPD population. Global Initiative for Obstructive Lung Disease (GOLD) 2017 Update resulted in a vertical shift of patients across COPD categories, with category B being the most populous and clinically heterogeneous. The aim of our study was to investigate whether respiratory parameters might be associated with increased all-cause mortality within GOLD category B patients. METHODS: The data were extracted from the Czech Multicentre Research Database, a prospective, noninterventional multicenter study of COPD patients. Kaplan-Meier survival analyses were performed at different levels of respiratory parameters (partial pressure of oxygen in arterial blood [PaO2], partial pressure of arterial carbon dioxide [PaCO2] and greatest decrease of basal peripheral capillary oxygen saturation during 6-minute walking test [6-MWT]). Univariate analyses using the Cox proportional hazard model and multivariate analyses were used to identify risk factors for mortality in hypoxemic and hypercapnic individuals with COPD. RESULTS: All-cause mortality in the cohort at 3 years of prospective follow-up reached 18.4%. Chronic hypoxemia (PaO2 <7.3 kPa), hypercapnia (PaCO2 >7.0 kPa) and oxygen desaturation during the 6-MWT were predictors of long-term mortality in COPD patients with forced expiratory volume in 1 second ≤60% for the overall cohort and for GOLD B category patients. Univariate analyses confirmed the association among decreased oxemia (<7.3 kPa), increased capnemia (>7.0 kPa), oxygen desaturation during 6-MWT and mortality in the studied groups of COPD subjects. Multivariate analysis identified PaO2 <7.3 kPa as a strong independent risk factor for mortality. CONCLUSION: Survival analyses showed significantly increased all-cause mortality in hypoxemic and hypercapnic GOLD B subjects. More important, PaO2 <7.3 kPa was the strongest risk factor, especially in category B patients. In contrast, the majority of the tested respiratory parameters did not show a difference in mortality in the GOLD category D cohort.

• Keywords
• COPD, GOLD 2017 update, hypercapnia, hypoxemia, mortality,
• MeSH
• Blood Gas Analysis MeSH
• Pulmonary Disease, Chronic Obstructive diagnosis   mortality   physiopathology   therapy   MeSH
• Databases, Factual MeSH
• Respiration * MeSH
• Hypercapnia diagnosis   mortality   physiopathology   therapy   MeSH
• Hypoxia diagnosis   mortality   physiopathology   therapy   MeSH
• Kaplan-Meier Estimate MeSH
• Comorbidity MeSH
• Middle Aged MeSH
• Humans MeSH
• Multivariate Analysis MeSH
• Lung physiopathology   MeSH
• Predictive Value of Tests MeSH
• Prognosis MeSH
• Proportional Hazards Models MeSH
• Risk Factors MeSH
• Aged MeSH
• Severity of Illness Index MeSH
• Walk Test MeSH
• Forced Expiratory Volume MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH

This study was undertaken to determine pattern sensitivity of phrenic nerve plasticity in respect to different respiratory challenges. We compared long-term effects of intermittent and continuous hypercapnic and hypoxic stimuli, and combined intermittent hypercapnia and hypoxia on phrenic nerve plasticity. Adult, male, urethane-anesthetized, vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats were exposed to: acute intermittent hypercapnia (AIHc or AIHc(O2)), acute intermittent hypoxia (AIH), combined intermittent hypercapnia and hypoxia (AIHcH), continuous hypercapnia (CHc), or continuous hypoxia (CH). Peak phrenic nerve activity (pPNA) and burst frequency were analyzed during baseline (T0), hypercapnia or hypoxia exposures, at 15, 30, and 60 min (T60) after the end of the stimulus. Exposure to acute intermittent hypercapnia elicited decrease of phrenic nerve frequency from 44.25+/-4.06 at T0 to 35.29+/-5.21 at T60, (P=0.038, AIHc) and from 45.5+/-2.62 to 37.17+/-3.68 breaths/min (P=0.049, AIHc(O2)), i.e. frequency phrenic long term depression was induced. Exposure to AIH elicited increase of pPNA at T60 by 141.0+/-28.2 % compared to baseline (P=0.015), i.e. phrenic long-term facilitation was induced. Exposure to AIHcH, CHc, or CH protocols failed to induce long-term plasticity of the phrenic nerve. Thus, we conclude that intermittency of the hypercapnic or hypoxic stimuli is needed to evoke phrenic nerve plasticity.

• MeSH
• Long-Term Potentiation physiology   MeSH
• Hypercapnia physiopathology   MeSH
• Hypoxia physiopathology   MeSH
• Rats MeSH
• Phrenic Nerve physiology   MeSH
• Neuronal Plasticity physiology   MeSH
• Periodicity * MeSH
• Rats, Sprague-Dawley MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Presence of an air pocket and its size play an important role in survival of victims buried in the avalanche snow. Even small air pockets facilitate breathing. We hypothesize that the size of the air pocket significantly affects the airflow resistance and work of breathing. The aims of the study are (1) to investigate the effect of the presence of an air pocket on gas exchange and work of breathing in subjects breathing into the simulated avalanche snow and (2) to test whether it is possible to breathe with no air pocket. The prospective interventional double-blinded study involved 12 male volunteers, from which 10 completed the whole protocol. Each volunteer underwent two phases of the experiment in a random order: phase "AP"--breathing into the snow with a one-liter air pocket, and phase "NP"--breathing into the snow with no air pocket. Physiological parameters, fractions of oxygen and carbon dioxide in the airways and work of breathing expressed as pressure-time product were recorded continuously. The main finding of the study is that it is possible to breath in the avalanche snow even with no air pocket (0 L volume), but breathing under this condition is associated with significantly increased work of breathing. The significant differences were initially observed for end-tidal values of the respiratory gases (EtO2 and EtCO2) and peripheral oxygen saturation (SpO2) between AP and NP phases, whereas significant differences in inspiratory fractions occurred much later (for FIO2) or never (for FICO2). The limiting factor in no air pocket conditions is excessive increase in work of breathing that induces increase in metabolism accompanied by higher oxygen consumption and carbon dioxide production. The presence of even a small air pocket reduces significantly the work of breathing.

• MeSH
• Asphyxia physiopathology   prevention & control   MeSH
• Work of Breathing physiology   MeSH
• Tidal Volume physiology   MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Hypercapnia physiopathology   MeSH
• Hypoxia physiopathology   MeSH
• Inspiratory Reserve Volume physiology   MeSH
• Disasters * MeSH
• Cross-Over Studies MeSH
• Oxygen physiology   MeSH
• Avalanches * MeSH
• Humans MeSH
• Monitoring, Physiologic MeSH
• Carbon Dioxide physiology   MeSH
• Snow MeSH
• Healthy Volunteers MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Oxygen MeSH
• Carbon Dioxide MeSH

Lifesaving therapy for patients with end-stage lung disease is lung transplantation. However, there are not enough available donors. A relatively new method of transplantation from non-heart-beating donors (NHBDs) allows the treatment of the lung outside the body and could increase the number of suitable lungs. We have focused on hypercapnic ventilation, which has the possibility of reducing reactive oxygen species damage. We used four experimental and two control groups of adult rats. Each experimental group underwent the protocol of NHBD lung harvesting. The lungs were than perfused in an ex vivo model and we measured weight gain, arterial-venous difference in partial pressure of oxygen and perfusion pressure. We observed that hypercapnic ventilation during reperfusion reduces the development of pulmonary oedema and has a protective effect on the oxygen transport ability of the lungs after warm ischemia. The effect of CO2 on pulmonary oedema and on oxygen transport ability after warm ischemia could be of clinical importance for NHBD transplantation.

• Keywords
• Hypercapnic ventilation, Lung transplantation, Non-heart-beating donors, Reactive oxygen species, ex vivo transplantation,
• MeSH
• Hypercapnia * MeSH
• Rats MeSH
• Disease Models, Animal MeSH
• Rats, Wistar MeSH
• Reperfusion Injury physiopathology   prevention & control   MeSH
• Lung Transplantation adverse effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH