Short-term exposure to high pCO2 leads to decreased branchial cytochrome C oxidase activity in the presence of octopamine in a decapod.

In a recent mechanistic study, octopamine was shown to promote proton transport over the branchial epithelium in green crabs, Carcinus maenas. Here, we follow up on this finding by investigating the involvement of octopamine in an environmental and physiological context that challenges acid-base homeostasis, the response to short-term high pCO2 exposure (400 Pa) in a brackish water environment. We show that hyperregulating green crabs experienced a respiratory acidosis as early as 6 h of exposure to hypercapnia, with a rise in hemolymph pCO2 accompanied by a simultaneous drop of hemolymph pH. The slightly delayed increase in hemolymph HCO3- observed after 24 h helped to restore hemolymph pH to initial values by 48 h. Circulating levels of the biogenic amine octopamine were significantly higher in short-term high pCO2 exposed crabs compared to control crabs after 48 h. Whole animal metabolic rates, intracellular levels of octopamine and cAMP, as well as branchial mitochondrial enzyme activities for complex I + III and citrate synthase were unchanged in posterior gill #7 after 48 h of hypercapnia. However, application of octopamine in gill respirometry experiments suppressed branchial metabolic rate in posterior gills of short-term high pCO2 exposed animals. Furthermore, branchial enzyme activity of cytochrome C oxidase decreased in high pCO2 exposed crabs after 48 h. Our results indicate that hyperregulating green crabs are capable of quickly counteracting a hypercapnia-induced respiratory acidosis. The role of octopamine in the acclimation of green crabs to short-term hypercapnia seems to entail the alteration of branchial metabolic pathways, possibly targeting mitochondrial cytochrome C in the gill. Our findings help advancing our current limited understanding of endocrine components in hypercapnia acclimation. SUMMARY STATEMENT: Acid-base compensation upon short-term high pCO2 exposure in hyperregulating green crabs started after 6 h and was accomplished by 48 h with the involvement of the biogenic amine octopamine, accumulation of hemolymph HCO3-, and regulation of mitochondrial complex IV (cytochrome C oxidase).

Acid-base imbalance as a risk factor for mortality among COVID-19 hospitalized patients.

Severe coronavirus disease 2019 (COVID-19) infection can lead to extensive lung infiltrate, a significant increase in the respiratory rate, and respiratory failure, which can affect the acid-base balance. No research in the Middle East has previously examined acid-base imbalance in COVID-19 patients. The present study aimed to describe the acid-base imbalance in hospitalized COVID-19 patients, determine its causes, and assess its impact on mortality in a Jordanian hospital. The study divided patients into 11 groups based on arterial blood gas data. Patients in normal group were defined as having a pH of 7.35-7.45, PaCO2 of 35-45 mmHg, and HCO3- of 21-27 mEq/L. Other patients were divided into 10 additional groups: mixed acidosis and alkalosis, respiratory and metabolic acidosis with or without compensation, and respiratory and metabolic alkalosis with or without compensation. This is the first study to categorize patients in this way. The results showed that acid-base imbalance was a significant risk factor for mortality (P<0.0001). Mixed acidosis nearly quadruples the risk of death when compared with those with normal levels (OR = 3.61, P=0.05). Furthermore, the risk of death was twice as high (OR = 2) for metabolic acidosis with respiratory compensation (P=0.002), respiratory alkalosis with metabolic compensation (P=0.002), or respiratory acidosis with no compensation (P=0.002). In conclusion, acid-base abnormalities, particularly mixed metabolic and respiratory acidosis, were associated with increased mortality in hospitalized COVID-19 patients. Clinicians should be aware of the significance of these abnormalities and address their underlying causes.

Changes in acid-base status in oxygen toxicity at 230 kPa oxygen as a function of exposure time.

Breathing less than 50 kPa of oxygen over time can lead to pulmonary oxygen toxicity (POT). Vital capacity (VC) as the sole parameter for POT has its limitations. In this study we try to find out the changes of acid-base status in a POT rat model. Fifty male rats were randomly divided into five groups, exposed to 230 kPa oxygen for three, six, nine and 12 hours, respectively. Rats exposed to air were used as controls. After exposure the mortality and behavior of rats were observed. Arterial blood samples were collected for acid-base status detection and wet-dry (W/D) ratios of lung tissues were tested. Results showed that the acid-base status in rats exposed to 230 kPa oxygen presented a dynamic change. The primary status was in the compensatory period when primary respiratory acidosis was mixed with compensated metabolic alkalosis. Then the status changed to decompensated alkalosis and developed to decompensated acidosis in the end. pH, PCO2, HCO3-, TCO2, and BE values had two phases: an increase and a later decrease with increasing oxygen exposure time, while PaO2 and lung W/D ratio showed continuously increasing trends with the extension of oxygen exposure time. Lung W/D ratio was significantly associated with PaO2 (r = 0.6385, p = 0.002), while other parameters did not show a significant correlation. It is concluded that acid-base status in POT rats presents a dynamic change: in the compensatory period first, then turns to decompensated alkalosis and ends up with decompensated acidosis status. Blood gas analysis is a useful method to monitor the development of POT.

Salbutamol-induced lactic acidosis in status asthmaticus survivor.

BACKGROUND: Salbutamol-induced lactic acidosis is a rare presentation that could manifest in specific clinical context as acute asthmatic attack treatment. An increase of glycolysis pathway leading to pyruvate escalation is the mechanism of hyperlactatemia in ß2-adrenergic agonist drug. CASE PRESENTATION: A 40-year-old man who had poor-controlled asthma, presented with progressive dyspnea with coryza symptom for 6 days. He was intubated and admitted into medical intensive care unit due to deteriorated respiratory symptom. Severe asthmatic attack was diagnosed and approximate 1.5 canisters of salbutamol inhaler was administrated within 24 h of admission. Initial severe acidosis consisted of acute respiratory acidosis from ventilation-perfusion mismatch and acute metabolic acidosis resulting from bronchospasm and hypoxia-related lactic acidosis, respectively. The lactate level was normalized in 6 h after hypoxemia and ventilation correction. Given the lactate level re-elevated into a peak of 4.6 mmol/L without signs of tissue hypoxia nor other possible etiologies, the salbutamol toxicity was suspected and the inhaler was discontinued that contributed to rapid lactate clearance. The patient was safely discharged on the 6th day of admission. CONCLUSION: The re-elevation of serum lactate in status asthmaticus patient who had been administrated with the vast amount of ß2-adrenergic agonist should be considered for salbutamol-induced lactic acidosis and promptly discontinued especially when there were no common potentials.

The effect of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) severity on cellular bioenergetic function.

Myalgic encephalomyelitis/ Chronic fatigue syndrome (ME/CFS) has been associated with abnormalities in mitochondrial function. In this study we have analysed previous bioenergetics data in peripheral blood mononuclear cells (PBMCs) using new techniques in order to further elucidate differences between ME/CFS and healthy control cohorts. We stratified our ME/CFS cohort into two individual cohorts representing moderately and severely affected patients in order to determine if disease severity is associated with bioenergetic function in PBMCs. Both ME/CFS cohorts showed reduced mitochondrial function when compared to a healthy control cohort. This shows that disease severity does not correlate with mitochondrial function and even those with a moderate form of the disease show evidence of mitochondrial dysfunction. Equations devised by another research group have enabled us to calculate ATP-linked respiration rates and glycolytic parameters. Parameters of glycolytic function were calculated by taking into account respiratory acidification. This revealed severely affected ME/CFS patients to have higher rates of respiratory acidification and showed the importance of accounting for respiratory acidification when calculating parameters of glycolytic function. Analysis of previously published glycolysis data, after taking into account respiratory acidification, showed severely affected patients have reduced glycolysis compared to moderately affected patients and healthy controls. Rates of ATP-linked respiration were also calculated and shown to be lower in both ME/CFS cohorts. This study shows that severely affected patients have mitochondrial and glycolytic impairments, which sets them apart from moderately affected patients who only have mitochondrial impairment. This may explain why these patients present with a more severe phenotype.

The evolutionary hypothesis of benign paroxysmal positional vertigo.

Human otoliths, primarily formed from salts of calcium and carbonate, are different from bones of the skeleton, which are composed of calcium phosphate. The echinoderms, which share the earliest common ancestor with us, began to protect the body by making an endoskeleton out of calcium and carbon dioxide dissolved in the sea. In subsequent vertebrates, aerobic respiration supported strong muscle activity, but an occasional shortage of oxygen led to low pH due to the accumulation of lactate produced by anaerobic respiration, increasing the risk of melting bones composed of calcium carbonate. So, all vertebrates used calcium phosphate to increase bone strength, having a stronger ionic bonding than calcium carbonate. But otoliths, which are in the inner ear and thereby not connected to muscles, still use calcium carbonate. Benign paroxysmal positional vertigo (BPPV) is a disorder in which otoliths detached from the utricle enter the semicircular canals and cause a sense of rotation. Otoliths, the calcium carbonate ear bones retaining a long evolutionary history, can be easily broken at low pH. During sleep, shallow breathing produces mild respiratory acidosis and low pH in the blood. Since otoliths are corroded at low pH during nighttime, BPPV occurs frequently in the morning. In addition, diabetes mellitus or gout often decreases pH in the blood and increases the occurrence of BPPV.

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.

Renal acid excretion contributes to acid-base regulation during hypercapnia in air-exposed swamp eel (Monopterus albus).

The swamp eel (Monopterus albus) uses its buccal cavity to air breathe, while the gills are strongly reduced. It burrows into mud during the dry season, is highly tolerant of air exposure, and experiences severe hypoxia both in its natural habitat and in aquaculture. To study the ability of M. albus to compensate for respiratory acidosis, we implanted catheters to sample both arterial blood and urine during hypercapnia (4% CO2) in either water or air, or during whole-animal air exposure. These hypercapnic challenges caused an immediate reduction in arterial pH, followed by progressive compensation through a marked elevation of plasma HCO3- over the course of 72 h. There was no appreciable rise in urinary acid excretion in fish exposed to hypercapnia in water, although urine pH was reduced and ammonia excretion did increase. In the air-exposed fish, however, hypercapnia was attended by a large elevation of ammonia in the urine and a large rise in titratable acid excretion. The time course of the increased renal acid excretion overlapped with the time period required to elevate plasma HCO3-, and we estimate that the renal compensation contributed significantly to whole-body acid-base compensation.

TRPM8 channel is involved in the ventilatory response to CO2 mediating hypercapnic Ca2+ responses.

The role of TRP channels in the ventilatory response to CO2 was investigated in vivo. To this end, the respiration of unrestrained adult TRPM8-, TRPV1- and TRPV4-channel knockout mice was measured using whole-body plethysmography. Under control conditions and hyperoxic hypercapnia, no difference in respiratory parameters was observed between adult wild-type mice and TRPV1- and TRPV4-channel knockout mice. However, TRPM8-channel knockout mice showed decreased tidal volume under both hypercapnia and resting conditions. In addition, the expression of TRPM8, TRPV1 and TRPV4 mRNAs was detected in EGFP-positive glial cells in the medulla of GFAP promoter-EGFP transgenic mice by real-time PCR. Furthermore, we measured intracellular Ca2+ responses of TRPM8-overexpressing HEK-293 cells to hypercapnic acidosis. Subpopulations of cells that exhibited hypercapnic acidosis-induced Ca2+ response also responded to the application of menthol. These results suggest that TRPM8 partially mediates the ventilatory response to CO2 via changes in intracellular Ca2+ and is a chemosensing protein that may be involved in detecting endogenous CO2 production.

Effects and Mechanisms by Which Hypercapnic Acidosis Inhibits Sepsis-Induced Canonical Nuclear Factor-κB Signaling in the Lung.

OBJECTIVE: Diverse effects of hypercapnic acidosis are mediated via inhibition of nuclear factor-κB, a pivotal transcription factor, in the setting of injury, inflammation, and repair, but the underlying mechanisms of action of hypercapnic acidosis on this pathway is unclear. We aim to examine the effect of hypercapnic acidosis on the nuclear factor-κB pathway in the setting of Escherichia coli-induced lung injury and characterize the underlying mechanisms in subsequent in vitro studies. DESIGN: In vivo animal study and subsequent in vitro studies. SETTING: University Research Laboratory. SUBJECTS: Adult male Sprague-Dawley rats and pulmonary epithelial cells. INTERVENTIONS: Following pulmonary IκBα-SuperRepressor transgene overexpression or sham and intratracheal E. coli inoculation, rats underwent 4 hours of mechanical ventilation under normocapnia or hypercapnic acidosis, and nuclear factor-κB activation, animal survival, lung injury, and cytokine profile were assessed. Subsequent in vitro studies examined the effect of hypercapnic acidosis on specific nuclear factor-κB canonical pathway kinases via overexpression of these components and in vitro kinase activity assays. The effect of hypercapnic acidosis on the p50/p65 nuclear factor-κB heterodimer was then assessed. MEASUREMENTS AND MAIN RESULTS: Hypercapnic acidosis and IκBα-SuperRepressor transgene overexpression reduced E. coli-induced lung inflammation and injury, decreased nuclear factor-κB activity, and increased animal survival. Hypercapnic acidosis inhibited canonical nuclear factor-κB signaling via reduced phosphorylative activation, reducing IκB kinase-ß activation and intrinsic activity, thereby decreasing IκBα degradation, and subsequent nuclear factor-κB translocation. Hypercapnic acidosis also directly reduced DNA binding of the nuclear factor-κB p65 subunit, although this effect was less marked. CONCLUSIONS: Hypercapnic acidosis reduced E. coli inflammation and lung injury in vivo and reduced nuclear factor-κB activation predominantly by inhibiting the activation and intrinsic activity of IκB kinase-ß.

Comparison of the effects of moderate and severe hypercapnic acidosis on ventilation-induced lung injury.

BACKGROUND: We have proved that hypercapnic acidosis (a PaCO2 of 80-100 mmHg) protects against ventilator-induced lung injury in rats. However, there remains uncertainty regarding the appropriate target PaCO2 or if greater CO2 "doses" (PaCO2 > 100 mmHg) demonstrate this effect. We wished to determine whether severe acute hypercapnic acidosis can reduce stretch-induced injury, as well as the role of nuclear factor-κB (NF-κB) in the effects of acute hypercapnic acidosis. METHODS: Fifty-four rats were ventilated for 4 hours with a pressure-controlled ventilation mode set at a peak inspiratory pressure (PIP) of 30 cmH2O. A gas mixture of carbon dioxide with oxygen (FiCO2 = 4-5%, FiCO2 = 11-12% or FiCO2 = 16-17%; FiO2 = 0.7; balance N2) was immediately administered to maintain the target PaCO2 in the NC (a PaCO2 of 35-45 mmHg), MHA (a PaCO2 of 80-100 mmHg) and SHA (a PaCO2 of 130-150 mmHg) groups. Nine normal or non-ventilated rats served as controls. The hemodynamics, gas exchange and inflammatory parameters were measured. The role of NF-κB pathway in hypercapnic acidosis-mediated protection from high-pressure stretch injury was then determined. RESULTS: In the NC group, high-pressure ventilation resulted in a decrease in PaO2/FiO2 from 415.6 (37.1) mmHg to 179.1 (23.5) mmHg (p < 0.001), but improved by MHA (379.9 ± 34.5 mmHg) and SHA (298.6 ± 35.3 mmHg). The lung injury score in the SHA group (7.8 ± 1.6) was lower than the NC group (11.8 ± 2.3, P < 0.05) but was higher than the MHA group (4.4 ± 1.3, P < 0.05). Compared with the NC group, after 4 h of high pressure ventilation, the MHA and SHA groups had decreases in MPO activity of 67% and 33%, respectively, and also declined the levels of TNF-α (58% versus 72%) and MIP-2 (76% versus 60%) in the BALF. Additionally, both hypercapnic acidosis groups reduced stretch-induced NF-κB activation (p < 0.05) and significantly decreased lung ICAM-1 expression (p < 0.05). CONCLUSIONS: Moderate hypercapnic acidosis (PaCO2 maintained at 80-100 mmHg) has a greater protective effect on high-pressure ventilation-induced inflammatory injury. The potential mechanisms may involve alterations in NF-κB activity.

Effects of acute respiratory and metabolic acidosis on diaphragm muscle obtained from rats.

BACKGROUND: Acute respiratory acidosis is associated with alterations in diaphragm performance. The authors compared the effects of respiratory acidosis and metabolic acidosis in the rat diaphragm in vitro. METHODS: Diaphragmatic strips were stimulated in vitro, and mechanical and energetic variables were measured, cross-bridge kinetics calculated, and the effects of fatigue evaluated. An extracellular pH of 7.00 was obtained by increasing carbon dioxide tension (from 25 to 104 mmHg) in the respiratory acidosis group (n = 12) or lowering bicarbonate concentration (from 24.5 to 5.5 mM) in the metabolic acidosis group (n = 12) and the results compared with a control group (n = 12, pH = 7.40) after 20-min exposure. RESULTS: Respiratory acidosis induced a significant decrease in maximum shortening velocity (-33%, P < 0.001), active isometric force (-36%, P < 0.001), and peak power output (-59%, P < 0.001), slowed relaxation, and decreased the number of cross-bridges (-35%, P < 0.001) but not the force per cross-bridge, and impaired recovery from fatigue. Respiratory acidosis impaired more relaxation than contraction, as shown by impairment in contraction-relaxation coupling under isotonic (-26%, P < 0.001) or isometric (-44%, P < 0.001) conditions. In contrast, no significant differences in diaphragmatic contraction, relaxation, or contraction-relaxation coupling were observed in the metabolic acidosis group. CONCLUSIONS: In rat diaphragm, acute (20 min) respiratory acidosis induced a marked decrease in the diaphragm contractility, which was not observed in metabolic acidosis.

Presentation of an experimental method to induce in vitro ("organ chambers") respiratory acidosis and its effect on vascular reactivity.

PURPOSE: To create in vitro a model to generate acidosis by CO2 bubbling "organ chambers", which would be useful for researchers that aim to study the effects of acid-base disturbs on the endothelium-dependent vascular reactivity. METHODS: Eighteen male Wistar rats (230-280 g) were housed, before the experiments, under standard laboratory conditions (12h light/dark cycle at 21°C), with free access to food and water. The protocol for promoting in vitro respiratory acidosis was carried out by bubbling increased concentrations of CO2. The target was to achieve an ideal way to decrease the pH gradually to a value of approximately 6.6.It was used, initially, a gas blender varying concentrations of the carbogenic mixture (95% O2 + 5% CO2) and pure CO2. RESULTS: 1) 100% CO2, pH variation very fast, pH minimum 6.0; 2) 90%CO2 pH variation bit slower, pH minimum 6.31; 3) 70%CO2, pH variation slower, pH minimum 6.32; 4) 50% CO2, pH variation slower, pH minimum 6:42; 5) 40 %CO2, Adequate record, pH minimum 6.61, and; 6) 30 %CO2 could not reach values below pH minimum 7.03. Based on these data the gas mixture (O2 60% + CO2 40%) was adopted. CONCLUSION: This gas mixture (O2 60% + CO2 40%) was effective in inducing respiratory acidosis at a speed that made, possible the recording of isometric force.

Presentation of an experimental method to induce in vitro ("organ chambers") respiratory acidosis and its effect on vascular reactivity

PURPOSE: To create in vitro a model to generate acidosis by CO2 bubbling "organ chambers", which would be useful for researchers that aim to study the effects of acid-base disturbs on the endothelium-dependent vascular reactivity. METHODS: Eighteen male Wistar rats (230-280g) were housed, before the experiments, under standard laboratory conditions (12h light/dark cycle at 21°C), with free access to food and water. The protocol for promoting in vitro respiratory acidosis was carried out by bubbling increased concentrations of CO2. The target was to achieve an ideal way to decrease the pH gradually to a value of approximately 6.6.It was used, initially, a gas blender varying concentrations of the carbogenic mixture (95% O2 + 5% CO2) and pure CO2. RESULTS: 1) 100% CO2, pH variation very fast, pH minimum 6.0; 2) 90%CO2 pH variation bit slower, pH minimum6.31; 3) 70%CO2, pH variation slower, pH minimum 6.32; 4) 50% CO2, pH variation slower, pH minimum 6:42; 5) 40 %CO2, Adequate record, pH minimum 6.61, and; 6) 30 %CO2 could not reach values below pH minimum 7.03. Based on these data the gas mixture (O2 60% + CO2 40%) was adopted, CONCLUSION: This gas mixture (O2 60% + CO2 40%) was effective in inducing respiratory acidosis at a speed that made, possible the recording of isometric force. .

The degradation of airway tight junction protein under acidic conditions is probably mediated by transient receptor potential vanilloid 1 receptor.

Acidic airway microenvironment is one of the representative pathophysiological features of chronic inflammatory respiratory diseases. Epithelial barrier function is maintained by TJs (tight junctions), which act as the first physical barrier against the inhaled substances and pathogens of airway. As previous studies described, acid stress caused impaired epithelial barriers and led the hyperpermeability of epithelium. However, the specific mechanism is still unclear. We have showed previously the existence of TRPV (transient receptor potential vanilloid) 1 channel in airway epithelium, as well as its activation by acidic stress in 16HBE cells. In this study, we explored the acidic stress on airway barrier function and TJ proteins in vitro with 16HBE cell lines. Airway epithelial barrier function was determined by measuring by TER (trans-epithelial electrical resistance). TJ-related protein [claudin-1, claudin-3, claudin-4, claudin-5, claudin-7 and ZO-1 (zonula occluden 1)] expression was examined by western blotting of insoluble fractions of cell extraction. The localization of TJ proteins were visualized by immunofluorescent staining. Interestingly, stimulation by pH 6.0 for 8 h slightly increased the epithelial resistance in 16HBE cells insignificantly. However, higher concentration of hydrochloric acid (lower than pH 5.0) did reduce the airway epithelial TER of 16HBE cells. The decline of epithelial barrier function induced by acidic stress exhibited a TRPV1-[Ca2+]i-dependent pathway. Of the TJ proteins, claudin-3 and claudin-4 seemed to be sensitive to acidic stress. The degradation of claudin-3 and claudin-4 induced by acidic stress could be attenuated by the specific TRPV1 blocker or intracellular Ca2+ chelator BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)].

Whole body acid-base and fluid-electrolyte balance: a mathematical model.

A cellular compartment was added to our previous mathematical model of steady-state acid-base and fluid-electrolyte chemistry to gain further understanding and aid diagnosis of complex disorders involving cellular involvement in critically ill patients. An important hypothesis to be validated was that the thermodynamic, standard free-energy of cellular H(+) and Na(+) pumps remained constant under all conditions. In addition, a hydrostatic-osmotic pressure balance was assumed to describe fluid exchange between plasma and interstitial fluid, including incorporation of compliance curves of vascular and interstitial spaces. The description of the cellular compartment was validated by close comparison of measured and model-predicted cellular pH and electrolyte changes in vitro and in vivo. The new description of plasma-interstitial fluid exchange was validated using measured changes in fluid volumes after isoosmotic and hyperosmotic fluid infusions of NaCl and NaHCO3. The validated model was used to explain the role of cells in the mechanism of saline or dilutional acidosis and acid-base effects of acidic or basic fluid infusions and the acid-base disorder due to potassium depletion. A module was created that would allow users, who do not possess the software, to determine, for free, the results of fluid infusions and urinary losses of water and solutes to the whole body.

Normalizing CO2 in chronic hyperventilation by means of a novel breathing mask: a pilot study.

INTRODUCTION: Chronic idiopathic hyperventilation (CIH) is a form of dysfunctional breathing that has proven hard to treat effectively. OBJECTIVES: To perform a preliminary test of the hypothesis that by periodically inducing normocapnia over several weeks, it would be possible to raise the normal resting level of CO2 and achieve a reduction of symptoms. METHODS: Six CIH patients were treated 2 h a day for 4 weeks with a novel breathing mask. The mask was used to induce normocapnia in these chronically hypocapnic patients. Capillary blood gases and acid/base parameters [capillary CO2 tension (PcapCO2 ), pH, and standard base excess (SBE)] were measured at baseline and once each week at least 3 h after mask use, as well as spirometric values, breath-holding tolerance and hyperventilation symptoms as per the Nijmegen Questionnaire (NQ). RESULTS: The mask treatment resulted in a significant increase of resting PcapCO2 (+0.45 kPa, P = 0.028), a moderate increase in SBE (+1.4 mEq/L, P = 0.035) and a small reduction in daily symptoms (-3.8 NQ units, P = 0.046). The effect was most pronounced in the first 2 weeks of treatment. CONCLUSION: By inducing normocapnia with the breathing mask 2 h a day for 4 weeks, the normal resting CO2 and acid/base levels in chronically hyperventilating patients were partially corrected, and symptoms were reduced.

Interaction of metabolic and respiratory acidosis with α and ß-adrenoceptor stimulation in rat myocardium.

BACKGROUND: The effects of acute respiratory versus metabolic acidosis on the myocardium and their consequences on adrenoceptor stimulation remain poorly described. We compared the effects of metabolic and respiratory acidosis on inotropy and lusitropy in rat myocardium and their effects on the responses to α- and ß-adrenoceptor stimulations. METHODS: The effects of acute respiratory and metabolic acidosis (pH 7.10) and their interactions with α and ß-adrenoceptor stimulations were studied in isolated rat left ventricular papillary muscle (n=8 per group). Intracellular pH was measured using confocal microscopy and a pH-sensitive fluorophore in isolated rat cardiomyocytes. Data are mean percentages of baseline±SD. RESULTS: Respiratory acidosis induced more pronounced negative inotropic effects than metabolic acidosis did both in isotonic (45±3 versus 63±6%, P<0.001) and isometric (44±5 versus 64±3%, P<0.001) conditions concomitant with a greater decrease in intracellular pH (6.85±0.07 versus 7.12±0.07, P<0.001). The response to α-adrenergic stimulation was not modified by respiratory or metabolic acidosis. The inotropic response to ß-adrenergic stimulation was impaired only in metabolic acidosis (137±12 versus 200±33%, P<0.001), but this effect was not observed with administration of forskolin or dibutiryl-cyclic adenosine monophosphate. This effect might be explained by a change in transmembrane pH gradient only observed with metabolic acidosis. The lusitropic response to ß-adrenergic stimulation was not modified by respiratory or metabolic acidosis. CONCLUSION: Acute metabolic and respiratory acidosis induce different myocardial effects related to different decreases in intracellular pH. Only metabolic acidosis impairs the positive inotropic effect of ß-adrenergic stimulation.

Newborn ventilatory response to maternal chronic hypercapnia.

This is a case of a neonate born with a respiratory acidosis with a compensatory metabolic alkalosis. This case demonstrates placental physiology of gas exchange as well as the blunted ventilatory response in the neonate from chronic hypercapnia.