Methazolamide does not impair respiratory work performance in anesthetized rabbits.

In human medicine, the carbonic anhydrase (CA) inhibitor acetazolamide is used to treat irregular breathing disorders. Previously, we demonstrated in the rabbit that this substance stabilized closed-loop gain properties of the respiratory control system, but concomitantly weakened respiratory muscles. Among others, the highly diffusible CA-inhibitor methazolamide differs from acetazolamide in that it fails to activate Ca(2+)-dependent potassium channels in skeletal muscles.

Pharmacological impact on loop gain properties to prevent irregular breathing.

Theory predicts respiratory instabilities at elevated system loop gain (G), determined by such factors as ventilatory CO(2) sensitivity, set-point PCO(2), and metabolic rate. In anesthetized rabbits, the effects on G of carbonic anhydrase (CA) inhibitors and of different sodium/proton exchanger type 3 (NHE3) inhibitors were studied. Acetazolamide significantly reduced G by 42.

The NHE3 inhibitor AVE1599 stimulates phrenic nerve activity in the rat.

The effect of AVE1599, an inhibitor of the sodium/proton exchanger type 3 (NHE3), on phrenic nerve (PN) activity was investigated using the working heart brainstem preparation (WHBP). Hypercapnia (Delta pH: -0.1) applied for 10 min reversibly increased PN frequency (f) by 66.

Patterns of intrathoracic gas volume and airway resistance in children with asthma.

Airway resistance (Raw) decreases with an increase of lung volume (ITGV) during body-growth. In asthmatic subjects, an increase of Raw may be modified by hyperinflation. In this study thirty five asthmatic children underwent histamine challenges with the monitoring of changes of Raw and ITGV.

Food composition and acid-base balance: alimentary alkali depletion and acid load in herbivores.

Alkali-enriched diets are recommended for humans to diminish the net acid load of their usual diet. In contrast, herbivores have to deal with a high dietary alkali impact on acid-base balance. Here we explore the role of nutritional alkali in experimentally induced chronic metabolic acidosis.

NHE3 in the human brainstem: implication for the pathogenesis of the sudden infant death syndrome (SIDS)?

Previous studies have demonstrated an inverse correlation between the degree of respiratory drive and NHE3 mRNA expression in the brainstem of awake rabbits. Here we show that the levels of NHE3 mRNA extractable from kryo-conserved tissue are highly variable also in the human brainstem. As an insufficient drive to breath may be a final event causing sudden infant death, we compared the expression of NHE3 mRNA in a collective of children who died from non-natural causes to an equal number of SIDS victims.

Role of brainstem sodium/proton exchanger 3 for breathing control during chronic acid base imbalance.

Rationale: The sodium/proton exchanger (NHE) 3 is expressed in brainstem areas with prevalence for central chemosensitivity. Selective NHE3 inhibitors can evoke CO(2) mimetic responses both in vitro and in vivo, demonstrating the functional significance of this pH-regulating protein. Moreover, levels of NHE3 expression are inversely correlated to interindividual differences of baseline ventilation in conscious rabbits.

Food mineral composition and acid-base balance in preterm infants.

Background: Due to a transient age-related low renal capacity for net acid excretion, preterm infants fed formula are at a considerable risk of spontaneously developing incipient late metabolic acidosis, clinically characterized by e.g., disturbed bone mineralization and impaired growth.

Sodium/Proton exchanger 3 in the medulla oblongata and set point of breathing control.

Rationale: In vivo inhibition of the sodium/proton exchanger 3 (NHE3) in chemosensitive neurons of the ventrolateral brainstem augments central respiratory drive in anesthetized rabbits.

Objectives: To further explore the possible role of this exchanger for the control of breathing, we examined the individual relationship between brainstem NHE3 abundance and ventilation in rabbits during wakefulness.

Methods: In 32 adult male rabbits on standard nutritional alkali load, alveolar ventilation, metabolic CO2 production, and blood gases were determined, together with arterial and urinary acid-base status and renal base control functions.

Food mineral composition and acid-base balance in rabbits.

Background: Alkali-rich diets are often recommended in human medicine to prevent the pathological consequences of nutritional acid load in conditions of impaired renal function.

Aim Of The Study: This study was undertaken in rabbits as common laboratory animals for basic medical research to explore the impact of high versus low dietary alkali intake on systemic acid-base balance and renal control in a typical herbivore.

Methods: Male rabbits (2.

Minimal-invasive approach to study pulmonary, metabolic and renal responses to alimentary acid-base changes in conscious rabbits.

Background: Systemic acid-base balance is maintained by the complex interplay of renal and pulmonary control functions and metabolic adaptations, whereby intake and mineral composition of feed are important factors.

Aim Of The Study: It was intended to explore the role of alimentary acid-base load and carbonic anhydrase activity for regulatory responses of renal, pulmonary or metabolic origin in rabbits as typical herbivores.

Methods: Sixty-eight conscious male rabbits (about 3.

A novel inhibitor of the Na+/H+ exchanger type 3 activates the central respiratory CO2 response and lowers the apneic threshold.

Cultured CO2-sensitive neurons from the ventrolateral medulla of newborn rats enhanced their bioelectric activity upon intracellular acidification induced by inhibition of the Na+/H+ exchanger type 3 (NHE3). Now we detected NHE3 also in the medulla oblongata of adult rabbits. Therefore, this animal model was employed to determine whether NHE3 inhibition also affects central respiratory chemosensitivity in vivo.

Low-dose acetazolamide does affect respiratory muscle function in spontaneously breathing anesthetized rabbits.

Patients with chronic obstructive pulmonary diseases (COPD) and/or central sleep apnea are sometimes treated with the carbonic anhydrase inhibitor acteazolamide to improve blood gas values. Studies have shown that this agent may have a complicated effect on lung ventilation, because carbonic anhydrase has a widespread distribution within the body, particularly in tissues involved in the control of breathing. To investigate whether acetazolamide may have (neuro)muscular effects on respiration, we measured the responses of ventilation, phrenic nerve activity, and transpulmonary pressure to changes in arterial PCO2 before and after intravenous administration of a low-dose (4.

The Haldane effect under different acid-base conditions in premature and adult humans.

The Haldane effect (HE) was investigated in human adults and prematures under normal metabolic acid-base conditions but at different levels of PCO2. Venous blood samples were equilibrated with low and high PCO2 in either O2 or N2. The change in plasma pH of oxygenated blood by deoxygenation did not differ between both groups.

The Haldane effect of rabbit blood under different acid-base conditions.

The Haldane effect (HE), i.e. the difference in plasma pH of oxygenated and deoxygenated blood, was investigated in rabbits over a wide range of respiratory (PCO2 2.

Hypoxia and the "reaction theory" of central respiratory chemosensitivity.

In peripherally chemodenervated and vagotomized cats and rabbits, either spontaneously breathing or artificially ventilated, we studied the reaction of the respiratory control system to changes in the extracellular fluid (ECF) pH at the ventral surface of the medulla oblongata. The brainstem ECF-pH was varied either by alternating periods of hypoxia and hyperoxia or by intravenous infusion of lactic acid to achieve endogenous or exogenous lactacidosis, respectively. Additionally, the arterial PCO2 was changed by varying the inspiratory CO2-fraction or the respirator's pumping rate.

The effects of CO2 and fixed acid on the O2-Hb affinity of rabbit and cat blood.

The action of respiratory and metabolic acid-base disturbances on the O2-Hb affinity was studied in rabbits and cats. Blood samples of both species were exposed to in vitro pH-changes, which were either achieved by variation of PCO2 (2.8-8.

On the seemingly diminished CO2-Bohr effect in hypoxic chemodenervated rabbits.

In hypoxic rabbits, different levels of Pco2 before and after carotid chemodenervation were applied in order to get information about the acid-base status and the position of the O2-Hb dissociation curve (ODC). A CO2-induced change in pH caused a smaller change in the half-saturation pressure (P50) than was to be expected from the CO2-Bohr effect alone. Considering both, the numerically different CO2- and fixed acid-Bohr factors as well as the corresponding respiratory or metabolic pH changes, a method is presented to calculate the position of the ODC with high accuracy.

The involvement of expiratory termination in the vagally mediated facilitation of ventilatory CO2 responsiveness during hyperoxia.

In anaesthetized rabbits the influence of differential vagal cold blockade on the ventilatory response to inhaled CO2 during hyperoxia was investigated. Following total inactivation, the relationship between ventilation (V) and arterial PCO2 (PaCO2) was shifted to the left and steepened slightly over a range of modest hypercapnia, but was progressively flattened as hypercapnia intensified. The latter effect, suggestive of a vagally mediated facilitation of ventilatory CO2 responsiveness, was studied further.