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Hypothalamic GABAergic mechanism involved in respiratory response to hypercapnia.

Previous studies have demonstrated that suprapontine areas of the brain modulate the respiratory responses to hypoxia and hypercapnia. The purpose of the present study was to determine if neurons in the posterior hypothalamus are responsible for this modulation. The respiratory (monitored from diaphragmatic activity) and cardiovascular responses to hypoxia and to hypercapnia were examined in anesthetized rats before and after microinjection of a GABA synthesis inhibitor (3-mercaptopropionic acid, 3-MP) into the posterior hypothalamus. Unilateral micro-injection of 3-MP into the posterior hypothalamus elicited an increase in minute diaphragmatic activity (+54.9 +/- 15.8%), arterial pressure (10.5 +/- 3.2 mmHg) and heart rate (26.8 +/- 10.7 min-1) after a delay of 15-20 minutes. The respiratory responses to hypercapnia but not the cardiovascular responses were greatly accentuated after hypothalamic microinjections of 3-mercaptopropionic acid. In contrast, none of the responses (increases in diaphragmatic activity and heart rate; fall in arterial pressure) elicited by hypoxia were altered after microinjections of the GABA synthesis inhibitor into the posterior hypothalamus. These findings indicate that a GABAergic inhibition of posterior hypothalamic neurons modulates the respiratory response to hypercapnia.

3-Mercaptopropionic Acid↗

Endothelin involvement in respiratory centre activity.

To evaluate the role of endothelin (ET) in respiratory homeostasis we studied the effects of the ET(A) and ET(B) receptor blocking agent bosentan on respiratory mechanics and control in seven anaesthetised spontaneously breathing pigs, for 180 min after single bolus administration (20 mg/kg i.v.). The results show that the block of ET receptors induced a significant increase in compliance and decrease in resistance of the respiratory system, entailing a significant reduction of diaphragmatic electromyographic activity, without affecting the centroid frequency of the power spectrum. Bosentan administration induced a significant increase in tidal volume (V(T)), accompanied by a significant decrease in respiratory frequency, without any significant change in pulmonary ventilation, CO(2) arterial blood gas pressure or pH. Since the relationship between V(T) and inspiratory time remained substantially constant after bosentan administration, the changes in respiratory pattern appear to be the result of an upward shift in inspiratory off-switch threshold. Both inspiratory and expiratory times during occluded breathing were increased by block of ET receptors, suggesting also a central respiratory neuromodulator effect of ET. In conclusion the present results suggest that the block of ET receptors in spontaneously breathing pigs exerts a role on mechanical properties of the respiratory system as well as on peripheral and central mechanisms of breathing control.

Airway Resistance↗

Ofloxacin concentrations in tissues involved in respiratory tract infections.

The literature on the penetration of ofloxacin from blood to respiratory tissue and secretions in patients is reviewed. In patients with acute purulent exacerbations of chronic bronchitis ofloxacin has a Cmax value in sputum of 2.7 mg/l after a 400 mg oral dose, 6.1 mg/l after 600 mg and 6.3 mg/l after 800 mg. Penetration from blood to sputum varied from 80 to 100%. The concentration of ofloxacin in bronchial aspirate, 1 to 6 h after a single oral dose of 400 mg, varied between 1.1 and 4.5 mg/l. The ratio between simultaneous mean bronchial aspirate and serum concentrations ranged between 0.53 in the second hour and 0.92 in the fourth hour. Ofloxacin concentrations in bronchoalveolar lavage fluid following an oral dose of 200 mg twice daily for at least four days amounted to 8.3 mg/l with a corresponding serum concentration of 1.7 mg/l five hours after the last dose. The distribution ratio between lavage fluid and serum was 4.9. The lung tissue penetration of ofloxacin after a dosage of 200 mg twice daily, reached a mean tissue plasma concentration ratio of 3.5 +/- 0.4 for healthy tissue and 3.9 +/- 0.4 for diseased tissue. Ofloxacin reaches high intracellular concentrations in polymorphonuclear leucocytes, alveolar macrophages, epithelial cells and fibroblasts. It is likely that these concentrations will have a sustained inhibitory and bactericidal activity against most potential respiratory pathogens including: Haemophilus influenzae, Branhamella catarrhalis, Gram-negative bacilli, Staphylococcus aureus, Legionella pneumophila, Chlamydia spp. and Coxiella burnetti.

Bronchi↗

Developing and managing a team to participate in trials involving acute respiratory failure: advice for the inexperienced.

PURPOSE OF REVIEW: Conducting large-scale clinical trials in the field of acute respiratory failure requires substantial collaboration. Teamwork is still in its infancy within the realm of clinical research. This review evaluates the need for and grassroots process of teamwork and considers the challenges facing teamwork in the specific context of conducting acute respiratory failure research today. RECENT FINDINGS: Acute respiratory failure research demands complex, interdependent tasks, dictating a teamwork approach. The team is comprised of a sponsor, a leader and members. The sponsor provides essential administrative support, the leader performs many of the functions of a traditional manager in addition to adopting three distinct roles of initiator, role model and coach, and members are selected not only on their technical expertise, but also on their problem-solving and interpersonal skills. SUMMARY: As large-scale (oftentimes international) multicenter trials are increasingly providing answers to our research questions, greater emphasis must be placed on team building within the clinical research environment. An urgent need for further work in this area is revealed. Critical care fellowships should integrate teamwork skills into the curriculum.

Clinical Trials as Topic↗

Specificity of respiratory pathways involved in the reduction of sulfur compounds by Salmonella enterica.

The tetrathionate (Ttr) and thiosulfate (Phs) reductases of Salmonella enterica LT2, together with the polysulfide reductase (Psr) of Wolinella succinogenes, are unusual examples of enzymes containing a molybdopterin active-site cofactor since all formally catalyse sulfur-sulfur bond cleavage. This is in contrast to the oxygen or hydrogen transfer reactions exhibited by other molybdopterin enzymes. Here the catalytic specificity of Ttr and Phs has been compared using both physiological and synthetic electron-donor systems. Ttr is shown to catalyse reduction of trithionate but not sulfur or thiosulfate. In contrast, Phs cannot reduce tetrathionate or trithionate but allows whole cells to utilize elemental sulfur as an electron acceptor. Mechanisms are proposed by which the bacterium is able to utilize an insoluble sulfur substrate by means of reactions at the cytoplasmic rather than the outer membrane.

Amino Acid Sequence↗

Characterisation of Mycoplasma gallisepticum strains involved in respiratory disease in pheasants and peafowl.

Two cases of Mycoplasma gallisepticum infection in different avian species in backyard gamebird operations in Slovenia were investigated. In the first case, M gallisepticum was associated with severe respiratory disease with almost 20 per cent mortality in pheasants, whereas the infection was less pathogenic for chickens and turkeys reared at the same site. The M gallisepticum isolates from pheasants had a unique pMGA gene sequence containing a repeat of 12 nucleotides, and they contained only small amounts of the cytadhesins MGC1 and MGC3 and no PvpA protein. However, they expressed some typical M gallisepticum proteins and several proteins which were immunogenic for pheasants, chickens and turkeys. A strain of M gallisepticum isolated from the sinus of a pheasant was highly pathogenic for chicken embryos. In the second case, the M gallisepticum strain that was associated with respiratory disease and mortality in peafowl also affected chickens. M gallisepticum strain ULB 992 was isolated from the infraorbital sinus of a dead peafowl. The ULB 992 strain synthesised a small amount of MGC3, a truncated form of MGC1 and lacked PvpA. However, it expressed several proteins which were immunogenic for the birds infected with M gallisepticum at both gamebird operations.

Animals↗

Involvement of respiratory perception in the resistive load compensation.

Relation of threshold for perception of added inspiratory flow resistance to ventilatory and occlusion pressure response to hypercapnia during external flow-resistive loading was examined in 8 healthy volunteers and 14 patients with chronic obstructive pulmonary disease. Occlusion pressure response to hypercapnia without the load and the threshold for perception were similar between normal subjects and patients. Occlusion pressure at end-tidal PCO2 of 60 mm Hg increased to 134 +/- (SD) 23.4% (p less than 0.01) in normal subjects, but it did not change in patients (113.7 +/- 25.3%). Occlusion pressure response to hypercapnia increased to 155.4 +/- 60% (p less than 0.05) during ventilatory loading in normal subjects but it did not change in patients (105.9 +/- 33%). Inverse correlation between threshold values and changes after loading in occlusion pressure response to hypercapnia was seen in patients as well as in normal subjects. These results indicate in both normal subjects and patients with chronic obstructive pulmonary disease that occlusion pressure response to hypercapnia during the ventilatory loading includes signals from the higher central nervous system and that the lower the threshold, the higher the respiratory drive during the loaded ventilation.

Adult↗

Maturation of brain stem neurons involved in respiratory rhythmogenesis: biochemical, bioelectrical and morphological properties.

Neonatal and adult respiratory-related functions of brain stem were compared using in vivo or in vitro approaches. The control of inspiratory off-switch by glutamate-like neurotransmitters was found active at birth. However, neurons from the nucleus tractus solitarius (NTS) are immature at birth because they present growth cones and the transient potassium current appears progressively during the first week of life in association with modification of the dendritic tree. These data support the hypothesis that the mechanisms of respiratory rhythmogenesis are different at birth and in the adult.

Animals↗