Osmotic regulation of airway reactivity by epithelium.
Inhalation of nonisotonic solutions can elicit pulmonary obstruction in asthmatic airways. We evaluated the hypothesis that the respiratory epithelium is involved in responses of the airways to nonisotonic solutions using the guinea pig isolated, perfused trachea preparation to restrict applied agents to the mucosal (intraluminal) or serosal (extraluminal) surface of the airway. In methacholine-contracted tracheae, intraluminally applied NaCl or KCl equipotently caused relaxation that was unaffected by the cyclo-oxygenase inhibitor, indomethacin, but was attenuated by removal of the epithelium and Na+ and Cl- channel blockers. Na+-K+-2Cl- cotransporter and nitric oxide synthase blockers caused a slight inhibition of relaxation, whereas Na+,K+-pump inhibition produced a small potentiation. Intraluminal hyperosmolar KCl and NaCl inhibited contractions in response to intra- or extraluminally applied methacholine, as well as neurogenic cholinergic contractions elicited with electric field stimulation (+/- indomethacin). Extraluminally applied NaCl and KCl elicited epithelium-dependent relaxation (which for KCl was followed by contraction). In contrast to the effects of hyperosmolarity, intraluminal hypo-osmolarity caused papaverine-inhibitable contractions (+/- epithelium). These findings suggest that the epithelium is an osmotic sensor which, through the release of epithelium-derived relaxing factor, can regulate airway diameter by modulating smooth muscle responsiveness and excitatory neurotransmission. (+info)
Rhythmicity in single fiber postganglionic activity supplying the rat tail.
Rhythmicity in single fiber postganglionic activity supplying the rat tail. The temporal pattern of ongoing sympathetic vasoconstrictor activity may play an important role for neurovascular transmission. Here we analyzed the activity of postganglionic fibers projecting into the ventral collector nerve of anesthetized and artificially ventilated vagotomized Wistar rats with respect to the presence of rhythmic firing under normocapnic conditions. Most of the fibers studied were likely vasoconstrictor and involved in thermoregulation. Accumulated histograms of sympathetic activity were produced synchronized with the electrocardiogram to detect cardiac rhythmicity, with phrenic nerve activity to detect modulation with the central respiratory cycle, and with tracheal pressure to uncover a reflex modulation associated with artificial ventilation. Sympathetic activity, phrenic activity, and tracheal pressure also were examined by spectral analysis and autocorrelation to detect rhythmicities distinct from respiration. Twenty-seven filaments containing two to seven fibers with spontaneous activity and 51 single fibers were analyzed. Ongoing activity was 1.12 +/- 0.65 imp/s (mean +/- SD, n = 51); conduction velocity was 0.62 +/- 0.06 m/s (n = 30). Cardiac rhythmicity in sympathetic activity was weak (46.2 +/- 16.4%). The dominant rhythm in the activity of 19/27 few-fiber preparations and 37/51 single fibers corresponded to the central respiratory cycle. The pattern consisted of an inhibition during inspiration and an activation in expiration. In 10/19 few-fiber preparations and 21/37 single fibers of this group, there was also a concomitant, less prominent rhythm related to artificial ventilation. By contrast, 8/27 few-fiber preparations and 11/51 single fibers exhibited a dominant pump-related modulation, whereas phrenic-related rhythmicity was subordinate. The dominant rhythm in the activity of two single fibers was related to neither central respiration nor artificial ventilation. We conclude that the ongoing activity of most postganglionic neurons supplying the rat tail is modulated by the central respiratory rhythm generator, suggesting that changes in respiratory drive may alter perfusion of the tail and therefore heat dissipation. Reflex modulation in parallel with artificial ventilation, independent of vagal afferents and possibly due to ventilatory changes of baroreceptor activity, is also an important source of rhythmicity in these neurons. (+info)
The effects of preperitoneal carbon dioxide insufflation on cardiopulmonary function in pigs.
BACKGROUND AND OBJECTIVES: Although considerable experimental and clinical knowledge exists on the physiology of pneumoperitoneum, insufflation of the preperitoneal space has not been extensively studied. The purpose of this study is to evaluate the physiology associated with preperitoneal carbon dioxide (CO2) insufflation in a porcine model. METHODS: Eleven pigs weighing 35 to 45 kg were anesthetized and placed on mechanical ventilation. A pulmonary artery catheter and an arterial line were inserted. Balloon dissection of the preperitoneal space and insufflation to 10 mm Hg for 1.5 hours, followed by an increase to 15 mm Hg for an additional 1.5 hours, was performed. Hemodynamic and arterial blood gas values were determined every 15 minutes throughout the stabilization and three-hour insufflation period. Hemodynamic parameters and blood gas values were analyzed using one-way analysis of variance with respect to insufflation time and pressure. RESULTS: Analysis of hemodynamics (CO, CVP, PAD, PAS, PCWP) did not demonstrate statistical significance with respect to time. However, there was a statistical difference in CO (p=.01), CVP (p<.01), and PCWP (p=.034) when comparing a pressure of 15 mm Hg to a pressure of 10 or 0 mm Hg. The other parameters did not demonstrate significant differences among the three pressure groups. Arterial PCO2 and pH were highly significant with respect to time (p<.01 and P<.01, respectively) and among the pressure groups (p<.01 and P<.01, respectively). CONCLUSIONS: Insufflation of the preperitoneal space with CO2 gas does not cause significant alterations in hemodynamics and blood gas changes at a pressure of 10 mm Hg. However, when a pressure of 15 mm Hg is used to insufflate this space, there is evidence of decreased pH and cardiac output, with elevated CVP and CO2 retention. This correlates with greater pneumodissection of the gas within the layers of the abdominal wall when elevated pressures are used. (+info)
Maximum static respiratory pressures in healthy elderly men and women: issues of reproducibility and interpretation.
BACKGROUND: Respiratory muscle strength is assessed using the static pressure generated at the mouth during a maximal inspiratory or expiratory effort [PImax and PEmax, respectively (MSRPs)]. Interpretation of MSRPs relies upon comparison with 'normal' values, but MSRPs show very weak associations with predictors such as physical characteristics. The influence of habitual physical activity upon MSRPs remains undefined. OBJECTIVES: We examined measurement reproducibility, as well as the influence of physical characteristics and habitual physical activity upon MSRPs in healthy elderly people. METHODS: MSRPs were assessed in 41 healthy subjects using a portable mouth pressure meter on two occasions, 1 week apart. Physical activity was assessed in 10 subjects by diary record. Pearson product-moment correlation coefficients were used to assess the association of MSRPs with other measured variables. RESULTS: There was good measurement reproducibility of MSRPs, with coefficients of reproducibility of 10.2 and 12.8% for PImax and PEmax, respectively. MSRPs showed statistically significant negative correlations with age, but correlations with physical characteristics were poor. In contrast, MSRPs were highly correlated with physical activity. CONCLUSIONS: We conclude that MSRPs can be measured reproducibly and that they decline with advancing age. Physical characteristics are not good predictors of MSRPs; this may be due to a strong confounding influence of physical activity making interpretation of measurements problematic. We suggest that the poor predictive power of physical characteristics indicate that reference to 'normal' values be made with caution and that it may be more appropriate to consider functional interpretations of MSRPs based upon factors such as lung and chest wall elastance. (+info)
Central control of the cardiovascular and respiratory systems and their interactions in vertebrates.
This review explores the fundamental neuranatomical and functional bases for integration of the respiratory and cardiovascular systems in vertebrates and traces their evolution through the vertebrate groups, from primarily water-breathing fish and larval amphibians to facultative air-breathers such as lungfish and some adult amphibians and finally obligate air-breathers among the reptiles, birds, and mammals. A comparative account of respiratory rhythm generation leads to consideration of the changing roles in cardiorespiratory integration for central and peripheral chemoreceptors and mechanoreceptors and their central projections. We review evidence of a developing role in the control of cardiorespiratory interactions for the partial relocation from the dorsal motor nucleus of the vagus into the nucleus ambiguus of vagal preganglionic neurons, and in particular those innervating the heart, and for the existence of a functional topography of specific groups of sympathetic preganglionic neurons in the spinal cord. Finally, we consider the mechanisms generating temporal modulation of heart rate, vasomotor tone, and control of the airways in mammals; cardiorespiratory synchrony in fish; and integration of the cardiorespiratory system during intermittent breathing in amphibians, reptiles, and diving birds. Concluding comments suggest areas for further productive research. (+info)
Pseudomonas aeruginosa binds to neoglycoconjugates bearing mucin carbohydrate determinants and predominantly to sialyl-Lewis x conjugates.
Pseudomonas aeruginosa plays an important role in the colonization of the airways of patients suffering from cystic fibrosis. It binds to the carbohydrate part of respiratory and salivary mucins and its binding to cystic fibrosis mucins is even higher, suggesting that qualitative or/and quantitative modifications of the carbohydrate chains may be involved in this process. In order to find out the best carbohydrate receptors for P.aeruginosa, a flow cytometry technique using a panel of polyacrylamide based glycoconjugates labeled with fluorescein was developed. The neoglycoconjugates contained neutral, sialylated or sulfated chains analogous to carbohydrate determinants found at the periphery of respiratory mucins (Le(a), Le(y), Le(x), sialyl- and 3'-sulfo-Le(x), and blood group A determinants). We used also neoglycoconjugates containing Gal(alpha1-2)Galbeta and sialyl- N -acetyllactosamine determinants. The interaction of these glycoconjugates with the nonpiliated strain of P.aeruginosa, 1244-NP, was saturable except for the glycoconjugates containing blood group A or sialyl- N -acetyllactosamine epitopes. The measure of Kd indicated that strain 1244-NP had a higher affinity for the glycoconjugate bearing the sialyl-Le(x)determinant than for all the other glycoconjugates studied. The role of sialic acid was confirmed by competition assay using mainly sialylated mucin glycopeptides. In order to find out if this behavior was the same for pathological strains as for the 1244-NP mutant, four mucoid strains of P.aeruginosa isolated from cystic fibrosis patients were analyzed with the Le(x)neoglycoconjugate, its sialylated and its sulfated derivatives. Individual variations in the binding of these strains to the three glycoconjugates were observed. However, three strains out of four had a higher affinity for the sialyl-Le(x)than for the 3'-sulfo-Le(x)derivative. (+info)
Pulmonary stretch receptor discharges and vagal regulation of respiration differ between two mouse strains.
1. Experiments were performed on adult pentobarbitone-anaesthetized mice of the OF1 and the C3H/HeJ (C3H) strains, to analyse the regulation of respiration by pulmonary stretch receptors (PSRs). 2. Although the mean respiratory period, inspiratory and expiratory durations, and tidal volume did not differ significantly between the two strains, the inspiratory onset was drastically inhibited in OF1 mice but only slightly inhibited in C3H mice in response to tracheal occlusion performed at the very end of inspiration. 3. Low current electrical stimulation of the vagus nerve induced inspiratory onset inhibition in both strains, suggesting that the weak inspiratory onset inhibition elicited by tracheal occlusion in C3H mice did not originate from a low sensitivity of the respiratory centres to PSRs. 4. During normal respiration, PSR firing rate increased with tidal volume, but reached significantly higher values in OF1 than C3H mice. During tracheal occlusion, PSR firing rate was significantly higher at the end of inspiration and during the first third of the occlusion period in OF1 than C3H mice. 5. The airway pressure resistance was significantly higher in OF1 than C3H mice. After abolishing the tracheo-bronchial muscle tone with atropine in OF1 mice, tracheal occlusions induced weak inspiratory onset inhibitions resembling the C3H mouse responses. 6. The possibility that differences in tracheo-bronchial tone between OF1 and C3H mice may lead to a greater PSR discharge and thus to a powerful inhibition on the OF1 medullary respiratory centres during tracheal occlusion is discussed. (+info)
Effects of single administration of a phosphodiesterase III inhibitor during cardiopulmonary bypass: comparison of milrinone and amrinone.
The effects of phosphodiesterase III (PDE III) inhibitors administered after aortic declamping during cardiopulmonary bypass (CPB) for open heart surgery were investigated. Ten patients (group M) were administered milrinone (50 microg/kg) after aortic declamping during CPB, 10 patients were administered amrinone (1 mg/kg) at the same time during their surgery (group A), and 10 patients served as controls with no drug administered (group C). Soon after bolus infusion of the PDE III inhibitor, perfusion pressure dropped significantly in groups M and A. However, after release of CPB and at the end of surgery, there was no difference in aortic pressure between the 3 groups. There were also no differences between the groups in heart rate, pulmonary artery pressure, and pulmonary capillary wedge pressure. After weaning from CPB, the cardiac index was high and systemic vascular resistance index was low in groups M and A. There were no significant differences in the need for additional catecholamines and time for rewarming between groups. No adverse reactions were observed. A single administration of a PDE III inhibitor during CPB was useful for post-CPB management of patients undergoing open heart surgery. Amrinone reduced perfusion pressures more than milrinone, but cardiac indices and aortic pressures after weaning from CPB showed no differences between group M and group A patients. (+info)