On the respiratory function of human blood platelets

A set of physiological parameters of the blood from healthy individuals and patients with hypochromic anemia was subjected to factor analysis in order to test the hypothesis that platelets perform a respiratory function in circulation. Platelets were shown to have no respiratory function comparable to that of erythrocytes; however, the state of the pool of circulating platelets was of significance for blood gas exchange and rheology. When interpreting the extracted factors and observing the type, strength, and dynamics of the correlations found, we suggested that the effects of platelets on blood gas exchange and rheology were indirect, mediated by the platelet pool of biologically active substances. Being involved in the regulation of microcirculation and vessel wall permeability, platelets modulate the erythrocyte transport function.     

Adaptation in the respiratory control system

Exposure to hypoxia, whether for short or prolonged periods or for repeated episodes, produces alterations in the ventilatory responses. This review presents evidence that these adaptations are likely to be mediated by adaptations in the respiratory chemoreflexes, particularly the peripheral chemoreflex, and proposes models of respiratory control explaining the observed changes in ventilation. After a brief introduction to the respiratory control system, a graphical model is developed that illustrates the operation of the system in the steady state, which will be used later. Next, the adaptations in ventilatory responses to hypoxia that have been observed are described, and methods of measuring the alterations in the chemoreflexes that might account for them are discussed. Finally, experimental data supporting the view that changes in the activity of the peripheral chemoreflex can account for the ventilatory adaptations to hypoxia are presented and incorporated into models of chemoreflex behaviour during exposures to hypoxia of various durations.     

Adaptation to respiratory acidosis in the turtle bladder

The effect of in vivo respiratory acidosis for 4 and 48 hr was examined in the turtle bladder by placing turtles in hypercapnic chambers. Blood pH was significantly lowered and pCO2 was significantly elevated over control values both 4 and 48 hr, while blood bicarbonate was only increased after 48 hr. In vitro rates for H+ secretion determined by the reverse short-circuit current were significantly greater in bladders from 48 hr of respiratory acidosis than those of controls (27.3 +/- 2.7 vs 20.6 +/- 1.7 microA, P less than 0.05). In vitro rates for HCO3- secretion determined by pH stat were not altered. Fluorescence microscopy was used to study cell morphology. The number of carbonic anhydrase cells (corrected for the total number of cells) as determined by four different fluorescence stains (6-carboxyfluorescein, rhodamine 123, acridine orange, and 3,3'-diethyloxacarbocyaninine iodide) was increased both after 4 and 48 hr of respiratory acidosis. However, the number of HCO3(-)-secreting (beta subtype) carbonic anhydrase cells, determined by a probe for the anion exchanger, NBD-taurine, was not increased. In vitro 1% CO2 for 4 hr also resulted in an increase in H+ secretion and in the number of 6-carboxyfluorescein-positive cells, both of which could be blocked with SITS pretreatment. We conclude that CO2 changes the mucosal cells more toward the carbonic anhydrase phenotype, and that if NBD-taurine accurately identifies the beta cells, that the adaptation produces or recruits more alpha-carbonic anhydrase cells.     

Central mechanisms of respiratory rhythmogenesis

The organization and role of a respiratory neuronal generator as a part of the medullary respiratory center, including the role of afferent systems in the mechanisms of initiation and regulation of the center cyclic activity, are considered. Intrinsic organization of the respiratory generator and specific features of its functioning are analyzed, and the two main hypotheses concerning the mechanisms of rhythmic respiratory activity generation are discussed.Neirofiziologiya/Neurophysiology, Vol. 26, No. 3, pp. 230–236, May–June, 1994.     

Divergence of mechanisms regulating respiratory burst in blood and sputum eosinophils and neutrophils from atopic subjects

Eosinophil respiratory burst is an important event in asthma and related inflammatory disorders. However, little is known concerning activation of the respiratory burst NADPH oxidase in human eosinophils. Conversely, neutrophils are known to assemble NADPH oxidase in intracellular and plasma membranes. We hypothesized that eosinophils and neutrophils translocate NADPH oxidase to distinct intracellular locations, consistent with their respective functions in O(2)(-)-mediated cytotoxicity. PMA-induced O(2)(-) release assayed by cytochrome c was 3.4-fold higher in atopic human eosinophils than in neutrophils, although membrane-permeable dihydrorhodamine-123 showed similar amounts of release. Eosinophil O(2)(-) release was dependent on Rac, in that it was 54% inhibited by Clostridium difficile toxin B (400-800 ng/ml). In eosinophils stimulated with PMA, a pronounced shift of cytosolic Rac to p22(phox)-positive plasma membrane was observed by confocal microscopy, whereas neutrophils directed Rac2 mainly to intracellular sites coexpressing p22(phox). Similarly, ex vivo sputum eosinophils from asthmatic subjects exhibited predominantly plasma membrane-associated immunoreactivity for Rac, whereas sputum neutrophils exhibited cytoplasmic Rac2 staining. Thus, activated sputum eosinophils, rather than neutrophils, may contribute significantly to the pathogenesis of asthma by extracellular release of tissue-damaging O(2)(-). Our findings suggest that the differential modes of NADPH oxidase assembly in these cells may have important implications for oxidant-mediated tissue injury.     

The respiratory function of blood in elderly and old age and the factors that determine it

Indices of pulmonary gas exchange, blood gases, the oxyhemoglobin dissociation curve, and intraerythrocytic metabolic parameters were analyzed in 62 apparently healthy elderly and senile subjects (60–92 years old) and 18 young healthy subjects (19–30 years old). PaO₂ was found to decrease in elderly and senile subjects. Arterial hypoxemia in old age is caused by an increase in the alveoloarterial PO₂ gradient, primarily as a result of the malcoordination of pulmonary ventilation and blood flow. A rightward compensatory shift of the oxyhemoglobin dissociation curve was observed, which was due to facilitated oxygen release in tissues owing to a pH decrease in erythrocytes (the Bohr effect). However, the facilitated oxygen release by oxyhemoglobin cannot compensate for the effect of factors deteriorating oxygen supply delivery to tissues, observed with aging, which is confirmed by the decrease in the partial pressure of oxygen in the venous blood of elderly and senile people, reflecting PO₂ in tissues.     

The neuronal mechanisms of respiratory rhythm generation

New, improved in vivo and in vitro approaches have led to a better understanding of the mechanisms that generate respiratory rhythm, which depends on a complex interaction between network and intrinsic membrane properties. The pre-Bötzinger complex in the ventrolateral medulla is particularly important for respiratory rhythm generation. This complex can be studied in isolation, and it contains all the known types of respiratory neurons that are now amenable to detailed cellular and molecular analyses.     

Adaptation and survival of surface-deprived red blood cells in mice

The consequences of lost membrane area for long-termerythrocyte survival in the circulation were investigated. Mouse red blood cells were treated with lysophosphatidylcholine to reduce membrane area, labeled fluorescently, reinfused into recipient mice,and then sampled periodically for 35 days. The circulating fraction ofthe modified cells decreased on an approximately exponential timecourse, with time constants ranging from 2 to 14 days. The ratio ofvolume to surface area of the surviving cells, measured usingmicropipettes, decreased rapidly over the first 5 days after infusionto within 5% of normal. This occurred by both preferential removal ofthe most spherical cells and modification of others, possibly due tomembrane stress developed during transient trapping of cells in themicrovasculature. After 5 days, the cell area decreased with time inthe circulation, but the ratio of volume to surface area remainedessentially constant. These results demonstrate that the ratio of cellvolume to surface area is a major determinant of the ability oferythrocytes to circulate properly.

     

Nasal respiratory turbinate function in birds

Nasal respiratory turbinates are complex, epithelially lined structures in nearly all birds and mammals that act as intermittent countercurrent heat exchangers during routine lung ventilation. This study examined avian respiratory turbinate function in five large bird species (115-1,900 g) inhabiting mesic temperate climates. Evaporative water loss and oxygen consumption rates of birds breathing normally (nasopharyngeal breathing) and with nasal turbinates experimentally bypassed (oropharyngeal breathing) were measured. Water and heat loss rates were calculated from lung tidal volumes and nasal and oropharyngeal exhaled air temperatures (T(ex)). Resulting data indicate that respiratory turbinates are equally adaptive across a range of avian orders, regardless of environment, by conserving significant fractions of the daily water and heat budget. Nasal T(ex) of birds was compared to that of lizards, which lack respiratory turbinates. The comparatively high nasal T(ex) of the lizards in similar ambient conditions suggests that their relatively low metabolic rates and correspondingly reduced lung ventilation rates may have constrained selection on similar respiratory adaptations.     

Development of respiratory function in perinatal ontogenesis

In development of respiratory function in rats, mice, and other representatives of placental animals there exists the general plan of formation of rhythm: from single contractions of respiratory musculature to formation of bursts and complexes alternating periodically with pauses and apnea intervals and subsequent rhythm stabilization. These peculiarities are closely connected with the states of sleep and wakefulness. A concept is put forward about a certain sequence of functional maturation and ways of regulation of activity of the breathing rhythm pacemaker. At the first stage the autogenic rhythmical activity is determined by pacemaker properties of a part of neurons of the medulla rostral ventrolateral part. It cannot be ruled out that the first respiratory discharges in spinal cord ventral roots might have been a manifestation of the nervous network rhythmogenic properties. The direct sensitivity of central neurons to chemical composition of the medium and to some neuromodulators serves as the first regulatory mechanism. Somewhat later, inhibitory control is established from supramedullary structures, with an increase of the role of peripheral receptors in regulation of respiration.     

Development of respiratory function in perinatal ontogenesis

In development of respiratory function in rats, mice, and other representatives of placental animals there exists the general plan of formation of rhythm: from single contraction of respiratory musculature to formation of bursts and complexes alternating periodically with pauses and apnea intervals and subsequent rhythm stabilization. These peculiarities are closely connected with the states of sleep and consciousness. A concept is put forward about a certain sequence of functional maturation and ways of regulation of activity of the respiratory rhythm central pacemaker. At the first stage the autogenic rhythmical activity is determined by pacemaker properties of a part of neurons of the medulla rostral ventrolateral part. It is not ruled out that the first respiratory discharges in spinal cord ventral roots might have been a manifestation of the nervous network rhythmogenic properties. The direct sensitivity of central neurons to chemical composition if the medium and to some neutomodulators serves as the first regulatory mechanism. Somewhat later, inhibitory control is established from supramedullary structures, with an increase of role of peripheral receptors in regulation of respiration.