This study was designed to investigate the early stages of particle deposition on airway and alveolar surfaces. To do this we used morphometric studies of aerosol deposition, in situ measurements of surface tension, and in vitro assays of... more
This study was designed to investigate the early stages of particle deposition on airway and alveolar surfaces. To do this we used morphometric studies of aerosol deposition, in situ measurements of surface tension, and in vitro assays of particle displacement and mathematical modelling. We observed that latex particles, equal or less than 6 microns in diameter deposited in hamster lungs were submerged in the subphase of the alveolar lining layer and became completely coated with an osmiophilic film. Similar results were obtained for particles deposited in the conductive airways which were also covered with a surface active film, having a surface tension of 32 +/- 2 dyn.cm-1. In vitro experiments showed that pulmonary surfactant promotes the displacement of particles from air to the aqueous phase and that the extent of particle immersion depends on the surface tension of the surface active film. The lower the surface tension the greater is the immersion of the particles into the aqu...
The lung is a dynamic organ that is subjected to mechanical forces throughout development and adult life. This review article addresses the types of mechanical forces in the lung and their effects on development and normal lung functions.... more
The lung is a dynamic organ that is subjected to mechanical forces throughout development and adult life. This review article addresses the types of mechanical forces in the lung and their effects on development and normal lung functions. The effects of mechanical forces on the various different cell types of the lung are discussed, as are the mechanisms underlying mechanotransduction.
Oxygen uptake (MO2) and carbon dioxide excretion (MCO2) by the skin, lungs and gills (if present) of Rana catesbeiana have been measured at 20 degrees C during 4 developmental stages - strictly water breathing tadpoles, air breathing... more
Oxygen uptake (MO2) and carbon dioxide excretion (MCO2) by the skin, lungs and gills (if present) of Rana catesbeiana have been measured at 20 degrees C during 4 developmental stages - strictly water breathing tadpoles, air breathing tadpoles, post-metamorphic bullfrogs and 4-year-old adult bullfrogs. In aquatic tadpoles, branchial performance is comparable to that of teleost fishes, but a large skin area to body mass ratio, particularly for the tail, plus a thin and highly vascularized skin, presumably facilitates a large (60% of total MO2) cutaneous O2 uptake. As development proceeds, MO2 by the gills decreases and the lungs assume importance in O2 uptake, but the skin remains the major organ of O2 uptake until metamorphosis is nearly complete. Immediately after metamorphosis, O2 uptake by the lung is elevated to 80% of total MO2. Carbon dioxide excretion in both aquatic and air breathing tadpoles was also achieved mostly by the skin (60% of total MCO2, R = 0.9). The lungs of air ...
The hypothesis that CO-binding pigments in the carotid body participate in O2 chemoreception was tested. The chemosensory nerve discharges of cat carotid body perfused and superfused in vitro at 36-37 degrees C with cell-free solution... more
The hypothesis that CO-binding pigments in the carotid body participate in O2 chemoreception was tested. The chemosensory nerve discharges of cat carotid body perfused and superfused in vitro at 36-37 degrees C with cell-free solution containing CO2-HCO3- (pH approximately equal to 7.39) were recorded to monitor O2 chemoreception. Several levels of PCO (60-550 Torr) at two levels of PO2 (50 Torr-140 Torr) were used. With high PCO of 500-550 Torr at any PO2 the discharge rate peaked promptly but the effect was significantly less than that to hypoxia. At any stage of the CO effect, exposure to light promptly attenuated or eliminated the response, as if the stimulatory effect of hypoxia was absent. Lower PCO of 60-70 Torr attenuated the response to hypoxia which was not suppressed by light. PCO of 140 Torr also attenuated the response to hypoxia and made the activity partially photolabile. During high PCO exposure the excitatory response to cyanide but not to nicotine was attenuated, c...
The mechanisms underlying the sudden infant death syndrome (SIDS) appear to have origins in the fetal environment resulting in neural damage which later compromises responses to breathing or blood pressure challenges during sleep. The... more
The mechanisms underlying the sudden infant death syndrome (SIDS) appear to have origins in the fetal environment resulting in neural damage which later compromises responses to breathing or blood pressure challenges during sleep. The deficits appear to involve alterations in neurotransmitter receptors within regions involved in chemoreception and cardiovascular control. SIDS risk is enhanced by pre- and postnatal nicotine exposure, and possibly by hypoxic experiences. The prone sleeping position plays a significant role in risk, as do head positions that minimize facial escape from enclosed spaces; elevated body temperature may also be a factor. Compensatory mechanisms, including diminished gasping ability, relative failure to arouse to a safer state, or a failure to recruit respiratory efforts to overcome a blood pressure loss have been the object of recent research efforts. The findings suggest that the fatal event involves a neurally-compromised infant, circumstances that challenge vital physiology, most likely during sleep, at a particular developmental period.
Gill ventilation, stroke volume and frequency, %O2 utilization and oxygen uptake, and dorsal aortic blood oxygen tension, content, pH and oxygen affinity have been determined during normoxia and during a range of hypoxic exposures in the... more
Gill ventilation, stroke volume and frequency, %O2 utilization and oxygen uptake, and dorsal aortic blood oxygen tension, content, pH and oxygen affinity have been determined during normoxia and during a range of hypoxic exposures in the sturgeon, Acipenser Transmontanus. In air-equilibrated water gill ventilation was 350 ml/kg/min, % utilization was 35--40%, and oxygen uptake at 15 degrees C was 55--60 ml O2/kg/h. Dorsal aortic blood PO2 was 90 mm Hg and blood O2 content at a normal pHa of 7.84 was 7.0 vol%. Vg fell considerably through a reduction in branchial stroke volume when PIO2 was reduced from 150 to 100 mm Hg. Although % utilization remained unchanged, VO2 was halved, clearly identifying Acipenser as an O2 conformer with a critical O2 tension just below air saturation. At a PIO2 of 60 mm Hg VO2 was only 15% of that at normoxic levels falling to only 5% at a PIO2 of 30 mm Hg. There was no hypoxic bradycardia. There was no repayment of an oxygen debt even after severe hypoxi...
Respiratory rhythm generation depends on a complex interaction between synaptic and membrane properties of functionally defined neurons. To gain a better understanding of how inhibitory and excitatory synaptic inputs lead to the... more
Respiratory rhythm generation depends on a complex interaction between synaptic and membrane properties of functionally defined neurons. To gain a better understanding of how inhibitory and excitatory synaptic inputs lead to the generation of the respiratory rhythm we analyzed the depolarization pattern of respiratory neurons that were recorded in the transverse slice preparation of mice (P8-22) and the in vivo adult cat. Using voltage-calmp recordings from respiratory neurons and specific antagonists for inhibitory synaptic transmission we demonstrate under in vitro conditions, that inspiratory (n = 7) and post-inspiratory neurons (n = 13) received concurrent glycinergic and glutamatergic synaptic input during inspiration. A similar conclusion was gained with chloride injections into in vivo respiratory neurons. The inhibitory input was essential not only for generating the characteristic depolarization pattern of respiratory neurons, but also for switching the respiratory rhythm b...
Sea turtles lay about 100 leathery-shelled eggs in a 25 cm diameter chamber carefully excavated about 50 cm deep in a nesting beach, where the eggs exchange gases (at approximately 28 degrees C) during their 60-day incubation period. The... more
Sea turtles lay about 100 leathery-shelled eggs in a 25 cm diameter chamber carefully excavated about 50 cm deep in a nesting beach, where the eggs exchange gases (at approximately 28 degrees C) during their 60-day incubation period. The sand surrounding the spherical nest chamber restricts the diffusion of gases into and out of the nest so that as embryonic development progresses, PO2 decreases and PCO2 increases in the gas inside the nest. PO2 falls to 80-100 torr and PCO2 rises to 40-60 torr inside 100-egg man-made Chelonia and Caretta nests. The change in gas tensions in the nest during development is very similar to that seen in the air cell of the chicken egg. Gas tensions inside the turtle nest and in the sand surrounding the nest can be described by a radial steady-state diffusion model. The rate of diffusion of gases in the sand is 30-50% of the rate found in the nest and 6-12% of the rate found in an equal volume of air. The sand surrounding the turtle nest appears to dete...
We investigated structural characteristics for high O2 flux in hummingbird flight muscle, i.e. the most O2 demanding skeletal muscle per unit tissue mass among vertebrates. Pectoralis and supracoracoideus muscles of 3-4 g hummingbirds... more
We investigated structural characteristics for high O2 flux in hummingbird flight muscle, i.e. the most O2 demanding skeletal muscle per unit tissue mass among vertebrates. Pectoralis and supracoracoideus muscles of 3-4 g hummingbirds (Selaphorus rufus) were perfusion fixed in situ, processed for electron microscopy and analyzed by morphometry. Small fiber size (group mean +/- SE, 201 +/- 14 microns 2 at 2.1 microns sarcomere length), large capillary length per fiber volume (8947 +/- 869 mm-2) and high mitochondrial volume density per volume of muscle fiber (34.5 +/- 0.9%) were characteristic features of the muscles. Considering capillary supply and mitochondrial volume on an individual fiber basis showed that the size of the capillary-to-fiber interface (i.e. capillary surface per fiber surface) was also high in the muscles. Comparison with mammalian hindlimb pointed to a major role of the size of the capillary-to-fiber interface in providing a great potential for O2 flux rate from...
Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by... more
Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by neurotransmitters to enhance HM excitability. In particular, we consider: (1) the membrane depolarization induced by a number of different putative transmitters [thyrotropin-releasing hormone (TRH), serotonin (5-HT), norepinephrine (NE)]; and
"" Organisms of gigantic proportions inhabited the world at a time of a hyperoxic prehistoric atmosphere (Palaeozoic gigantism). Extant giants are found in cold polar waters, with large quantities of dissolved oxygen (polar gigantism).... more
"" Organisms of gigantic proportions inhabited the world at a time of a hyperoxic prehistoric atmosphere (Palaeozoic gigantism). Extant giants are found in cold polar waters, with large quantities of dissolved oxygen (polar gigantism). Oxygen is usually deemed central to explain such gigantism. Examples of one category of gigantism are often cited in support of the other, but novel insights into the bioavailability of oxygen imply that they cannot be taken as equivalent manifestations of the effect of oxygen on body size.
Recently, the availability of oxygen has been shown to be lower in cold waters, despite greater oxygen solubility. Consequently, gigantism in cold, oxygenated waters and gigantism in an oxygen pressurized world are fundamentally different: Palaeozoic gigantism likely arose because of greater oxygen availability, while polar gigantism arises in spite of lower oxygen availability.
The traditional view of respiration focuses on meeting the challenge of extracting sufficient amounts of oxygen, which essentially is a toxic gas. We present a broader perspective, which specifically includes risks of oxygen poisoning. We discuss how challenges pertaining to balancing oxygen uptake capacity and risks of oxygen poisoning are very different for animals breathing either air or water.
We propose a novel explanation for polar gigantism in aquatic ectotherms, arguing that their larger body size represents a respiratory advantage that helps to overcome the larger viscous forces in water. Being large helps organisms to balance the opposing risks of asphyxiation and poisoning, especially in colder, more viscous, water. This results in a selection for larger sizes, with polar gigantism as the extreme manifestation. Hence, a larger size provides respiratory benefits to water breathing ectotherms but not terrestrial ectotherms. This can explain why clines in body size across temperature and latitude are stronger in aquatic ectotherms.""
Blood and tissue gas exchange properties of mole rats in normoxic and hypoxic-hypercapnic conditions were compared to the common mammalian pattern. RBC count was 14.0 +/- 1.2-10(6)/microliter. Hb concentration was 15.0 +/- 0.4g/100 ml.... more
Blood and tissue gas exchange properties of mole rats in normoxic and hypoxic-hypercapnic conditions were compared to the common mammalian pattern. RBC count was 14.0 +/- 1.2-10(6)/microliter. Hb concentration was 15.0 +/- 0.4g/100 ml. P50 (at pH 7.4 and 37 degrees C) was 29.5 +/- 0.5 mm Hg. Oxygen capacity averaged 20.2 +/- 0.4 vol% and the Hill coefficient was 2.9 +/- 0.1. The Bohr effect was -0.53 +/- 0.02 (deltalog P/deltapH). The temperature coefficient was 0.0152 +/- 0.0014 (deltalog P/delta degrees C). The Haldane effect was 4.8 +/- 0.5 (deltaCCO2 vol%)at PCO2 =40 mm Hg. Steady-state partial pressures in gas pockets were PO2 = 15.1 +/- 1.4 mm Hg and PCO2 = 85.8 +/- 3.9 mm Hg in normoxia, and 11.5 +/- 3.0 and 101.8 +/- 3.5 repectively in hypoxia-hypercapnia (PIO2 congruent to 85 mm Hg). Under the same conditions 2,3-DPG dropped from 0.87 and 0.88 to 0.62 and 0.65 (mol/mol Hb) in the rat and in the white rat, respectively. Heart muscle myoglobin concentration of the mole rat (1...
Nitric oxide (NO) of endogenous origin is present in exhaled breath. An increase in exhaled NO concentration (ENO) has been described in bronchial asthma and ENO falls after inhaled steroid therapy. The sources of ENO may include... more
Nitric oxide (NO) of endogenous origin is present in exhaled breath. An increase in exhaled NO concentration (ENO) has been described in bronchial asthma and ENO falls after inhaled steroid therapy. The sources of ENO may include pulmonary blood, the gas exchange region, conducting airways and the nasal cavity. In four healthy volunteers, a catheter was placed in a main bronchus after topical anesthesia in order to sample airway NO (CNO). Exhaled nitric oxide of bronchopulmonary and oropharyngeal origin (ENO(b/o)) was measured while excluding nasal NO and was controlled for expiratory flow. During the same exhalation, ENO(b/o) was compared to CNO at multiple sites in the airway as the catheter was progressively withdrawn. Mean CNO concentration in a position corresponding to a main bronchus was 51.4 +/- 10.8% of ENO(b/o). As the catheter was withdrawn, mean CNO concentration progressively increased both in absolute values and as a proportion of ENO(b/o), until in the oropharynx, it was 96.1 +/- 5.2% ENO(b/o). We conclude that a significant proportion of ENO(b/o) arises in the large airways and trachea in normal subjects and contains a minor oropharyngeal component.
The pattern of circulating monocyte subtypes and the concentration of the soluble intercellular adhesion molecule-1 (ICAM-1) were compared in middle-aged female moderate smokers and lifetime non-smokers. Total leukocyte and monocyte... more
The pattern of circulating monocyte subtypes and the concentration of the soluble intercellular adhesion molecule-1 (ICAM-1) were compared in middle-aged female moderate smokers and lifetime non-smokers. Total leukocyte and monocyte counts were higher in smokers. The pattern of circulating monocytes of smokers was changed toward lower absolute counts of activated (CD16+/CD64+) monocytes and (CD16+/CD14+) monocyte-macrophages and higher counts of nonactivated monocytes. The serum concentration of soluble ICAM-1 was significantly higher in smokers than in non-smokers. It is supposed that even moderate cigarette smoking leads to an activation of the circulating monocytes and their increased adhesion to the endothelium.
For most smokers, tobacco dependence begins in childhood or adolescence. This review summarizes the state of social science with respect to the prevention of tobacco use. Social ecology is introduced as a theoretical framework useful for... more
For most smokers, tobacco dependence begins in childhood or adolescence. This review summarizes the state of social science with respect to the prevention of tobacco use. Social ecology is introduced as a theoretical framework useful for organizing prevention approaches. In recent years, the field has shifted from approaches directed at individuals, towards appreciation of additional, more comprehensive social and environmental influences on initiation. These range from intra-individual factors (including physiological responses to nicotine and the psychology of use) to individual, interpersonal, organizational, community, and population factors affecting access and demand. This review highlights prevention approaches that address social and societal influences, from school programs that attempt to change susceptibility of individual youth to tobacco, to community projects, media campaigns, restrictive policies, and tobacco pricing. The most promising approaches are those designed w...
When oxygen is lacking the cellular production of some hormones, cytokines and glycolytic enzymes can be dramatically increased by a hypoxia-induced increase in the expression of the respective genes that encode for these proteins. The... more
When oxygen is lacking the cellular production of some hormones, cytokines and glycolytic enzymes can be dramatically increased by a hypoxia-induced increase in the expression of the respective genes that encode for these proteins. The most progress in understanding how the transcription of genes is increased under hypoxic conditions has been made by studying the hypoxia-inducible expression of the erythropoietin gene. Elucidating the oxygen sensitive enhancer elements of the erythropoietin gene has prompted studies on other oxygen-regulated genes. The transcription-regulating proteins that are induced with hypoxia bind to closely related regulatory DNA sequences that control the expression of the genes for erythropoietin, the vascular endothelial growth factor and a number of glycolytic enzymes. It became evident that the hypoxia-inducible enhancer may be part of a widespread oxygen-sensing mechanism acting in a wide variety of mammalian cells. Comparison with the oxygen sensor sys...
Isolated rabbit lungs were buffer-perfused under constant flow-conditions with separate control of alveolar (PAO2) and mixed venous (PvO2) O2 tension. Alveolar hypoxia caused an increase in pulmonary artery pressure (PAP) with sigmoidal... more
Isolated rabbit lungs were buffer-perfused under constant flow-conditions with separate control of alveolar (PAO2) and mixed venous (PvO2) O2 tension. Alveolar hypoxia caused an increase in pulmonary artery pressure (PAP) with sigmoidal dose-dependency. Erythrocytes increased the strength of the hypoxic pulmonary vasoconstriction (HPV). The contractile and vasorelaxant responses to the onset and release of alveolar hypoxia, respectively, occurred within seconds. Kinetics of the PAP increase, but not the magnitude of response, were related to the velocity of PAO2 decline. In contrast, changes in PvO2, both in the absence and presence of erythrocytes, did neither provoke any pressor response nor amplify the response to concomitant alveolar hypoxia. Repeatedly performed HPV manoeuvres revealed excellent reproducibility, and long-term alveolar hypoxia (90 min) provoked a biphasic pressor response. We conclude that the isolated rabbit lung is a feasible model for the characterization of ...