Effects of changes in CO2 partial pressure on the sensation of respiratory drive

The purpose of this study was to determine whether a change in respiratory sensation accompanies an increase in CO2 partial pressure (PCO2) in the absence of any changes in the level and pattern of thoracic displacement and respiratory muscle force. Eleven normal subjects were artificially hyperventilated with a positive-pressure mechanical respirator. In separate trials the tidal volume (VT) was set at 10 and 18 ml/kg and the frequency of ventilation (f) was adjusted to maintain the base-line end-tidal PCO2 at approximately 30 Torr. Thereafter, at a constant controlled VT and f, the PCO2 was progressively increased by raising the inspired CO2 concentration. There were no changes in respiratory motor activity as determined from the peak inspiratory airway pressure (Paw) until the PCO2 reached 40.8 +/- 1.0 and 40.1 +/- 1.0 (SE) Torr in the large and small VT trials, respectively. Initially there was no conscious awareness of the change in respiratory activity. Subjects first signaled that ventilatory needs were not being satisfied only after a further increase in PCO2 to 44.7 +/- 1.3 and 42.3 +/- 1.0 (SE) Torr in the large and small VT trials and after the Paw had fallen to 55-60% of the base-line value. The results suggest that changes in respiratory sensation produced by increasing chemical drive are a consequence of increases in respiratory efferent activity, but a direct effect of changes in PCO2 on respiratory sensation cannot be excluded.     

Impaired pressure sensation in mice lacking TRPV4

The sensation of pressure, mechanosensation, in vertebrates remains poorly understood on the molecular level. The ion channel TRPV4 is in the TRP family and is a candidate for a mechanosensitive calcium-permeable channel. It is located in dorsal root ganglia. In the present study, we show that disrupting the Trpv4 gene in mice markedly reduced the sensitivity of the tail to pressure and acidic nociception. The threshold to noxious stimuli and the conduction velocity of myelinated nerve responding to stimuli were also impaired. Activation of unmyelinated nerve was undetected. However, the mouse still retained olfaction, taste sensation, and heat avoidance. The TRPV4 channel expressed in vitro in Chinese hamster ovary cells was opened by low pH, citrate, and inflation but not by heat or capsaicin. These data identify the TRPV4 channel as essential for the normal detection of pressure and as a receptor of the high-threshold mechanosensory complex.     

Hydrostatic pressure sensation in cells: integration into the tensegrity model.

Hydrostatic pressure (HP) is a mechanical stimulus that has received relatively little attention in the field of the cell biology of mechanotransduction. Generalized models, such as the tensegrity model, do not provide a detailed explanation of how HP might be detected. This is significant, because HP is an important mechanical stimulus, directing cell behaviour in a variety of tissues, including cartilage, bone, airways, and the vasculature. HP sensitivity may also be an important factor in certain clinical situations, as well as under unique environmental conditions such as microgravity. While downstream cellular effects have been well characterized, the initial HP sensation mechanism remains unclear. In vitro evidence shows that HP affects cytoskeletal polymerization, an effect that may be crucial in triggering the cellular response. The balance between free monomers and cytoskeletal polymers is shifted by alterations in HP, which could initiate a cellular response by releasing and (or) activating cytoskeleton-associated proteins. This new model fits well with the basic tenets of the existing tensegrity model, including mechanisms in which cellular HP sensitivity could be tuned to accommodate variable levels of stress.     

Effects of changes in level and pattern of breathing on the sensation of dyspnea

Breathing during hypercapnia is determined by reflex mechanisms but may also be influenced by respiratory sensations. The present study examined the effects of voluntary changes in level and pattern of breathing on the sensation of dyspnea at a constant level of chemical drive. Studies were carried out in 15 normal male subjects during steady-state hypercapnia at an end-tidal PCO2 of 50 Torr. The intensity of dyspnea was rated on a Borg category scale. In one experiment (n = 8), the level of ventilation was increased or decreased from the spontaneously adopted level (Vspont). In another experiment (n = 9), the minute ventilation was maintained at the level spontaneously adopted at PCO2 of 50 Torr and breathing frequency was increased or decreased from the spontaneously adopted level (fspont) with reciprocal changes in tidal volume. The intensity of dyspnea (expressed as percentage of the spontaneous breathing level) correlated with ventilation (% Vspont) negatively at levels below Vspont (r = -0.70, P less than 0.001) and positively above Vspont (r = 0.80, P less than 0.001). At a constant level of ventilation, the intensity of dyspnea correlated with breathing frequency (% fspont) negatively at levels below fspont (r = -0.69, P less than 0.001) and positively at levels above fspont (r = 0.75, P less than 0.001). These results indicate that dyspnea intensifies when the level or pattern of breathing is voluntarily changed from the spontaneously adopted level. This is consistent with the possibility that ventilatory responses to changes in chemical drive may be regulated in part to minimize the sensations of respiratory effort and discomfort.     

Effect of pressure on thermal insulation in humans wearing wet suits

The present work was undertaken to determine the critical water temperature (Tcw), defined as the lowest water temperature a subject can tolerate at rest for 3 h without shivering, of wet-suited subjects during water immersion at different ambient pressures. Nine healthy males wearing neoprene wet suits (5 mm thick) were subjected to immersion to the neck in water at 1, 2, and 2.5 ATA while resting for 3 h. Continuous measurements of esophageal (T(es)) and skin (Tsk) temperatures and heat loss from the skin (Htissue) and wet suits (Hsuit) were recorded. Insulation of the tissue (Itissue), wet suits (Isuit), and overall total (Itotal) were calculated from the temperature gradient and the heat loss. The Tcw increased curvilinearly as the pressure increased, whereas the metabolic heat production during rest and immersion was identical over the range of pressure tested. During the 3rd h of immersion, Tes was identical under all atmospheric pressures; however, Tsk was significantly higher (P less than 0.05) at 2 and 2.5 ATA compared with 1 ATA. A 42 (P less than 0.001) and 50% (P less than 0.001), reduction in Isuit from the 1 ATA value was detected at 2 and 2.5 ATA, respectively. However, overall mean Itissue was maximal and independent of the pressure during immersion at Tcw. The Itotal was also significantly smaller in 2 and 2.5 ATA compared with 1 ATA. The Itissue provided most insulation in the extremities, such as the hand and foot, and the contribution of Isuit in these body parts was relatively small. On the other hand, Itissue of the trunk areas, such as the chest, back, and thigh, was not high compared with the extremities, and Isuit played a major role in the protection of heat drain from these body parts.     

Modified pressure distribution patterns in walking following reduction of plantar sensation

The aim of the present study was to investigate the influence of reduced plantar sensation on pressure distribution patterns during gait of 40 healthy subjects (25.3+/-3.3 yr, 70.8+/-10.6 kg and 176.5+/-7.8 cm) with no history of sensory disorders. Plantar sensation in the subjects was reduced by using an ice immersion approach, and reduced sensitivity was tested with Semmes-Weinstein monofilaments. All subjects performed six trials of barefoot walking over a pressure distribution platform under normal as well as iced conditions. Plantar cutaneous sensation was significantly reduced after the cooling procedure (p<0.0001). Pressure distribution analysis showed substantially modified plantar pressure distribution patterns during the roll-over process (ROP) under iced conditions. Analysis of peak pressures revealed significant reductions under the toes and under the heel (p<0.001). The contact time and the relative impulse for the whole foot did not change significantly between the two conditions. For the different areas, a significant load shift from the heel and toes towards the central and lateral forefoot and the lateral midfoot was observed. The results indicate the strong influence of reduced afferent information of the sole of the foot on the ROP in walking.     

Effects of changes in inspiratory muscle strength on the sensation of respiratory force

The sensation of respiratory muscle force was compared in seven normal subjects before and after inspiratory muscle strength training. Subjects performed 20 sustained maximal inspiratory maneuvers daily for 6-18 wk. Maximal inspiratory pressures (MIP) increased from 124 +/- 10 to 187 +/- 9 (SE) cmH2O (P less than 0.005). Exponents of the power function relationships between mouth pressure (Pm) and the intensity of the sensation of force, corrected for inspiratory duration, during magnitude scaling of resistive and elastic ventilatory loads were the same before and after training (P greater than 0.05). However, absolute sensation intensity (S) during resistive and elastic loading was reduced significantly after strength training but returned toward baseline levels greater than or equal to 8 wk after the cessation of training when the MIP had fallen to 150 +/- 5 cmH2O. The absolute S at a given Pm during ventilatory loading changed inversely with changes in MIP (P less than 0.001). Furthermore the relationship between absolute S and Pm expressed as a proportion of the MIP (Pm/MIP) was constant over testing periods. These results suggest that the sensation of respiratory muscle force reflects the proportion of the maximum force utilized in breathing and may be based on the level of respiratory motor command signals.     

Cephalometric evaluation of the changes in mandibular symphysis after 7 years of denture wearing

Objective: To evaluate changes in mandibular symphysis during 7 years of complete denture wearing following extraction of natural anterior teeth. Design: Comparison among measurements taken at four different occasions in a prospective cephalometric study. Setting: The study was conducted at the Dental School of Athens University. Subjects: 10 complete denture wearers (5 women, 5 men) with average age of 53.2 years, at the beginning of the study. Measures: Linear and area measurements of the mandibular symphysis. Results: The overall reduction in the anterior mandibular height was 7.87 mm and in the mandibular symphysis area 54.8 mm² (p<0.05). Females presented higher total average reduction in both variables tested, and more rapid bone loss during the first two years of denture wear, compared to men. Superimposition of the tracings revealed considerable individual variation in mandibular symphysis changes. Conclusion: Results are in line with the findings of other authors indicating continuous reduction and dramatic inter-subject variation in the mandibular alveolar bone, following extraction of natural teeth and wearing of complete dentures.     

Alternative prion structural changes revealed by high pressure

At high temperature, recombinant hamster prion protein (SHaPrP(90-231)) undergoes aggregation and changes from a predominantly alpha-helical to beta-sheet conformation. We then applied high pressure (200 MPa) to the beta-sheet-rich conformation. The aggregation was reversed, and the original tertiary and secondary structures were recovered at ambient pressure, after pressure release. The application of a pressure of 200 MPa thus allowed studying the heat-induced equilibrium refolding in the absence of protein aggregation. Prion protein unfolding as a function of high pressure was also investigated. Simple two-state, reversible unfolding transitions were observed, as monitored by spectral changes in the UV and fluorescence of the hydrophobic probe 8-anilino-1-naphthalene sulfonate. However, these heat- and pressure-induced conformers differed in their unfolding free energy. At pressures over 400 MPa, strong thioflavin-T binding was observed, suggesting a further structural change to a metastable oligomeric structure.     

Influence of extravascular pressure on changes induced in vascular resistance in the small intestine by elevated venous pressure

The influence of the extravascular pressure on the size of the increase in vascular resistance after elevation of venous outflow pressure (venous-vasomotor response) was studied in an intestinal segment, perfused at a constant rate, in anaesthetized dogs. If pressure in the lumen of the intestine was elevated (spontaneously, pharmacologically, mechanically) or pressure in the plethysmograph was raised, venous-vasomotor responses were either smaller or absent. When pressure in the intestinal lumen was raised, blood volume increments produced in the segment by elevated venous pressure were significantly smaller than those observed in the presence of resting pressure. The presence of a venous-vasomotor response was correlated to the quantitative relationship between the extravascular and the venous pressure. Its induction was dependent on whether the outflow venous pressure was higher than the pressure values in the intestinal lumen or the plethysmograph; in that case it developed to an extent corresponding to the increment in transmural vascular pressure.     

Thoracic gas volume in rabbits by low-frequency ambient pressure changes

R. Peslin et al. measured thoracic gas volume (TGV) in adults using a new method employing low-frequency ambient pressure changes (APC) (J. Appl. Physiol. 62: 359-363, 1987). We extended that methodology and then tested the hypothesis that this technique was applicable to small mammals. TGV [at functional residual capacity (FRC)] by APC and by conventional Boyle's law was compared in 12 rabbits. The rabbits were anesthetized, tracheostomized, intubated, and placed in a pressure plethysmograph. Although in the method of Peslin et al. box pressure was oscillated at a single frequency, in our extension box pressure was oscillated simultaneously at two frequencies (0.1 and 0.2 Hz). Flow at the airway opening consisted of rapid events due to spontaneous breathing, superposed on slower events due to the alveolar gas compression. The slower events were analyzed to yield alveolar gas compliance and, by Boyle's law, FRC. FRC by APC was highly correlated to FRC by conventional plethysmography (r = 0.85). Compared with the methodology of Peslin et al., our extension relaxes a key limitation and yields systematically higher estimates of FRC. We conclude that this method is applicable to small mammals, despite an inherently more compliant chest wall, and that the methodological extension improves the estimate of FRC.     

The oral sensation of carbonated water: cross-desensitization by capsaicin and potentiation by amiloride

The oral sensation elicited by carbonated water is reduced by capsaicin and by blockers of carbonic anhydrase. We have investigated the temporal profile of this sensation and its cross-desensitization by capsaicin. We additionally tested if the sensation is influenced by amiloride. Following pretreatment of half of the dorsal tongue with 33 p.p.m. capsaicin, carbonated water was flowed over the tongue bilaterally for 5, 15 or 60 s. Subjects then performed a two-alternative forced choice test by indicating which side of the tongue had a stronger sensation and separately rated the sensory intensity on each side. Capsaicin significantly reduced the intensity of sensation elicited by carbonated water, consistent with cross-desensitization. This effect was weaker at 60 s because of a significant decline (desensitization) in ratings of the intensity of carbonated water on both sides of the tongue. Pretreatment with amiloride resulted in a small but significant increase in the intensity of the sensation elicited by the 15 s carbonated water stimulus, suggesting an amiloride-sensitive transduction mechanism.