Fixed breathing frequency decreases end-tidal PCO2 in humans.

We tested the effect of a fixed breathing frequency on the partial pressure of CO2 in the end-tidal air (PETCO2) in resting healthy subjects. In the first experiment, three different rates of breathing were dictated: the same frequency of breathing as the subject's control one (1f), a double frequency (2f), and half of the control frequency (0.5f). 10 min dictate of 1f and 2f induced a decrease of PETCO2. The dictate of 0.5f had no significant effect on PETCO2. In the second experiment, 1f was dictated for 30 min, inducing a decrease of PETCO2 throughout the duration of the dictate. These results demonstrate that fixing the breathing frequency by the dictate affects the chemostatic control of ventilation.     

Ventilatory effects of hypercapnic end-tidal PCO2 clamps during aerobic exercise of varying intensity

Nine subjects performed a sequence of sustained and randomised changes between 40 W and 100 W on a cycle ergometer while the end-tidal PO2 was kept close to 17.3 kPa (130 mm Hg) by means of a dynamic forcing technique (reference experiment). In a second series inspiratory CO2 was additionally manipulated so as to hold end-tidal PCO2 (PETCO2) near 6.5 kPa (49 mm Hg; 'CO2-clamp' experiment). By this forcing PETCO2 oscillations were attenuated and more evenly distributed over the frequency range. Ventilation (VT) responded to this manoeuvre with an upward trend that could not be ascribed to a slow CO2-response component, changes in metabolic rate or a dissociation of end-tidal and arterial PCO2. VT differences between reference and CO2-clamp experiments were abolished within a 3-min period following the termination of the external CO2 control. The present results suggest that the CO2-H+ stimulus plays a major role in adjusting ventilation when exercise intensity is decreased. The underlying CO2 effect appears to be neither additive nor bi-directionally symmetrical.     

Fast and slow components of cerebral blood flow response to step decreases in end-tidal PCO2 in humans

This study examined the dynamics of the middlecerebral artery (MCA) blood flow response to hypocapnia in humans(n = 6) by using transcranial Dopplerultrasound. In a control protocol, end-tidalPCO₂(PET_CO2) was heldnear eucapnia (1.5 Torr above resting) for 40 min. In ahypocapnic protocol, PET_CO2was held near eucapnia for 10 min, then at 15 Torr below eucapnia for20 min, and then near eucapnia for 10 min. During both protocols,subjects hyperventilated throughout andPET_CO2 and end-tidalPO₂ were controlled by using thedynamic end-tidal forcing technique. Beat-by-beat values werecalculated for the intensity-weighted mean velocity (_IWM),signal power (), and theirinstantaneous product(_IWM).A simple model consisting of a delay, gain terms, time constants(_f,on, _f,off) and baseline levels offlow for the on- and off-transients, and a gain term(g_s) and time constant(_s) for a second slower component was fitted to the hypocapnic protocol. The cerebral bloodflow response to hypocapnia was characterized by a significant (P < 0.001) slowprogressive adaptation in_IWM, with g_s = 1.26 %/Torr and_s = 427 s, that persistedthroughout the hypocapnic period. Finally, the responses at the onsetand relief of hypocapnia were asymmetric(P < 0.001), with_f,on (6.8 s) faster than_f,off (14.3 s).

     

Respiratory effects of the scalene and sternomastoid muscles in humans.

Previous studies have shown that in normal humans the change in airway opening pressure (DeltaPao) produced by all the parasternal and external intercostal muscles during a maximal contraction is approximately -18 cmH(2)O. This value is substantially less negative than DeltaPao values recorded during maximal static inspiratory efforts in subjects with complete diaphragmatic paralysis. In the present study, therefore, the respiratory effects of the two prominent inspiratory muscles of the neck, the sternomastoids and the scalenes, were evaluated by application of the Maxwell reciprocity theorem. Seven healthy subjects were placed in a computed tomographic scanner to determine the fractional changes in muscle length during inflation from functional residual capacity to total lung capacity and the masses of the muscles. Inflation induced greater shortening of the scalenes than the sternomastoids in every subject. The inspiratory mechanical advantage of the scalenes thus averaged (mean +/- SE) 3.4 +/- 0.4%/l, whereas that of the sternomastoids was 2.0 +/- 0.3%/l (P < 0.001). However, sternomastoid muscle mass was much larger than scalene muscle mass. As a result, DeltaPao generated by a maximal contraction of either muscle would be 3-4 cmH(2)O, which is about the same as DeltaPao generated by the parasternal intercostals in all interspaces.     

Simple contrivance "clamps" end-tidal PCO(2) and PO(2) despite rapid changes in ventilation.

The device described in this study uses functionally variable dead space to keep effective alveolar ventilation constant. It is capable of maintaining end-tidal PCO(2) and PO(2) within +/-1 Torr of the set value in the face of increases in breathing above the baseline level. The set level of end-tidal PCO(2) or PO(2) can be independently varied by altering the concentration in fresh gas flow. The device comprises a tee at the mouthpiece, with one inlet providing a limited supply of fresh gas flow and the other providing reinspired alveolar gas when ventilation exceeds fresh gas flow. Because the device does not depend on measurement and correction of end-tidal or arterial gas levels, the response of the device is essentially instantaneous, avoiding the instability of negative feedback systems having significant delay. This contrivance provides a simple means of holding arterial blood gases constant in the face of spontaneous changes in breathing (above a minimum alveolar ventilation), which is useful in respiratory experiments, as well as in functional brain imaging where blood gas changes can confound interpretation by influencing cerebral blood flow.     

Respiratory control in humans after 8 h of lowered arterial PO2, hemodilution, or carboxyhemoglobinemia.

In humans exposed to 8 h of isocapnic hypoxia, there is a progressive increase in ventilation that is associated with an increase in the ventilatory sensitivity to acute hypoxia. To determine the relative roles of lowered arterial PO2 and oxygen content in generating these changes, the acute hypoxic ventilatory response was determined in 11 subjects after four 8-h exposures: 1) protocol IH (isocapnic hypoxia), in which end-tidal PO2 was held at 55 Torr and end-tidal PCO2 was maintained at the preexposure value; 2) protocol PB (phlebotomy), in which 500 ml of venous blood were withdrawn; 3) protocol CO, in which carboxyhemoglobin was maintained at 10% by controlled carbon monoxide inhalation; and 4) protocol C as a control. Both hypoxic sensitivity and ventilation in the absence of hypoxia increased significantly after protocol IH (P < 0.001 and P < 0.005, respectively, ANOVA) but not after the other three protocols. This indicates that it is the reduction in arterial PO2 that is primarily important in generating the increase in the acute hypoxic ventilatory response in prolonged hypoxia. The associated reduction in arterial oxygen content is unlikely to play an important role.     

Morphofunctional properties of red blood cells of humans in 5-day dry immersion

The blood of six healthy male volunteers sampled before, immediately after, and 7 days after 5-day dry immersion was analyzed for morphological parameters, erythrocyte metabolism, and lipid and phospho-lipid levels. The experimental 5-day exposure was shown to increase the erythrocyte count. On the first day after the experiment, upward trends were exhibited by hemoglobin and packed cell volume (PCV). The significant decrease in adenosine triphosphate and low level of reduced glutathione that were also detected on the first day after the experiment could be the result of enhanced oxidation in the cell, possibly due to the activation of lipid peroxidation. A downward trend in the phospholipid fraction of the erythrocyte membrane against constant levels of cholesterol and its ethers could be associated with a significant increase in the fraction of nonesterified fatty acids on day 1 and triglycerides on days 1 and 7 after the experiment.     

Digital Computer Simulation of Respiratory Response to Cerebrospinal Fluid PCO2 in the Cat

The respiratory control system is treated as linear with a transmission delay between ventilation and sensing points (chemoreceptors). To the accepted variables involving body gas stores, ventilatory effects, transmission effects, and steady state pH, P(CO2), P(O2) chemoreceptor response, certain detailed analysis of the central receptors have been added. By construction of a model for medullary CO(2) receptor utilizing expected values of CNS (central nervous system) circulation, CO(2) production, and tissue-buffering effects, results of experimental observation of the effects of alteration of CSF were simulated. The inclusion of CSF effects also allowed simulation of the response to alteration in inspired CO(2), hyperventilation, and the periodic breathing with prolongation of circulation time.     

Evaluation of a dual-function pH and PCO2 in vivo sensor.

A newly developed, dual-function pH and PCO2 sensor was evaluated in this study. The sensors were placed in the femoral arteries of dogs anesthetized with sodium pentobarbital. Comparisons were made between systemic arterial pH and PCO2 measured using the sensor and those measured from blood samples drawn at 15-min intervals over a 7-h period using a bench instrument. The mean pH of the bench instrument measurements was 7.43. The mean difference of the sensor measurements from the bench instrument measurements for 207 comparisons was 0.0003 pH +/- 0.061 SD. The mean PCO2 of the bench instrument measurements was 40 mmHg. The mean difference of the sensor measurements from those of the bench instrument for 212 comparisons was -1.43 mmHg +/- 5.17 SD. The sensors performed equally well in the presence of metabolic or respiratory acidosis and alkalosis. The dual-function sensors evaluated in this study are useful for trend monitoring of pH and PCO2 over at least a 7-h period without recalibration. With improvement in the consistency of sensor construction, these sensors will be reliable in vivo sensing devices for blood pH and PCO2 and thus valuable research and clinical instruments.     

Respiratory responses induced by the activation of somatic nociceptive afferents in humans.

To further investigate the role of somatic nociceptive afferents in the neural control of breathing, we studied the respiratory effects of their activation by means of either electrical stimulation or ischemic pain in 14 healthy volunteers. Painful electrical cutaneous stimulation increased respiratory frequency (f), mean inspiratory flow (VT/TI), and rate of rise (XP/TI) of integrated electromyographic activity of diaphragm (IEMGdi). Painful muscular electrical stimulation caused similar but larger changes accompanied by increases in tidal volume (VT), peak XP of IEMGdi, and ventilation (VE); it also entrained respiratory rhythm. Ischemic pain, which was characterized by a progressively increasing intensity, caused augmentation in respiratory activity that displayed an increasing trend: VE, f, VT, XP, VT/TI, and XP/TI increased. In the light of available literature, it seems conceivable to suggest that respiratory responses to painful electrical stimulation are mediated through the activation of cutaneous (A delta) and muscular (group III) fine-myelinated afferents, and responses to ischemic pain are mediated by the activation of both fine myelinated (group III) and unmyelinated (group IV) muscular afferents. The input conveyed by these afferents may constitute an effective stimulus to respiration in humans.     

Antagonism of marihuana effects by indomethacin in humans.

To investigate whether the nonsteroidal anti-inflammatory drug (NSAID) indomethacin antagonized the effects of marihuana, an exploratory single-blind, placebo-controlled study was conducted. Subjects (n = 4) smoked marihuana after pre-treatment with placebo and indomethacin. The subjective rating of marihuana "high", heart rate, word recall, time estimation/production, and plasma concentrations of THC and PGE2 were measured. It was found that: 1) indomethacin pre-treatment decreased the elevation of prostaglandins induced by THC; 2) indomethacin significantly attenuated the subjective "high" and the heart rate accelerating effects of THC, although the magnitude of this effect was modest; 3) indomethacin abolished the profound effect of THC on time estimation and production; and 4) indomethacin pretreatment did not affect the decremental effects of THC on word recall. We conclude that prostaglandins are involved in the neurophysiologic mechanisms that mediate some of the typical clinical effects of THC, particularly the distortion of time perception.     

Constant urinary proteins in healthy humans in a 520-day isolation experiment

The aim of this study was the search of permanent proteins of the urinary proteome during a 520-day isolation experiment at the Institute of Biomedical Problems (IBMP) Ground-Based Test Facility in controlled conditions, using an autonomous life support system. The object of the study was urine sampled from 6 normal male subjects aged 25 to 37. The biological material samples (the second morning urine fractions) were collected for proteomic investigations against the background, on the 50th, 93rd, 124th, 153rd, 180th, 251st, 274th, 303rd, 330th, 371st, 400th, and 427th days of isolation, and on the 7th day after its completion. The samples were analyzed using chromatography–mass spectrometry, while the obtained results were analyzed using bioinformatics resources. The following seven permanent proteins were identified and observed during the entire period of urine investigations: epidermal growth factor, polymeric immunoglobulin receptor, plasma serine protease inhibitor, Alpha 1 microglobulin/bikunin precursor (AMBP), keratin (type II cytoskeletal 1), collagen alpha-1 (VI) chain, and serum albumin.