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At least 991 records · Page 55Linked to original sources
PubMed2006

Tyk2 tyrosine kinase expression is required for the maintenance of mitochondrial respiration in primary pro-B lymphocytes.

Tyk2, a member of the Jak family of protein tyrosine kinases, is critical for the biological actions of alpha/beta interferon (IFN-alpha/beta). Although Tyk2(-/-) mice are phenotypically normal, they exhibit abnormal responses to inflammatory challenges in a variety of cells isolated from Tyk2(-/-) mice. The reported phenotypic alterations in both Tyk2-null cells and mice are consistent with the possibility that the expression of this tyrosine kinase may regulate mitochondrial function. We report here that Tyk2-null pro-B cells are markedly deficient in basal oxygen consumption and exhibit a significant decrease in steady-state cellular ATP levels compared to wild-type cells. Tyk2-null cells also exhibit impaired complex I, III, and IV function of the mitochondrial electron transport chain. Reconstitution of Tyk2-null pro-B cells with either the wild type or a kinase-inactive mutant of Tyk2 restores basal mitochondrial respiration. By contrast, the kinase activity of Tyk2 is required for maintenance of both complex I-dependent mitochondrial respiration as well as induction of apoptosis in cells incubated with IFN-beta. Consistent with the role of Tyk2 in the regulation of tyrosine phosphorylation of Stat3, expression of a constitutively active Stat3 can restore the mitochondrial respiration in Tyk2-null cells treated with IFN-beta. Finally, Tyk2(-/-) mice show decreased exercise tolerance compared to wild-type littermates. Our results implicate a novel role for Tyk2 kinase and Stat3 phosphorylation in mitochondrial respiration.

Adenosine Triphosphate↗
PubMed2001

Cognitive impairment in heart failure with Cheyne-Stokes respiration.

OBJECTIVES: To document the degree of cognitive impairment in stable heart failure, and to determine its relation to the presence of Cheyne-Stokes respiration during sleep. SUBJECTS: 104 heart failure patients and 21 healthy normal volunteers. METHODS: Overnight oximetry was used (previously validated as a screening tool for Cheyne-Stokes respiration in heart failure). Cognitive function was assessed using a battery of neuropsychological tests. Left ventricular function was assessed by echocardiography. RESULTS: Heart failure patients performed worse than the healthy volunteers in tests that measured vigilance. Reaction times were 48% slower (0.89 (0.03) s v 0.60 (0.05) s p < 0.005) and they hit twice as many obstacles on the Steer Clear simulator (75 (6.4) v 33 (4.6); p < 0.005). Cognitive impairment within the heart failure group was unrelated to either the presence of Cheyne-Stokes respiration, the degree of left ventricular dysfunction, or indices of nocturnal oxygenation. CONCLUSIONS: Vigilance was impaired in heart failure but this did not appear to be related to the presence of Cheyne-Stokes respiration during sleep. Impaired vigilance as measured on the Steer Clear test has been associated with an increased risk of motor vehicle accidents. The issue of fitness to drive in heart failure requires further attention.

Aged↗
PubMed1996

Deriving respiration from pulse wave: a new signal-processing technique.

Investigations of autonomic nervous system activity using spectral analysis of heart rate (HR) and blood pressure (BP) variability is very popular in many scientific disciplines, and yet only half of all studies involving spectral analysis control for respiration. Because respiration modulates HR and BP variability, knowledge of the respiratory rate is necessary for the proper interpretation of HR and BP power spectra. We devised and validated a new signal-processing technique to derive respiration from the blood pressure wave. This technique is based on the relationship between oscillations in the area under the dicrotic notch of the pulse wave and respiration. The results of our view signal-processing technique yielded significant correlations between protocols of the actual number of respiratory cycles and our blood pressure-derived respiratory cycles and their respective spectra for a number of standard autonomic tests (P < 0.05). Our method will allow retrospective extraction of the respiratory wave and as such afford a more precise interpretation of HR and BP spectra.

Adult↗
PubMed1998

One-dimensional, nonlinear determinism characterizes heart rate pattern during paced respiration.

This study focuses on the dynamic pattern of heart rate variability in the frequency range of respiration, the so-called respiratory sinus arrhythmia. Forty experimental time series of heart rate data from four healthy adult volunteers undergoing a paced respiration protocol were used as an empirical basis. For pacing-cycle lengths >8 s, the heartbeat intervals are shown to obey a rule that can be expressed by a one-dimensional circle map (next-angle map). Circle maps are introduced as a new type of model for time series analyses to characterize the nonlinear dynamic pattern underlying the respiratory sinus arrhythmia during voluntary paced respiration. Although these maps are not chaotic, the dynamic pattern shows typical imprints of nonlinearity. By starting from a piecewise linear model, which describes the different circle maps obtained from the empirical time series for various pacing frequencies, time invariant measures can be introduced that characterize the dynamic pattern of heart rate variability during voluntary slow-paced respiration.

Adult↗
PubMed2001

Bioenergetics in cardiac hypertrophy: mitochondrial respiration as a pathological target of NO*.

A rat aortic banding model of cardiac hypertrophy was used to test the hypothesis that reversible inhibition of mitochondrial respiration by nitric oxide (NO*) elicits a bioenergetic defect in the hypertrophied heart. In support of this hypothesis, the respiration of myocytes isolated from hypertrophied hearts was more sensitive to exogenous NO* (IC(50) 200 +/- 10 nM vs. 290 +/- 30 nM in controls, P = 0.0064). Hypertrophied myocytes also exhibited significantly elevated inducible NO* synthase (iNOS). Consistent with this endogenous source for NO*, the respiration of hypertrophied myocytes was significantly inhibited at physiological O(2) tensions versus controls. Both the nonspecific NOS inhibitor nitro-L-arginine and the iNOS-specific inhibitor N-[3-(aminomethyl)- benzyl]acetamidine. 2HCl reversed this inhibition, with no effect on respiration of control myocytes. Consistent with an NO*-mediated mitochondrial dysfunction, the ability of intact perfused hearts to respond to a pacing workload was impaired in hypertrophy, and this effect was reversed by NOS inhibition. We conclude that endogenously generated NO* can modulate mitochondrial function in the hypertrophied heart and suggest that this bioenergetic defect may underlie certain pathological features of hypertrophy.

Amidines↗
PubMed2002

Influence of vestibular activation on respiration in humans.

The purpose of this study was to determine the effects of the semicircular canals and otolith organs on respiration in humans. On the basis of animal studies, we hypothesized that vestibular activation would elicit a vestibulorespiratory reflex. To test this hypothesis, respiratory measures, arterial blood pressure, and heart rate were measured during engagement of semicircular canals and/or otolith organs. Dynamic upright pitch and roll (15 cycles/min), which activate the otolith organs and semicircular canals, increased respiratory rate (Delta2 +/- 1 and Delta3 +/- 1 breaths/min, respectively; P < 0.05). Dynamic yaw and lateral pitch (15 cycles/min), which activate the semicircular canals, increased respiration similarly (Delta3 +/- 1 and Delta2 +/- 1, respectively; P < 0.05). Dynamic chair rotation (15 cycles/min), which mimics dynamic yaw but eliminates neck muscle afferent, increased respiration (Delta3 +/- 1; P < 0.05) comparable to dynamic yaw (15 cycles/min). Increases in respiratory rate were graded as greater responses occurred during upright (Delta5 +/- 2 breaths/min) and lateral pitch (Delta4 +/- 1) and roll (Delta5 +/- 1) performed at 30 cycles/min. Increases in breathing frequency resulted in increases in minute ventilation during most interventions. Static head-down rotation, which activates otolith organs, did not alter respiratory rate (Delta1 +/- 1 breaths/min). Collectively, these data indicate that semicircular canals, but not otolith organs or neck muscle afferents, mediate increased ventilation in humans and support the concept that vestibular activation alters respiration in humans.

Adult↗
PubMed1997

Convection as one of the limiting factors of human respiration during normoxic exercise.

Each of the pathways within respiration has been suspected of limiting maximal performance, suggesting that O2 transport may be affected by each single pathway. The use of the stable, isotopic O2 molecules 16O2 and 16O18O is presented as a novel method for assessing respiration. Because of their different molecular weights, 16O2 diffuses 3% more rapidly than 16O18O, whereas 16O2 is convectively transported as rapidly as 16O18O. This can be quantified by using the overall fractionation factor alpha O. The more diffusion becomes limiting, the more 16O2 is transported in preference to 16O18O and alpha O is increased to 1.03. By contrast, the more respiration is limited by convection, the closer alpha O comes to 1.0 during the entire O2 transport. Six untrained subjects underwent normoxic exercise on a cycle ergometer. Isotopic analysis was performed at rest and during exercise loads of 50, 100, 150, 200, and 250 W using respiratory mass spectrometry. With increasing workload, a decrease in alpha O from 1.0072 at rest to 1.0033 at 250 W was determined in all subjects. On the basis of a serial resistance model of respiration, we concluded that, in our subjects, O2 transport was increasingly affected by convection but decreasingly limited by diffusion. The relative contribution of convection to the entire resistance to O2 flow ranged from > or = 44.6% at rest to > or = 74.6% at the most strenuous level of exercise, whereas the diffusive pathways decreasingly contributed to resistance to O2 flow by < or = 24% at rest and < or = 11% at 250 W.

Adolescent↗
PubMed1983

Regional left ventricular performance during normal and obstructed spontaneous respiration.

To clarify the effects of respiration on left ventricular (LV) dimensions and shortening, we studied chronically instrumented dogs with endocardial sonomicrometer crystals in the anterior-posterior (AP), septal to lateral (SL), and long axes (LA) following pericardiectomy. Ten anesthetized dogs were examined during spontaneous unobstructed respiration, partial inspiratory obstruction (PIO), and Mueller maneuvers (MM). During unobstructed inspiration, end-diastolic dimensions (EDD) demonstrated a significant increase in the AP and a similar decrease in the SL axis (i.e., noncongruent shape changes). During PIO only the SL EDD diminished significantly, while no significant changes occurred in any EDD during MM. Individual dogs also demonstrated noncongruent shape changes at end systole during inspiration. However, the end-systolic dimensions for the entire group demonstrated a significant increase in one dimension during each inspiratory mode with no significant changes in the other two axes suggesting an increased ventricular volume. Regional shortening declined only in the SL axis during both unobstructed respiration and PIO. Spontaneous sighs with large tidal volumes, yet smaller changes in pleural pressure than during the MM, were associated with marked noncongruent shape changes in both diastole and systole. We conclude that 1) estimates of LV volumes during respiration based on only one or two axes and assuming regional congruent shape changes may be misleading; and 2) lung volume changes can affect LV geometry independently of changes in pleural pressure.

Airway Obstruction↗
PubMed1994

Coordination between respiration and swallowing: respiratory phase relationships and temporal integration.

The coordination of breathing and swallowing was studied in 13 young healthy adult subjects during the administration of graduated volumes of water (3, 10, and 20 ml). Simultaneous submental electromyography, respiratory plethysmography, and fiber-optic endoscopy revealed a well-timed pattern between physiological respiratory events and related swallowing events. Expiration was the phase of respiration that was most closely associated with deglutition. Respiration was usually maintained at the onset of deglutition and halted before the onset of laryngeal elevation. The apneic interval was approximately 1 s for the 3-, 10-, and 20-ml boluses. A large-volume (100-ml) straw swallow resulted in variable respiration-swallowing patterns and in statistically significant differences (P < 0.01) in the duration of apneic pause and laryngeal excursion. The expiratory phase of respiration resumed nearly 0.50 s before the completion of swallowing. Clinical implications of the findings are addressed and related to aspiration and pulmonary complications in dysphagic patients.

Adolescent↗
PubMed1998

Effects of 4 wk of hindlimb suspension on skeletal muscle mitochondrial respiration in rats.

We investigated in rats the effect of 4 wk of hypodynamia on the respiration of mitochondria isolated from four distinct muscles [soleus, extensor digitorum longus, tibial anterior, and gastrocnemius (Gas)] and from subsarcolemmal (SS) and intermyofibrillar (IMF) regions of mixed hindlimb muscles that mainly contained the four cited muscles. With pyruvate plus malate as respiratory substrate, 4 wk of hindlimb suspension produced an 18% decrease in state 3 respiration for IMF mitochondria compared with those in the control group (P < 0.05). The SS mitochondria state 3 were not significantly changed. Concerning the four single muscles, the mitochondrial respiration was significantly decreased in the Gas muscle, which showed a 59% decrease in state 3 with pyruvate + malate (P < 0.05). The other muscles presented no significant decrease in respiratory rate in comparison with the control group. With succinate + rotenone, there was no significant difference in the respiratory rate compared with the respective control group, whatever the mitochondrial origin (SS, or IMF, or from single muscle). We conclude that 4 wk of hindlimb suspension alters the respiration of IMF mitochondria in hindlimb skeletal muscles and seems to act negatively on complex I of the electron-transport chain or prior sites. The muscle mitochondria most affected are those isolated from the Gas muscle.

Animals↗
PubMed1995

Modification of mastication and respiration during swallowing in the adult human.

1. The normal interactions between respiration, mastication, and swallowing were studied in seated adult humans. Respiratory movements and movements of the larynx were recorded with mercury-elastic strain gauges placed around the rib cage and neck. A rigid body containing infrared-emitting diodes (IREDs) was attached to the forehead, and a single IRED was applied to the chin. Jaw and head movements were transduced using the OPTOTRAK spatial motion analysis system. Recordings were made before, during, and after the mastication of pieces of carrot. 2. Movements of the larynx were used as a marker for swallowing. Measurements were made of the duration of masticatory and respiratory cycles, and the phase relationship between the two rhythms was determined. Deviations in masticatory and respiratory movements during swallowing were detected; the phases of the masticatory and respiratory cycles in which the deviations occurred were determined, and the interval between each deviation and the swallowing marker was calculated. 3. Three characteristic swallowing patterns were observed: interposed, terminal, and spontaneous. Interposed swallows occurred within a masticatory sequence, terminal swallows ended the sequence, and spontaneous swallows occurred sporadically between masticatory sequences. 4. Results revealed that mastication could have a profound effect on the respiratory rhythm in some subjects. One subject, whose data were excluded from further analyses, became apneic for a long period, followed by short and shallow breaths near the end of the masticatory sequence. In most subjects, respiratory rate increased during mastication and then dropped below baseline as soon as mastication ended. The end-inspiration diameter of the rib cage tended to decrease in the preswallow period and increase postmastication relative to baseline. 5. There was a weak but significant tendency for inspiration to begin during the jaw opening phase of mastication, but phase coupling did not become stronger as swallowing was approached. 6. Deviations in respiration during swallowing occurred during the late expiratory phase of the breathing cycle. Swallows within a masticatory sequence occurred most frequently during the early opening phase of the masticatory cycle, and terminal swallows occurred after the end of the sequence with the mandible in the resting, postural position. Swallowing temporarily reset both the masticatory and respiratory rhythms. Most swallows prolonged the duration of one or two respiratory cycles, however; swallows were often repetitive, and in some subjects two or three swallows fell within a single respiratory cycle, prolonging it for several seconds. 7. A tight temporal relationship was observed between deviations in respiration and the swallowing marker: all deviations occurred before or coincident with the marker. The time of deviations in mastication relative to the swallowing marker depended on swallow type. There was no link between the start of pauses in the two rhythms, suggesting that the commands from the swallowing central pattern generator to the other two pattern generators are independent. 8. We suggest that disordered coordination of mastication and swallowing with respiration may cause prolonged apnea in susceptible individuals.

Adult↗
PubMed1984

Interaction of respiration with coughing, feeding, vision and oculomotor control in fish.

Data on the interaction between respiration, coughing, feeding, vision and oculomotor control in fish have been analyzed. A self-contained respiratory rhythm generator in the brainstem reticular formation is, at times, interrupted by a coughing generator, which is partly autorhythmic and partly under vagal afferent control. A number of cranial muscles are shared by the respiratory and masticatory systems. Others are predominately allocated to one of these systems but are recruited by the other under heavy loading conditions. The effect of retinal image displacements caused by respiration-induced eye movements appears to be centrally corrected during normal respiration. In addition, excessive eye movements are reduced by extraocular muscle contraction during intense respiration and cough. Both the central visual and the oculomotor corrections are based on open-loop control through input from the respiratory center.

Afferent Pathways↗
PubMed2000

Effects of respiration and gravity on infradiaphragmatic venous flow in normal and Fontan patients.

BACKGROUND: In the Fontan circulation, pulmonary and systemic vascular resistances are in series. The implications of this unique arrangement on infradiaphragmatic venous physiology are poorly understood. METHODS AND RESULTS: We studied the effects of respiration and gravity on infradiaphragmatic venous flows in 20 normal healthy volunteers (control) and 48 Fontan patients (atriopulmonary connection [APC] n=15, total cavopulmonary connection [TCPC] n=30). Hepatic venous (HV), subhepatic inferior vena caval (IVC), and portal venous (PV) flow rates were measured with Doppler ultrasonography during inspiration and expiration in both the supine and upright positions. The inspiratory-to-expiratory flow rate ratio was calculated to reflect the effect of respiration, and the supine-to-upright flow rate ratio was calculated to assess the effect of gravity. HV flow depended heavily on inspiration in TCPC compared with both control and APC subjects (inspiratory-to-expiratory flow rate ratio 3.4, 1.7, and 1.6, respectively; P:<0.0001). Normal PV flow was higher in expiration, but this effect was lost in TCPC and APC patients (inspiratory-to-expiratory flow rate ratio 0.8, 1.0, and 1.1, respectively; P:=0.01). The respiratory influence on IVC flow was the same in all groups. Gravity decreased HV flow more in APC than in TCPC patients (supine-to-upright flow rate ratio 3.2 versus 2.1, respectively; P:<0.04) but reduced PV flow equally in all groups. CONCLUSIONS: Gravity and respiration have important influences on infradiaphragmatic venous return in Fontan patients. Although gravity exerts a significant detrimental effect on lower body venous return, which is more marked in APC than in TCPC patients, the beneficial effects of respiration in TCPC patients are mediated primarily by an increase in HV flow. These effects may have important short- and long-term implications for the hemodynamics of the Fontan circulation.

Adolescent↗
PubMed1984

Cranio-caudal movements of the liver, pancreas and kidneys in respiration.

The range of movement of the liver, pancreas and kidneys in maximum and normal respiration, and the ability to suspend respiration repeatedly leaving the organs in exactly the same position with the aid of given instructions or a combination of instructions and a simple tool were investigated. The range of movement of the most mobile organ (liver) was 5.5 cm during maximum, 2.5 cm during normal, 0.9 cm during suspended respiration, and 0.2 cm during suspended respiration with a bar placed above the abdomen.

Adult↗
PubMed2001

Neural control of tongue movement with respect to respiration and swallowing.

The tongue must move with remarkable speed and precision between multiple orofacial motor behaviors that are executed virtually simultaneously. Our present understanding of these highly integrated relationships has been limited by their complexity. Recent research indicates that the tongue s contribution to complex orofacial movements is much greater than previously thought. The purpose of this paper is to review the neural control of tongue movement and relate it to complex orofacial behaviors. Particular attention will be given to the interaction of tongue movement with respiration and swallowing, because the morbidity and mortality associated with these relationships make this a primary focus of many current investigations. This review will begin with a discussion of peripheral tongue muscle and nerve physiology that will include new data on tongue contractile properties. Other relevant peripheral oral cavity and oropharyngeal neurophysiology will also be discussed. Much of the review will focus on brainstem control of tongue movement and modulation by neurons that control swallowing and respiration, because it is in the brainstem that orofacial motor behaviors sort themselves out from their common peripheral structures. There is abundant evidence indicating that the neural control of protrusive tongue movement by motoneurons in the ventral hypoglossal nucleus is modulated by respiratory neurons that control inspiratory drive. Yet, little is known of hypoglossal motoneuron modulation by neurons controlling swallowing or other complex movements. There is evidence, however, suggesting that functional segregation of respiration and swallowing within the brainstem is reflected in somatotopy within the hypoglossal nucleus. Also, subtle changes in the neural control of tongue movement may signal the transition between respiration and swallowing. The final section of this review will focus on the cortical integration of tongue movement with complex orofacial movements. This section will conclude with a discussion of the functional and clinical significance of cortical control with respect to recent advances in our understanding of the peripheral and brainstem physiology of tongue movement.

Animals↗
PubMed2005

Cheyne-Stokes respiration and supine dependency.

The influence of position during sleep on central apnoeas during Cheyne-Stokes respiration has not previously been studied systematically. The current authors aimed to study the effect of body position and sleep stages on central sleep apnoeas during Cheyne-Stokes respiration. A total of 20 consecutive patients with cardiovascular diseases and central sleep apnoea during Cheyne-Stokes respiration were investigated using nocturnal polysomnography, including a body position sensor mounted on the patient's sternum. The mean central apnoea-hypopnoea index was significantly higher in the supine position than in nonsupine positions (41+/-13 versus 26+/-12). The central apnoea-hypopnoea index was highest in sleep stages 1 and 2, and lowest in slow-wave sleep and rapid eye movement sleep. In every sleep stage, central apnoeas and hypopnoeas were more prevalent in the supine position compared with nonsupine positions. In conclusion, sleep in the supine body position increases the frequency of apnoeas and hypopnoeas in patients with Cheyne-Stokes respiration.

Adult↗
PubMed1989

Electrophrenic respiration in patients with high quadriplegia.

After determining that 15 patients with high spinal cord injuries who were permanently apneic had viable phrenic nerves, electrophrenic respiration units were implanted. Thirteen of the patients (86%) achieved full-time respiration and two more achieved half-time respiration. Despite the loss of 8 patients to unrelated problems, 7 now use electrophrenic respiration continuously, one having done so for 16 years. The patient selection criteria, neurophysiological evaluation method, surgical procedure, postoperative care, and methods for diagnosis of system failures are presented. A comparison of the cervical and thoracic procedures is made. The cervical approach is preferred. Complications consisted primarily of equipment failures. For the external components there were several cases of antenna connection and battery connection failures. The implanted receivers failed in 6 cases with an average lifetime of 48 months, ranging from 24 to 108 months. In one case fibrosis around the electrode resulted in failure to stimulate the phrenic nerve effectively. In another case, infection required removal of the system which was reimplanted later and has continued to provide successful ventilation.

Adolescent↗
PubMed2006

Overexpression of wheat alternative oxidase gene Waox1a alters respiration capacity and response to reactive oxygen species under low temperature in transgenic Arabidopsis.

Under low temperature conditions, the cytochrome pathway of respiration is repressed and reactive oxygen species (ROS) are produced in plants. Mitochondrial alternative oxidase (AOX) is the terminal oxidase responsible for the cyanide-insensitive and salicylhydroxamic acid-sensitive respiration. To study functions of wheat AOX genes under low temperature, we produced transgenic Arabidopsis by introducing Waox1a expressed under control of the cauliflower mosaic virus (CaMV) 35S promoter in Arabidopsis thaliana. The enhancement of endogenous AOX1a expression via low temperature stress was delayed in the transgenic Arabidopsis. Recovery of the total respiration activity under low temperature occurred more rapidly in the transgenic plants than in the wild-type plants due to a constitutively increased alternative pathway capacity. Levels of ROS decreased in the transgenic plants under low temperature stress. These results support the hypothesis that AOX alleviates oxidative stress when the cytochrome pathway of respiration is inhibited under abiotic stress conditions.

Arabidopsis↗