摘要 :
The assessment of chemoreflex sensitivity (CRS) is of major importance in studies investigating the adaptation of ventilation to the needs of human body. Increased sensitivity of chemoreceptors to both hypoxia and hypercapnia has ...
展开
The assessment of chemoreflex sensitivity (CRS) is of major importance in studies investigating the adaptation of ventilation to the needs of human body. Increased sensitivity of chemoreceptors to both hypoxia and hypercapnia has recently been shown to be a powerful and independent prognosticator in heart failure (HF) patients, thus highlighting the importance of the assessment of CRS also in the clinical setting. In spite of this, the measurement of CRS is currently limited to the research setting. One possible reason might be the lack of suitable commercial equipments.On the basis of these considerations, we designed a system to carry out a comprehensive assessment of CRS, including both central and peripheral chemoreceptors. The system is based on the integration of different commercial devices and is entirely managed by a custom software written in Matlab language. The main features of our system are: (1) the implementation of standard methods (the Read's rebreathing test, the CO2 single breath test and the transient hypoxia test) suitable for both pathological and healthy subjects, (2) data quality assurance and reduction of subjective judgment in the analysis through advanced analysis procedures and statistical outliers rejection, and (3) full interactive control of every step of the recording and analysis procedures.The system is currently used in our Institution in the assessment of CRS in HF patients, chronic obstructive pulmonary disease patients and healthy subjects. It has proven to be very effective and easy to use even by clinical personnel without a specific background in respiratory function assessment.
收起
摘要 :
We evaluated the effects of parasympathetic activation by pyridostigmine (PYR) on chemoreflex sensitivity in a rat model of heart failure (HF rats). HF rats demonstrated higher pulmonary ventilation (PV), which was not affected by...
展开
We evaluated the effects of parasympathetic activation by pyridostigmine (PYR) on chemoreflex sensitivity in a rat model of heart failure (HF rats). HF rats demonstrated higher pulmonary ventilation (PV), which was not affected by PYR. When HF and control rats treated or untreated with PYR were exposed to 15% O_2, all groups exhibited prompt increases in respiratory frequency (RF), tidal volume (TV) and PV. When HF rats were exposed to 10% O_2 they showed greater PV response which was prevented by PYR. The hypercapnia triggered by either 5% CO_2 or 10% CO_2 promoted greater RF and PV responses in HF rats. PYR blunted the RF response in HF rats but did not affect the PV response. In conclusion, PYR prevented increased peripheral chemoreflex sensitivity, partially blunted central chemoreflex sensitivity and did not affect basal PV in HF rats.
收起
摘要 :
Key points Chronic hypercapnia per se has distinct effects on the mechanisms regulating steady‐state ventilation and the CO 2 /H + chemoreflex. Chronic hypercapnia leads to sustained hyperpnoea that exceeds predicted ventilation ...
展开
Key points Chronic hypercapnia per se has distinct effects on the mechanisms regulating steady‐state ventilation and the CO 2 /H + chemoreflex. Chronic hypercapnia leads to sustained hyperpnoea that exceeds predicted ventilation based upon the CO 2 /H + chemoreflex. There is an integrative ventilatory, cardiovascular and metabolic physiological response to chronic hypercapnia. Chronic hypercapnia leads to deterioration of cognitive function. Abstract Respiratory diseases such as chronic obstructive pulmonary disease (COPD) often lead to chronic hypercapnia which may exacerbate progression of the disease, increase risk of mortality and contribute to comorbidities such as cognitive dysfunction. Determining the contribution of hypercapnia per se to adaptations in ventilation and cognitive dysfunction within this patient population is complicated by the presence of multiple comorbidities. Herein, we sought to determine the role of chronic hypercapnia per se on the temporal pattern of ventilation and the ventilatory CO 2 /H + chemoreflex by exposing healthy goats to either room air or an elevated inspired CO 2 (InCO 2 ) of 6% for 30?days. A second objective was to determine whether chronic hypercapnia per se contributes to cognitive dysfunction. During 30?days of exposure to 6% InCO 2 , steady‐state (SS) ventilation ( V ? I ) initially increased to 335% of control, and then within 1–5?days decreased and stabilized at ～230% of control. There was an initial respiratory acidosis that was partially mitigated over time due to increased arterial [HCO 3 ? ]. There was a transient decrease in the ventilatory CO 2 /H + chemoreflex, followed by return to pre‐exposure levels. The SS V ? I during chronic hypercapnia was greater than predicted from the acute CO 2 /H + chemoreflex, suggesting separate mechanisms regulating SS V ? I and the chemoreflex. Finally, as assessed by a shape discrimination test, we found a sustained decrease in cognitive function during chronic hypercapnia. We conclude that chronic hypercapnia per se results in: (1) a disconnect between SS V ? I and the CO 2 /H + chemoreflex, and (2) deterioration of cognitive function.
收起
摘要 :
Ventilatory long-term facilitation (LTF; defined as gradual increase of minute ventilation following repeated hypoxic exposures) is well described in adult mammals and is hypothesized to be a protective mechanism against apnea. In...
展开
Ventilatory long-term facilitation (LTF; defined as gradual increase of minute ventilation following repeated hypoxic exposures) is well described in adult mammals and is hypothesized to be a protective mechanism against apnea. In newborns, LTF is absent during the first postnatal days, but its precise developmental pattern is unknown. Accordingly, this study describes this pattern of postnatal development. Additionally, we tested the hypothesis that chronic intermittent hypoxia (CIH) from birth alters this development. LTF was estimated in vivo using whole body plethysmography by exposing rat pups at postnatal days 1, 4, and 10 (P1, P4, and P10) to 10 brief hypoxic cycles (nadir 5% O_2) and respiratory recordings during the following 2 h (recovery, 21% O_2). Under these conditions, ventilatory LTF (gradual increase of minute ventilation during recovery) was clearly expressed in P10 rats but not in P1 and P4. In a second series of experiments, rat pups were exposed to CIH during the first 10 postnatal days (6 brief cyclic exposures at 5% O_2 every 6 min followed by 1 h under normoxia, 24 h a day). Compared with P10 control rats, CIH enhanced hypoxic ventilatory response (estimated during the hypoxic cycles) specifically in male rat pups. Ventilatory LTF was drastically reduced in P10 rats exposed to CIH, which was associated with higher apnea frequency during recovery. We conclude that CIH from birth enhances hypoxic chemoreflexand disrupts LTF development, thus likely contributing to increase apnea frequency.
收起
摘要 :
Abstract The purpose of this study was to determine whether there are sex differences in the cardiorespiratory and sympathetic neurocirculatory responses to central, peripheral, and combined central and peripheral chemoreflex acti...
展开
Abstract The purpose of this study was to determine whether there are sex differences in the cardiorespiratory and sympathetic neurocirculatory responses to central, peripheral, and combined central and peripheral chemoreflex activation. Ten women (29?±?6 years, 22.8?±?2.4?kg/m2: mean?±?SD) and 10 men (30?±?7 years, 24.8?±?3.2?kg/m2) undertook randomized 5?min breathing trials of: room air (eucapnia), isocapnic hypoxia (10% oxygen (O2); peripheral chemoreflex activation), hypercapnic hyperoxia (7% carbon dioxide (CO2), 50% O2; central chemoreflex activation) and hypercapnic hypoxia (7% CO2, 10% O2; central and peripheral chemoreflex activation). Control trials of isocapnic hyperoxia (peripheral chemoreflex inhibition) and hypocapnic hyperoxia (central and peripheral chemoreflex inhibition) were also included. Muscle sympathetic nerve activity (MSNA; microneurography), mean arterial pressure (MAP; finger photoplethysmography) and minute ventilation (V?$\dot{\rm{V}}$E; pneumotachometer) were measured. Total MSNA (P?=?1.000 and P?=?0.616), MAP (P?=?0.265) and V?$\dot{\rm{V}}$E (P?=?0.587 and P?=?0.472) were not different in men and women during eucapnia and during isocapnic hypoxia. Women exhibited attenuated increases in V?$\dot{\rm{V}}$E during hypercapnic hyperoxia (27.3?±?6.3 vs. 39.5?±?7.5?l/min, P?收起
摘要 :
Stimulation of peripheral chemoreceptors by acute hypoxia causes an increase in minute ventilation (VI), heart rate (HR) and arterial blood pressure (BP). However, the contribution of particular chemosensory areas, such as carotid...
展开
Stimulation of peripheral chemoreceptors by acute hypoxia causes an increase in minute ventilation (VI), heart rate (HR) and arterial blood pressure (BP). However, the contribution of particular chemosensory areas, such as carotid (CB) vs. aortic bodies, to this response in humans remains unknown. We performed a blinded, randomized and placebo-controlled study in 11 conscious patients (nine men, two women) undergoing common carotid artery angiography. Doses of adenosine ranging from 4 to 512g or placebo solution of a matching volume were administered in randomized order via a diagnostic catheter located in a common carotid artery. Separately, ventilatory and haemodynamic responses to systemic hypoxia were also assessed. Direct excitation of a CB with intra-arterial adenosine increased VI, systolic BP, mean BP and decreased HR. No responses in these variables were seen after injections of placebo. The magnitude of the ventilatory and haemodynamic responses depended on both the dose of adenosine used and on the level of chemosensitivity as determined by the ventilatory response to hypoxia. Percutaneous radiofrequency ablation of the CB abolished the adenosine evoked respiratory response and partially depressed the cardiovascular response in one participant. The results of the present study confirm the excitatory role of purines in CB physiology in humans and suggest that adenosine may be used for selective stimulation and assessment of CB activity. The trial is registered at ClinicalTrials.gov NCT01939912.
收起
摘要 :
Peripheral vis-cerosensory afferent signals are transmitted to the nucleus tractus solitarii (nTS) via release of glutamate. Following release, glutamate is removed from the extrasynaptic and synaptic cleft via excitatory amino ac...
展开
Peripheral vis-cerosensory afferent signals are transmitted to the nucleus tractus solitarii (nTS) via release of glutamate. Following release, glutamate is removed from the extrasynaptic and synaptic cleft via excitatory amino acid transporters (EAATs), thus limiting glutamate receptor activation or over activation, and maintaining its working range. We have shown that EAAT block with the antagonist threo-beta-benzyloxyaspartic acid (TBOA) depolarized nTS neurons and increased spontaneous excitatory postsynaptic current (sEPSC) frequency yet reduced the amplitude of afferent (TS)-evoked EPSCs (TS-EPSCs). Interestingly, chronic intermittent hypoxia (CIH), a model of obstructive sleep apnea (OSA), produces similar synaptic responses as EAAT block. We hypothesized EAAT expression or function are downregulated after CIH, and this reduction in glutamate removal contributes to the observed neurophysiological responses. To test this hypothesis. we used brain slice electrophysiology and imaging of glutamate release and TS-afferent Ca2+ to compare nTS properties of rats exposed to 10 days of normoxia (Norm; 21%O-2) or CIH. Results show that EAAT blockade with (3S)-3-[[3-[[4-(trifluoromethyl)benzoyl]-amino]phenyl]methoxy]-L-aspartic acid (TFB-TBOA) in Norm caused neuronal depolarization, generation of an inward current, and increased spontaneous synaptic activity. The latter augmentation was eliminated by inclusion of tetrodotoxin in the perfusate. TS stimulation during TFB-TBOA also elevated extracellular glutamate and decreased presynaptic Ca2- and TS-EPSC amplitude. In CIH. the effects of EAAT block are eliminated or attenuated. CIH reduced EAAT expression in nTS, which may contribute to the attenuated function seen in this condition. Therefore, CIH reduces EAAT influence on synaptic and neuronal activity. which may lead to the physiological consequences seen in OSA and CIH.
收起
摘要 :
Aim: Although periaqueductal grey matter activation is known to elicit respiratory and cardiovascular responses, the role of this midbrain area in the compensatory responses to hypoxia is still unknown. To test the participation o...
展开
Aim: Although periaqueductal grey matter activation is known to elicit respiratory and cardiovascular responses, the role of this midbrain area in the compensatory responses to hypoxia is still unknown. To test the participation of the periaqueductal grey matter in cardiorespiratory and thermal responses to hypoxia in adult male Wistar rats, we performed a chemical lesion of the dorsolateral/dorsomedial or the ventrolateral/lateral periaqueductal grey matter using ibotenic acid. Methods: Pulmonary ventilation, mean arterial pressure, heart rate and body temperature were measured in unanaesthetized rats during normoxic and hypoxic exposure (5, 15, 30 min, 7% O2). Results: An ibotenic acid lesion of the dorsolateral/dorsomedial periaqueductal grey matter caused a higher increase in pulmonary ventilation (67.1%, 1730 ± 282.5 mL kg-1 min-1) compared to the Sham group (991.4 ± 194 mL kg-1 min-1) after 15 min in hypoxia, whereas for the ventrolateral/Lateral periaqueductal grey matter lesion, no differences were observed between groups. Mean arterial pressure, heart rate and body temperature were not affected by a dorsolateral/dorsomedial or ventrolateral/lateral periaqueductal grey matter lesion. Conclusion: Middle to caudal portions of the dorsolateral/dorsomedial periaqueductal grey matter neurones modulate the hypoxic ventilatory response, exerting an inhibitory modulation during low O2 situations. In addition, the middle to caudal portions of the dorsolateral/dorsomedial or ventrolateral/lateral periaqueductal grey matter do not appear to exert a tonic role on cardiovascular or thermal parameters during normoxic and hypoxic conditions.
收起
摘要 :
Electrical stimulation of the carotid baroreflex has been thoroughly investigated for treating drug-resistant hypertension in humans. However, a previous study from our laboratory, performed in conscious rats, has demonstrated tha...
展开
Electrical stimulation of the carotid baroreflex has been thoroughly investigated for treating drug-resistant hypertension in humans. However, a previous study from our laboratory, performed in conscious rats, has demonstrated that electrical stimulation of the carotid sinus/nerve (CS) activated both the carotid baroreflex as well as the carotid chemoreflex, resulting in hypotension. Additionally, we also demonstrated that the carotid chemoreceptor deactivation potentiated this hypotensive response. Therefore, to further investigate this carotid baroreflex/chemoreflex interaction, besides the hemodynamic responses, we evaluated the respiratory responses to the electrical stimulation of the CS in both intact (CONT) and carotid chemoreceptors deactivated (CHEMO-X) conscious rats. CONT rats showed increased ventilation in response to electrical stimulation of the CS as measured by the respiratory frequency (fR), tidal volume (V-T) and minute ventilation (V-E), suggesting a carotid chemoreflex activation. The carotid chemoreceptor deactivation abolished all respiratory responses to the electrical stimulation of the CS. Regarding the hemodynamic responses, the electrical stimulation of the CS caused hypotensive responses in CONT rats, which were potentiated by the carotid chemoreceptors deactivation. Heart rate (HR) responses did not differ between groups. In conclusion, the present study showed that the electrical stimulation of the CS, in conscious rats, activates both the carotid baroreflex and the carotid chemoreflex driving an increase in ventilation and a decrease in AP. These findings further contribute to our understanding of the electrical stimulation of CS.
收起
原文获取