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Relative responses of aortic body and carotid body chemoreceptors to carboxyhemoglobinemia
Abstract
The effects of carbon monoxide inhalation and of consequent carboxyhemoglobinemia (HbCO) on the discharge rates of aortic body and carotid body chemoreceptor afferents were investigated in 18 anesthetized cats. In 10 experiments both aortic and carotid chemoreceptor activities were monitored simultaneously. Carbon monoxide inhalation during normoxia always stimulated aortic chemoreceptors before carotid chemoreceptors, and the steady-state response of aortic chemoreceptors to HbCO was greater than that of most carotid chemoreceptors. Only 2 of the 18 carotid chemoreceptor fibers tested showed a distinct increase in activity in response to moderate increases in HbCO%. Thus, oxyhemoglobin contributed substantially to maintain tissue PO2 of all aortic chemoreceptors and of a few carotid chemoreceptors. Hyperoxia diminished the response of both aortic and carotid chemoreceptors to HbCO, indicating a lowered tissue PO2 as the stimulus source. We hypothesize that the aortic bodies have a much lower perfusion relative to their O2 utilization compared to the carotid bodies. As a consequence, the aortic chemoreceptors are able to act as a sensitive monitor of O2 delivery and to generate a circulatory chemoreflex for O2 homeostasis. carotid chemoreceptors monitor O2 tension and initiate strong reflex effects on the level of ventilation.
... While the function of the ABs remains controversial, Lahiri and co-workers, based on experiments performed in cats >30 years ago, proposed that AB chemoreceptors monitor circulatory O 2 content and, to a lesser extent, arterial P O 2 , eliciting adaptive cardiovascular reflexes in response to reductions in O 2 delivery to the tissues (Hatcher et al. 1978;Lahiri et al. 1980aLahiri et al. ,b, 1981. In support of this hypothesis, stimuli that reduced arterial O 2 content while maintaining normal arterial P O 2 and pH, such as anaemia, hypotension and carboxyhemoglobinaemia, excited AB chemoafferents (in the aortic nerve) but had little or no effect on CB chemoafferents (Hatcher et al. 1978;Lahiri et al. 1980aLahiri et al. , 1981. As stimuli that reduced O 2 flow to the tissues activated AB but not CB chemoreceptors, Lahiri et al. (1981) postulated that oxygenated haemoglobin must contribute to the tissue P O 2 in the AB and not in the CB. ...
... In support of this hypothesis, stimuli that reduced arterial O 2 content while maintaining normal arterial P O 2 and pH, such as anaemia, hypotension and carboxyhemoglobinaemia, excited AB chemoafferents (in the aortic nerve) but had little or no effect on CB chemoafferents (Hatcher et al. 1978;Lahiri et al. 1980aLahiri et al. , 1981. As stimuli that reduced O 2 flow to the tissues activated AB but not CB chemoreceptors, Lahiri et al. (1981) postulated that oxygenated haemoglobin must contribute to the tissue P O 2 in the AB and not in the CB. In fact, the CB is known to have a very high blood flow per unit volume (Daly et al. 1954), and this might provide a large safety margin against stimuli that reduce O 2 delivery. ...
... In fact, the CB is known to have a very high blood flow per unit volume (Daly et al. 1954), and this might provide a large safety margin against stimuli that reduce O 2 delivery. In contrast, the blood flow in the AB is estimated to be approximately one-sixth of that in the CB (Lahiri et al. 1981), rendering it very sensitive to reductions in O 2 content. ...
New Findings
What is the central question of this study?
How do aortic bodies monitor blood O 2 content? We investigated whether ATP, known to be released from red blood cells during hypoxia, could contribute via interactions with local neurons.
What is the main finding and its importance?
In dissociated aortic body cultures from the vagus and recurrent laryngeal nerves, some local neurons expressed functional P2X2/3 purinoceptors and were electrically coupled; there was also the potential for cholinergic neurotransmission. Large molecules, such as Evans Blue, had easy access to local neurons via the circulation. We hypothesize that sensing of low blood O 2 content may involve ATP release from red blood cells, leading to stimulation of local ‘sensory’ aortic body neurons.
Aortic bodies are arterial chemoreceptors presumed to monitor blood O 2 content by unknown mechanisms, in contrast to their well‐studied carotid body counterparts, which monitor and /pH. We recently showed that rat aortic body chemoreceptors (type I cells), located at the left vagus–recurrent laryngeal nerve bifurcation, responded to and /pH in a manner similar to carotid body type I cells. These aortic bodies are uniquely associated with a group of local neurons, which are also sensitive to these stimuli. Here, we hypothesized that these local neurons may contribute to monitoring blood O 2 content. During perforated patch recordings, ATP, known to be released from (carotid body) type I cells and red blood cells during hypoxia, induced inward currents and excited ∼45% of local neurons (EC 50 ∼1 μ m ), mainly via heteromeric P2X2/3 purinoceptors. While ATP also induced a rise in intracellular [Ca ²⁺ ] in a subpopulation of these neurons, almost all of them responded to nicotinic cholinergic agonists. During paired recordings, several juxtaposed neurons showed strong bidirectional electrical coupling, suggesting a local co‐ordination of electrical activity. Perfusion with Evans Blue dye resulted in labelling of aortic body paraganglia, suggesting they have ready access to circulatory factors, e.g. ATP released from red blood cells during hypoxia. When combined with confocal immunofluorescence, the dye‐labelled regions coincided with areas containing tyrosine hydroxylase‐positive type I cell clusters and P2X2‐positive nerve endings. We propose a working model whereby local neurons, red blood cells, ATP signalling and low blood flow contribute to the unique ability of the aortic body to monitor blood O 2 content.
... This may simply be due to the naturally small a-v O 2 content difference across the carotid body which would ensure that the a-v Po 2 difference was correspondingly small and perhaps even less than 4 mmHg (187, 237) meaning that a substantial change in the blood O 2 capacity would be required to observe any effect on carotid body tissue Po 2 . Thus, inmost but not all cases, (498), the carotid chemoreceptor afferent discharge frequency remains unchanged by decreasing O 2 content, induced either by hemodilution (74) or by carbon monoxide (CO) poisoning of blood hemoglobin (230). HbCO needs to be > 20% before an increase in discharge is noted but even up to 50% HbCO (498), the effect is small and an explanation for this lack of excitation by HbCO may lie with the relatively high blood flow of the carotid body and thus its intrinsic inability to sense O 2 delivery per se. ...
... In marked contrast, the intrathoracic, aortic chemoreceptors are believed to be sensors of arterial O 2 content, increasing their afferent discharge significantly in vivo in an exponentiallike fashion during an experimental protocol of graded increases in blood HbCO, induced by inhalation of sublethal doses of CO (346,498). Whilst the anemia-induced increased discharge from aortic chemoreceptors was not associated with a ventilatory chemoreflex response, variations in cardiovascular parameters, most notably blood volume and red blood cell count as well as systemic vascular resistance, were noted (182). ...
... Blood flow through aortic chemoreceptors has not been measured but the anatomical and anecdotal evidence seems to indicate that it is little likely to be much different from the excess to metabolic requirement observed in carotid body blood flow, with blood being supplied by adjacent large arteries to a lobular, highly vascular tissue and with the color of the venous blood draining the aortic bodies of cats being described as arterial by Howe in his 1957 Ph.D. thesis, as described by De Burgh Daly (186). However, hyperoxia reduced the aortic chemoreceptor discharge induced by HbCO (498), which might indicate that the stimulus for both aortic and carotid chemoreceptors is most likely a reduced tissue Po 2 . The possibility remains, however, that these two organs represent evolutionary different systems with their anatomical positions determining their precise cardiovascular or ventilatory function (582). ...
The discovery of the sensory nature of the carotid body dates back to the beginning of the 20th century. Following these seminal discoveries, research into carotid body mechanisms moved forward progressively through the 20th century, with many descriptions of the ultrastructure of the organ and stimulus-response measurements at the level of the whole organ. The later part of 20th century witnessed the first descriptions of the cellular responses and electrophysiology of isolated and cultured type I and type II cells, and there now exist a number of testable hypotheses of chemotransduction. The goal of this article is to provide a comprehensive review of current concepts on sensory transduction and transmission of the hypoxic stimulus at the carotid body with an emphasis on integrating cellular mechanisms with the whole organ responses and highlighting the gaps or discrepancies in our knowledge. It is increasingly evident that in addition to hypoxia, the carotid body responds to a wide variety of blood-borne stimuli, including reduced glucose and immune-related cytokines and we therefore also consider the evidence for a polymodal function of the carotid body and its implications. It is clear that the sensory function of the carotid body exhibits considerable plasticity in response to the chronic perturbations in environmental O2 that is associated with many physiological and pathological conditions. The mechanisms and consequences of carotid body plasticity in health and disease are discussed in the final sections of this article. © 2012 American Physiological Society. Compr Physiol 2:141-219, 2012.
... By contrast, another group of peripheral chemoreceptors known as the aortic bodies (ABs) has been poorly studied, and only recently has their cellular physiology been investigated . These ABs are scattered diffusely along the thoracic and cervical vagus nerve and its branches, and are thought to act as 'O 2 -content' rather than 'P O 2 ' sensors, eliciting primarily cardiovascular reflexes (Comroe, 1939;Lahiri et al. 1981). While there is a wealth of information on potential mechanisms by which the CB senses P O 2 (Buckler, 2007;Peers et al. 2010), and the role of neurotransmitters in signal processing (Nurse, 2010;, virtually nothing is known about the mechanisms underlying the ability of ABs to monitor O 2 content. ...
... From the time ABs were first considered 'O 2 -content' sensors, a role for red blood cells (RBCs) was implicated (Lahiri et al. 1981). Because of their low blood flow, ABs were thought to depend on O 2 carried by haemoglobin (Hb) to satisfy their energy demands (Lahiri et al. 1981). ...
... From the time ABs were first considered 'O 2 -content' sensors, a role for red blood cells (RBCs) was implicated (Lahiri et al. 1981). Because of their low blood flow, ABs were thought to depend on O 2 carried by haemoglobin (Hb) to satisfy their energy demands (Lahiri et al. 1981). In view of the emerging role of the RBCs as O 2 sensors, and the evidence that hypoxia evokes ATP release from RBCs (Ellsworth et al. 1995), it may well be that these cells play a direct role in AB chemosensing. ...
In mammals, peripheral arterial chemoreceptors monitor blood chemicals (e.g. O(2), CO(2), H(+), glucose) and maintain homeostasis via initiation of respiratory and cardiovascular reflexes. Whereas chemoreceptors in the carotid bodies (CBs), located bilaterally at the carotid bifurcation, control primarily respiratory functions, those in the more diffusely- distributed aortic bodies (ABs) are thought to regulate mainly cardiovascular functions. Functionally, CBs sense partial pressure of O(2) (PO(2)), whereas ABs are considered sensors of O(2) content. How these organs, with essentially a similar complement of chemoreceptor cells, differentially process these two different types of signals remains enigmatic. Here, we review evidence that implicates ATP as a central mediator during information processing in the CB. Recent data allow an integrative view concerning its interactions at purinergic P2X and P2Y receptors within the chemosensory complex that contains elements of a "quadripartite synapse". We also discuss recent studies on the cellular physiology of ABs located near the aortic arch, as well as immunohistochemical evidence suggesting the presence of pathways for P2X receptor signaling. Finally, we present a hypothetical "quadripartite model" to explain how ATP, released from red blood cells during hypoxia, could contribute to the ability of ABs to sense O(2) content.
... For example, CBs located bilaterally near the carotid artery bifurcations are highly perfused and sense Pa O 2 (282). In contrast, aortic bodies are diffusely located, receive much less blood flow per gram of tissue, and are thought to functionally sense primarily arterial O 2 content (56, 197,278,387). Activation of CB chemoreceptors markedly increases ventilation, whereas the influence of aortic chemoreceptors is minimal (282). As discussed above, during apnea or in the absence of changes in ventilation, CB chemoreceptor activation decreases heart rate whereas aortic chemoreceptor activation increases heart rate and myocardial contractility. ...
... The unique ability of aortic chemoreceptors to sense decreases in arterial O 2 content (56, 278) and evoke reflex increases in heart rate and myocardial contractility may provide a means to restore O 2 delivery to peripheral tissues. Carboxyhemoglobinemia and anemia, conditions in which arterial O 2 content is reduced (and arterial PO 2 is approximately normal), have been shown to preferentially activate aortic body chemoreceptors (278,387). Although it is established that activation of aortic body chemoreceptors evokes reflex changes in cardiovascular function with little or no effect on ventilation, the mechanisms integrating CB and aortic chemoreceptor, lung inflation, and baroreceptor inputs during physiological and pathophysiological challenges are poorly understood and in need of further investigation. ...
The carotid body (CB) is the main peripheral chemoreceptor for arterial respiratory gases O 2 and CO 2, and pH, eliciting reflex ventilatory, cardiovascular and humoral responses to maintain homeostasis. This review examines the fundamental biology underlying CB chemoreceptor function, its contribution to integrated physiologic responses, and its role in maintaining health and potentiating disease. Emphasis will be placed on: i) Transduction mechanisms in chemoreceptor (type I) cells, highlighting the role played by the hypoxic inhibition of O 2 -dependent K ⁺ channels and mitochondrial oxidative metabolism, and their modification by intracellular molecules and other ionic channels; ii) Synaptic mechanisms linking type I cells and petrosal nerve terminals, focusing on the role played by the main proposed transmitters and modulatory gases, and the participation of glial cells in regulation of the chemosensory process; iii) Integrated reflex responses to CB activation, emphasizing that the responses differ dramatically depending on the nature of the physiological, pathological or environmental challenges, and the interactions of the chemoreceptor reflex with other reflexes in optimizing oxygen delivery to the tissues; and iv) The contribution of enhanced CB chemosensory discharge to autonomic and cardiorespiratory pathophysiology in obstructive sleep apnea, congestive heart failure, resistant hypertension and metabolic diseases, and how modulation of enhanced CB reactivity in disease conditions may attenuate pathophysiology.
... Therefore, the effect of hematocrit changes on tissue Po2 is compensated by the flow velocity changes, the result being a nearly constant tissue Po2 histogram for the whole organ. Several authors have tried to rule out the importance of the local hematocrit on chemoreceptor activity [10, 13, 14, 19]. It has been shown that most carotid body chemoreceptor fibers do not respond to a moderate decrease in Oz content of the arterial blood, but that aortic chemoreceptors do [12, 19]. ...
... Several authors have tried to rule out the importance of the local hematocrit on chemoreceptor activity [10, 13, 14, 19]. It has been shown that most carotid body chemoreceptor fibers do not respond to a moderate decrease in Oz content of the arterial blood, but that aortic chemoreceptors do [12, 19]. In a more detailed study Lahiri [J8] came to the conclusion, that in aortic body circulation O~ supply is critical and, therefore, the chemoreceptors are sensitive to 02 transport capacity, whereas carotid body chemoreceptors are not, presumably because of a large blood flow. ...
The
$P_{O_2 }$
histogram of the carotid body tissue was calculated on the basis of a microscopical serial reconstruction, published physiological data, and a mathematical model. The calculation was made for glomoid as the subunit of the carotid body and the total organ by varying the following parameters: arterial
$P_{O_2 }$
, oxygen consumption, hematocrit, diameter of the vessels, perfusion pressure, and capillary length. The results provide explanations for differences in the literature about the tissue
$P_{O_2 }$
distribution in the cat carotid body. Differences in the capillary length of the carotid bodies seem to be the main reason for different
$P_{O_2 }$
histograms. Furthermore, it is shown that the local flow velocities in the carotid body are in the range of local flow velocities known from other organs.
... 2.6.1. Background studies (Fitzgerald, et al., 1979;Fitzgerald and Traystman, 1980;Lahiri, et al.,1981) showed that both carotid bodies and aortic bodies increased their neural output to the nucleus tractus solitarius (NTS) in response to lowered partial pressures of oxygen in the arterial blood (P a O 2 ); this also lowered arterial oxygen saturation (S a O 2 ). However, the carotid bodies (cbs) did not respond to a lowering of S a O 2 with carbon monoxide, whereas the aortic bodies (abs) did respond with increased neural output. ...
... According to previous studies in both dog and cat, we (Dehghani and Fitzgerald, 1977;Fitzgerald and Traystman,1980) and others (Lahiri, et al., 1981) have found the reduction in P a O 2 stimulates both cbs and abs whereas reductions in S a O 2 due to CO stimulated only the abs. This condition was assumed to exist in the present study. ...
This study aimed to dissect the roles played by the autonomic interoreceptors, the carotid bodies (cbs) and the aortic bodies (abs) on the vascular resistances of several organs in anesthetized, paralyzed, artificially ventilated cats challenged by systemic hypoxemia. Two 15min challenges stimulated each of 5 animals in two different groups: (1) in the intact group hypoxic hypoxia (10% O2 in N2; HH) stimulated both abs and cbs, increasing neural output to the nucleus tractus solitarius (NTS); (2) in this group carbon monoxide hypoxia (30% O2 in N2 with the addition of CO; COH) stimulated only the abs, increasing neural output to the NTS. (3) In the second group in which their bilateral aortic depressor nerves had been transected only the cbs increased neural output to the NTS during the HH challenge; (4) in this aortic body resected group during COH neither abs nor cbs increased neural traffic to the NTS. CO and 10% O2 reduced Hb saturation to the same level. With the use of radiolabeled microspheres blood flow was measured in a variety of organs. Organ vascular resistance was calculated by dividing the aortic pressure by that organ's blood flow. The spleen and pancreas revealed a vasoconstriction in the face of systemic hypoxemia, thought to be sympathetic nervous system (SNS)-mediated. The adrenals and the eyes vasodilated only when cbs were stimulated. Vasodilation in the heart and diaphragm showed no effect of chemoreceptor stimulated increase in SNS output. Different chemoreceptor involvement had different effects on the organs.
... Examination of humans with high Hb-O 2 affinity provides support for low P O 2 being a strong stimulus in the hypoxic ventilatory response, rather than arterial O 2 saturation or content (Hebbel et al., 1977;Rossoff et al., 1980;Dominelli et al., 2019). Some evidence suggests that aortic chemosensors sense changes in arterial O 2 content and heart rate is adjusted accordingly (Lugliani et al., 1971;Wasserman, 1978;Lahiri et al., 1980Lahiri et al., , 1981. Therefore, the lower heart rate during hypoxia among humans with high Hb-O 2 affinity compared to controls may be caused by decreased sensory stimulus of the aortic chemosensors . ...
Humans elicit a robust series of physiological responses to maintain adequate oxygen delivery during hypoxia, including a transient reduction in hemoglobin-oxygen (Hb-O2) affinity. However, high Hb-O2 affinity has been identified as a beneficial adaptation in several species that have been exposed to high altitude for generations. The observed differences in Hb-O2 affinity between humans and species adapted to high altitude pose a central question: is higher or lower Hb-O2 affinity in humans more advantageous when O2 availability is limited? Humans with genetic mutations in hemoglobin structure resulting in high Hb-O2 affinity have shown attenuated cardiorespiratory adjustments during hypoxia both at rest and during exercise, providing unique insight into this central question. Therefore, the purpose of this review is to examine the influence of high Hb-O2 affinity during hypoxia through comparison of cardiovascular and respiratory adjustments elicited by humans with high Hb-O2 affinity compared to those with normal Hb-O2 affinity.
... Sympathetic stimulation of the central nervous system initiates multiple compensatory mechanisms, including increased ventilation and heart rate, but also affects cells by increasing brain glucose uptake and oxygen usage (Whipp and Wasserman 1980;Dienel and Cruz 2016;Joyner et al. 2018). Similar activation may not be seen from CO exposure; for example, carotid or aortic chemoreceptors are not engaged by moderate CO stimulation (Duke et al. 1952;Lahiri et al. 1981). In addition, exposure to CO resulted in a net increase in cerebral oxygen delivery (7.8%), which would ensure normal oxygen pressure in the cells, which may explain the missing chemoreceptor stimulation from hypoxia in the CO group. ...
Exposure to moderate hypoxia in humans leads to cerebral lactate production, which occurs even when the cerebral metabolic rate of oxygen (CMRO2) is unaffected. We searched for the mechanism of this lactate production by testing the hypothesis of upregulation of cerebral glycolysis mediated by hypoxic sensing. Describing the pathways counteracting brain hypoxia could help us understand brain diseases associated with hypoxia.
A total of 65 subjects participated in this study: 30 subjects were exposed to poikilocapnic hypoxia, 14 were exposed to isocapnic hypoxia, and 21 were exposed to carbon monoxide (CO). Using this setup, we examined whether lactate production reacts to an overall reduction in arterial oxygen concentration or solely to reduced arterial oxygen partial pressure. We measured cerebral blood flow (CBF), CMRO2, and lactate concentrations by magnetic resonance imaging and spectroscopy.
CBF increased (P < 10−4), whereas the CMRO2 remained unaffected (P > 0.076) in all groups, as expected. Lactate increased in groups inhaling hypoxic air (poikilocapnic hypoxia: $0.0136\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}_{\mathrm{a}}{\mathrm{O}}_2}$, P < 10−6; isocapnic hypoxia: $0.0142\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}_{\mathrm{a}}{\mathrm{O}}_2}$, P = 0.003) but was unaffected by CO (P = 0.36).
Lactate production was not associated with reduced CMRO2. These results point toward a mechanism of lactate production by upregulation of glycolysis mediated by sensing a reduced arterial oxygen pressure. The released lactate may act as a signaling molecule engaged in vasodilation.
... Indeed, carotid artery occlusion and therefore lower carotid body blood flow has been shown to increase the sensitivity of the hypoxic chemoreflex response in animals 16 . Further, reductions of blood pressure have been noted to increase aortic and carotid chemoreceptor firing in animal models [17][18][19] . These studies in animal models suggest that increased carotid body blood flow may decrease the sensitivity of the hypoxic chemoreflex in humans. ...
Head-down bed rest (HDBR) has previously been shown to alter cerebrovascular and autonomic control. Previous work found that sustained HDBR (≥ 20 days) attenuates the hypercapnic ventilatory response (HCVR); however, little is known about shorter-term effects of HDBR nor the influence of HDBR on the hypoxic ventilatory response (HVR). We investigated the effect of 4-h HDBR on HCVR and HVR and hypothesized attenuated ventilatory responses due to greater carotid and brain blood flow. Cardiorespiratory responses of young men (n = 11) and women (n = 3) to 5% CO 2 or 10% O 2 before and after 4-h HDBR were examined. HDBR resulted in lower HR, lower cardiac output index, lower common carotid artery flow, higher SpO 2 , and higher pulse wave velocity. After HDBR, tidal volume and ventilation responses to 5% CO 2 were enhanced (all P < 0.05), yet no other changes in cardiorespiratory variables were evident. There was no influence of HDBR on the cardiorespiratory responses to hypoxia (all P > 0.05). Short-duration HDBR does not alter the HVR, yet enhances the HCVR, which we hypothesize is a consequence of cephalic CO 2 accumulation from cerebral congestion.
... This would suggest there are tissues that are sensitive to Ca O 2 or the associated cellular effects and may be involved in HR regulation. Evidence for this come from studies finding that while the carotid chemosensors only respond to oxygen tensions, the aortic chemosensors also respond to Ca O 2 (7,15,16,23). In line with our findings, others have also demonstrated that those with HAH have a blunted increase in heart rate in response to acute (9) and chronic (8) hypoxia. ...
... La première réponse à l'hypoxie est la réponse ventilatoire (Schoene 1997). Afin de limiter la chute de la PaO 2 due à l'hypoxie, une hyperventilation reflexe se met en place (Dempsey et al. 1977;Rice et al. 1999 (Lahiri et al. 1981). ...
A l’heure actuelle aucun consensus n’existe sur l’utilisation des substrats énergétiques lors d’un exercice en altitude. Certaines études ont montré une utilisation accrue des glucides en altitude comparée à la plaine mais les intensités d’exercices utilisées sont discutables et l’utilisation de méthodes biochimiques traditionnelles ont permis de doser qu’un nombre restreint de molécules. Aujourd’hui grâce à la métabolomique, il est possible d’analyser les variations d’un grand nombre de métabolites simultanément. Le but de cette thèse est d’étudier l’incidence de l’altitude modérée sur l’utilisation des substrats énergétiques à l’effort à l’aide de la métabolomique par résonnance magnétique nucléaire du proton. Des échantillons de plasmas et d’urines ont été collectés lors d’exercices d’endurance en plaine et en altitude modérée chez des sujets non acclimatés. Nos premiers résultats, dans les plasmas, ont montré une baisse de la glycémie et une utilisation accrue des acides aminés ramifiés entre avant et après un exercice d’endurance en altitude, ce qui n’a pas été observé en plaine. Ces résultats ont ensuite été confirmé lors d’un exercice d’endurance jusqu’à épuisement. De plus, nous avons montré que l’utilisation des urines permet de mettre en avant les résultats obtenus dans les plasmas, ce qui est très encourageant pour la compréhension des adaptations métaboliques en altitude par des méthodes non invasives. Pour finir, nous avons utilisé une méthode statistique innovante appelée « analyse en composantes communes et poids spécifiques ». Les résultats ont permis d’observer les variabilités communes entre les paramètres physiologiques mesurés et les variations des métabolites plasmatiques.
... Consequently, the aortic body can act as a sensor of reduced oxygen delivery as a result of either low PO 2 or low haematocrit (unlike the carotid body). 55 At local tissue level, oxygen delivery can be adjusted to changes in local oxygen consumption. For example, exercising skeletal muscle receives a greater proportion of total cardiac output than resting skeletal muscle. ...
... Carotid bodies act as sensitive monitors of arterial O 2 tension (PaO 2 ), whereas aortic chemoreceptors mainly monitor arterial O 2 content (CaO 2 ). So, carotid bodies evoke stronger respiratory responses than aortic chemoreceptors [16]. A study in humans exposed to hypoxia demonstrated that carotid bodies are chiefly responsible for ventilatory and vascular response, whereas aortic chemoreceptors mainly mediated the tachycardic response [17]. ...
High-altitude exposure has been well recognized as a hypoxia exposure that significantly affects cardiovascular function. However, the pathophysiologic adaptation of cardiovascular system to high-altitude hypoxia (HAH) varies remarkably. It may depend on the exposed time and oxygen partial pressure in the altitude place. In short-term HAH, cardiovascular adaptation is mainly characterized by functional alteration, including cardiac functional adjustments, pulmonary vascular constriction, transient pulmonary hypertension, and changes in cerebral blood flow (CBF). These changes may be explained mainly by ventilatory acclimatization and variation of autonomic nervous activity. In long-term HAH, cardiovascular adaptation is mainly characterized by both functional and structural alterations. These changes include right ventricle (RV) hypertrophy, persistent pulmonary hypertension, lower CBF and reduced uteroplacental and fetal volumetric blood flows.
... The carotid bodies are highly vascular and are the major chemoreceptor site for hypoxia, sensing PaO 2 , but not oxyhemoglobin saturation or oxygen content. The carotid bodies are also very sensitive to changes in PCO 2 and [H þ ]. [13][14][15] The carotid bodies' hypoxic response is curvilinear, increasing in slope once PaO 2 drops to < 60 mm Hg. The steeper slope leads to higher ventilation for a given change in PaO 2 and hence more pronounced hypocapnia. ...
Control of ventilation occurs at different levels of the respiratory system via a negative feedback system that allows for precise regulation of levels of arterial carbon dioxide and oxygen. Mechanisms for ventilatory instability leading to sleep disordered breathing include changes in respiratory rhythm genesis and chemoresponsiveness to hypoxia and hypercapnia, cerebrovascular reactivity, abnormal chest wall and airway reflexes, and sleep state oscillations. One can potentially stabilize breathing during sleep-related breathing disorders by identifying one or more of these pathophysiological mechanisms. This review describes the current concepts in ventilatory control that pertain to breathing instability during wakefulness and sleep, delineates potential avenues for alternative therapies to stabilize breathing during sleep and proposes recommendations for future research.
... L'hypoxémie déclenche une hyperventilation réflexe par stimulation des chémorécepteurs périphériques (corpuscules carotidiens et aortiques) (Heymans et Bouckaert, 1930). Les chémorécepteurs carotidiens sont sensibles aux changement de PO 2 tandis que les chémorécepteurs aortiques sont sensibles aux changements de SaO 2 (Lahiri et al., 1981). Ces récepteurs réagissent en augmentant la fréquence des décharges le long du neuvième nerf crânien qui conduit les impulsions directement au centre respiratoire qui régulent la V̇E au niveau central (Dempsey et Forster, 1982) (figure 8). ...
En plaine, la moitié des athlètes entrainés en endurance sont susceptibles de développer une hypoxémie induite par l’exercice (HIE). Actuellement, la pratique des sports d’endurance de montagne est en plein essor. Dans ces disciplines, les athlètes très entrainés en endurance et donc susceptibles de développer une HIE, évoluent régulièrement en altitude modérée. Ce travail s’est intéressé à l’évolution de la HIE en altitude modérée, ainsi qu’à ses conséquences et sa relation avec la modification des composantes cardio-respiratoires à l’exercice. Nos résultats indiquent que : 1) la désaturation artérielle n’est pas potentialisée en altitude aiguë chez les athlètes HIE par rapport à des athlètes non-HIE alors que les athlètes HIE ont une chute de consommation maximale d’oxygène et de fréquence cardiaque maximale plus importante, 2) les athlètes HIE développent un stress hémodynamique important associé à des réponses vasculaires pulmonaires spécifiques à l’exercice en plaine, 3) tous les athlètes présentent une limitation de la diffusion pulmonaire à l’exercice maximal en altitude aiguë et nos résultats ne permettent pas d’affirmer une limitation cardiaque plus importante chez les athlètes HIE, 4) en hypoxie chronique, la désaturation artérielle est influencée par les modalités de pratique sportive. Notre travail a permis d’établir des recommandations pour les athlètes entrainés en endurance, de plus en plus nombreux, désirant performer en altitude modérée.
... The responses of O 2 chemoreceptors to changes in arterial Co 2 have not been well studied. Mammalian aortic bodies are sensitive to moderate decreases in Co 2 independent of changes in Po 2 (Hatcher et al., 1978;Lahiri et al., 1981) whereas mammalian carotid bodies respond only to more severe changes in Co 2 (Paintal, 1967;Mills and Edwards, 1968). This has not been studied at the receptor level in any other group. ...
SYNOPSIS. Research on the sensory inputs regulating ventilation and perfusion in vertebrates has slowly moved from studies of receptor cells to studies of the receptor proteins on receptor cells involved in signal transduction. With this new emphasis and the insights gained from this work, questions arise about the significance of specific transduction mechanisms and their link to whole animal responses to various stimuli. This is illustrated in the present chapter using two examples. The first describes pulmonary mechanoreceptors in identical locations but with different orientations. As a result of the differences in their orientation, although the receptors have identical signal transduction mechanisms and identical roles in terms of the reflex effects they elicit, they respond to different stimuli at the whole animal level. The second example suggests that different populations of O2 sensitive chemoreceptors may exist that have identical signal transduction mechanisms but, because of differences in their balance of oxygen supply to demand, may respond to different stimuli at the whole animal level. The lesson to be learned from these examples is that accompanying the growing knowledge of receptor cell function at the molecular level is a growing need to integrate this knowledge with empirical observations of whole animal responses.
... The PO 2 within the glomus cells is determined by oxygen delivery (the product of blood flow and blood O 2 content) and O 2 consumption of the chemoreceptor structure. A chemoreceptor can, therefore, sense blood O 2 content if hemoglobin bound O 2 participates in O 2 delivery to the receptor (Lahiri et al. 1980Lahiri et al. , 1981). In reptiles and amphibians, the ventilatory responses to hypoxia at different temperatures are well correlated with arterial O 2 content (Glass et al. 1983) and this correlation has fostered the hypothesis that the arterial chemoreceptors in these animals are sensitive to arterial O 2 content, or alternatively hemoglobin oxygen saturation (reviewed by Boggs 1995 ). ...
... The finding that blood O 2 content appears to alter Q pu , and net shunt flows in the absence of changes in P a o 2 could be explained by the existence of an O 2 content sensitive chemoreceptor that selectively influences the cardiovascular system. In mammals, the aortic bodies respond to changes in arterial O 2 content and predominantly influence the cardiovascular system {e.g., Lahiri et al., 1981), while ventilatory responses are controlled by the Po 2 sensitive carotid bodies. The aortic bodies are believed to be sensitive to O 2 content because they are supplied with a low perfusion relative to O 2 uptake. ...
SYNOPSIS. The pulmonary and systemic circulations are not completely separated in reptiles and amphibians, so oxygen-rich blood returning from the lungs can mix with oxygen-poor blood returning from the systemic circuit (cardiac shunts). In these animals, the arterial blood gas composition is determined by both lung ventilation and the cardiac shunt. Therefore, changes in cardiac shunting patterns may participate actively in the regulation of arterial blood gases. In turtles the cardiac shunt pattern changes independently of ventilation and the cardiac R-L shunt (pulmonary bypass of systemic venous blood) is reduced under circumstances where the demands on efficient gas exchange are high (hypoxia, hypoxemia or exercise). We propose, therefore, that the size of cardiac shunts is regulated independently of ventilation and hypothesize that there exist at least two groups of peripheral chemoreceptors with different reflex roles.
... Another possibility is that the same receptors are involved in producing both hypoxic and hypercarbic ventilatory responses, but, the response to changes in CO 2 /pH is a consequence of their effects on the O 2 carrying capacity of the blood rather than on a CO 2 /pH sensing mechanism. If the ventilatory responses to hypercarbia are acting via a depression of blood oxygen carrying capacity, then the chemoreceptors that activate these reflexes must be sensitive to changes in oxygen content as is the case in the mammalian aortic body (Lahiri et al., 1981). Since the data suggest that the ventilatory responses to hypoxia arise primarily from externally-oriented receptors (Sundin et al., 1999), however, it is unlikely that these effects can be due solely to a decrease in blood oxygen content. ...
To examine the distribution and physiological role of CO2/pH-sensitive chemoreceptors in the gills of the tropical fish, traira (Hoplias malabaricus), fish were exposed to acute environmental hypercarbia (1.25, 2.5 and 5.0% CO2 in air) and subjected to injections of HCl into the ventral aorta and buccal cavity. This was done before and after selective denervation of branchial branches of the IXth and Xth cranial nerves to various gills arches. Hypercarbia produced a significant decrease in heart rate, a mild hypotension as well as increases in both ventilation rate and ventilation amplitude. The data suggest that the hypercarbic bradycardia and increase in ventilation frequency arise from receptors exclusively within the gills but present on more than the first gill arch, while extra-branchial receptors may also be involved in controlling the increase in ventilation amplitude. With the exception of a decrease in heart rate in response to HCl injected into the ventral aorta, the acid injections (internal and external) did not mimic the cardiorespiratory responses observed during hypercarbia suggesting that changes in CO2 are more important than changes in pH in producing cardiorespiratory responses. Finally, the data indicate that chemoreceptors sensitive to CO2/pH and to O2 in the gills of this species involved in producing ventilatory responses are distributed in a similar fashion, but that those involved in producing the bradycardia are not.
... Rogers, 1963; Kusakabe, 1990), and discharge frequency from the carotid nerve increases as arterial PO 2 decreases and this increase is exacerbated by increased PaCO 2 (Fig. 6; Lahiri et al., 1981a; Lahiri et al., 1981b; Van Vliet and West, 1992). Reduced blood oxygen delivery does not stimulate the carotid labyrinth (Van Vliet and West, 1992), in line with the responses in the carotid bodies of mammals (Lahiri et al., 1981b; Lee and Mattenheimer , 1964). Based on these findings, Kusakabe (2002) concluded that the amphibian carotid labyrinth corresponds to the mammalian carotid body and carotid sinus. ...
Purpose: In endovascular surgery, knowing the morphometry of the aortic arch increases the success of surgery. The aim of this study was to examine the angle and morphometry of aortic arch in Covid 19 patients and to compare these with healthy individuals to find out the effect of the disease on the vessel. Methods: A total of 120 individuals - 60 COVID 19 (30 Females, 30 Males) patients and 60 healthy (30 Females, 30 Males) individuals participated in the study. In the study, the parameters of aortic arch angle (AAA), aortic arch diameter (AAD), aortic arch (AA) branches of brachiocephalic trunk diameter (TBD), left common carotid artery diameter (ACCSD), left subclavian artery diameter (ASSD), transverse superior thoracic aperture length (ATSD-TR) and anteroposterior superior thoracic aperture length (ATSD-AP), transverse inferior thoracic aperture length (ATID-TR) and anteroposterior inferior thoracic aperture length (ATID-AP) were measured from thoracic computed tomography images. Results: As a result of the study, when female and male patients with COVID-19 were compared, ACCSD, ASSD, ATID-AP, ATID-TR values were found to be higher in favour of male patients. While Proximal AAD, TBD, ACCSD and ASSD values were higher in female patients with COVID 19 when compared with control group female patients, Proximal AAD, TBD, ACCSD, ASSD, ATSD-AP, ATSD-TR, ATID-AP, ATID-TR values were higher in male patients with COVID 19 when compared with control group male patients. When the measurements of COVID 19 and control group individuals were compared, Proximal AAD, TBD, ACCS, ASSD, ATSD-TR, ATID-AP and ATID-TR values were found to be higher in favour of COVID 19 patients. Conclusions: COVID 19 is an important disease that causes dilatation of the AA and its branches. We think that diseases that can change oxygen saturation such as COVID19 can change aortic morphology.
During hypoxic exposure, humans with high affinity hemoglobin (and compensatory polycythemia) have blunted increases in heart rate compared to healthy humans with typical oxyhemoglobin dissociation curves. This response may be associated with altered autonomic control of heart rate. Our hypothesis-generating study aimed to investigate cardiac baroreflex sensitivity and heart rate variability among nine humans with high affinity hemoglobin (6 females, O2 partial pressure at 50% SaO2 (P50) = 16±1 mmHg) compared to 12 humans with typical affinity hemoglobin (6F, P50 = 26±1 mmHg). Participants breathed normal room air for a 10-minute baseline followed by 20-minutes of isocapnic hypoxic exposure, designed to lower the arterial partial pressure O2 (PaO2) to ~50 mmHg. Beat-by-beat heart rate and arterial blood pressure were recorded. Data were averaged in five-minute periods throughout the hypoxia exposure beginning with the last five minutes of baseline in normoxia. Spontaneous cardiac baroreflex sensitivity and heart rate variability were determined using the sequence method, and time and frequency domain analyses, respectively. Cardiac baroreflex sensitivity was lower in humans with high affinity hemoglobin than controls at baseline and during isocapnic hypoxic exposure [normoxia: 7±4 vs. 16±10 ms/mmHg, hypoxia minutes 15-20: 4±3 vs. 14±11 ms/mmHg; group effect: p=0.02, high affinity hemoglobin vs. control, respectively]. Heart rate variability calculated in both the time (standard deviation of the NN Interval) and frequency (low frequency) domains were lower in humans with high affinity hemoglobin than controls (all p<0.05). Our data suggest that humans with high affinity hemoglobin may have attenuated cardiac autonomic function.
Current evidence indicates that the toxicity of carbon monoxide (CO) poisoning results from increases in ROS generation plus tissue hypoxia resulting from decreases in capillary PO 2 evoked by effects of increases in blood [carboxyhemoglobin] on the oxyhemoglobin dissociation curve. There has not been consideration of how increases in P CO could influence metabolism - blood flow coupling, a physiological mechanism that regulates the uniformity of tissue PO 2 , and alveolar ventilation - blood flow coupling, a mechanism that increases the efficiency of pulmonary O 2 uptake. Using published data I consider hypotheses that these coupling mechanisms, triggered by O 2 and CO sensors located in arterial and arteriolar vessels in the coronary and cerebral circulations, and in lung intra-lobar arteries, are disrupted during acute CO poisoning. These hypotheses are supported by calculations that show that the P CO in these vessels can reach levels during CO poisoning that would exert effects on signal transduction molecules involved in these coupling mechanisms.
The newborn ventilatory response to acute isocapnic hypoxaemia is biphasic. An initial increase in breathing (phase 1), mediated by stimulation of the peripheral chemoreceptors, is followed 1-3 minutes after the onset of hypoxia by a decline to, or to, below pre-hypoxic levels (phase 2). The mechanism(s) underlying phase 2 are not known. This thesis pursues the hypothesis that phase 2 is mediated by CNS mechanisms. First, this hypothesis was tested by investigating the effects of isocapnic hypoxia on respiratory reflexes in anaesthetized newborn rabbits. These experiments showed that (1) Phase 2 cannot be attributed to a failure in peripheral chemoreceptor function during isocapnic hypoxia. (2) Carotid chemoreflex effects on respiratory output during normoxia are inhibited during isocapnic hypoxia, even though the afferent limb of the reflex is maintained (3) Somatophrenic reflexes are not affected by isocapnic hypoxia. These findings support the idea that isocapnic hypoxia causes a centrally mediated inhibition of breathing, which is not attributable to global hypoxic depression. These findings led to the neurophysiological investigation of CNS function, in a novel in vivo decerebrate rabbit preparation. Electrical stimulation in the mesencephalon identified a discrete area (the red nucleus), and its efferents, as mediating apnoea; chemical microinjections supported the idea that cell bodies mediate an inhibition of breathing from such a locus. Furthermore, this inhibitory area was also shown to be involved in mediating the newborn biphasic ventilatory response, since the fall in ventilation was abolished by placing lesions bilaterally in the red nuclei. Pontine inhibitory influences on breathing were also demarcated by electrical stimulation and chemical microinjection, indicating that pontine structures are probably also involved directly in mediating the newborn biphasic ventilatory response. These results suggest that suprapontine CNS mechanisms play a key role in shaping the newborn biphasic ventilatory response, and that hypoxia activates these descending projections to inhibit breathing. The newborn mechanism that decreases breathing in hypoxia is considered likely to be operative in the fetus, and to account also for the adult breathing response to hypoxia. Potential cellular mechanisms for the initiation of this inhibition, and precedents for CNS mechanisms being involved in adaptive strategies to cope with hypoxia, are discussed.
This chapter discusses the physiology of normal breathing, including the metabolic and behavioral systems controlling respiration, the neurons responsible for respiratory control, the role of chemoreceptors, mechanisms of physiological and pathological central apneas, and the impact of sleep on all these processes. This chapter also briefly describes the clinical relevance of these aspects of respiratory physiology in various sleep disorders.
Recreational use of concentrated oxygen has increased. Claims have been made that hyperoxic breathing can help reduce fatigue, increase alertness, and improve attentional capacities; however, few systematic studies of these potential benefits exist. Here, we examined the effects of short‐term (15 min) hyperoxia on resting states in awake human subjects by measuring spontaneous EEG activity between normoxic and hyperoxic situations, using a within‐subject design for both eyes‐opened and eyes‐closed conditions. We also measured respiration rate, heart rate, and blood oxygen saturation levels to correlate basic physiological changes due to the hyperoxic challenge with any brain activity changes. Our results show that breathing short‐term 100% oxygen led to increased blood oxygen saturation levels, decreased heart rate, and a slight, but nonsignificant, decrease in breathing rate. Changes of brain activity were apparent, including decreases in low‐alpha (7–10 Hz), high‐alpha (10–14 Hz), beta (14–30 Hz), and gamma (30–50 Hz) frequency ranges during eyes‐opened hyperoxic conditions. During eyes‐closed hyperoxia, increases in the delta (0.5–3.5 Hz) and theta (3.5–7 Hz) frequency range were apparent together with decreases in the beta range. Hyperoxia appeared to accentuate the decrease of low alpha and gamma ranges across the eyes‐opened and eyes‐closed conditions, suggesting that it modulated brain state itself. As decreased alpha during eyes‐opened conditions has been associated with increased attentional processing and selective attention, and increased delta and theta during eyes‐closed condition are typically associated with the initiation of sleep, our results suggest a state‐specific and perhaps opposing influence of short‐term hyperoxia.
The carotid and aortic bodies are the sensory organs for monitoring arterial blood oxygen (O2) and carbon dioxide (CO2) levels. The type I cells, which are of neuronal phenotype, are the primary site of sensory transduction in the carotid and aortic bodies. Although the carotid bodies sense the reduction in partial pressure of O2, the aortic bodies are more sensitive to changes in arterial blood O2 content. Emerging evidence suggests that complex interplay among three gases—oxygen, carbon monoxide, and hydrogen sulfide—and their interaction with K+ channels and/or mitochondrial electron transport chain in type I cells is necessary for carotid body sensory nerve excitation by hypoxia. CO2 sensing by the carotid body requires changes in intracellular pH in type I cells. Available evidence, albeit limited, suggests that transduction processes similar to those identified in the carotid body also contribute to O2 and CO2 sensing by the aortic body.
The golden-mantled ground squirrel, Spermophilus lateralis, shows a brisk hypoxic ventilatory response but a blunted hypercapnic ventilatory response while euthermic at 37°C body temperature (T
B) (1). This is typical of all fossorial (burrowing) species of mammal (2). During hibernation minute ventilation and the ventilatory sensitivities of these animals to hypercapnia and hypoxia appear greatly reduced compared to euthermic values. When expressed in relative terms(∆\(\dot V\)
E/∆MCO2), CO2 sensitivity is actually increased (1,3). The ventilatory response to hypoxia, however, still remains reduced. In fact, if inspired levels of O2 are reduced slowly to as low as 1%, respiratory depression and death will occur in some species before any significant respiratory stimulation or arousal occurs (1,3). The goal of the present study was to examine whether the reduction in hypoxic sensitivity that occurs in animals in hibernation could be explained by cold (or other) inhibition of carotid body discharge.
At birth, arterial Po2 (Pao2) in the lamb rises from a fetal value of ca. 25 mm Hg towards the adult value of ca. 100 mm Hg (1), over the first few days (2). One consequence of this rise is that spontaneous carotid chemoreceptor discharge is abolished or greatly reduced for the first 2–3 postnatal days (3). After this period, spontaneous discharge returns (3) and gradually increases (4) as the Po2 stimulus-response curve for these receptors adjusts to the new Pao2. This resetting of chemosensitivity is reflected by a maturation of respiratory chemoreflexes leading to a greater ventilatory response to hypoxia with increasing postnatal age (5,6). However, a failure to reset can result in impaired respiratory control such as seen in rat pups and kittens made chronically hypoxic from birth (7,8). As inadequate respiratory control may contribute towards infant morbidity and mortality, the clinical importance of resetting is clear.
This chapter describes the influence of the peripheral arterial chemoreceptors on respiration and also examines the transduction mechanism of these receptors. It is our intention to concentrate mainly on the recent literature; readers requiring information about historical aspects, or more detailed evidence than it is possible to give in this chapter, are referred to reviews on chemoreceptors (e.g. Schmidt & Comroe, 1940; Heymans & Neil, 1958; Dejours, 1962; Anichkov & Belen’kii, 1963; Torrance, 1968; Biscoe, 1971; Eyzaguirre & Fidone, 1980) and the proceedings of recent international meetings on arterial chemoreceptors (Purves, 1975; Paintal, 1976; Acker et al, 1977; Belmonte et al, 1981).
studies of the high-altitude natives in the South American Andes focused attention for the first time on aspects of respiratory adaptation that were different from those of sojourners at the same high altitude (4, 9, 12, 28; see also 7, 14, 15). Previously it was thought that the level of adaptation in the fully acclimatized sojourners would be the same as in the native high-altitude residents (1; see also 9). To understand high-altitude adaptation, researchers at the Andean Institute of Biology in Peru compared sea-level natives and high-altitude natives in their own respective environments. Recently respiratory control has gained particular attention because of the striking observation that the adult natives of high altitude ventilate less at a given resting metabolic rate so that their partial pressure of carbon dioxide in alveolar gas (PaCO2) is higher and partial pressure of oxygen in alveolar gas (PaO2) lower (4, 13, 14). It was also established that hyperpnea of exercise was less in the high-altitude natives than in the sojourners (14, 15).
A wealth of information exists on the control and co-ordination of gas exchange in air-breathing vertebrates. Fortunately, much of this literature has been reviewed, in depth, in the last few years2. These reviews give an excellent summary of existing knowledge and, consequently, the emphasis of the present chapter has been placed on a selective review of some of the more recent advances which have been made in the field, particularly emphasizing those areas about which little is yet known but which are now ripe for further study.
This brief review addresses the regulation of cardiac output (Q) at rest and during submaximal exercise in acute and chronic hypoxia. To preserve systemic O2 delivery in acute hypoxia Q is increased by an acceleration of heart rate, whereas stroke volume (SV) remains unchanged. Tachycardia is governed by activation of carotid and aortic chemoreceptors and a concomitant reduction in arterial baroreflex activation, all balancing sympathovagal activity toward sympathetic dominance. As hypoxia extends over several days a combination of different adaptive processes restores arterial O2 content to or beyond sea level values and hence Q normalizes. The latter however occurs as a consequence of a decrease in SV whereas tachycardia persists. The diminished SV reflects a lower left ventricular end-diastolic volume which is primarily related to hypoxia-generated reduction in plasma volume. Hypoxic pulmonary vasoconstriction may contribute by increasing right ventricular afterload and thus decreasing its ejection fraction. In summary, the Q response to hypoxia is the result of a complex interplay between several physiological mechanisms. Future studies are encouraged to establish the individual contributions of the different components from an integrative perspective.
Breathing is a complex process that involves the coordinated activities of specific regions of the central nervous system, the musculature responsible for developing the force necessary to "drive" movement of air, the system of respiratory tubes through which the air is conducted and transported across, and numerous sensory structures that alter breathing patterns according to homeostatic changes. Although the mechanisms governing the act of breathing vary between mammals of different sizes and habitats, some elements (e.g., response to hyperthermia) are consistent across species. Thus, the study of the similar and divergent properties of the respiratory control system yields a greater understanding of how the process of breathing is finely tuned and integrated with the body as a whole.
As a counterpoint to the volumes of beautiful work exploring how the carotid bodies (CBs) sense and transduce stimuli into neural traffic, this study explored one organismal reflex response to such stimulation. We challenged the anesthetized, paralyzed, artificially ventilated cat with two forms of acute hypoxemia: 10 % O2/balance N2 (hypoxic hypoxia [HH] and carbon monoxide hypoxia [COH]). HH stimulates both CBs and aortic bodies (ABs), whereas COH stimulates only the ABs. Our design was to stimulate both with HH (HHint), then to stimulate only the ABs with COH (COHint); then, after aortic depressor nerve transaction, only the CBs with HH (HHabr), and finally neither with COH (COHabr). We recorded whole animal responses from Group 1 cats (e.g., cardiac output, arterial blood pressure, pulmonary arterial pressure/and vascular resistance) before and after sectioning the aortic depressor nerves. From Group 2 cats (intact) and Group 3 cats (aortic body resected) we recorded the vascular resistance in several organs (e.g., brain, heart, spleen, stomach, pancreas, adrenal glands, eyes). The HHint challenge was the most effective at keeping perfusion pressures adequate to maintain homeostasis in the face of a systemic wide hypoxemia with locally mediated vasodilation. The spleen and pancreas, however, showed a vasoconstrictive response. The adrenals and eyes showed a CB-mediated vasodilation. The ABs appeared to have a significant impact on the pulmonary vasculature as well as the stomach. Chemoreceptors via the sympathetic nervous system play the major role in this organism's response to hypoxemia.
Peripheral chemoreceptors are localised in cervical, thoracic and abdominal regions of mammals with the cervical-located, carotid bodies appearing to be the most physiologically relevant for the initiation of cardiorespiratory reflexes in response to hypoxia. These organs have a characteristic morphology and receive an arterial blood supply in excess of their metabolic requirements, which may be important for their function, and they receive an afferent and efferent innervation. Type 1 cells are believed to contain the necessary transducing elements of these chemoreceptors and are pre-synaptic to afferent nerve terminals. Type 1 cells respond to falls in the partial pressure, but possibly also the O2 content of blood, by inactivating species-dependent K channels to induce cell depolarisation, voltage-gated Ca2+ entry, neurotransmission and augmented afferent nerve discharge frequency. The identity of the protein sensor responsible for detecting hypoxia is not known with certainty but a number of candidates, including the enzymes AMPK and HO-2, have recently been proposed. In addition, these organs sense many other blood-borne, natural stimuli and are therefore most probably acting as polymodal receptors.
Amphibians exhibit cardiorespiratory responses to hypoxia and, although several oxygen-sensitive chemoreceptor sites have been identified, the specific oxygen stimulus that triggers these responses remains controversial. This study investigates whether the cardiovascular response to oxygen shortage correlates with decreased oxygen partial pressure of arterial blood (PaO2) or reduced oxygen concentration ([O2]) in toads. Toads, equipped with blood flow probes and an arterial catheter, were exposed to graded hypoxia [fraction of oxygen in the inspired air (FIO2)=0.21, 0.15, 0.10, 0.07 and 0.05] before and after reductions in arterial [O2] by isovolemic anaemia that reduced haematocrit by approximately 50%. Toads responded to hypoxia by increasing heart rate (fH) and pulmocutaneous blood flow (Q̇pc) and reducing the net cardiac right-to-left-shunt. When arterial [O2] was reduced by anaemia, the toads exhibited a similar cardiovascular response to that observed in hypoxia. While arterial CO2 partial pressure (PaCO2) decreased significantly during hypoxia, indicative of increased alveolar ventilation, anaemia did not alter PaCO2). This suggests that reductions in [O2] mediate cardiovascular adjustments, while ventilatory responses are caused by reduced PaO2.
Le contrôle de la ventilation procède d’une interaction complexe entre des efférences provenant de centres bulbaires et suprapontiques à destination des groupes musculaires ventilatoires et des afférences ventilatoires provenant de mécano- et de chémorécepteurs. La commande ainsi produite est transmise en premier lieu aux muscles dilatateurs des voies aériennes supérieures puis aux muscles thoraciques, dont le diaphragme. Cette distribution de la commande ventilatoire est modifiée face à une contrainte à l’écoulement de l’air.
Historically, and at present, carbon monoxide is a major gaseous poison responsible for widespread morbidity and mortality. From threshold to maximal nonlethal levels, a variety of cardiovascular changes occur, both immediately and in the long term, whose homeostatic function it is to renormalize tissue oxygen delivery. However, notwithstanding numerous studies over the past century, the literature remains equivocal regarding the hemodynamic responses in animals and humans, although CO hypoxia is clearly different in several respects from hypoxic hypoxia. Factors complicating interpretation of experimental findings include species, CO dose level and rate, route of CO delivery, duration, level of exertion, state of consciousness, and anesthetic agent used. Augmented cardiac output usually observed with moderate COHb may be compromised in more sever poisoning for the same reasons, such that regional or global ischemia result. The hypotension usually seen in most animal studies is thought to be a primary cause of CNS damage resulting from acute CO poisoning, yet the exact mechanism(s) remains unproven in both animals and humans, as does the way in which CO produces hypotension. This review briefly summarizes the literature relevant to the short- and long-term hemodynamic responses reported in animals and humans. It concludes by presenting an overview using data from a single species in which the most complete work has been done to date.
This chapter will discuss the transport of carbon monoxide (CO) from the environment to the tissues of the body and physiological effects on blood-borne cells and perivascular tissues. It will review the physiology of CO exchange between alveolar gas and pulmonary capillary blood, dynamics of hemoglobin transport, the effects of CO on blood elements, and the effects of CO on extravascular tissues at the capillary bed. Effects of CO from exogenous and endogenous sources on the activities of different proteins will be reviewed. Because CO binds competitively to heme-containing proteins its effects depend on CO concentration relative to alternative ligands. Therefore, some discussion is devoted to how nitric oxide and hydrogen sulfide influence CO effects. © 2011 American Physiological Society. Compr Physiol 1:421-446, 2011.
Hibernation in endotherms and ectotherms is characterized by an energy-conserving metabolic depression due to low body temperatures and poorly understood temperature-independent mechanisms. Rates of gas exchange are correspondly reduced. In hibernating mammals, ventilation falls even more than metabolic rate leading to a relative respiratory acidosis that may contribute to metabolic depression. Breathing in some mammals becomes episodic and in some small mammals significant apneic gas exchange may occur by passive diffusion via airways or skin. In ectothermic vertebrates, extrapulmonary gas exchange predominates and in reptiles and amphibians hibernating underwater accounts for all gas exchange. In aerated water diffusive exchange permits amphibians and many species of turtles to remain fully aerobic, but hypoxic conditions can challenge many of these animals. Oxygen uptake into blood in both endotherms and ectotherms is enhanced by increased affinity of hemoglobin for O2 at low temperature. Regulation of gas exchange in hibernating mammals is predominately linked to CO2/pH, and in episodic breathers, control is principally directed at the duration of the apneic period. Control in submerged hibernating ectotherms is poorly understood, although skin-diffusing capacity may increase under hypoxic conditions. In aerated water blood pH of frogs and turtles either adheres to alphastat regulation (pH ∼8.0) or may even exhibit respiratory alkalosis. Arousal in hibernating mammals leads to restoration of euthermic temperature, metabolic rate, and gas exchange and occurs periodically even as ambient temperatures remain low, whereas body temperature, metabolic rate, and gas exchange of hibernating ectotherms are tightly linked to ambient temperature. © 2011 American Physiological Society. Compr Physiol 1:397-420, 2011.
This study aimed to determine the roles played by the autonomic interoreceptors, the carotid bodies (cbs) and the aortic bodies (abs) in anesthetized, paralyzed, artificially ventilated cats' response to systemic hypoxemia. Four 15min challenges stimulated each of 15 animals: (1) hypoxic hypoxia (10%O(2) in N(2); HH) in the intact (int) cat where both abs and cbs sent neural traffic to the nucleus tractus solitarius (NTS); (2) carbon monoxide hypoxia (30%O(2) in N(2) with the addition of CO; COH) in the intact cat where only the abs sent neural traffic to the NTS; (3) HH in the cat after transection of both aortic depressor nerves, resecting the aortic bodies (HHabr), where only the cbs sent neural traffic to the NTS; (4) COH to the abr cat where neither abs nor cbs sent neural traffic to the NTS. Cardiac output (C.O.), contractility (dP/dt(MAX)), systolic/diastolic pressures, aortic blood pressure, total peripheral resistance, pulmonary arterial pressure, and pulmonary vascular resistance (PVR) were measured. When both cbs and abs were active the maximum increases were observed except for PVR which decreased. Some variables showed the cbs to have a greater effect than the abs. The abs proved to be important during some challenges for maintaining blood pressure. The data support the critically important role for the chemoreceptor-sympathetic nervous system connection during hypoxemia for maintaining viable homeostasis, with some differences between the cbs and the abs.
Nitrite-exposed (1 mM) rainbow trout Oncorhynchus mykiss fell into two distinct groups with regard to susceptibility and physiological response. Group 1 accumulated nitrite in plasma to a concentration of 2·9 mM within 24 h and died before 48 h. Group 2 survived for 96–144 h, and the accumulation of nitrite was slower, levelling off at a concentration c. 2·3 mM at 72 h. Methaemoglobin (metHb) formation was faster in group 1 than in group 2, but both groups had a metHb fraction c. 70% before dying. The extracellular electrolyte balance was perturbed significantly only in group 1, where plasma [Cl-] decreased and plasma [K+] increased. Heart rate increased rapidly, more in group 1 than in group 2. The tachycardia occurred before any significant changes in metHb or [K+] had developed, suggesting that it was due to nitrite-induced vasodilation, possibly via nitric oxide generated from nitrite, that was countered by an increased cardiac pumping to re-establish blood pressure. Arterial blood pressure and pulse pressure were accordingly kept reasonably constant. Heart rate variability was significantly depressed in group 1. The ventilation rate was significantly increased after 9 h of nitrite exposure in group 1, while the ventilation in group 2 did not increase significantly before 21 h. The data reveal that nitrite has substantial influence on the cardio-respiratory function in fishes.
The sections in this article are:
The sections in this article are:
Body CO Stores
Location
Carbon Monoxide Exchanges Between Lung and Body Stores and Processes That Determine Hb CO and Body CO Stores
Endogenous CO Production
Carbon Monoxide Metabolism as a CO Sink
Carbon Monoxide Binding to Proteins Found in Mammalian Tissues
Structure and Reactivity of CO
Carbon Monoxide and O 2 Competition
Carbon Monoxide Binding to Hb
Effects of CO Binding to Hb on Oxygenation in Peripheral Tissues
Extravascular CO ‐Binding Proteins
The sections in this article are:
The sections in this article are:
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