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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comprehensive model of oxygen (O2) and carbon dioxide (CO2) exchange, transport, and storage in the adult human is presented, and its ability to provide realistic responses under different physiological conditions is evaluated. The model comprises three compartments (i.e., lung, body tissue, and brain tissue) and incorporates a controller that adjusts alveolar ventilation and cardiac output dynamically integrating stimuli coming from peripheral and central chemoreceptors. A new realistic CO2 dissociation curve based on a two-buffer model of acid-base chemical regulation is included. In addition, the model explicitly considers relevant physiological factors such as buffer base, the nonlinear interaction between the O2 and CO2 chemoreceptor responses, pulmonary shunt, dead space, variable time delays, and Bohr and Haldane effects. Model simulations provide results consistent with both dynamic and steady-state responses measured in subjects undergoing inhalation of high CO2 (hypercapnia) or low O2 (hypoxia) and subsequent recovery. An analysis of the results indicates that the proposed model fits the experimental data of ventilation and gas partial pressures as some meaningful simulators now available and in a very large range of gas intake fractions. Moreover, it also provides values of blood concentrations of CO2, HCO3-, and hydrogen ions in good agreement with more complex simulators characterized by an implicit formulation of the CO2 dissociation curve. In the experimental conditions analyzed, the model seems to represent a single theoretical framework able to appropriately describe the different phenomena involved in the control of respiration.
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PMID:A comprehensive simulator of the human respiratory system: validation with experimental and simulated data. 939 44

Because melatonin is a cerebral vasoconstrictor agent, we tested whether it could shift the lower limit of cerebral blood flow autoregulation to a lower pressure level, by improving the cerebrovascular dilatory reserve, and thus widen the security margin. Cerebral blood flow and cerebrovascular resistance were measured by hydrogen clearance in the frontal cortex of adult male Wistar rats. The cerebrovasodilatory reserve was evaluated from the increase in the cerebral blood flow under hypercapnia. The lower limit of cerebral blood flow autoregulation was evaluated from the fall in cerebral blood flow following hypotensive hemorrhage. Rats received melatonin infusions of 60, 600, or 60,000 ng . kg-1 . h-1, a vehicle infusion, or no infusion (n = 9 rats per group). Melatonin induced concentration-dependent cerebral vasoconstriction (up to 25% of the value for cerebrovascular resistance of the vehicle group). The increase in vasoconstrictor tone was accompanied by an improvement in the vasodilatory response to hypercapnia (+50 to +100% vs. vehicle) and by a shift in the lower limit of cerebral blood flow autoregulation to a lower mean arterial blood pressure level (from 90 to 50 mmHg). Because melatonin had no effect on baseline mean arterial blood pressure, the decrease in the lower limit of cerebral blood flow autoregulation led to an improvement in the cerebrovascular security margin (from 17% in vehicle to 30, 55, and 55% in the low-, medium-, and high-dose melatonin groups, respectively). This improvement in the security margin suggests that melatonin could play an important role in the regulation of cerebral blood flow and may diminish the risk of hypoperfusion-induced cerebral ischemia.
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PMID:Melatonin improves cerebral circulation security margin in rats. 968 6

Since the nitric oxide (NO) and cyclooxygenase pathways have been suggested to have important roles in most vasodilations, our aim was to study the influence of cyclooxygenase inhibitors and nitrovasodilators on cerebrovascular reserve capacity. Corticocerebral blood flow was measured by hydrogen polarography during hypercapnia and acetazolamide stimuli in conscious rabbits. The measurements were repeated in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME) and indomethacin as nitric oxide synthase (NOS) and cyclooxygenase inhibitors. The effects of nitroglycerin and isosorbide-5-nitrate were also tested. L-NAME completely, while indomethacin markedly inhibited the hypercapnic corticocerebral blood flow response. Nitroglycerin and isosorbide-5-nitrate significantly attenuated hypercapnia elicited corticocerebral blood flow increase. The different treatments reduced only moderately the acetazolamide-induced corticocerebral blood flow response. These results lend support to the hypothesis that antithrombotic and antiinflammatory medication (cyclooxygenase inhibitors) and nitrovasodilator treatments could interfere with the measurement of cerebrovascular reactivity resulting in underestimation of the cerebrovascular reserve capacity in patients taking these drugs.
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PMID:Influence of nitrovasodilators and cyclooxygenase inhibitors on cerebral vasoreactivity in conscious rabbits. 1116 94

The hydrogen ion is an important factor in the alteration of vascular tone in pulmonary circulation. Endothelial cells modulate vascular tone by producing vasoactive substances such as prostacyclin (PGI2) through a process depending on intracellular Ca2+ concentration ([Ca2+]i). We studied the influence of CO2-related pH changes on [Ca2+]i and PGI2 production in human pulmonary artery endothelial cells (HPAECs). Hypercapnic acidosis appreciably increased [Ca2+]i from 112 +/- 24 to 157 +/- 38 nmol/l. Intracellular acidification at a normal extracellular pH increased [Ca2+]i comparable to that observed during hypercapnic acidosis. The hypercapnia-induced increase in [Ca2+]i was unchanged by the removal of Ca2+ from the extracellular medium or by the depletion of thapsigargin-sensitive intracellular Ca2+ stores. Hypercapnic acidosis may thus release Ca2+ from pH-sensitive but thapsigargin-insensitive intracellular Ca2+ stores. Hypocapnic alkalosis caused a fivefold increase in [Ca2+]i compared with hypercapnic acidosis. Intracellular alkalinization at a normal extracellular pH did not affect [Ca2+]i. The hypocapnia-evoked increase in [Ca2+]i was decreased from 242 +/- 56 to 50 +/- 32 nmol/l by the removal of extracellular Ca2+. The main mechanism affecting the hypocapnia-dependent [Ca2+]i increase was thought to be the augmented influx of extracellular Ca2+ mediated by extracellular alkalosis. Hypercapnic acidosis caused little change in PGI2 production, but hypocapnic alkalosis increased it markedly. In conclusion, both hypercapnic acidosis and hypocapnic alkalosis increase [Ca2+]i in HPAECs, but the mechanisms and pathophysiological significance of these increases may differ qualitatively.
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PMID:Effects of hypercapnia and hypocapnia on [Ca2+]i mobilization in human pulmonary artery endothelial cells. 1135 71

Cardiac sympathetic afferents are known to reflexly activate the cardiovascular system, leading to increases in blood pressure, heart rate, and myocardial contractile function. During myocardial ischemia, these sensory nerves also transmit the sensation of pain (angina pectoris) and cause tachyarrhythmias. The authors' laboratory has been interested in defining the mechanisms of activation of this neural system during ischemia and reperfusion. During these periods, reactive oxygen species, particularly hydroxyl radicals, are produced from the breakdown of purine metabolites and lead to stimulation of sympathetic (and vagal) ventricular chemosensitive nerve endings. For example, stimulation with hydrogen peroxide leads to a small reflex increase in blood pressure from the predominant sympathetic afferent activation that is reduced by simultaneous activation of cardiac vagal afferents (known to exert predominantly depressor reflexes). Central integration of these two opposing reflexes likely occurs at several regions of the brain stem, including the nucleus tractus solitarii, where neural occlusion occurs during simultaneous cardiac sympathetic and vagal-afferent stimulation. Activation of platelets also appears to play a role during myocardial ischemia, leading to local release of serotonin (5HT), which, through a 5HT3 mechanism, stimulates sympathetic afferents. Finally, regional changes in pH from lactic acid (but not hypercapnia), stimulate ventricular afferents and may activate kallikrein to increase bradykinin (BK), which, in turn, breaks down arachidonic acid to form prostaglandins. Prostaglandins sensitize cardiac sympathetic afferents to BK. Thus, stimulation of cardiac sympathetic afferents during ischemia and reperfusion and the resulting reflex events form a multifactorial process resulting from activation of a number of chemical pathways in the myocardium.
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PMID:Cardiac sympathetic afferent activation provoked by myocardial ischemia and reperfusion. Mechanisms and reflexes. 1145 9

Chronic experiments on conscious rabbits with needle electrodes implanted into cortex, thalamus, and hypothalamus were used to study variations in the local blood flow (BF) and the cerebral vessel response to hypercapnia and hyperoxia by method of hydrogen clearance. Variations of the partial oxygen pressure (PO2) in the tissues of these structures was measured by the polarographic technique. The general vibration action (modeled in a special testing device) decreased the local BF in the cortex and hipothalamus, suppressed the response of cerebral vessel (especially of the constrictor ones) to hyperoxia, and reduced PO2 in all the structures studied. Acting upon the neuron energy exchange and reducing their oxygen consumption, thiotriazolin prevented the drop in PO2 and even increased this parameter, while not preventing the decrease in BF and the inhibition of vessel response.
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PMID:[Effect of thiotriazoline on the blood supply and oxygen balance in the brain in models of exposure to general vibration]. 1154 45

To determine whether the excitabilities of pulmonary C fibers to chemical and mechanical stimuli are altered by CO(2)-induced acidosis, single-unit pulmonary C-fiber activity was recorded in anesthetized, open-chest rats. Transient alveolar hypercapnia (HPC) was induced by administering CO(2)-enriched gas mixture (15% CO(2), balance air) via the respirator inlet for 30 s, which rapidly lowered the arterial blood pH from a baseline of 7.40 +/- 0.01 to 7.17 +/- 0.02. Alveolar HPC markedly increased the responses of these C-fiber afferents to several chemical stimulants. For example, the C-fiber response to right atrial injection of the same dose of capsaicin (0.25-1.0 microg/kg) was significantly increased from 3.07 +/- 0.70 impulses/s at control to 8.48 +/- 1.52 impulses/s during HPC (n = 27; P < 0.05), and this enhanced response returned to control within approximately 10 min after termination of HPC. Similarly, alveolar HPC also induced significant increases in the C-fiber responses to right atrial injections of phenylbiguanide (4-8 microg/kg) and adenosine (0.2 mg/kg). In contrast, HPC did not change the response of pulmonary C fibers to lung inflation. Furthermore, the peak response of these C fibers to capsaicin during HPC was greatly attenuated when the HPC-induced acidosis was buffered by infusion of bicarbonate (1.36-1.82 mmol. kg(-1). min(-1) for 35 s). In conclusion, alveolar HPC augments the responses of these afferents to various chemical stimulants, and this potentiating effect of CO(2) is mediated through the action of hydrogen ions on the C-fiber sensory terminals.
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PMID:Alveolar hypercapnia augments pulmonary C-fiber responses to chemical stimulants: role of hydrogen ion. 1207 Feb 3

Carbon dioxide interacts both with reactive nitrogen species and reactive oxygen species. In the presence of superoxide, NO reacts to form peroxynitrite that reacts with CO2 to give nitrosoperoxycarbonate. This compound rearranges to nitrocarbonate which is prone to further reactions. In an aqueous environment, the most probable reaction is hydrolysis producing carbonate and nitrate. Thus the net effect of CO2 is scavenging of peroxynitrite and prevention of nitration and oxidative damage. However, in a nonpolar environment of membranes, nitrocarbonate undergoes other reactions leading to nitration of proteins and oxidative damage. When NO reacts with oxygen in the absence of superoxide, a nitrating species N2O3 is formed. CO2 interacts with N2O3 to produce a nitrosyl compound that, under physiological pH, is hydrolyzed to nitrous and carbonic acid. In this way, CO2 also prevents nitration reactions. CO2 protects superoxide dismutase against oxidative damage induced by hydrogen peroxide. However, in this reaction carbonate radicals are formed which can propagate the oxidative damage. It was found that hypercapnia in vivo protects against the damaging effects of ischemia or hypoxia. Several mechanisms have been suggested to explain the protective role of CO2 in vivo. The most significant appears to be stabilization of the iron-transferrin complex which prevents the involvement of iron ions in the initiation of free radical reactions.
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PMID:The role of carbon dioxide in free radical reactions of the organism. 1244 30

This study investigated 1) whether pulmonary C fibers are activated by a transient increase in the CO2 concentration of alveolar gas; and 2) if the CO2 sensitivity of these afferents is altered during airway inflammation. Single-unit pulmonary C-fiber activity was recorded in anesthetized, open-chest rats. Transient alveolar hypercapnia (HPC) was induced by administering a CO2-enriched gas mixture (25-30% CO2, 21% O2, balance N2) for five to eight breaths, which increased alveolar CO2 concentration progressively to near or above 13% for 3-5 s and lowered the arterial pH transiently to 7.10 +/- 0.05. Our results showed the following. 1) HPC evoked only a mild stimulation in a small fraction (4/47) of pulmonary C fibers, and there was no significant change in fiber activity (change in fiber activity = 0.22 +/- 0.16 imp/s; P > 0.1, n = 47). 2) In sharp contrast, after airway exposure to poly-L-lysine, a cationic protein known to induce mucosal injury, the same challenge of transient HPC activated 87.5% of the pulmonary C fibers tested and evoked a distinct stimulatory effect on these afferents (change in fiber activity = 6.59 +/- 1.78 imp/s; P < 0. 01, n = 8). 3) Similar potentiation of the C-fiber response to HPC was also observed after acute exposure to ozone (n = 6) and during a constant infusion of inflammatory mediators such as adenosine (n = 15) or prostaglandin E2 (n = 12). 4) The enhanced C-fiber sensitivity to CO2 after poly-L-lysine was completely abrogated by infusion of NaHCO3 (1.82 mmol.kg(-1).min(-1)) that prevented the reduction in pH during HPC (n = 6). In conclusion, only a small percentage (<10%) of the bronchopulmonary C fibers exhibit CO2 sensitivity under control conditions, but alveolar HPC exerts a consistent and pronounced stimulatory effect on the C-fiber endings during airway inflammation. This effect of CO2 is probably mediated through the action of hydrogen ions.
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PMID:Stimulatory effect of CO2 on vagal bronchopulmonary C-fiber afferents during airway inflammation. 1599 40

This paper uses a steady-state modeling approach to describe the effects of changes in acid-base balance on the chemoreflex control of breathing. First, a mathematical model is presented, which describes the control of breathing by the respiratory chemoreflexes; equations express the dependence of pulmonary ventilation on Pco(2) and Po(2) at the central and peripheral chemoreceptors. These equations, with Pco(2) values as inputs to the chemoreceptors, are transformed to equations with hydrogen ion concentrations [H(+)] in brain interstitial fluid and arterial blood as inputs, using the Stewart approach to acid-base balance. Examples illustrate the use of the model to explain the regulation of breathing during acid-base disturbances. They include diet-induced changes in sodium and chloride, altitude acclimatization, and respiratory disturbances of acid-base balance due to chronic hyperventilation and carbon dioxide retention. The examples demonstrate that the relationship between Pco(2) and [H(+)] should not be neglected when modeling the chemoreflex control of breathing. Because pulmonary ventilation controls Pco(2) rather than the actual stimulus to the chemoreceptors, [H(+)], changes in their relationship will alter the ventilatory recruitment threshold Pco(2), and thereby the steady-state resting ventilation and Pco(2).
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PMID:Role of acid-base balance in the chemoreflex control of breathing. 1610 29


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