Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is intriguing evidence suggesting pathophysiologic relationships among dyspnea, hyperventilation, and panic anxiety. The symptoms of panic attacks and pulmonary disease overlap, so that panic anxiety can reflect underlying cardiopulmonary disease and dyspnea can reflect an underlying anxiety disorder. The pathogenesis of panic may be related to respiratory physiology by several mechanisms: the anxiogenic effects of hyperventilation, the catastrophic misinterpretation of respiratory symptoms, and/or a neurobiologic sensitivity to CO2, lactate, or other signals of suffocation. In a subset of patients with PD, incipient pulmonary dysfunction may also contribute to their anxiety symptoms. Patients with pulmonary disease, particularly those with obstructive lung disease, have a high rate of panic symptoms and PD. There is reason to believe that pulmonary disease constitutes a risk factor for the development of panic related to repeated experiences with dyspnea and life-threatening exacerbations of pulmonary dysfunction, repeated episodes of hypercapnia or hyperventilation, the use of anxiogenic medications, and the stress of coping with chronic disease. Panic in pulmonary patients may carry significant morbidity, including phobic avoidance of activity, overly aggressive treatment with anxiogenic medications, and more prolonged and frequent hospitalization. Successful treatment of panic in these patients can improve functional status and quality of life by relieving anxiety and dyspnea. Nonpharmacologic treatment of panic, including cognitive-behavioral approaches, can be useful in patients with concomitant respiratory disease. Sedating medications such as benzodiazepines should be used with caution in patients with pulmonary disease to avoid respiratory depression. Serotonergic antidepressants (SSRIs) and anxiolytics (buspirone) may be effective treatments for panic or generalized anxiety in pulmonary patients and have relatively little potential for significant adverse effects.
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PMID:Panic anxiety, dyspnea, and respiratory disease. Theoretical and clinical considerations. 868 Jul

Panic disorder (PD) is a severe anxiety disorder characterized by susceptibility to induction of panic attacks by subthreshold interoceptive stimuli such as sodium lactate infusions or hypercapnia induction. Here we review a model of panic vulnerability in rats involving chronic inhibition of GABAergic tone in the dorsomedial/perifornical hypothalamic (DMH/PeF) region that produces enhanced anxiety and freezing responses in fearful situations, as well as a vulnerability to displaying acute panic-like increases in cardioexcitation, respiration activity and "flight" associated behavior following subthreshold interoceptive stimuli that do not elicit panic responses in control rats. This model of panic vulnerability was developed over 15 years ago and has provided an excellent preclinical model with robust face, predictive and construct validity. The model recapitulates many of the phenotypic features of panic attacks associated with human panic disorder (face validity) including greater sensitivity to panicogenic stimuli demonstrated by sudden onset of anxiety and autonomic activation following an administration of a sub-threshold (i.e., do not usually induce panic in healthy subjects) stimulus such as sodium lactate, CO(2), or yohimbine. The construct validity is supported by several key findings; DMH/PeF neurons regulate behavioral and autonomic components of a normal adaptive panic response, as well as being implicated in eliciting panic-like responses in humans. Additionally, patients with PD have deficits in central GABA activity and pharmacological restoration of central GABA activity prevents panic attacks, consistent with this model. The model's predictive validity is demonstrated by not only showing panic responses to several panic-inducing agents that elicit panic in patients with PD, but also by the positive therapeutic responses to clinically used agents such as alprazolam and antidepressants that attenuate panic attacks in patients. More importantly, this model has been utilized to discover novel drugs such as group II metabotropic glutamate agonists and a new class of translocator protein enhancers of GABA, both of which subsequently showed anti-panic properties in clinical trials. All of these data suggest that this preparation provides a strong preclinical model of some forms of human panic disorders.
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PMID:An animal model of panic vulnerability with chronic disinhibition of the dorsomedial/perifornical hypothalamus. 2248 12

Central sleep apnea (CSA) results from a reduction in lack of output from the central respiratory generator in the brainstem, manifesting as apneas and hypopneas without discernible efforts. CSA can lead to hypercarbia, arrhythmias, pulmonary hypertension, and heart failure. Indeed, the patient may develop a disturbed breathing during sedation procedures. We report a patient who was diagnosed with CSA and had been on continuous positive airway pressure (CPAP) therapy for 5 years. He was referred for multiple tooth extractions under sedation owing to severe gag reflex and phobic anxiety disorder. The treatment was completed uneventfully under N(2)O and sevoflurane inhalation accompanied by midazolam and ketamine induction. The role of sedative, analgesic, and anesthetic agents as a precipitating factor for CSA is of particular concern. The combined administration of midazolam, ketamine, sevoflurane, and N(2)O/O(2) is a useful and safe option for patients requiring sedation.
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PMID:Dental treatment of a patient with central sleep apnea and phobic anxiety under sedation: report of a case and clinical considerations. 2308 86

Early life events have a crucial role in programming the individual phenotype and exposure to traumatic experiences during infancy can increase later risk for a variety of neuropsychiatric conditions, including mood and anxiety disorders. Animal models of postnatal stress have been developed in rodents to explore molecular mechanisms responsible for the observed short and long lasting neurobiological effects of such manipulations. The main aim of this study was to compare the behavioral and hormonal phenotype of young and adult animals exposed to different postnatal treatments. Outbred mice were exposed to (i) the classical Handling protocol (H: 15 min-day of separation from the mother from day 1 to 14 of life) or to (ii) a Repeated Cross-Fostering protocol (RCF: adoption of litters from day 1 to 4 of life by different dams). Handled mice received more maternal care in infancy and showed the already described reduced emotionality at adulthood. Repeated cross fostered animals did not differ for maternal care received, but showed enhanced sensitivity to separation from the mother in infancy and altered respiratory response to 6% CO2 in breathing air in comparison with controls. Abnormal respiratory responses to hypercapnia are commonly found among humans with panic disorders (PD), and point to RCF-induced instability of the early environment as a valid developmental model for PD. The comparisons between short- and long-term effects of postnatal handling vs. RCF indicate that different types of early adversities are associated with different behavioral profiles, and evoke psychopathologies that can be distinguished according to the neurobiological systems disrupted by early-life manipulations.
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PMID:Early handling and repeated cross-fostering have opposite effect on mouse emotionality. 2595 70

Orexin neurons originating in the perifornical and lateral hypothalamic area are highly reactive to anxiogenic stimuli and have strong projections to anxiety and panic-associated circuitry. Recent studies support a role for the orexin system and in particular the orexin 1 receptor (OX1R) in coordinating an integrative stress response. However, no selective OX1R antagonist has been systematically tested in two preclinical models of using panicogenic stimuli that induce panic attack in the majority of people with panic disorder, namely an acute hypercapnia-panic provocation model and a model involving chronic inhibition of GABA synthesis in the perifornical hypothalamic area followed by intravenous sodium lactate infusion. Here we report on a novel brain penetrant, selective and high affinity OX1R antagonist JNJ-54717793 (1S,2R,4R)-7-([(3-fluoro-2-pyrimidin-2-ylphenyl)carbonyl]-N-[5-(trifluoromethyl)pyrazin-2-yl]-7-azabicyclo[2.2.1]heptan-2-amine). JNJ-54717793 is a high affinity/potent OX1R antagonist and has an excellent selectivity profile including 50 fold versus the OX2R. Ex vivo receptor binding studies demonstrated that after oral administration JNJ-54717793 crossed the blood brain barrier and occupied OX1Rs in the rat brain. While JNJ-54717793 had minimal effect on spontaneous sleep in rats and in wild-type mice, its administration in OX2R knockout mice, selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. JNJ-54717793 attenuated CO2 and sodium lactate induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. These data confirm that selective OX1R antagonism may represent a novel approach of treating anxiety disorders, with no apparent sedative effects.
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PMID:Evaluation of JNJ-54717793 a Novel Brain Penetrant Selective Orexin 1 Receptor Antagonist in Two Rat Models of Panic Attack Provocation. 2864 1

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is one of the leading causes of hospitalization in the United States. Prior investigations suggest clinical and physiological parameters are important determinants for AECOPD readmissions. Strategies aimed at addressing these factors have not resulted in a major reduction of readmissions. We compared patients readmitted after an index AECOPD admission with non-readmitted patients. Patients' age, gender, body mass index, comorbidities (obstructive sleep apnea, chronic hypercapnia, congestive heart failure, lung cancer, pulmonary arterial hypertension, pneumonia, interstitial lung disease, atrial fibrillation, musculoskeletal disorders, cognitive disorders, and anxiety disorders), substance abuse and smoking status were assessed. Some 272 patients were included: 20 patients were readmitted within 30 days of their index hospitalization; 252 patients were not readmitted within 30 days of their index admission. Readmitted patients were significantly more likely to have pneumonia than non-readmitted patients (30.0% versus 13.1%, p<0.05). No statistically significant difference was seen with respect to other clinical comorbidities. Patients readmitted within 30 days were significantly more likely than non-readmitted patients to have safety issues at home (80.0% versus. 39.3%, p<0.001), anxiety (60.0% versus 29.8%, p<0.01), and lack of transportation (35.0% versus 15.5%, p<0.05). Implementation of a comprehensive care management program (CCMP) was associated with a reduction in readmissions from 21.5% to 13.6% (p<0.01, 95% confidence interval [CI] 2.08-12.45). A CCMP can reduce readmissions through attention to social variables, optimization of in-hospital care, improved coordination of pre- and post-discharge, a system to better identify problems after discharge, and an office setup that accommodates same-day visits.
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PMID:The Effects of a Comprehensive Care Management Program on Readmission Rates After Acute Exacerbation of COPD at a Community-Based Academic Hospital. 3058 82

Behaviorally inhibited (BI) temperament is marked by heightened behavioral sensitivity to environmental threats. The degree to which threat sensitivity is reflected in cardiorespiratory responses has been relatively unexplored. Female college students were exposed to modest hypercapnia (7.0% CO2) or ambient air (AA) while engaging in a computerized task with cued reinforcement features. All physiological variables except for blood pressure were processed in 4 min epochs corresponding to pre-exposure, exposure, and post-exposure. Primary respiratory measures were respiratory frequency (fb), tidal volume (VT), and minute ventilation (VE). Electrocardiograms (ECGs) were processed using ARTiiFACT software with resultant heart rate variability (HRV) measures in the frequency domain and time domain. Consistent with the literature, modest hypercapnia increased VT, Fb, and VE. No differences in respiratory parameters were detected between BI and non-behaviorally inhibited individuals (NI). For HRV in the time domain, RMSSD and NN50 values increased during CO2 inhalation which then returned to pre-exposure levels after CO2 cessation. Hypercapnia increased high frequency (HF) power which then recovered. BI exhibited reduced low frequency (LF) power during the pre-exposure period. For NI, LF power reduced over the subsequent phases ameliorating differences between BI and NI. Hypercapnia improved the task performance of BI. This is the largest study of female reactivity to hypercapnia and associated HRV to date. In general, hypercapnia increased time domain HRV and HF power, suggesting a strong vagal influence. Those expressing BI exhibited similar respiratory and HRV reactivity to NI despite inherently reduced LF power. Although 7% CO2 represents a mild challenge to the respiratory and cardiovascular systems, it is nonetheless sufficient to explore inherent difference in stress reactivity in those vulnerable to develop anxiety disorders.
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PMID:Cardiorespiratory Response to Moderate Hypercapnia in Female College Students Expressing Behaviorally Inhibited Temperament. 3328 46