Behavioral and cardiovascular effects of 7.5% CO2 in human volunteers

Abstract

The study of carbon dioxide (CO2) inhalation in psychiatry has a long and varied history, with recent interest in using inhaled CO2 as an experimental tool to explore the neurobiology and treatment of panic disorder. As a consequence, many studies have examined the panic-like response to the gas either using the single or double breath 35% CO2 inhalation or 5-7% CO2 inhaled for 15-20 min, or rebreathing 5% CO2 for a shorter time. However, this lower dose regime produces little physiological or psychological effects in normal volunteers. For this reason we have studied the effects of a higher concentration of CO2, 7.5%, given over 20 min. Twenty healthy volunteers were recruited to a double blind, placebo-controlled study where air and 7.5% CO2 were inhaled for 20 min. Cardiovascular measures and subjective ratings were obtained. When compared to air, inhaling 7.5% CO2 for 20 min increases systolic blood pressure and heart rate, indicating increased autonomic arousal. It also increases ratings of anxiety and fear and other subjective symptoms associated with an anxiety state. The inhalation of 7.5% CO2 for 20 min is safe for use in healthy volunteers and produces robust subjective and objective effects. It seems promising as an anxiety provocation test that could be beneficial in the study of the effects of anxiety on sustained performance, the discovery of novel anxiolytic agents, and the study of brain circuits and mechanisms of anxiety.

Activation of the Orexin 1 Receptor is a Critical Component of CO2-Mediated Anxiety and Hypertension but not Bradycardia

“…However, exposing rats to higher concentrations of hypercarbic gas (eg, X10% CO 2 ) elicits additional components of a panic-associated responses as evidenced by increases in sympathetic activity (Elam et al, 1981), blood pressure (Walker, 1987), anxiety-like behaviors (Cuccheddu et al, 1995;Johnson et al, 2011), and mobilization of the hypothalamic-pituitary-adrenal axis (Marotta et al, 1976;. In humans, a single breath of air containing 35% CO 2 increases anxiety and sympatheticadrenal responses (Griez and Van den Hout, 1983;Argyropoulos et al, 2002;Kaye et al, 2004) and inhaling 7.5% CO 2 for 20 min also leads to increases in anxiety and cardiorespiratory responses (Bailey et al, 2005). Therefore, understanding the neural mechanisms underlying severe hypercapnia-induced anxiety and autonomic hyperactivity that can occur in chronic obstructive pulmonary disease (COPD), asthma, or bronchitis could lead to novel treatments for these symptoms.…”

The effect of carbon dioxide flow rate on the euthanasia of laboratory mice

“…4 Humans describe the experience of dyspnea as distressing [5][6][7][8] and this sensation has been used to induce fear and panic in humans using CO 2 concentrations between 7.5 and 35%. [9][10][11][12] Different types of dyspneic sensations have been identified resulting from pathological breathlessness, including air hunger, tightness and work. 13 In the human literature, the term dyspnea contains both an affective and behavioral response, as the negative emotional response resulting from dyspneic experiences results in aversion.…”

The carbon dioxide challenge test in panic disorder: a systematic review of preclinical and clinical research

“…Details of the response of healthy subjects to different CO 2 challenge protocols have been reported by several authors. Activation of the HPA axis (cortisol levels, heart rate, and systolic blood pressure) was assessed by Argyropoulos et al 69 using 35% CO 2 , with similar results to those of Bailey et al 70 (using 7% CO 2 ) and Colasanti et al 71 The latter randomly exposed their 64 subjects to four breathing mixtures -normal air, low CO 2 (9%), medium CO 2 (17.5%), and high CO 2 (35% CO 2 ) -so that all subjects breathed every mixture. The results led their team to group the subjects into three distinct clusters: respiratory, neurovegetative, and cognitive, according to the most prominent symptom reported.…”