Browsing by Subject "hypercapnia"

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    Anxiogenic CO2 Stimulus Elicits Exacerbated Hot Flash-like Responses in a Rat Menopause Model and Hot Flashes in Menopausal Women
    (Lippincott, Williams & Wilkins, 2016-11) Federici, Lauren M.; Roth, Sarah Dorsey; Krier, Connie; Fitz, Stephanie D.; Skaar, Todd C.; Shekhar, Anantha; Carpenter, Janet S.; Johnson, Philip L.; Anatomy and Cell Biology, School of Medicine
    Objective Since longitudinal studies determined that anxiety is a strong risk factor for hot flashes, we hypothesized that an anxiogenic stimulus that signals air hunger (hypercapnic, normoxic gas) would trigger an exacerbated hot flash-associated increase in tail skin temperature (TST) in a rat ovariectomy (OVEX) model of surgical menopause and hot flashes in symptomatic menopausal women. We also assessed TST responses in OVEX serotonin transporter (SERT)+/− rats that models a common polymorphism that is associated with increased climacteric symptoms in menopausal women and increases in anxiety traits. Methods OVEX and sham-OVEX rats (initial experiment) and wildtype and SERT+/− OVEX rats (subsequent experiment) were exposed to a 5 min infusion of 20%CO2 normoxic gas while measuring TST. Menopausal women were given brief 20% and 35%CO2 challenges, and hot flashes were self-reported and objectively verified. Results Compared to controls, OVEX rats had exacerbated increases in TST, and SERT+/− OVEX rats had prolonged TST increases following CO2. Most women reported mild/moderate hot flashes after CO2 challenges, and the hot flash severity to CO2 was positively correlated with daily hot flash frequency. Conclusions The studies demonstrate that this anxiogenic stimulus is capable of inducing cutaneous vasomotor responses in OVEX rats, and eliciting hot flashes in menopausal women. In rats, the severity of the response was mediated by loss of ovarian function and increased anxiety traits (SERT+/−), and, in women, by daily hot flash frequency. These findings may provide insights into anxiety related triggers and genetic risk factors for hot flashes in thermoneutral environments.
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    A Closed-Loop Model of the Respiratory System: Focus on Hypercapnia and Active Expiration
    (2014-10) Molkov, Yaroslav I; Shevtsova, Natalia A; Park, Choongseok; Ben-Tal, Alona; Smith, Jeffrey C; Rubin, Jonathan E; Rybak, Ilya A
    Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. During quiet breathing, pumping air from the lungs is mostly performed by contraction of the diaphragm during inspiration, and muscle contraction during expiration does not play a significant role in ventilation. In contrast, during intense exercise or severe hypercapnia forced or active expiration occurs in which the abdominal “expiratory” muscles become actively involved in breathing. The mechanisms of this transition remain unknown. To study these mechanisms, we developed a computational model of the closed-loop respiratory system that describes the brainstem respiratory network controlling the pulmonary subsystem representing lung biomechanics and gas (O2 and CO2) exchange and transport. The lung subsystem provides two types of feedback to the neural subsystem: a mechanical one from pulmonary stretch receptors and a chemical one from central chemoreceptors. The neural component of the model simulates the respiratory network that includes several interacting respiratory neuron types within the Bötzinger and pre-Bötzinger complexes, as well as the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) representing the central chemoreception module targeted by chemical feedback. The RTN/pFRG compartment contains an independent neural generator that is activated at an increased CO2 level and controls the abdominal motor output. The lung volume is controlled by two pumps, a major one driven by the diaphragm and an additional one activated by abdominal muscles and involved in active expiration. The model represents the first attempt to model the transition from quiet breathing to breathing with active expiration. The model suggests that the closed-loop respiratory control system switches to active expiration via a quantal acceleration of expiratory activity, when increases in breathing rate and phrenic amplitude no longer provide sufficient ventilation. The model can be used for simulation of closed-loop control of breathing under different conditions including respiratory disorders.