Ventilatory and integrated physiological responses to chronic hypercapnia in goats. 2018

Nicholas J Burgraff, and Suzanne E Neumueller, and Kirstyn Buchholz, and Thomas M Langer, and Matthew R Hodges, and Lawrence Pan, and Hubert V Forster
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.

Chronic hypercapnia per se has distinct effects on the mechanisms regulating steady-state ventilation and the CO2 /H+ chemoreflex. Chronic hypercapnia leads to sustained hyperpnoea that exceeds predicted ventilation based upon the CO2 /H+ chemoreflex. There is an integrative ventilatory, cardiovascular and metabolic physiological response to chronic hypercapnia. Chronic hypercapnia leads to deterioration of cognitive function. Respiratory diseases such as chronic obstructive pulmonary disease (COPD) often lead to chronic hypercapnia which may exacerbate progression of the disease, increase risk of mortality and contribute to comorbidities such as cognitive dysfunction. Determining the contribution of hypercapnia per se to adaptations in ventilation and cognitive dysfunction within this patient population is complicated by the presence of multiple comorbidities. Herein, we sought to determine the role of chronic hypercapnia per se on the temporal pattern of ventilation and the ventilatory CO2 /H+ chemoreflex by exposing healthy goats to either room air or an elevated inspired CO2 (InCO2 ) of 6% for 30 days. A second objective was to determine whether chronic hypercapnia per se contributes to cognitive dysfunction. During 30 days of exposure to 6% InCO2 , steady-state (SS) ventilation ( I ) initially increased to 335% of control, and then within 1-5 days decreased and stabilized at ∼230% of control. There was an initial respiratory acidosis that was partially mitigated over time due to increased arterial [HCO3- ]. There was a transient decrease in the ventilatory CO2 /H+ chemoreflex, followed by return to pre-exposure levels. The SS I during chronic hypercapnia was greater than predicted from the acute CO2 /H+ chemoreflex, suggesting separate mechanisms regulating SS I and the chemoreflex. Finally, as assessed by a shape discrimination test, we found a sustained decrease in cognitive function during chronic hypercapnia. We conclude that chronic hypercapnia per se results in: (1) a disconnect between SS I and the CO2 /H+ chemoreflex, and (2) deterioration of cognitive function.

UI MeSH Term Description Entries
D012018 Reflex An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord.
D012119 Respiration The act of breathing with the LUNGS, consisting of INHALATION, or the taking into the lungs of the ambient air, and of EXHALATION, or the expelling of the modified air which contains more CARBON DIOXIDE than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration ( Breathing
D002245 Carbon Dioxide A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. Carbonic Anhydride,Anhydride, Carbonic,Dioxide, Carbon
D003071 Cognition Intellectual or mental process whereby an organism obtains knowledge. Cognitive Function,Cognitions,Cognitive Functions,Function, Cognitive,Functions, Cognitive
D005260 Female Females
D006041 Goats Any of numerous agile, hollow-horned RUMINANTS of the genus Capra, in the family Bovidae, closely related to the SHEEP. Capra,Capras,Goat
D006935 Hypercapnia A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood.
D000222 Adaptation, Physiological The non-genetic biological changes of an organism in response to challenges in its ENVIRONMENT. Adaptation, Physiologic,Adaptations, Physiologic,Adaptations, Physiological,Adaptive Plasticity,Phenotypic Plasticity,Physiological Adaptation,Physiologic Adaptation,Physiologic Adaptations,Physiological Adaptations,Plasticity, Adaptive,Plasticity, Phenotypic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015656 Respiratory Mechanics The physical or mechanical action of the LUNGS; DIAPHRAGM; RIBS; and CHEST WALL during respiration. It includes airflow, lung volume, neural and reflex controls, mechanoreceptors, breathing patterns, etc. Breathing Mechanics,Breathing Mechanic,Mechanic, Breathing,Mechanic, Respiratory,Mechanics, Breathing,Mechanics, Respiratory,Respiratory Mechanic

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