Microbiota and cardiorespiratory control: Chronic intermittent hypoxia related cardiorespiratory dysfunction in rat
Authors: O'Connor Karen M. , Lucking Eric F. , Clarke Ger , Cryan John F. , O'Halloran Ken D. 
Published: June 2021

Obstructive sleep apnoea syndrome, a respiratory disorder characterised by exposure to chronic intermittent hypoxia (CIH), has maladaptive outcomes for integrative body systems. CIH functions as a major driving force at the gut epithelium, leading to inescapable microbial diversity. We sought to explore the effects of CIH on major homeostatic control systems with a particular interest in cardio‐respiratory physiology. We hypothesise that host‐microbe interactions contribute to the development of aberrant cardiorespiratory plasticity evident in CIH exposed rats.

Sprague Dawley male rats were exposed to repeated cycles consisting of hypoxia (FiO2=0.05 nadir) and normoxia (FiO2=0.21) for 8 hours per day for two weeks (n=11). Sham animals (n=12) were constantly exposed to room air and similar environmental cues. Whole‐body plethysmography was used to record breathing in the unanesthetised animals during quiet rest. Oxygen consumption and carbon dioxide production were measured as an index of whole‐body metabolism. Under urethane anaesthesia, cardiorespiratory challenges were performed. Plasma corticosterone and bronchoalveolar fluid pro‐inflammatory cytokines were measured using commercially available kits. High performance liquid chromatography coupled to electrochemical detection was used to analyse monoamines in brainstem regions. Data are presented as mean±SD and were analysed using unpaired Student t tests or Mann‐Whitney unpaired t tests.

The ventilatory equivalent during normoxia (FiO2=0.21) and hypercapnia (FiCO2 =0.05) were unaffected by exposure to CIH (p=0.38, p=0.91 respectively). Alterations in sigh frequency during hypercapnia were noted in CIH‐exposed animals (p=0.009). CIH exposure increased apnoea index during normoxia and hypercapnia (p=0.04, p=0.006 respectively). Elevated baseline mean arterial blood pressure occurred in CIH‐exposed animals (p=0.003). β‐adrenoceptor blockade (propranolol 1 mg/kg i.v.) elicited an enhanced bradycardic response in CIH animals (p=0.03). Moreover, sympathetic ganglion block (25 μg/kg hexamethonium i.v.) produced a significant bradycardia in CIH exposed animals compared with shams (p=0.04). Corticosterone and pro‐inflammatory cytokine levels were equivalent in both CIH‐exposed animals and shams (p=0.7, p=0.46 respectively). Neuromodulators in brainstem regions were decreased in CIH exposed animals.

Our study employing a CIH‐exposed rat model of sleep apnoea reveals dysregulated cardiorespiratory control. Our results reveal that two weeks of CIH does not create systemic stress or pulmonary inflammation. However, alterations in the neurochemistry of brainstem regions occur. We hypothesise that CIH directly or indirectly disrupts microbial composition, associated with impaired cardiorespiratory homeostasis. Investigation into the association between host‐microbiome and cardiorespiratory homeostasis is underway in our laboratory. Manipulating the microbiota may function as an adjunct therapy for the treatment of sleep apnoea.

Support or Funding Information

This abstract has emanated from research supported by research grant from Science Foundation Ireland (SFI) to the APC Microbiome Institute. Supported by the Department of Physiology and the Department of Anatomy and Neuroscience.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.