Vagal Integration of Cardiopulmonary Regulation

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Domnik, Nicolle Jasmin
Airway Hyperresponsiveness , Vagus Nerve , Ovalbumin , Heart Rate Variability , Slowly-Adapting Receptors , Oyster , Acclimation , Murine , Cardiorespiratory , Calcium-Sensing Receptor
Cardiopulmonary control relies on local and central integration of sensory inputs and reflex efferent signaling. Heart and lung sensors, integrators, and effectors are routinely studied in a reductionist manner to elucidate molecular mechanisms. This is accompanied by a need to explore mechanisms of cardiopulmonary integration within the autonomic nervous system. I focused on two elements of cardiopulmonary regulation: in vivo afferent signaling from the lung, and the use of whole animal heart rate variability (HRV) as a window into cardiac control in mammals and an aquatic invertebrate. In the former I characterized the mechanosensitivity of 85 single murine slowly-adapting receptors (SARs) to address the hypothesis that polymodal neuroepithelial bodies (NEBs) are linked with mechanosensitive SARs via a common vagal afferent population by assessing the impact of: i) chemostimulation (10% O2 or 10% CO2); ii) pharmacologic blockade (serotonergic - tropisetron or purinergic-suramin); and iii) loss of the calcium-sensing receptor (CaSR) on quasi-static SAR signaling. Expression of CaSR is reported in murine NEBs and implicated in asthma pathogenesis. Loss of CaSR increased NEB size and proliferative markers (immunohistochemical staining); however, we found no evidence for NEB-SAR interactions based on Na+/K+-ATPase staining. Murine SARs possess greater mechanosensitivity than reported for large mammals, and loss of CaSR reduced SAR mechanosensitivity by > 35%. Chemostimulation/pharmacologic antagonism had minor effects on SAR behaviour, consistent with minimal NEB-mechanosensor interactions. To address the later, I applied in vivo HRV analysis to assess autonomic (ANS) control in the development of murine airway hyperresponsiveness. Sensitization decreased HRV prior and subsequent to antigen challenge, suggesting that HRV reflects early changes in ANS function and may be useful in the detection of early lung disease. I also applied HRV analysis for the first time in juvenile Pacific oysters using a novel, non-invasive video-microscopy method developed to assess HR/HRV during acute temperature changes in oysters acclimated to 22°C or 10°C. Acclimation to 10°C reduced the incidence of asystole and increased HRV vs. warm-temperature acclimation. HRV increased as temperature (and HR) decreased in both acclimation groups. Application of HR/HRV analyses in oysters may provide a new tool to optimize aquaculture rearing protocols and explore the ontogeny of cardiac control in a simple model organism.
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