Breathing And Oxygen Carrying Capacity in Ts65Dn And Down Syndrome

Lara R DeRuisseau; Candace N Receno; Caitlin Cunningham; Melissa L Bates; Morgan Goodell; Chen Liang; Brianna Eassa; Jessica Pascolla; Keith DeRuisseau

doi:10.1093/function/zqad058

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Breathing And Oxygen Carrying Capacity in Ts65Dn And Down Syndrome

Journal article

Open access

Peer reviewed

Breathing And Oxygen Carrying Capacity in Ts65Dn And Down Syndrome

Lara R DeRuisseau, Candace N Receno, Caitlin Cunningham, Melissa L Bates, Morgan Goodell, Chen Liang, Brianna Eassa, Jessica Pascolla and Keith DeRuisseau

Function (Oxford, England), Vol.4(6), zqad058

2023

DOI: 10.1093/function/zqad058

PMCID: PMC10634617

PMID: 37954975

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Abstract

Individuals with Down Syndrome are at increased risk of respiratory infection, aspiration pneumonia, and apnea. The Ts65Dn mouse is a commonly used model of Ds, but there have been no formal investigations of awake breathing and respiratory muscle function in these mice. We hypothesized that breathing would be impaired in Ts65Dn vs. wild-type (WT), and would be mediated by both neural and muscular inputs. Baseline minute ventilation with room air was not different at 3, 6 or 12 months of age. However, VT/Ti, a marker of the neural drive to breathe, was lower in Ts65Dn vs. WT. Central apneas were more prevalent in Ts65Dn compared to WT. The response to breathing hypoxia was not different, but the response to hypercapnia was attenuated in Ts65Dn at 3 and 12 months, revealing a difference in carbon dioxide sensing, and/or motor output. Oxygen desaturations were present in room air, demonstrating that ventilation may not be sufficient to maintain adequate oxygen saturation in Ts65Dn. We observed no differences in arterial PO2 or PCO2, but Ts65Dn mice had lower hemoglobin and hematocrit. A retrospective medical record review of 52 346 Ds and 52 346 controls confirmed an elevated relative risk of anemia in Ds individuals. To determine the muscular contribution to respiratory impairment, we performed eupneic in vivo electromyography and in vitro muscle function and histological fiber typing of the diaphragm, and found no difference between strains. Overall, conscious respiration is impaired in Ts65Dn mice, is mediated by neural mechanisms, and results in reduced hemoglobin saturation. Oxygen carrying capacity is reduced in Ts65Dn vs. WT, and we demonstrate that individuals with Ds are also at increased risk of anemia.

Hypoxia

plethysmography

hypoxemia

apnea

ventilation

Trisomy 21

diaphragm

hypercapnia

Details

Title: Subtitle: Breathing And Oxygen Carrying Capacity in Ts65Dn And Down Syndrome
Creators: Lara R DeRuisseau - University of Health Sciences and Pharmacy
Candace N Receno - Ithaca College
Caitlin Cunningham - Le Moyne College
Melissa L Bates - University of Iowa, Fraternal Order of Eagles Diabetes Research Center
Morgan Goodell
Chen Liang - University of Rochester Medical Center
Brianna Eassa - University of Health Sciences and Pharmacy
Jessica Pascolla - University of Health Sciences and Pharmacy
Keith DeRuisseau
Resource Type: Journal article
Publication Details: Function (Oxford, England), Vol.4(6), zqad058
DOI: 10.1093/function/zqad058
PMID: 37954975
PMCID: PMC10634617
NLM abbreviation: Function (Oxf)
ISSN: 2633-8823
eISSN: 2633-8823
Publisher: Oxford University Press
Language: English
Electronic publication date: 10/06/2023
Date published: 2023
Academic Unit: Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology ; Internal Medicine
Record Identifier: 9984473206802771

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