Abstract
Age-related changes in cardiac contractility in a mouse model of Down syndrome
Physiology (Bethesda, Md.), Vol.38(S1)
05/2023
DOI: 10.1152/physiol.2023.38.S1.5733470
Abstract
Abstract only
Over the last couple of decades, the median survival of individuals with Down syndrome (Ds) increased from 30 to 60 years. The Ts65Dn mouse model recapitulates most of the cognitive and neural phenotypes described in Ds individuals and its use continues to expand into other fields. The Ds population is at risk for cardiovascular comorbidities. We hypothesized that contractility in Ts65Dn mice will be lower compared to controls, and differences between strains will become exacerbated with age. The aim of this study was to comprehensively access the cardiac function in the Ts65Dn model across the lifespan. Ts65Dn and C57BL/6J mice (n = 3-5) were tested at 3, 6, and 12 months of age. Left ventricular function was assessed in closed-chest mice using a microtip pressure-volume catheter (PVR-1030, Millar) which was introduced via the right carotid artery and coupled to a digital converter (ADInstruments). By transiently compressing the inferior abdominal vena cava, different preloads were induced, accessing hemodynamic assessment of the left ventricle. Finally, the heart was excised, trimmed, & weighed to assess the Fulton index. The end-diastolic pressure-volume relationship (ESPVR) increased at 12 months in Ts65Dn mice compared to controls. Comparison of the maximal velocity of pressure rise (+ dP/dt) did not differ between ages and genotypes. The maximal velocity of pressure fall (− dP/dt), however, was significantly lower in 12 months Ts65Dn compared to the 6-month group. Cardiac output (Q̇) decreased with aging in Ts65Dn mice compared to controls, therefore decreasing stroke volume (SV) and stroke work (SW). The index of arterial elastance (Ea) increased with aging in Ts65Dn mice compared to the control. Together, Ts65Dn mice have decreased systolic performance accompanied by increased contractility of the heart and increased aortic elastance, and these parameters are revealed as mice age.
NIH R21HD099573
This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Details
- Title: Subtitle
- Age-related changes in cardiac contractility in a mouse model of Down syndrome
- Creators
- Anastasiia Vasileva - University of IowaMikhail Vasilyev - University of IowaMichael Tomasson - University of Iowa, Hematology, Oncology, and Blood & Marrow TransplantationLara DeRuisseau - University of Health Sciences and PharmacyMelissa Bates - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Physiology (Bethesda, Md.), Vol.38(S1)
- DOI
- 10.1152/physiol.2023.38.S1.5733470
- ISSN
- 1548-9213
- eISSN
- 1548-9221
- Language
- English
- Date published
- 05/2023
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology; Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984648259902771
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