Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes.
Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF...
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doaj-4d14fa0c1b1a47c1bd0494e009dc5f5c2020-11-25T01:17:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014801010.1371/journal.pone.0148010Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes.Jennifer M PetrosinoValerie J HeissSantosh K MauryaAnuradha KalyanasundaramMuthu PeriasamyRichard A LaFountainJacob M WilsonOrlando P SimonettiOuliana ZiouzenkovaFunctional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT). Additionally, they often lack multiple cardio-metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J) to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover) observed in human-GXTs. Next, theses assays were tested on established diet-induced (obese-C57BL/6J) and genetic (cardiac isoform Casq2-/-) models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio-metabolic phenotype of various animal models or the effects of novel therapeutics.http://europepmc.org/articles/PMC4747552?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jennifer M Petrosino Valerie J Heiss Santosh K Maurya Anuradha Kalyanasundaram Muthu Periasamy Richard A LaFountain Jacob M Wilson Orlando P Simonetti Ouliana Ziouzenkova |
spellingShingle |
Jennifer M Petrosino Valerie J Heiss Santosh K Maurya Anuradha Kalyanasundaram Muthu Periasamy Richard A LaFountain Jacob M Wilson Orlando P Simonetti Ouliana Ziouzenkova Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes. PLoS ONE |
author_facet |
Jennifer M Petrosino Valerie J Heiss Santosh K Maurya Anuradha Kalyanasundaram Muthu Periasamy Richard A LaFountain Jacob M Wilson Orlando P Simonetti Ouliana Ziouzenkova |
author_sort |
Jennifer M Petrosino |
title |
Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes. |
title_short |
Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes. |
title_full |
Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes. |
title_fullStr |
Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes. |
title_full_unstemmed |
Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes. |
title_sort |
graded maximal exercise testing to assess mouse cardio-metabolic phenotypes. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT). Additionally, they often lack multiple cardio-metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J) to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover) observed in human-GXTs. Next, theses assays were tested on established diet-induced (obese-C57BL/6J) and genetic (cardiac isoform Casq2-/-) models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio-metabolic phenotype of various animal models or the effects of novel therapeutics. |
url |
http://europepmc.org/articles/PMC4747552?pdf=render |
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