title: Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes.
abstract: 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.
authors: Department of Human Sciences, The Ohio State University, College of Education & Human Ecology, Columbus, Ohio, United States of America.|Biomedical Sciences Program, The Ohio State University, College of Medicine, Columbus, Ohio, United States of America.
authors: Jennifer M
authors: JM
authors: Petrosino
authors: Department of Human Sciences, The Ohio State University, College of Education & Human Ecology, Columbus, Ohio, United States of America.
authors: Valerie J
authors: VJ
authors: Heiss
authors: Cardiovascular Pathobiology Program, Sanford Burnham Medical Research Institute at Lake Nona, Orland, Florida, United States of America.
authors: Santosh K
authors: SK
authors: Maurya
authors: Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.
authors: Anuradha
authors: A
authors: Kalyanasundaram
authors: Cardiovascular Pathobiology Program, Sanford Burnham Medical Research Institute at Lake Nona, Orland, Florida, United States of America.
authors: Muthu
authors: M
authors: Periasamy
authors: Department of Human Sciences, The Ohio State University, College of Education & Human Ecology, Columbus, Ohio, United States of America.
authors: Richard A
authors: RA
authors: LaFountain
authors: Department of Human Performance, The University of Tampa, Tampa, Florida, United States of America.
authors: Jacob M
authors: JM
authors: Wilson
authors: Department of Radiology, The Ohio State University, College of Medicine, Columbus, Ohio, United States of America.|Department of Cardiovascular Medicine, The Ohio State University, College of Medicine, Columbus, Ohio, United States of America.
authors: Orlando P
authors: OP
authors: Simonetti
authors: Department of Human Sciences, The Ohio State University, College of Education & Human Ecology, Columbus, Ohio, United States of America.
authors: Ouliana
authors: O
authors: Ziouzenkova
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D005080:Exercise Test / Q000379:methods*; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010641:Phenotype; D055815:Young Adult