Low Intrinsic Aerobic Capacity Limits Recovery Response to Hindlimb Ischemia

Introduction: In this study, we determined the influence of intrinsic exercise capacity on the vascular adaptive responses to hind limb ischemia. High Capacity Running, HCR; Low Capacity Running, LCR, rats were used to assess intrinsic aerobic capacity effects on adaptive responses to ischemia.Metho...

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Main Authors: Elizabeth Granier, Madaniah O. Zakari, Musaad B. Alsahly, Lauren G. Koch, Steven Britton, Laxmansa C. Katwa, Robert M. Lust
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2021.752955/full
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author Elizabeth Granier
Elizabeth Granier
Madaniah O. Zakari
Madaniah O. Zakari
Musaad B. Alsahly
Musaad B. Alsahly
Lauren G. Koch
Steven Britton
Laxmansa C. Katwa
Robert M. Lust
Robert M. Lust
author_facet Elizabeth Granier
Elizabeth Granier
Madaniah O. Zakari
Madaniah O. Zakari
Musaad B. Alsahly
Musaad B. Alsahly
Lauren G. Koch
Steven Britton
Laxmansa C. Katwa
Robert M. Lust
Robert M. Lust
author_sort Elizabeth Granier
collection DOAJ
description Introduction: In this study, we determined the influence of intrinsic exercise capacity on the vascular adaptive responses to hind limb ischemia. High Capacity Running, HCR; Low Capacity Running, LCR, rats were used to assess intrinsic aerobic capacity effects on adaptive responses to ischemia.Methods: Muscle samples from both ischemic and non-ischemic limb in both strains were compared, histologically for the muscle-capillary relationship, and functionally using microspheres to track blood flow and muscle stimulation to test fatigability. PCR was used to identify the differences in gene expression between the phenotypes following occlusive ischemia.Results: Prior to ligation, there were not significant differences between the phenotypes in the exhaustion time with high frequency pacing. Following ligation, LCR decreased significantly in the exhaustion time compare with HCRs (437 ± 47 vs. 824 ± 56, p < 0.001). The immediate decrease in flow was significantly more severe in LCRs than HCRs (52.5 vs. 37.8%, p < 0.001). VEGF, eNOS, and ANG2 (but not ANG1) gene expression were decreased in LCRs vs. HCRs before occlusion, and increased significantly in LCRs 14D after occlusion, but not in HCRs. LCR capillary density (CD) was significantly lower at all time points after occlusion (LCR 7D = 564.76 ± 40.5, LCR 14D = 507.48 ± 54.2, both p < 0.05 vs. HCR for respective time point). NCAF increased significantly in HCR and LCR in response to ischemia.Summary: These results suggest that LCR confers increased risk for ischemic injury and is subject to delayed and less effective adaptive response to ischemic stress.
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spelling doaj.art-accf8cde6b2b486aaa07fce44942de0d2022-12-21T19:22:17ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-11-01810.3389/fcvm.2021.752955752955Low Intrinsic Aerobic Capacity Limits Recovery Response to Hindlimb IschemiaElizabeth Granier0Elizabeth Granier1Madaniah O. Zakari2Madaniah O. Zakari3Musaad B. Alsahly4Musaad B. Alsahly5Lauren G. Koch6Steven Britton7Laxmansa C. Katwa8Robert M. Lust9Robert M. Lust10Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United StatesDepartment of Biological Science, St. Louis Community College-Meremac, St. Louis, MO, United StatesDepartment of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United StatesDepartment of Physiology, College of Medicine, Taibah University, Medina, Saudi ArabiaDepartment of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United StatesDepartment of Physiology, College of Medicine, King Saud University, Riyadh, Saudi ArabiaDepartment of Physiology and Pharmacology, University of Toledo, Toledo, OH, United StatesDepartments of Anesthesiology and Molecular and Integrative Medicine, University of Michigan, Ann Arbor, MI, United StatesDepartment of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United StatesDepartment of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United StatesEast Carolina Diabetes and Obesity Center, East Carolina University, Greenville, NC, United StatesIntroduction: In this study, we determined the influence of intrinsic exercise capacity on the vascular adaptive responses to hind limb ischemia. High Capacity Running, HCR; Low Capacity Running, LCR, rats were used to assess intrinsic aerobic capacity effects on adaptive responses to ischemia.Methods: Muscle samples from both ischemic and non-ischemic limb in both strains were compared, histologically for the muscle-capillary relationship, and functionally using microspheres to track blood flow and muscle stimulation to test fatigability. PCR was used to identify the differences in gene expression between the phenotypes following occlusive ischemia.Results: Prior to ligation, there were not significant differences between the phenotypes in the exhaustion time with high frequency pacing. Following ligation, LCR decreased significantly in the exhaustion time compare with HCRs (437 ± 47 vs. 824 ± 56, p < 0.001). The immediate decrease in flow was significantly more severe in LCRs than HCRs (52.5 vs. 37.8%, p < 0.001). VEGF, eNOS, and ANG2 (but not ANG1) gene expression were decreased in LCRs vs. HCRs before occlusion, and increased significantly in LCRs 14D after occlusion, but not in HCRs. LCR capillary density (CD) was significantly lower at all time points after occlusion (LCR 7D = 564.76 ± 40.5, LCR 14D = 507.48 ± 54.2, both p < 0.05 vs. HCR for respective time point). NCAF increased significantly in HCR and LCR in response to ischemia.Summary: These results suggest that LCR confers increased risk for ischemic injury and is subject to delayed and less effective adaptive response to ischemic stress.https://www.frontiersin.org/articles/10.3389/fcvm.2021.752955/fullvascular occlusionaerobic running capacityexerciseperipheral artery occlusionlimb ischemia
spellingShingle Elizabeth Granier
Elizabeth Granier
Madaniah O. Zakari
Madaniah O. Zakari
Musaad B. Alsahly
Musaad B. Alsahly
Lauren G. Koch
Steven Britton
Laxmansa C. Katwa
Robert M. Lust
Robert M. Lust
Low Intrinsic Aerobic Capacity Limits Recovery Response to Hindlimb Ischemia
Frontiers in Cardiovascular Medicine
vascular occlusion
aerobic running capacity
exercise
peripheral artery occlusion
limb ischemia
title Low Intrinsic Aerobic Capacity Limits Recovery Response to Hindlimb Ischemia
title_full Low Intrinsic Aerobic Capacity Limits Recovery Response to Hindlimb Ischemia
title_fullStr Low Intrinsic Aerobic Capacity Limits Recovery Response to Hindlimb Ischemia
title_full_unstemmed Low Intrinsic Aerobic Capacity Limits Recovery Response to Hindlimb Ischemia
title_short Low Intrinsic Aerobic Capacity Limits Recovery Response to Hindlimb Ischemia
title_sort low intrinsic aerobic capacity limits recovery response to hindlimb ischemia
topic vascular occlusion
aerobic running capacity
exercise
peripheral artery occlusion
limb ischemia
url https://www.frontiersin.org/articles/10.3389/fcvm.2021.752955/full
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