title: Passive hind-limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury.
abstract: Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio-metabolic responses to SCI and to establish whether passive hind-limb cycling elicits a cardio-protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind-limb cycling (SCI-EX; 2 × 30 min day(-1), 5 days week(-1) for 4 weeks beginning 6 days post-SCI). On day 32, cardio-metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats (n = 6 SCI and n = 6 SCI-EX) underwent in vivo echocardiography and basal haemodynamic assessments pre-SCI and at days 7, 14 and 32 post-SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up-regulation of transforming growth factor beta-1 (TGFβ1) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI-EX, the initial reduction in left ventricular dimensions and function at day 7 post-SCI was completely reversed by day 32 post-SCI, and there were no differences in myocardial contractility between SCI-EX and CON. Collagen deposition was similar between SCI-EX and CON. TGFβ1 and Smad3 were down-regulated in SCI-EX. Blood lipid profiles were improved in SCI-EX versus SCI. We provide compelling novel evidence that passive hind-limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI.
authors.affiliation: ICORD-BSCC, UBC, 818 West 10th Avenue, Vancouver, BC, Canada, V5Z 1M9. krassioukov@icord.org.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: West
authors.forename: Mark A
authors.initials: MA
authors.lastname: Crawford
authors.forename: Malihe-Sadat
authors.initials: MS
authors.lastname: Poormasjedi-Meibod
authors.forename: Katharine D
authors.initials: KD
authors.lastname: Currie
authors.forename: Andre
authors.initials: A
authors.lastname: Fallavollita
authors.forename: Violet
authors.initials: V
authors.lastname: Yuen
authors.forename: John H
authors.initials: JH
authors.lastname: McNeill
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Krassioukov
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D006439:Hemodynamics; D006614:Hindlimb / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D009068:Movement; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014463:Ultrasonography; D016276:Ventricular Function
chemical_list: D008077:Lipoproteins, LDL; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D016212:Transforming Growth Factor beta; D003094:Collagen