Passive hind-limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury

J Physiol. 2014 Apr 15;592(8):1771-83. doi: 10.1113/jphysiol.2013.268367. Epub 2014 Feb 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control*
  • Collagen / genetics
  • Collagen / metabolism
  • Heart Ventricles / diagnostic imaging
  • Hemodynamics
  • Hindlimb / physiology*
  • Lipoproteins, LDL / blood
  • Male
  • Movement*
  • Myocardial Contraction
  • Myocardium / metabolism
  • Rats
  • Rats, Wistar
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / physiopathology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Ultrasonography
  • Ventricular Function*

Substances

  • Lipoproteins, LDL
  • Smad3 Protein
  • Smad3 protein, rat
  • Transforming Growth Factor beta
  • Collagen