A comparison of passive hindlimb cycling and active upper-limb exercise provides new insights into systolic dysfunction after spinal cord injury

Abstract

Active upper-limb and passive lower-limb exercise are two interventions used in the spinal cord injury (SCI) population. Although the global cardiac responses have been previously studied, it is unclear how either exercise influences contractile cardiac function. Here, the cardiac contractile and volumetric responses to upper-limb (swim) and passive lower-limb exercise were investigated in rodents with a severe high-thoracic SCI. Animals were divided into control (CON), SCI no exercise (NO-EX), SCI passive hindlimb cycling (PHLC), or SCI swim (SWIM) groups. Severe contusion SCI was administered at the T2 level. PHLC and SWIM interventions began on day 8 postinjury and lasted 25 days. Echocardiography and dobutamine stress echocardiography were performed before and after injury. Cardiac contractile indexes were assessed in vivo at study termination via a left ventricular pressure-volume conductance catheter. Stroke volume was reduced after SCI (91 µl in the NO-EX group vs. 188 µl in the CON group, P < 0.05) and was reversed at study termination in the PHLC (167 µl) but not SWIM (90 µl) group. Rates of contraction were reduced in NO-EX versus CON groups (6,079 vs. 9,225 mmHg, respectively, P < 0.05) and were unchanged by PHLC and SWIM training. Similarly, end-systolic elastance was reduced in the NO-EX versus CON groups (0.67 vs. 1.37 mmHg/µl, respectively, P < 0.05) and was unchanged by PHLC or SWIM training. Dobutamine infusion normalized all pressure indexes in each SCI group (all P < 0.05). In conclusion, PHLC improves flow-derived cardiac indexes, whereas SWIM training displayed no cardiobeneficial effect. Pressure-derived deficits were corrected only with dobutamine, suggesting that reduced β-adrenergic stimulation is principally responsible for the impaired cardiac contractile function after SCI. NEW & NOTEWORTHY This is the first direct comparison between the cardiac changes elicited by active upper-limb or passive lower-limb exercise after spinal cord injury. Here, we demonstrate that lower-limb exercise positively influences flow-derived cardiac indexes, whereas upper-limb exercise does not. Furthermore, neither intervention corrects the cardiac contractile dysfunction associated with spinal cord injury.

Spinal cord injury‐induced cardiomyocyte atrophy and impaired cardiac function are severity dependent

“…It is important to note, however, that rodents with a MODERATE T3 contusion injury recover some weight-bearing stepping (Squair et al 2017b), and are therefore likely to maintain their preload, in part, through muscle-pump-mediated increases in flow back to the heart. Although this is likely to contribute to the maintenance of SV, we do not believe it contributes to the maintenance of radial strain and contractile function in our MODERATE group, as we have previously found that hindlimb exercise can improve only stroke volume and not systolic contractile function (DeVeau et al 2017). In fact, the only intervention we have found that normalizes contractile function post-SCI is dobutamine, a specific β 1 -agonist (Squair et al 2017a).…”

“…Although we cannot specifically rule this out, we believe it is unlikely to be the principal cause of our between-group differences, as we have shown that upper limb exercise alone (i.e. swim training) exerts no influence on contractile cardiac function (DeVeau et al 2017). It is important to note, however, that rodents with a MODERATE T3 contusion injury recover some weight-bearing stepping (Squair et al 2017b), and are therefore likely to maintain their preload, in part, through muscle-pump-mediated increases in flow back to the heart.…”

“…swim training) exerts no influence on contractile cardiac function (DeVeau et al . ). It is important to note, however, that rodents with a MODERATE T3 contusion injury recover some weight‐bearing stepping (Squair et al .…”

“…Although this is likely to contribute to the maintenance of SV, we do not believe it contributes to the maintenance of radial strain and contractile function in our MODERATE group, as we have previously found that hindlimb exercise can improve only stroke volume and not systolic contractile function (DeVeau et al . ). In fact, the only intervention we have found that normalizes contractile function post‐SCI is dobutamine, a specific β 1 ‐agonist (Squair et al .…”

Temporal analysis of cardiovascular control and function following incomplete T3 and T10 spinal cord injury in rodents

“…Dobutamine is a sympathomimetric drug and has been used previously following SCI to increase the chronotrophy and inotrophy of the heart (DeVeau et al. , ; Squair et al. ).…”