Markers of susceptibility to cardiac arrhythmia in experimental spinal cord injury and the impact of sympathetic stimulation and exercise training

Abstract

Injury to descending autonomic (sympathetic) pathways is common after high-level spinal cord injury (SCI) and associated with abnormal blood pressure and heart rate regulation. In individuals with high-level SCI, abnormal sympathovagal balance (such as during autonomic dysreflexia; paroxysmal hypertension provoked by sensory stimuli below the injury) is proarrhythmogenic. Exercise training is a key component of SCI rehabilitation and management of cardiovascular disease risk, but it is unclear whether exercise training influences susceptibility to cardiac arrhythmia. We aimed to evaluate: (i) whether susceptibility to arrhythmia increases in a rodent-model of SCI; (ii) the impact of the sympathomimetic drug dobutamine (DOB) on arrhythmia risk; (iii) whether exercise training ameliorates arrhythmia risk. Twenty-one Wistar rats were divided into 3 subgroups: T2-contusive SCI (T2, n = 7), T2-contusive SCI completing passive hindlimb cycling training (PHLC, n = 7), and T10-contusive SCI (T10, n = 7). Known electrocardiographic arrhythmia markers and heart rate variability parameters were evaluated before (PRE), 1-week (POST) and 5-weeks post-SCI (TERM) at baseline and during DOB infusion (30 μg/kg/min). Baseline markers of arrhythmia risk were increased in both T2 and T10 animals. DOB decreased R-R interval (p < 0.001), and increased markers of risk for ventricular arrhythmia, particularly in high-level (T2) animals (p < 0.05). Exercise training blunted the exacerbation of markers of arrhythmia risk in the presence of DOB. Markers of risk for cardiac arrhythmia are increased in experimental SCI, and DOB further increases arrhythmia risk in high-level SCI. Exercise training did not improve markers of arrhythmia risk at rest, but did ameliorate markers of arrhythmia risk during sympathetic stimulation.

Cardiovascular and cerebrovascular responses to urodynamics testing after spinal cord injury: The influence of autonomic injury

“…The sustained and high blood pressures observed during UDS in those with autonomically-complete SCI were associated with an increased risk for both atrial (PWD variability) and ventricular arrhythmia (T peak -T end variability). These results are consistent with past reports (Forrest, 1991;Claydon et al, 2006;Ravensbergen et al, 2012;Lucci et al, 2020), and likely represent a combination of cardiac remodelling secondary to loss of cardiac sympathetic drive after SCI, and the presence of autonomic conflict during AD (Collins, Rodenbaugh and DiCarlo, 2006;Lucci et al, 2021b). These data highlight consistent increases in these markers for arrhythmia risk seen in both acute and chronic SCI compared to reference data in controls (Ravensbergen et al, 2012;Lucci et al, 2021a) and recapitulate the observation that these markers are more severely impaired with autonomically-complete lesions (Ravensbergen et al, 2012) and increase further with paroxysmal sympathetic activation (Lucci et al, 2021b).…”

“…These results are consistent with past reports (Forrest, 1991;Claydon et al, 2006;Ravensbergen et al, 2012;Lucci et al, 2020), and likely represent a combination of cardiac remodelling secondary to loss of cardiac sympathetic drive after SCI, and the presence of autonomic conflict during AD (Collins, Rodenbaugh and DiCarlo, 2006;Lucci et al, 2021b). These data highlight consistent increases in these markers for arrhythmia risk seen in both acute and chronic SCI compared to reference data in controls (Ravensbergen et al, 2012;Lucci et al, 2021a) and recapitulate the observation that these markers are more severely impaired with autonomically-complete lesions (Ravensbergen et al, 2012) and increase further with paroxysmal sympathetic activation (Lucci et al, 2021b). Interestingly, QTVI data were closer to zero in all participants than previous reports in healthy controls (Ravensbergen et al, 2012), confirming greater susceptibility to ventricular arrhythmia.…”

“…We showed that the cardiovascular and cerebrovascular responses during UDS were more pronounced in those with autonomically-complete lesions, based on quantitative measurements of remaining sympathetic function inferred from markers of sympathetic vascular tone (LF SAP) and circulating levels of NE. These measures have also been shown previously to predict the severity of cardiovascular dysfunction such as the severity of AD, prevalence of OH, self-reported symptoms of OH and AD, risk for both atrial and ventricular arrhythmia, and the presence of abnormal heart rhythms (Claydon and Krassioukov, 2007;Ravensbergen et al, 2012;Sahota et al, 2012;Lucci et al, 2020;Lucci et al, 2021a;Lucci et al, 2021b), highlighting the utility of this approach in research, clinical and basic science settings. While both LF SAP and plasma NE were useful markers of autonomic function, LF SAP is non-invasive and simple to perform and thus may be more convenient for routine autonomic function assessment (Claydon and Krassioukov, 2007;Lucci et al, 2021a).…”

“…The P-end was identified from the point at which regressions applied to the section between the P-peak and Q-waves intersect. (Ravensbergen et al, 2012;Lucci et al, 2021a;Lucci et al, 2021b). The total variabilities for each ECG interval parameter were determined as the standard deviation squared while QTVI was determined using the following formula: QTVI log 10…”