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

Abstract

Spinal cord injury (SCI) is a devastating condition that results in whole-body dysfunction, notably cardiovascular (CV) disruption and disease. Injury-induced destruction of autonomic pathways in conjunction with a progressive decline in physical fitness contribute to the poor CV status of SCI individuals. Despite the wide use of exercise training as a therapeutic option to reduce CV dysfunction, little is known about the acute hemodynamic responses to the exercise itself. We investigated CV responses to an exercise challenge (swimming) following both high and low thoracic contusion to determine if the CV system is able to respond appropriately to the challenge of swimming. Blood pressure (BP) telemetry and echocardiography were used to track the progression of dysfunction in rodents with T3 and T10 SCI (n = 8 each) for 10 weeks postcontusion. At 1 week postinjury, all animals displayed a drastic decline in heart rate (HR) during the exercise challenge, likely a consequence of neurogenic shock. Furthermore, over time, all groups developed a progressive inability to maintain BP within a narrow range during the exercise challenge despite displaying normal hemodynamic parameters at rest. Echocardiography of T10 animals revealed no persistent signs of cardiac dysfunction; T3 animals exhibited a transient decline in systolic function that returned to preinjury levels by 10 weeks postinjury. Novel evidence provided here illustrates that incomplete injuries produce hemodynamic instability that only becomes apparent during an exercise challenge. Further, this dysfunction lasts into the chronic phase of disease progression despite significant recovery of hindlimb locomotion and cardiac function.

Keywords: Cardiovascular; exercise; spinal cord injury.

Figure 1

Incomplete contusion results in severity dependent tissue damage and locomotor deficits. (A) Percent spared white matter at the injury epicenter following T3 and T10 contusion. (B) Group comparisons of weekly BBB scores over time in T3 and T10 animals. Significant group differences were noted at weeks one and nine postinjury. (C) Group comparisons of weekly performance during swimming assessments. Significant group differences are noted at three and ten weeks post‐SCI. Statistical significance was assessed using Mixed Model ANOVA with Bonferroni post hoc t‐test. Data are displayed as mean ± SD (n = 8 each group) and statistical significance was set as * P ≤ 0.05.

Figure 2

Rodents with high thoracic contusion are unable to maintain cardiovascular control during swimming exercise challenge. Representative MBP (A) and HR (C) responses to swimming exercise challenge before (black lines) and one week post‐T3 moderate contusion (red lines). Note the postexertional hypotension during the Exercise Recovery period acutely after injury (A, arrow). Representative MBP (B) and HR (D) responses to swimming exercise challenge before (black lines) and 10 weeks post‐T3 moderate contusion (red lines). Note the elevated pressor response to swim challenge at ten weeks post‐SCI. Data have been down sampled from 1000 Hz to display one data point per second. Individual recordings of In Cage Rest (4 min), Lap Swim (4 min), and Exercise Recovery (6 min) are displayed as one continuous MBP or HR trace. Each tick on the x‐axis represents one minute.

Figure 3

Rodents with low thoracic contusion are unable to maintain cardiovascular control during swimming exercise challenge. Representative MBP (A) and HR (C) responses to swimming exercise challenge before (black lines) and one week post‐T10 moderate contusion (red lines). Note the drastic fall in HR from the beginning to the end of the four minute swimming exercise challenge. Representative MBP (B) and HR (D) responses to swimming exercise challenge before (black lines) and 10 weeks post‐T10 moderate contusion (red lines). Note the elevated pressor response to swim challenge at ten weeks post‐SCI. Data have been down sampled from 1000 Hz to display one data point per second. Individual recordings of In Cage Rest (4 min), Lap Swim (4 min), and Exercise Recovery (6 min) are displayed as one continuous MBP or HR trace. Each tick on the x‐axis represents one minute.

Figure 4

Lack of cardiovascular control during exercise challenge persists for many weeks following moderate T3 contusion. (A) Average MBP Excursion measured prior to SCI and each week following injury. Oscillatory changes in MBP during each swim lap are averaged for each time point. The inability to maintain MBP during exercise challenge increased with time postinjury. (B) Average MBP during the four‐minute swim session. Note the exertional hypotension one week after injury. (C) Average MBP during the Exercise Recovery period. (D) HR Excursion during the four‐minute swim session. Note the drastic drop in HR from the beginning to the end of swimming acutely after injury. (E) Average HR during the four‐minute swim session. (F) Average HR during the Exercise Recovery period. Statistical significance was assessed using Mixed Model ANOVA with Bonferroni post hoc t‐test. Data are displayed as mean ± SD (n = 4 for week 1, n = 8 for all other time points) and statistical significance was set as * P ≤ 0.05 vs. preinjury, ^ϕ P ≤ 0.05 vs. week 1, and ^Ϭ P ≤ 0.05 vs. week 2.

Figure 5

The inability to regulate blood pressure control in response to exercise challenge persists for many weeks following T10 contusion. (A) Average MBP Excursion measured prior to SCI and each week following injury. Oscillatory changes in MBP during each swim lap are averaged for each time point. The inability to maintain MBP during exercise challenge increased with time postinjury. (B) Average MBP during the four‐minute swim session. Note the increased pressor response chronically after injury. (C) Average MBP during the Exercise Recovery period. Note the postexertional hypotension one week after injury. (D) HR Excursion during the four‐minute swim session. Note the drastic drop in HR from the beginning to the end of swimming acutely after injury. (E) Average HR during the four‐minute swim session. (F) Average HR during the Exercise Recovery period. Statistical significance was assessed using Mixed Model ANOVA with Bonferroni post hoc t‐test. Data are displayed as mean ± SD (n = 4 for week 1, n = 8 for all other time points) and statistical significance was set as * P ≤ 0.05 vs. preinjury and ^ϕ P ≤ 0.05 vs. week 1.

Figure 6

Timewise comparison of cardiac function following T3 moderate contusion using echocardiography. Compared to preinjury, pressor responses in the presence of isoflurane anesthesia were blunted at all time points assessed (SBP (A), DBP (B), and MBP (C)). Measures of systolic function (SV (D), CO (F), and EF (G)) over time indicate a recovery of function at 10 weeks post‐SCI. End‐diastolic volume (H) was significantly lower at chronic time points; ESV (I) and HR (E) were not different from preinjury. Data are displayed as mean ± SD (n = 4) and significance is set at * P ≤ 0.05 vs. preinjury.