Investigating the temporal effects of spinal cord injury on cardiac function and structure in male rats with T3 complete transection and determining the primary cause of cardiac decline following spinal cord injury using male rats with T3 or L2 complete transection, or T2 severe contusion

STUDY PURPOSE: High-level spinal cord injury (SCI) alters cardiac function and causes cardiac atrophy
in the chronic phase post-injury. How such events manifest over time post-injury and the primary cause of these cardiac changes were unknown. The first study (manuscript Part I) investigated the temporal changes in the heart on the acute-to-chronic continuum post-SCI. The remaining studies (manuscript Part II) investigated whether the primary cause of altered cardiac function post-SCI was the loss of sympathetic control to the heart. DATA COLLECTED: In Part I a total of 66 male Wistar rats (10-11 weeks old at SCI) were randomly assigned to T3 complete transection SCI (performed with microscissors and suction) or a SHAM injury; rats were assessed for outcomes at different time-points along the acute-to-chronic continuum. Part I represents the complete data of 61 rats - the SCI was fatal in 4 rats (6.1% mortality rate, below UBC animal ethical board’s expectations of 10%), while one rat was excluded from data analysis due to poor health at termination. To study cardiac volumes, echocardiography was performed in the same rats over-time, at pre-surgery, 1 day, 2 days, 4 days, 6 days and 8 weeks post-SCI (n=6-10 per time-point). To study cardiac function, we performed left-ventricular (LV) catheterization in different rats at termination: 1 day, 3 days, 5 days, 7 days and 8 weeks post-SCI (n=6-9 per group). To estimate the temporal changes in sympathetic activity post-SCI, we collected blood at 1 day, 7 days and 8 weeks post-SCI to detect plasma norepinephrine (NE) levels via an ELISA (n=4-7 per group). To measure LV cardiomyocyte dimensions, we collected mid-ventricular cross-sectional discs of the heart for histology at 12 hours, 1 day, 3 days, 5 days, 7 days and 8 weeks post-SCI (n=5-9 per group). To investigate whether and when protein degradation pathways were at play post-SCI in the heart causing cardiac atrophy, we collected LV apex tissue at all acute time-points, 12 hours to 7 days, to perform qPCR (n=5 per group).

In Part II, we performed three rodent studies. The first study aimed to determine whether the reduction in cardiac function post-SCI was neurally mediated. We performed in order: LV catheterization, a T3 complete transection SCI (same injury model as Part I) and a chemical ganglionic blockade (hexamethonium bromide, HEX; I.V. 20 mg/kg) in male rats (total n=7; n=4 Sprague Dawley 23 weeks old at SCI, n=3 Wistar 11-12 weeks old at SCI). We compared the cardiac functional outcomes nadir post-SCI and post-HEX. The second study (n=20 male Wistar rats, 10-11 weeks old at SCI), investigated the involvement of bulbospinal sympathetic control in reduced cardiac function post-SCI by comparing LV catheterization outcomes at 13 weeks following complete transections (same injury model as Part I) at the T3 (interrupted bulbospinal sympathetic control; n=6) and L2 level (intact bulbospinal sympathetic control; n=7), compared to SHAM controls (n=7). To further isolate the role of the bulbospinal sympathetic control in mediating these reductions, we treated T3 severely contused rats (400 kdyn, 5 second dwell time with Infinite Horizon impactor) with the neuroprotective agent minocycline or a vehicle control (total n=19; male Wistar rats, 10-12 weeks old at SCI). At eight weeks post-SCI, we performed LV catheterization to obtain cardiac functional outcomes (n=5 minocycline treated rats and n=6 vehicle treated controls), and histology to assess preservation of bulbospinal sympathetic fibers in the spinal cord (n=4 per treatment group). Encompassing all sub-studies, this dataset contains the data of 112 rats. DATA USAGE NOTES:

【研究目的】高位脊髓损伤（spinal cord injury, SCI）可在损伤后慢性期引发心脏功能改变与心脏萎缩。目前学界尚未明确此类病理变化在损伤后随时间的演进过程，以及心脏功能异常的核心诱因。本研究第一项实验（论文第一部分）探究了脊髓损伤后心脏在急性至慢性连续进程中的时序变化；其余实验（论文第二部分）则旨在明确脊髓损伤后心脏功能异常的核心诱因是否为心脏交感神经支配的丧失。

【数据采集】
在第一部分实验中，共计66只雄性Wistar大鼠（脊髓损伤时为10~11周龄）被随机分配至T3节段完全横断性脊髓损伤组（使用显微剪和抽吸法造模）或假手术（SHAM）损伤组。研究人员在急性至慢性连续进程中的多个时间点对大鼠进行结局指标评估。第一部分实验最终纳入61只大鼠的完整数据：4只大鼠因脊髓损伤致死（死亡率6.1%，低于不列颠哥伦比亚大学（UBC）动物伦理委员会设定的10%上限），另有1只大鼠因终末期健康状况不佳被排除出数据分析。
为探究心脏容积变化，研究人员对同一批大鼠在术前、脊髓损伤后1天、2天、4天、6天及8周进行时序性超声心动图检测（每个时间点样本量n=6~10）。
为评估心脏功能，研究人员在不同时间点处死大鼠前对其进行左心室（left-ventricular, LV）导管插管检测：脊髓损伤后1天、3天、5天、7天及8周（每组样本量n=6~9）。
为估算脊髓损伤后交感神经活动的时序变化，研究人员在脊髓损伤后1天、7天及8周采集血液样本，通过酶联免疫吸附试验（ELISA）检测血浆去甲肾上腺素（norepinephrine, NE）水平（每组样本量n=4~7）。
为测量左心室心肌细胞尺寸，研究人员在脊髓损伤后12小时、1天、3天、5天、7天及8周采集心脏左心室中部横切片样本用于组织学分析（每组样本量n=5~9）。
为探究脊髓损伤后心脏蛋白降解通路是否参与介导心脏萎缩及其激活时序，研究人员在所有急性时间点（12小时至7天）采集左心室心尖组织进行实时定量聚合酶链式反应（qPCR）检测（每组样本量n=5）。

在第二部分实验中，共计开展三项啮齿类动物研究：
第一项研究旨在明确脊髓损伤后心脏功能下降是否由神经介导。研究人员依次对雄性大鼠开展左心室导管插管、T3节段完全横断性脊髓损伤（与第一部分实验采用相同造模方式）以及化学神经节阻断剂干预（溴己铵（hexamethonium bromide, HEX）；静脉注射20 mg/kg）。本次实验共计7只大鼠：4只为脊髓损伤时23周龄的斯普拉格-道利（Sprague Dawley）大鼠，3只为脊髓损伤时11~12周龄的Wistar大鼠。研究人员对比了脊髓损伤后及HEX干预后的心脏功能最低点结局指标。
第二项研究（共计20只雄性Wistar大鼠，脊髓损伤时为10~11周龄）通过对比不同脊髓损伤节段的左心室导管插管检测结果，探究脊髓损伤后心脏功能下降是否与延髓脊髓交感神经支配相关：研究人员分别在T3节段（打断延髓脊髓交感神经支配；n=6）和L2节段（保留延髓脊髓交感神经支配；n=7）进行完全横断性脊髓损伤，并与假手术对照组（n=7）对比，所有检测均在损伤后13周开展。
为进一步明确延髓脊髓交感神经支配在介导心脏功能下降中的作用，研究人员对T3节段重度撞击型脊髓损伤大鼠（撞击力度400 kdyn，接触时间5秒，采用Infinite Horizon脊髓撞击仪造模）分别给予神经保护剂米诺环素或溶剂对照。本次实验共计19只雄性Wistar大鼠，脊髓损伤时为10~12周龄。在脊髓损伤后8周，研究人员通过左心室导管插管获取心脏功能结局指标（米诺环素处理组n=5，溶剂对照组n=6），并通过组织学检测评估脊髓内延髓脊髓交感神经纤维的保留情况（每组n=4）。

本数据集涵盖所有子研究，共计纳入112只大鼠的相关数据。

【数据使用说明】