Reorganisation of the Autonomic Nervous System

Canada Spinal cord injury (SCI) results not only in a devastating paralysis but is also associated with a myriad of secondary conditions including autonomic dysfunctions [1]. For example cardiovascular responses to orthostatic challenge and exercise following SCI are significantly altered. When able-bodied individual assumes standing position a typical blood pressure response associated with redistribution of blood within the body and approximately 500 ml transfers caudally to the abdominal and lower extremities vasculature. This typically associated with central baroreceptors activation, decreasing vagal tone to the heart, and increasing in peripheral sympathetic activity. The increase in sympathetic tone with standing result in increased heart rate and peripheral vasoconstriction that responsible in maintenance of stable level of arterial blood pressure. After SCI, although the baroreceptors certainly detect reductions in central blood volume during orthostatic stress, disrupted descending spinal sympathetic pathways precludes the capacity for the peripheral vasoconstriction, often resulting in abnormal fluctuation in blood pressure with changing position by individuals with SCI. Latest evidence from preclinical studies and clinical evaluations of individuals with SCI demonstrated that disruption of autonomic spinal pathways and plastic alterations within the spinal cord and periphery that occur after SCI are among the leading causes for the dysfunctional cardiovascular control affecting both: 1) the heart, and 2) the systemic vasculature. Cardiac function is under the combined control of sympathetic (SPNs from T1-T5 levels) and parasympathetic vagal divisions of autonomic nervous systems. After a cervical SCI, sympathetic tonic control is disrupted, while vagal control is intact. Alternatively, when the SCI is below the T6 level, both sympathetic and vagal control of the heart is intact. These divergent scenarios of cardiac autonomic control lead to quite different cardiovascular responses in various physiological circumstances such as rest, exercise, or orthostatic challenge [2]. It is not just the heart that can have these differing autonomic effects (i.e., disrupted sympathetic control yet intact parasympathetic pathways). These same considerations have important outcomes for a variety of essential functions including the cerebrovasculature, urinary bladder, bowel, temperature and sweat glands control. We are just beginning to unravel the mechanisms underlying abnormal cardiovascular function after SCI. The morphological changes within the spinal autonomic circuits after SCI have been established relatively recently. [3] Furthermore, the role these changes are playing in the development of autonomic dysfunction has only just been solidified. A variety of autonomic circuits have been highlighted that possibly contribute to abnormal cardiovascular control after SCI. The disruption of descending spinal cardiovascular pathways leads to a minimum of six neuroanatomical changes that influence autonomic cardiovascular control:

• initial sympathetic hypoactivity due to loss of supraspinal tonic sympathetic excitation,

• alterations in the morphology of SPN's,

• plastic changes of the spinal circuits (i.e., dorsal root afferent sprouting, potential formation of aberrant synaptic connections, or aberrant inputs to the spinal interneurons,

• altered symapatho-sensory plasticity,

• altered peripheral neurovascular responsiveness, and

• cumulative effect of tertiary factors.

The disruption of descending sympathetic pathways that exert control over large vascular beds leads to aberrant blood pressure regulation and, therefore, frequent episodes of either extremely low or extremely high blood pressure frequently observed among individuals with high thoracic and cervical SCI (i.e., conditions known as orthostatic hypotension [OH] and autonomic dysreflexia [AD]) [4;5]. The recognition and management of these two most commonly recognized clinically cardiovascular consequences of SCI are continued to be a challenging clinical issues in many individuals with SCI. The understanding of plastic changes that occur within central and peripheral autonomic nervous system following SCI and search for experimental therapeutic interventions could play a significant role in the development of appropriate clinical rehabilitation strategies. (Research support: CINR; CFI; Heart & Stroke Foundation of Canada; C. Neilsen Foundation; Christopher and Dana Reeve's Foundation).

Fig. 1: Cardiovascular responses to various stimulations in man with spinal cord injury.

A. Case of AD in man with cervical SCI (C7 AIS B – American Spinal Injury Association Impairment Scale, motor complete, sensory incomplete) during the vibrostimulation (VS) procedure for sperm retrieval. Blood pressure (BP, using a finger cuff) and three leads ECG were recorded continuously during the procedure. BP (top diagram) during the procedure and a 10 s sample of ECG recorded at the time of ejaculation (bottom diagram) are shown. Prior to VS there was relative hypotension (100/65 mmHg) with a regular heart rate of 78 bpm. With initiation of VS there was a gradual increase in arterial blood pressure suggestive of a typical episode of AD. Finally, at the time of ejaculation arterial blood pressure surged to 280/150 mmHg accompanied by bradycardia (38 bpm) and a short run of premature ventricular contractions (PVCs, indicated by asterisk on the blood pressure recording) was observed three minutes following ejaculation (ECG recording at the bottom). At 15 min following ejaculation arterial BP was still slightly elevated (130 mmHg, HR 66 bpm). During the next 30 – 35 minutes arterial blood pressure and heart rate gradually returned to resting values. (Personal observations).

B. Case of orthostatic hypotension in individual with cervical C8 AIS A SCI during the orthostatic challenge testing (sit-up test). Instrumentation for blood pressure and ECG was conducted using the same settings as in Case A. Supine resting arterial blood pressure was measured as 95/65 mmHg, with HR of 74 bpm. Following passive sit up (indicated by arrow) the arterial blood pressure decreased and at 3 minutes of seating was measured at 70/55 mmHg with HR of 90 bpm. Patient also complained on slight dizziness. During the next ten minutes of monitoring arterial blood pressure continued to be low and test was stopped due to increased dizziness and light-headedness. (Personal observations).

References:

[1] Krassioukov A. Autonomic function following cervical spinal cord injury. Respir Physiol Neurobiol 2009 Nov 30;169(2):157 – 64.

[2] West CR, Romer LM, Krassioukov A. Autonomic function and exercise performance in elite athletes with cervical spinal cord injury. Med Sci Sports Exerc 2013 Feb;45(2):261 – 7.

[3] Krassioukov AV, Weaver LC. Morphological changes in sympathetic preganglionic neurons after spinal cord injury in rats. Neurosci 1996;70:211 – 26.

[4] Krassioukov A, Eng JJ, Warburton DE, Teasell R. A systematic review of the management of orthostatic hypotension after spinal cord injury. Arch Phys Med Rehabil 2009 May;90(5):876 – 85.

[5] Krassioukov A, Warburton DE, Teasell R, Eng JJ. A systematic review of the management of autonomic dysreflexia after spinal cord injury. Arch Phys Med Rehabil 2009 Apr;90(4):682 – 95.