Cardiovascular dysfunction following spinal cord injury

Abstract

Both sensorimotor and autonomic dysfunctions often occur after spinal cord injury (SCI). Particularly, a high thoracic or cervical SCI interrupts supraspinal vasomotor pathways and results in disordered hemodynamics due to deregulated sympathetic outflow. As a result of the reduced sympathetic activity, patients with SCI may experience hypotension, cardiac dysrhythmias, and hypothermia post-injury. In the chronic phase, changes within the CNS and blood vessels lead to orthostatic hypotension and life-threatening autonomic dysreflexia (AD). AD is characterized by an episodic, massive sympathetic discharge that causes severe hypertension associated with bradycardia. The syndrome is often triggered by unpleasant visceral or sensory stimuli below the injury level. Currently the only treatments are palliative - once a stimulus elicits AD, pharmacological vasodilators are administered to help reduce the spike in arterial blood pressure. However, a more effective means would be to mitigate AD development by attenuating contributing mechanisms, such as the reorganization of intraspinal circuits below the level of injury. A better understanding of the neuropathophysiology underlying cardiovascular dysfunction after SCI is essential to better develop novel therapeutic approaches to restore hemodynamic performance.

Keywords: autonomic dysreflexia; bladder distension; blood pressure; bradycardia; heart rate; hypertension; plasticity; relay; spinal cord lesion; sprouting; sympathetic activity.

Figure 1

Schematic illustrating mechanisms involved in the development of autonomic dysreflexia (AD) following SCI. (A) In intact rats, primary pelvic CGRP⁺ C-fiber afferents convey sensory information to ascending propriospinal neurons, which relay the transmission from lumbosacral levels to the SPNs in the thoracolumbar spinal cord, eliciting sympathetic response in the peripheral vessels. (B) After high-level SCI, endogenous levels of NGF in the spinal cord are up-regulated and contribute to the plasticity of spinal neuronal pathways, including sprouting of lumbosacral CGRP⁺ fibers (purple) and propriospinal projections (Lavdas et al., 1997). Thisresults in an exaggerated signal triggered by sensory stimuli, such as distension of the bladder or colon, that is relayed to the reorganized propriospinal projections and then to the uninhibited SPNs. This culminates in a massive sympathetic discharge and baro-reflexic reaction. CGRP: Calcitonin gene-related peptide; SPNs: sympathetic preganglionic neurons; SCI: spinal cord injury.