Sympathetic neuroplasticity following T5 spinal cord transection increases the susceptibility to ischemia-induced sustained ventricular tachycardia

Spinal cord injury-induced neuroplasticity within sympathetic pathways causes cardiac dysfunction and increases the susceptibility to life-threatening ventricular arrhythmias. For example, using coronary artery occlusion we documented a dramatic increase in the susceptibility to ventricular tachy-arrhythmias in conscious rats with mid-thoracic spinal cord injury (T₅X). Furthermore, using injection of cholera toxin B into the left and right stellate ganglia, as well as pericardial sac, and using the Sholl analyses, we documented that stellate-projecting sympathetic pre-ganglionic neurons within spinal segments T₁–T₅ as well as cardiac projecting sympathetic post-ganglionic neurons within the stellate ganglia from T₅X rats have larger dendritic trees than uninjured rats. The hearts of rats with T₅X are also hyper-innervated by tyrosine hydroxylase (TH)-immunoreactive sympathetic axons. These neuroplastic changes are associated with an increased nerve growth factor content within the heart and stellate ganglia. Thus, by using a combination of techniques and lines of evidence, we documented that mid-thoracic spinal cord injury results in cardiac sympathetic hyper-innervation and increased susceptibility to life-threatening ventricular arrhythmias. These results have important implications for understanding the mechanisms responsible for the high mortality rates and incidence of cardiovascular disease in individuals with spinal cord injury.