We recently documented that paraplegia (T₅ spinal cord transection) alters cardiac electrophysiology and increases the susceptibility to ventricular tachy-arrhythmias induced by programmed electrical stimulation. However, coronary artery occlusion is the leading cause of death in industrially developed countries and will be the major cause of death in the world by the year 2020. The majority of these deaths result from tachy-arrhythmias that culminate in ventricular fibrillation. Beta-adrenergic receptor antagonists have been shown to reduce the incidence of sudden cardiac death. Therefore, we tested the hypothesis that chronic T₅ spinal cord transection increases the susceptibility to clinically relevant ischemia/reperfusion-induced sustained ventricular tachycardia due to enhanced sympathetic activity. Intact and chronic (4 weeks post transection) T₅ spinal cord transected (T₅X) male rats were instrumented to record arterial pressure, body temperature, and ECG. In addition, a snare was placed around the left main coronary artery. The susceptibility to sustained ventricular tachycardia produced by 2.5 minutes of occlusion and reperfusion of the left main coronary artery was determined in conscious rats by pulling on the snare. Reperfusion culminated in sustained ventricular tachycardia in 100% of T₅X rats (susceptible T₅X, 10/10) and 0% of intact rats [susceptible intact, 0/10 (p<0.05 T5X vs intact)]. Beta-adrenergic receptor blockade prevented reperfusion-induced sustained ventricular tachycardia in T₅X rats [susceptible T₅X 0/8, 0% (p<0.05)]. Thus paraplegia increases the susceptibility to reperfusion-induced sustained ventricular tachycardia due to enhanced sympathetic activity.