Real-time in vivo thoracic spinal glutamate sensing reveals spinal hyperactivity during myocardial ischemia

Abstract

Myocardial ischemia-reperfusion (IR)-induced ventricular arrhythmias are the leading cause of death. The spinal cord neural network plays a critical role in triggering ventricular arrhythmias. Assessing the spinal neural signaling during IR is essential to develop neuromodulation therapies that target the spinal neural network. In this study, we have developed a flexible glutamate-sensing multielectrode array to evaluate the spinal cord network activity in a large animal model using amperometry. IR injury was induced by ligating the left anterior descending artery for 1 hour and releasing the ligation suture. A glutamate sensing probe was inserted into the dorsal horn of the thoracic spinal cord at the T2-T3 level which processes the neural information that is generated by the cardiac sensory neurons and provides sympathoexcitatory feedback to the heart. Using the glutamate sensing probe, we have shown that the spinal neural network is excited during the IR, particularly after 15 mins of the onset of the ischemia and it is elevated even during the reperfusion. The glutamate release signal is correlated with the reduction in the cardiac myocyte activation recovery interval which is a surrogate for the action potential duration, as well as dispersion of the repolarization which is a marker for increased risk of arrhythmias. This study illustrates a new technique that is capable of measuring the spinal glutamate at different levels of the spinal cord as a surrogate for the spinal neural network activity during cardiac interventions that engage the cardio-spinal neural pathway.