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

Myocardial ischemia-reperfusion (IR) can cause ventricular arrhythmias and sudden cardiac death via sympathoexcitation. The spinal cord neural network is crucial in triggering these arrhythmias and evaluating its neurotransmitter activity during IR is critical for understanding ventricular excitability control. To assess the real-time in vivo spinal neural activity in a large animal model, we developed a flexible glutamate-sensing multielectrode array. To record the glutamate signaling during IR injury, we inserted the probe into the dorsal horn of the thoracic spinal cord at the T2-T3 where neural signals generated by the cardiac sensory neurons are processed and provide sympathoexcitatory feedback to the heart. Using the glutamate sensing probe, we found that the spinal neural network was excited during IR, especially after 15 mins, and remained elevated during reperfusion. Higher glutamate signaling was correlated with the reduction in the cardiac myocyte activation recovery interval, showing higher sympathoexcitation, as well as dispersion of the repolarization which is a marker for increased risk of arrhythmias. This study illustrates a new technique for measuring the spinal glutamate at different spinal cord levels as a surrogate for the spinal neural network activity during cardiac interventions that engage the cardio-spinal neural pathway.