Abstract 18408: Cortical Spreading Depolarizations After Cardiac Arrest in an Asphyxial Rat Model

Abstract

Introduction: Delayed neuronal cell death is observed following cardiac arrest (CA). The exact mechanisms remain unknown. Cortical spreading depolarization (CSD) is characterized by depolarization of neurons and glia cells, spreading as a wave that travels across the cortex. CSDs are known to occur in peri-infarct tissue and have been associated with poor outcome after stroke, and might contribute to the progression of neuronal injury after CA. Objective: To investigate if spontaneous CSDs occur during the post resuscitation period following CA, and to describe the characteristics of induced CSDs. Methods: Isoflurane-anesthetized Sprague-Dawley rats were randomized into one control group observed for 90 min (n=8), and two CA groups observed for 90 min (CA90min, n=7) and 360 min (CA360min, n=7), respectively, before data collection started. Animals underwent 8 min of asphyxial CA. Electrophysiological recordings were obtained over the right hemisphere through a burr hole. Potassium chloride (KCL) was applied onto the cortex through a separate burr hole in order to induce CSDs. Direct current recordings were gathered using an AgCl glass electrode. Induced abnormal CSDs were defined as CSDs with prolonged duration, low peak value, altered propagation speed and/or epileptiform discharges. Data collection (210 min) was divided into two periods: 1) In the 1 st period no stimulation was applied in order to detect spontaneous elicited CSDs. 2) In the 2 nd period KCl was applied. Results: Spontaneous CSDs were observed in one CA360min animal with prolonged CPR and time to return of spontaneous circulation of 298 sec. Significantly fewer CSDs were induced following KCl application in CA animals when compared with healthy controls (median(IQR) Control: 6(5-7) CA90min: 2(1-4) CA360min: 1(1-3), p<0.05). Induced abnormal CSDs were seen in both CA groups but not in controls (control vs. CA90min p=0.004, control vs. CA360min p=0.054). KCl application elicited multiple CSDs in rapid succession in 50% of CA animals and none of the controls (p=0.052). Conclusion: CSDs can occur following prolonged CA and resuscitation, and may lead to additional neuronal injury. The appearance and number of induced CSDs were altered in CA animals in comparison with healthy controls.