Threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survival

BACKGROUND: Vagus nerve stimulation (VNS) has shown therapeutic potential in a variety of different diseases with many ongoing clinical trials. The role of VNS in reducing ischemic injury in the brain requires further evaluation. Cardiac arrest (CA) causes global ischemia and leads to the injury of vital organs, especially the brain. In this study, we investigated the protective effects of customized threshold-adjusted VNS (tVNS) in a rat model of CA and resuscitation. METHODS: Sprague-Dawley rats underwent 12 min asphyxia-CA followed by resuscitation. Rats were assigned to either post-resuscitation tVNS for 2 h or no-tVNS (control). tVNS was applied by electrode placement in the left cervical vagus nerve. To optimize a threshold, we used animal’s heart rate and determined a 15–20% drop from baseline levels as the effective and physiological threshold for each animal. The primary endpoint was 72 h survival; secondary endpoints included neurological functional recovery, reduction in brain cellular injury (histopathology), cardiac and renal injury parameters (troponin I and creatinine levels, respectively). RESULTS: In comparison to the control group, tVNS significantly improved 72 h survival and brain functional recovery after 12 minutes of CA. The tVNS group demonstrated significantly reduced numbers of damaged neurons in the CA1 hippocampal region of the brain as compared to the control group. Similarly, the tVNS group showed decreased trend in plasma troponin I and creatinine levels as compared to the control group. CONCLUSIONS: Our findings suggest that using tVNS for 2 h after 12 minutes of CA attenuates ischemia neuronal cell death, heart and kidney damage, and improves 72 h survival with improved neurological recovery.