Abstract 197: Establishing a Novel Pulse Wave Velocity-Guided Mouse Model of Cardiac Arrest With Different Durations

Abstract

Background: Neurological and cardiovascular injuries are the leading causes of death following cardiac arrest (CA). Few rodent models recapitulate these post-resuscitation symptoms. Aims: To develop extended ischemic CA models under Pulse Wave Velocity ( PWV) guidance with consistent post-CA brain injury (PCABI) and coronary dysfunction as potential therapeutic targets and mechanical studies. Methods: Forty-eight mice were randomized into four experimental groups (control, 8-, 12-, and 16-min CA). Potassium chloride (KCL) was intravenously injected, resulting in immediate asystole. Mice were resuscitated with an injection of epinephrine and manual chest compressions. PWV was monitored for the left carotid artery velocity and coronary flow reserve (CFR). Resuscitability, synaptic density in the hippocampal CA1 region, blood-brain barrier (BBB), and neurologic deficit scores (NDS) were also evaluated. Results: The PWV could monitor rapid asystole after KCL injection, improve cardiopulmonary resuscitation (CPR) success rates, and avoid the pre-matured end of resuscitation. Compared to the standard control, mice with 8-min CA had preserved CFR, mild loss of synaptic density (p>0.05), mild hypothermal, and a normal electrocardiogram. They maintained BBB integrity with no significant change to neurologic function. Compared with a 92% CPR success rate in 8 min-CA mice, 12 min-CA mice had 83%, and 16 min-CA mice had 58% resuscitability. Twelve min-CA mice had significantly impaired CFR at 24 hours and high lethality (40%, P<0.05) within the first three days; 16 min-CA mice worsened (33% survival rate, p<0.01). The 24 hrs electron microscope showed that CA-induced synaptic vesicle densities were ischemic time-dependent [350±60 (control) vs. 289±64 (8 min CA) vs. 269±34 (12 min CA) vs. 181±41/field (16 min CA)], consistent with NDS. The cerebrum and hippocampus were the most valuable regions, indicated by Evans blue evaluation at 48 hrs after CA. Conclusions: We established elongated PWV-guided CA models as with successful CPR, post-CA neurological deficits, leaky BBB, loss of synaptic density, coronary endothelial dysfunction, and even death in mice, which closely recapitulated the post-resuscitation symptoms in survived patients after CPR.