Abstract 179: Reversal of Clinical Death by Intra-Arterial Infusion of Phospholipid Nanoparticles (VBI-1)

Introduction: Ninety percent of deaths from potentially survivable injuries on the battlefield are attributed to hemorrhagic shock, leading to clinical death (CD) with the loss of pulse and respiratory drive before reaching a surgeon. However, currently available fluids are inadequate for rescuing warfighters who have experienced exsanguination. Furthermore, these fluids have the potential to cause reperfusion injury in vital organs. We developed a rat model of CD to evaluate the effectiveness of two phospholipid nanoparticle formulations (VBI-1, VBI-S) and compared intra-arterial (IA) versus intravenous (IV) infusion on resuscitation.

Hypothesis: We hypothesized that the nanoparticles would restore breathing and blood pressure (BP) in rats after CD induced by hemorrhagic shock.

Goals: To establish a model that reliably restores breathing and maintains a survivable BP for 240 minutes after CD.

Methods: Male and female Sprague Dawley rats were divided into four groups (n=6-7). The rats were anesthetized with isoflurane, followed by cannulation of femoral arteries. Blood was withdrawn over two minutes until respiration ceased. Equal volumes of either Ringer’s Lactate (LR), shed blood, VBI-1, or VBI-S were infused over one minute, with continuous monitoring of BP.

Results: Loss of respiration occurred with blood withdrawal ranging from 39.8% to 43.2% of the predicted total blood volume. Post-IA infusion, the survival rates of the four groups for 240 minutes were as follows: 100% with VBI-1 (n=6), 83.3% with blood (n=7), 66.7% with VBI-S (n=6), and 0% with LR (n=6). Two-way ANOVA analysis revealed a significant difference in mean arterial pressure (MAP) among the four fluids (p=0.0004). Post-hoc analysis indicated the fluid responsiveness in elevating MAP as follows: VBI-1 > VBI-S = shed blood > LR. Regarding the VBI-1 infusion routes, the IA infusion demonstrated 100% survival (n=6) compared to the IV infusion with 40% (n=6) survival.

Conclusion: VBI-1 outperformed all other fluids, including blood, in achieving reanimation and elevating MAP. IA infusion of VBI-1 demonstrated a higher reanimation rate compared to IV infusion. Based on these findings, VBI-1 is a promising new treatment for CD due to severe hemorrhagic shock; potentially saving lives.