(1603) Reanimation After Hemorrhagic Shock Using Intra-Arterially Infused Phospholipid Nanoparticles

Introduction: On the battlefield, 91% of potentially survivable mortality is due to blood loss leading to clinical death (CD) before transport to a medical facility. Therefore, we developed a rat model of CD due to severe rapid blood loss. In prior experiments, we found that intraarterial (IA) infusion was superior to intravenous (IV) in restoring cardiac contraction and respiration. Blood cannot be available to the battlefield. There is a need for an effective reanimation fluid. Therefore, we investigated the use of VBI-1, which is a phospholipid nanoparticle emulsion (particle diameter is 17 nm) that absorbs nitric oxide (NO). NO is produced early during hemorrhagic shock and induces hypotension. These findings have led us to hypothesize that the IA infusion of VBI-1 will be superior to other fluids in increasing mean arterial blood pressure (MAP).

Methods: Six female and 6 male rats were subjected to reanimation with either shed blood or VBI-1. Under isoflurane anesthesia, both femoral arteries were canulated. CD was induced by withdrawing blood until respiration ceased. This occurred after withdrawing 40 to 45% of the blood at a rate of 1.5 mL/min. Immediately following CD, shed blood or VBI-I was infused IA in an equivalent volume to the blood loss at a rate of 10 mL/min. MAP was continuously measured for 12 hours post infusion. Data are mean ± SE.

Results: In preliminary experiments, VBI-1 was superior to blood, Ringer’s lactate, and VBI-S, another phospholipid particle formulation (diameter is 250 nm), in elevating MAP at 4 hours after CD. Therefore, we decided to directly compare blood and VBI-1 to extend reanimation to 12 hours. MAP ± SE prior to blood withdrawal for blood was 79.9 ± 4.9 and VBI-1 was 80.1 ± 2.7. At CD, MAP for blood was 10.6 ± 1.5 and VBI-1 was 8.8 ± 1.9. MAP 12 hours post-blood infusion was 65.4 ± 13.0, whereas post-VBI-1 infusion was 53.4 ± 8.6 mmHg. 2-way ANOVA showed no significant difference between shed blood and VBI-1 infusion (p = 0.2120).

Conclusions: After CD, IA infusion of VBI-1 increased MAP to a level that was equivalent to blood and spontaneous respiration returned. No adverse effects of VBI-1 were observed. Future research should establish the effects of VBI-1 on different organ systems.