Abstract Rationale Our lab previously developed a model of clinical death from severe hemorrhagic shock, defined by a mean arterial pressure 20 mmHg and loss of spontaneous respiration. In that study, our proprietary phospholipid nanoparticle-based fluid, VBI-1, reanimated animals from clinical death but subsequently was found to impair coagulation. We combined our clinical death model with an uncontrolled liver laceration for an in vivo coagulopathy model. We hypothesized that specific modifications of VBI-1 would reduce bleeding time (BT). Methods Sprague Dawley rats (n = 30, 5 groups, 3M/3F) underwent hemorrhagic shock by withdrawal of blood until respirations ceased. Animals were resuscitated with an equivalent volume of one of five fluids: whole blood, VBI-1, VBI-1 diluted with an electrolyte solution, a 1: 1 mixture of diluted VBI-1 and blood, or VBI-160 (reformulated VBI-1 that contains less egg lecithin). After a 5-minute equilibration period, a 1. 2 cm punch biopsy was used to make a full thickness liver laceration. BT was measured by weighing gauze exchanged every 2 minutes. BT ended when two consecutive gauze weights showed no bleeding. Animals were monitored for 20 minutes post-hemostasis. Results VBI-1-treated animals exhibited significantly prolonged BTs. Compared to VBI-1, the blood group exhibited a 44. 8% decrease in BT (95% CI = 8. 9%, 66. 5%, p = 0. 01), the diluted VBI-1 group a decrease of 47. 8% (95% CI = 12. 3%, 69. 0%, p = 0. 009), the diluted VBI-1 mixed with blood group a decrease of 55. 9% (95% CI = 25. 9%, 73. 8%, p = 0. 0008), and the VBI-160 group a decrease of 55. 5% (95% CI = 25. 2%, 73. 5%, p = 0. 0009). A one-way ANOVA was performed (p = 4. 9*10^-4) with Tukeys post hoc analysis. No other pairs in the post hoc analysis were found to be significant (p. 05). Conclusion This bleeding model tested the efficacy of 3 methods for improving upon VBI-1. All three methods; simple dilution, dilution with the addition of blood, and reformulation, were shown to significantly decrease the BT. Further testing to ensure these preparations maintain all of the beneficial effects of VBI-1 (inhibition of ischemia reperfusion injury, rapid recovery of motor/ cognitive function, long-term shelf stability) will be tested next. If promising, the resulting fluid could be a possible treatment for hemorrhagic shock. This abstract is funded by: None
Aldaz et al. (Fri,) studied this question.