Abstract WMP74: Resuscitation Fluid With Drag Reducing Additive Reduces Microthrombosis and Oxidative Stress After Traumatic Brain Injury Complicated by Hemorrhagic Shock

Abstract

Objective: Traumatic brain injury (TBI) is frequently accompanied by hemorrhagic shock (HS) significantly worsening morbidity and mortality. Existing colloid or crystalloid resuscitation fluids (RF) for volume expansion do not adequately mitigate impaired microvascular cerebral blood flow (mCBF) and causes post-reperfusion mitochondrial oxidative stress. We previously showed that resuscitation fluid with drag reducing polymers (DRP-RF) improves CBF by rheological modulation of hemodynamics. In this work, we have evaluated the efficiency of DRP-RF in the reduction of microthrombosis and post-reperfusion mitochondrial oxidative stress. Methods: TBI was induced in rats by fluid percussion (1.5 ATA, 50 ms) and followed by controlled hemorrhage to a mean arterial pressure (MAP) =40 mmHg. DRP-RF or Lactated Ringers (LR-RF) was infused to MAP =60 mmHg for one hour (pre-hospital), followed by blood re-infusion to a MAP=70 mmHg (hospital). In vivo 2-photon laser scanning microscopy over the parietal cortex was used to monitor microvascular blood flow, tissue hypoxia (NADH) and level of superoxide in the cortex as a measure of mitochondrial oxidative stress (i.v. hydroethidine [HEt], 1 mg/kg) for 5 hours after TBI/HS, followed by DiI vascular painting during perfusion-fixation. Temperatures, MAP, blood gases and electrolytes were monitored. Results: TBI/HS compromised CBF leading to capillary microthrombosis and tissue hypoxia. As in our previous work, DRP-RF better than LR-RF improved mCBF and tissue oxygenation (p<0.05). Reperfusion-induced oxidative stress, reflected by HEt fluorescence, was 32 ± 6% higher in LR-RF vs. DRP-RF (p < 0.05). Post-mortem whole-brain visualization of DiI painted vessels revealed multiple microthromboses in both hemispheres that were 29 ± 3% less in DRP-RF vs. LR-RF group (p < 0.05). Conclusions: Resuscitation after TBI/HS using DRP-RF effectively restores mCBF, reduces hypoxia, microthrombosis formation and mitochondrial oxidative stress compared to conventional volume expansion with LR-RF. Supported by DOD DM160142.