Introduction: Hemorrhagic shock (HS), causing arterial hypotension, often occurs after traumatic brain injury (TBI). Current resuscitation fluids do not ameliorate the impaired cerebral microvascular perfusion leading to hypoxia, neuronal death, increased mortality and poor neurological outcome. Nanomolar concentrations of intravascular blood soluble drag reducing polymers (DRP) were shown to increase tissue perfusion and oxygenation and decrease peripheral vascular resistance by rheological modulation of hemodynamics. We hypothesized that the resuscitation fluid with DRP would improve cerebral microcirculation, oxygenation and neuronal recovery after TBI combined with HS (TBI+HS).
Methods: Mild TBI was induced in rats by fluid percussion pulse (1.5 ATA, 50 ms duration) followed by induced by phlebotomy arterial hypotension (40 mmHg). Resuscitation fluid (lactated Ringers, LR) with DRP (DRP/LR) or without (LR) was infused to restore mean arterial pressure (MAP) to 60 mmHg for one hour (pre-hospital care), followed by re-infusion of blood to a MAP of 100 mmHg (hospital care). Using in vivo 2-photon laser scanning microscopy over the parietal cortex we monitored changes in microvascular blood flow, tissue oxygenation (NADH) and neuronal necrosis (i.v. propidium Iodide) for 5 hr after TBI+HS. Doppler cortical flow, rectal and cranial temperatures, arterial pressure, blood gases and electrolytes were monitored.
Results: TBI+HS compromised brain microvascular flow leading to tissue hypoxia followed by neuronal necrosis. Resuscitation with DRP/LR compared to LR better improved cerebral microvascular perfusion (82 ± 9.7% vs. 62 ± 9.7%, respectively from pre-TBI baseline, p<0.05, n=7), attenuated capillary microtrombi formation and re-recruited collapsed during HS capillaries. Improved microvascular perfusion increased cortical oxygenation reducing hypoxia (77 ± 8.2% vs. 60 ± 10.5%, by DRP-LR vs. LR, respectively from baseline, p<0.05) and decreased neuronal necrosis (21 ± 7.2% vs. 36 ± 7.3%, respectively as a percentage of total neurons, p<0.05).
Conclusions: DRP/LR resuscitation fluid is superior in the restoration of the cerebral microcirculation and neuroprotection following TBI + HS compared to volume expansion with LR.