Cerebral Vasoactivity and Oxygenation with Oxygen Carrier M101 in Rats

Abstract

The severity of traumatic brain injury (TBI) may be reduced if oxygen can be rapidly provided to the injured brain. This study evaluated if the oxygen-carrier M101 causes vasoconstricton of pial vasculature in healthy rats (Experiment 1) and if M101 improves brain tissue oxygen (PbtO) in rats with controlled cortical impact (CCI)-TBI (Experiment 2). M101 (12.5 mL/kg intravenous [IV] over 2 h) caused a mild (9 mm Hg) increase in the mean arterial blood pressure (MAP) of healthy rats without constriction of cerebral pial arterioles. M101 (12 mL/kg IV over 1 h) caused a modest (27 mm Hg) increase in MAP (peak, 123 ± 5 mm Hg [mean ± standard error of the mean]) of CCI-TBI rats and restored PbtO to near pre-injury levels. In both M101 and untreated control (NON) groups, PbtO was ∼30 ± 2 mm Hg pre-injury and decreased (p ≤ 0.05) to ∼16 ± 2 mm Hg 15 min after CCI. In NON, PbtO remained ∼50% of baseline but M101 administration resulted in a sustained increase in PbtO (peak, 25 ± 5 mm Hg), which was not significantly different from pre-injury until the end of the study, when it decreased again below pre-injury (but was still higher than NON). Histopathology showed no differences between groups. In conclusion, M101 increased systemic blood pressures without concurrent cerebral pial vasoconstriction (in healthy rats) and restored PbtO to 86% of pre-injury for at least 80 min when given soon after CCI-TBI. M101 should be evaluated in a clinically-relevant large animal model for pre-hospital treatment of TBI.

Brain oxygenation with a non‐vasoactive perfluorocarbon emulsion in a rat model of traumatic brain injury

“…Therefore, P bt O 2 was measured contralateral to the injury site. As previously shown, the non‐penetrating CCI TBI model used in this study resulted in a global cerebral injury as evidenced by histological injury at the site of impact as well as a significant reduction in P bt O 2 contralateral to the impact site. Therefore, the model was deemed acceptable for determining whether Oxycyte had a beneficial effect on cerebral brain oxygenation following TBI.…”

“…Measurements were made using a frequency domain phosphorescence lifetime instrument (PMOD 5000; Oxygen Enterprises) and the data were analyzed using software developed by Vinogradov and colleagues . The technique has been successfully used in our laboratory to evaluate P bt O 2 after TBI . Briefly, the validity of PQM was established in pilot animals that reliably showed P bt O 2 values (1) increased with increasing fraction of inspired oxygen (FiO 2 ), (2) decreased with increase in TBI severity, and (3) decreased to near zero after euthanasia.…”

Cerebral Microvascular and Systemic Effects Following Intravenous Administration of the Perfluorocarbon Emulsion Perftoran

“…HR was significantly different among the groups at baseline (T0) but was still within the normal range for rats under the anesthesia regimen used in this study [13,14,15,16,17] and did not exhibit any cumulative change (comparing T0 to T150) over time within any of the groups (Table 1). The only significant change in HR after an individual infusion was a slight transient increase in the 0.9% NaCl group after the third infusion.…”

“…A cranial window was prepared as previously described [13,14,17]. Briefly, pial microvasculature was accessed through a rectangular craniotomy prepared in the right parietal bone.…”

Sanguinate's effect on pial arterioles in healthy rats and cerebral oxygen tension after controlled cortical impact

“…HBOC and NON groups were analyzed for within-group changes over time as well as being compared to each other. An omnibus 2 (group) × 15 (observation period) mixed-model ANOVA (Moon-Massat et al, 2015) was used to compare PbtO 2 , blood pressures, heart rate, temperatures, blood gases, electrolytes, glucose and lactate data in the HBOC group to the NON group. Specifically, this test was used to determine whether the differences between HBOC and NON differed as a function of group and observation period.…”