Effects of Perfluorocarbon Dodecafluoropentane (NVX-108) on Cerebral Microvasculature in the Healthy Rat

Abstract

NVX-108, a dodecafluoropentane-based perfluorocarbon (PFC) emulsion, has therapeutic potential as an oxygen- carrying fluid for emergency medical treatment for traumatic brain injury (TBI) and hemorrhagic shock. Potential cerebral vasoactive properties were assessed by directly measuring pial arteriolar vessel diameters before and after a 30 minute intravenous (IV) infusion of 1.0 ml/kg (high dose [H]) or 0.25 ml/kg (low dose [L]) NVX-108 compared to 2.0 ml/kg Saline (control) in healthy anesthetized rats (N = 6/group). Results showed that post-infusion vessel diameters for small (< 50 µm) and medium (50-100 µm)-sized pial arterioles were significantly (p < 0.05) narrower after only the NVX- 108 H infusion although this vasoconstriction was not statistically significant when analyzed as a percentage change in these vessels. Pial arteriolar vessel diameters were not significantly different for mean value or percentage change after either NVX-108 L or Saline infusions. There were no significant post-infusion changes from baseline in systolic, mean or diastolic blood pressures after any of the treatments although post-infusion blood pressure was statistically higher in the NVX-108 L group compared to NVX-108 H and Saline groups. Arterial blood gases, methemoglob in and lactate were not different from baseline or among groups. No adverse events were observed at either dose of NVX-108. In conclusion, neither 0.25 nor 1.0 ml/kg NVX-108 caused vasoconstriction in cerebral pial arterioles of healthy rats nor resulted in blood pressure changes; the compound should be considered for further investigation for TBI therapy.

Perfluorocarbon NVX-108 increased cerebral oxygen tension after traumatic brain injury in rats

“…In the current study NVX-108 had no effect on systemic blood pressures or HR, which is consistent with the findings in a previous study in healthy rats where the same cumulative dose of NVX-108 was not associated with any effect on MAP (Moon-Massat et al, 2014). There were also no adverse effects of NVX-108 treatment on blood gases, hemoglobin, pH, electrolytes, acid-base status, blood glucose, or lactate as all measurements were in the normal physiologic ranges for rats.…”

Exposure to Blast Overpressure Impairs Cerebral Microvascular Responses and Alters Vascular and Astrocytic Structure

“…For analysis of microvascular diameter changes, pial microvessels were grouped into either a ''small'' (<50 lm) or ''medium'' (50-100 lm) size category based on the pre-treatment baseline size. [28][29][30][31][32][33][34][35] The increase in the amount of smooth muscle with vessel size correlates with the ability of vessels to contract justifies dividing the vessels into size categories. 27 A power analysis of pilot data indicated that 40 vessels per size category were required to detect a 10% change in diameter with 80% power.…”

Current perspectives of artificial oxygen carriers as red blood cell substitutes: a review of old to cutting-edge technologies using in vitro and in vivo assessments

“…It improved the prognosis of spinal cord injuries (Mahon et al 2013a ), but was discontinued due to indemnity concerns in 2014 (Castro and Briceno 2010 ; Lambert et al 2019 ; Jägers et al 2021 ). Dodecafluoropentane (DDFPe) alone neither enhances the survival rate nor improves oxygen transport compared to fresh whole blood (FWB) after resuscitation in swine (Bonanno et al 2018 ); however, it provided more oxygenation and increased oxygen transport in rat brain tissue (Moon-Massat et al 2014 ). Therefore, DDFPe requires further pre-clinical evaluation, although it has completed phase Ib/II trials for acute ischemic stroke (Culp et al 2019 ; Graham et al 2019 ; Jägers et al 2021 ).…”