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

Rania Abutarboush,Charles Auker,Paula Moon-Massat,Anke Scultetus,Saad Mullah,Chioma Aligbe,Richard Mccarron,Anke Scultetus,Ashraful Haque,Biswajit Saha,Francoise Arnaud,Richard Mccarron,Georgina Pappas

doi:10.3390/jfb7040029

Abstract

Oxygen-carrying perfluorocarbon (PFC) fluids have the potential to increase tissue oxygenation during hypoxic states and to reduce ischemic cell death. Regulatory approval of oxygen therapeutics was halted due to concerns over vasoconstrictive side effects. The goal of this study was to assess the potential vasoactive properties of Perftoran by measuring brain pial arteriolar diameters in a healthy rat model. Perftoran, crystalloid (saline) or colloid (Hextend) solutions were administered as four sequential 30 min intravenous (IV) infusions, thus allowing an evaluation of cumulative dose-dependent effects. There were no overall changes in diameters of small-sized (<50 μm) pial arterioles within the Perftoran group, while both saline and Hextend groups exhibited vasoconstriction. Medium-sized arterioles (50–100 μm) showed minor (~8–9%) vasoconstriction within saline and Hextend groups and only ~5% vasoconstriction within the Perftoran group. For small- and medium-sized pial arterioles, the mean percent change in vessel diameters was not different among the groups. Although there was a tendency for arterial blood pressures to increase with Perftoran, pressures were not different from the other two groups. These data show that Perftoran, when administered to healthy anesthetized rats, does not cause additional vasoconstriction in cerebral pial arterioles or increase systemic blood pressure compared with saline or Hextend.

Highlights

Restoring tissue oxygenation following a hypoxic or ischemic event, such as hemorrhage, traumatic brain injury (TBI), or stroke, is critical for preventing hypoxia-induced pathophysiology and cell death
Chemical modifications led to a newer generation of oxygen therapeutics, including PFCs, which may offer the benefits of oxygen delivery to tissues and a lower incidence of vasoconstrictive side effects
This study demonstrated that the PFC emulsion Perftoran did not cause acute vasoconstriction in cerebral pial arterioles compared to 0.9% NaCl- and Hextend-treated animals in a healthy anesthetized rat cranial window model

Summary

Introduction

Restoring tissue oxygenation following a hypoxic or ischemic event, such as hemorrhage, traumatic brain injury (TBI), or stroke, is critical for preventing hypoxia-induced pathophysiology and cell death. In the United States, the first-generation PFC Fluosol-DA® (Green Cross Corp., Osaka, Japan) was approved by the Food and Drug Administration (FDA) for treatment of ischemia during balloon angioplasty in 1989. It was withdrawn from the market after five years due to its cumbersome preparation and pulmonary hypertensive effects [4]. Oxygent (Alliance Pharmaceutical Corp., San Diego, CA, USA) was a ‘second-generation’ commercial PFC that reached phase III clinical trials but failed to receive FDA approval for human use due to an increased incidence of strokes [5,6]. Perftoran is approved for human use for several indications, mainly as a substitute for blood during surgery, trauma and hemorrhagic shock; for treatment of various ischemic disorders including cerebral ischemia; and for organ preservation [8]

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