Influence of Perflubron Emulsion Particle Size on Blood Half-Life and Febrile Response in Rats

Abstract

Perfluorochemical (PFC) emulsions are particulate in nature and, as such, can cause delayed febrile reactions when injected intravenously. This study investigated the influence of emulsion particle size on intravascular retention and on body temperature changes in unrestrained conscious rats. Concentrated (60% to 90% w/v) emulsions based on perflubron (perfluorooctyl bromide [PFOB]) with mean particle sizes ranging from 0.05 microns to 0.63 microns were tested. Rats were fitted with a chronic jugular catheter and an abdominal body temperature telemetry unit. Fully recovered, conscious rats were monitored for 24 hours after infusion (dose = 2.7 g PFC/kg). Emulsion blood half-life (T1/2) was determined from blood perflubron levels measured by gas chromatography. Emulsions with a particle size of 0.2-0.3 microns caused fevers (6 to 8 hour duration) which peaked at 1-1.5 degrees C above normal (approximately 37.5 degrees C). Fevers could be blocked by i.v. treatment with either cyclooxygenase inhibitors (ibuprofen) or corticosteroids (dexamethasone). Both intensity and duration of the temperature response, quantified by area under the temperature curve, was decreased significantly for emulsions with a particle size < or = 0.12 micron. Blood T1/2 varied inversely with particle size, and was 3 to 4 fold longer for emulsions with a mean particle size < or = 0.2 micron. Thus, smaller emulsion particles more effectively evaded the reticuloendothelial system, which resulted in longer intravascular retention, less macrophage activity, and reduced febrile responses.

Intranasal Perfluorochemical Spray for Preferential Brain Cooling in Sheep

“…Follow-up of primates have shown small amounts of PFC 3 years following liquid PFC ventilation, without deleterious effects [64]. Blood levels following intratracheal PFC administration are orders of magnitude lower than those following intravascular administration (40-80 mg PFC/ml of blood) of PFC emulsion clinically approved for angioplasty in humans and under investigation as an oxygen carrier or temporary ''blood substitute'' [67,69].…”

Perfluorochemical Liquids Do Not Stimulate Endothelin-1 or Nitric Oxide Production in Human Blood Leukocytes

“…The intention of this study was to examine if PFD or PFB may induce responses in blood leukocytes that induce production of tonus modulators such as NO and ET-1. The rationale to study blood leukocytes was that during intratracheal administration small concentrations of PFC may be detected in blood, and given intravenously PFC at much higher concentrations are exposed to blood leukocytes [29,30]. Because PFC liquids may be used as a breathing medium to relieve respiratory distress in patients that also may have persistent pulmonary hypertension, the presence of selective pulmonary vasodilators such as NO may be favorable, whereas the constriction induced by ET-1 would be unfavorable.…”

Künstliche Sauerstoffträger als Alternative zur Fremdbluttransfusion

“…Gewöhnlich sistieren diese Symptome innerhalb von 12-24 h nach ihrem Auftreten spontan [7,24,34]. Die Mehrzahl dieser Symptome kann auch durch Zyklooxygenaseinhibitoren und Kortikosteroide verhindert oder therapiert werden [22]. Die unerwünschten Wirkungen beruhen auf der Phagozytose der Partikel, durch die es in Abhängigkeit von der PFC-Präparation zu einer Monozyten-/Makrophagenaktivierung unterschiedlichen Ausmaßes mit Freisetzung von Prostaglandinen, Endoperoxiden und Zytokinen sowie zur Induktion von Akute-Phase-Proteinen kommen kann [34,47].…”