title: Perflubron emulsion reduces inflammation during extracorporeal circulation.
abstract: The recovery from cardiac surgery and cardiopulmonary bypass can be complicated by an acute inflammatory response. Circulating blood through an extracorporeal circuit (ECC) contributes to this complication. Perfluorocarbon-based blood substitutes (PFCs) are under investigation for use as a component of the ECC "prime" solution, because PFCs increase the oxygen-carrying capacity of the diluted blood. Some PFCs may provide the additional benefit of attenuating the ECC-induced inflammatory response. Earlier, we reported that perflubron emulsion (PFE, Alliance Pharmaceutical Corp.) reduced neutrophil (PMN) activation in vivo. However, the potential of PFE to reduce ECC-induced PMN activation has not been investigated. In this study, we used a small-scale ECC model to quantify the extent of PMN activation during circulation and to examine if PFE treatment attenuated PMN activation. ECC circuits were filled with a mixture of blood and Plasmalyte. Two groups were studied: an untreated group containing blood plus PlasmaLyte and a treated group in which some of the Plasmalyte was substituted with PFE (4.5 g/100 ml). Hematology and measures of whole blood PMN activation were made from blood samples taken periodically throughout the 120-min ECC circulation period. We found, for the untreated group, a significant decrease in the number of circulating PMNs and an increase in PMN activation with time. PMN activation was demonstrated as a significant increase in the expression of the PMN adhesion protein CD11b (P < 0.05) and an increase in PMN oxygen free radical production (reactive oxygen species (ROS)). After 120 min of circulation, the PMNs remained capable of a significant response to a second inflammatory stimulus, but PFE treatment significantly attenuated the fMLP-induced increase in PMN ROS at t = 120 min (P < 0.05). These results suggest that PFE may have dual utility in cardiac surgery, to increase oxygen delivery and to serve as an antiinflammatory agent.
authors: Department of Surgery, Cardiovascular and Thoracic Surgery, Tucson, Arizona 85718, USA. pmcdonag@u.arizona.edu
authors: P
authors: P
authors: McDonagh
authors: K
authors: K
authors: Cerney
authors: J
authors: J
authors: Hokama
authors: G
authors: G
authors: Lai
authors: R
authors: R
authors: Gonzales
authors: G
authors: G
authors: Davis-Gorman
authors: J
authors: J
authors: Copeland
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D004655:Emulsions / Q000494:pharmacology; D005112:Extracorporeal Circulation / Q000009:adverse effects*; D005466:Fluorocarbons / Q000494:pharmacology*; D005740:Gases / Q000097:blood; D006842:Hydrocarbons, Brominated; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D007958:Leukocyte Count; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D004655:Emulsions; D005466:Fluorocarbons; D005740:Gases; D006842:Hydrocarbons, Brominated; D009240:N-Formylmethionine Leucyl-Phenylalanine; C003072:perflubron