title: A review of leukofiltration in cardiac surgery: the time course of reperfusion injury may facilitate study design of anti-inflammatory effects.
abstract: The systemic inflammatory response syndrome (SIRS) is a well-recognized phenomenon attending cardiopulmonary bypass (CPB) surgery. SIRS leads to costly complications and several strategies intended to ameliorate the symptoms have been studied, including leukocyte reduction using filtration. Although the body of work suggests that leukoreduction attenuates SIRS, discrepancies remain within the literature. The recent literature is reviewed, highlighting the areas where concordance is lacking. Investigations into many promising device-related technologies are often deterred by the high costs of clinical trials. Adding to costs is the fact that clinical end points generally require large sample sizes. An understanding, however, of the pathogenesis of reperfusion injury can guide the investigator to choose physiologic response measures that correlate well with clinical outcome, but feature low inherent variability, allowing for clinical trials with smaller sample sizes. With this goal in mind, a model for the pathogenesis of reperfusion injury is described. Using a model of reperfusion injury as underpinnings for the design of prospective pilot studies, we show that salvaged blood reinfused following CPB elicits time-dependent effects on pulmonary function as predicted by the model. Data are illustrative of principles that could expand the scope of clinical investigations designed to validate the use of physiologic response measures as correlates of clinical outcome. Such investigations would target surrogate markers of clinical outcome, measured at clinically relevant times. Once validated, these surrogate markers would, thereafter, become economical screening tools for clinical studies of device-related or pharmacological anti- inflammatory interventions.
authors.affiliation: Pall Medical, Pall Corporation, East Hills, New York, USA. jerry_ortolano@pall.com
authors.forename: Girolamo A
authors.initials: GA
authors.lastname: Ortolano
authors.forename: Gabriel S
authors.initials: GS
authors.lastname: Aldea
authors.forename: Kevin
authors.initials: K
authors.lastname: Lilly
authors.forename: Paul
authors.initials: P
authors.lastname: O'Gara
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Alkon
authors.forename: Frederick
authors.initials: F
authors.lastname: Mader
authors.forename: Tarek
authors.initials: T
authors.lastname: Murad
authors.forename: Charles P
authors.initials: CP
authors.lastname: Altenbern
authors.forename: Charles S
authors.initials: CS
authors.lastname: Tritt
authors.forename: Anthony
authors.initials: A
authors.lastname: Capetandes
authors.forename: Nicolas S
authors.initials: NS
authors.lastname: Gikakis
authors.forename: Barry
authors.initials: B
authors.lastname: Wenz
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Shemin
authors.forename: Francis X
authors.initials: FX
authors.lastname: Downey
mesh_terms: D006348:Cardiac Surgical Procedures; D006440:Hemofiltration; D006801:Humans; D007937:Leukapheresis / Q000379:methods*; D015427:Reperfusion Injury / Q000503:physiopathology; D013997:Time Factors