title: The effect of haemodilution on blood-biomaterial contact-mediated CD11b expression on neutrophils: ex vivo studies.
abstract: Modern cardiopulmonary bypass (CPB) systems are getting smaller, both in terms of the exposed surface area of biomaterials and the priming volume. In a series of studies utilizing a rat recirculation model, we demonstrated that the magnitude of the inflammatory response seen under these conditions is proportional to the surface area of exposed material, a finding that supports the use of miniature systems in terms of moderating the inflammatory response. However, the second impact of miniature perfusion systems, the reduced priming volume with concomitant reduction in haemodilution, was not investigated with reference to inflammation. The present study was designed to determine whether this change in CPB haematocrit profile has any effect on the inflammatory response. In common with previous studies by this group, we employed the expression of the integrin CD11b on neutrophils as a marker of neutrophil activation, and hence the inflammatory response, in a rat recirculation biomaterial testing model, containing di-(2-ethyl-hexyl)-phthalate plasticized polyvinyl chloride of the type commonly employed in CPB circuits. The results demonstrated that neutrophil activation is influenced by haemodilution. We studied five groups of animals, each with different mean induced haematocrit: Group 1 (41.3 +/- 1.27%); Group 2 (30.93 +/- 2.85%); Group 3 (24.83 +/- 1.36%); Group 4 (20.60 +/- 3.47%); Group 5 (20.48 +/- 1.31%). Groups 1 and 5 animals were controls, neither of which underwent the period of recirculation. Rather, these controls were employed to isolate the noncontact effect of haemodilution on CD11b expression. We found that there were differences in per cent change in CD11b expression from start to end of the recirculation period between Group 1 (109.54 +/- 49.53%), Group 2 (189.1 +/- 18.68%), Group 3 (224.28 +/- 43.97), Group 4 (368.97 +/- 24.28%) and Group 5 (127 +/- 57.8%). There were intergroup statistically significant differences (p < 0.05). These results confirm that there is a relationship between haematocrit level and biomaterial contact-mediated activation of neutrophils. Furthermore, these studies confirm that haemodilution alone has no effect on neutrophil activation. One possible explanation for this outcome is that with higher levels of haemodilution, neutrophils have a greater opportunity to contact surface 'receptor' sites on the biomaterial, resulting in more neutrophil activation. Whatever the mechanism, these data tend to support the modern trend towards lower circuit surface area and higher haematocrit.
authors.affiliation: Department of Cardiac Surgery, NHLI, Imperial College London, Faculty of Medicine, Hammersmith Hospital, London, UK. t.gourlay@ic.ac.uk
authors.forename: Terence
authors.initials: T
authors.lastname: Gourlay
authors.forename: Ioannis
authors.initials: I
authors.lastname: Samartzis
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Taylor
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects*; D001775:Blood Circulation; D039481:CD11b Antigen / Q000032:analysis / Q000096:biosynthesis*; D006400:Hematocrit; D006438:Hemodilution / Q000009:adverse effects*; D007249:Inflammation / Q000209:etiology; D008297:Male; D008422:Materials Testing; D023421:Models, Animal; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011143:Polyvinyl Chloride / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001672:Biocompatible Materials; D039481:CD11b Antigen; D011143:Polyvinyl Chloride