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.

Rewarming From Hypothermic Cardiac Arrest Applying Extracorporeal Life Support: A Systematic Review and Meta-Analysis

“…Technically, ECMO consists of a closed loop system with active venous drainage, which limits the size of the priming volume. Experiments on rats and piglets indicate that less hemodilution is associated with reduced activation of polymorph nuclear neutrophil granulocytes ( 125 , 126 ). Smaller air-blood interface causes less contact activation in comparison with a traditional CPB ( 127 ).…”

The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology

“…Large observational studies have demonstrated an association between the lowest haematocrit recorded during CPB and post-operative mortality [43]. One suggested explanation for this is that haemodilution leads to increased neutrophil activation [44]. …”

Clinical evaluation of minimized extracorporeal circulation in high-risk coronary revascularization: impact on air handling, inflammation, hemodilution and myocardial function

“…Consequently, there is also growing interest in the field of cardiovascular surgery regarding the reduction of blood product use via a significant reduction in hemodilution. The use of homologous blood products has been linked to increased frequency of organ dysfunction/failure, neurological dysfunction and longterm morbidity/mortality risk, in addition to the risk of transfusion-related communicable diseases (17,18). The reduced priming volume of our mini-CPB and, consequently, the possibility of maintaining a normal hematocrit during the CPB processing, certainly explains the decreased blood transfusion requirement, a factor clearly associated with postoperative outcome in cardiac surgical procedures.…”