Invited commentary

Abstract

This is a very interesting piece of clinical research, focusing on the continued investigation of the clinical efficacy and efficiency of leukocyte filtration technology, applied during routine cardiopulmonary bypass (CPB). The authors focus on molecules thought to be involved in neutrphil-endothelial interaction, in particular the study focused on molecules known to be involved in tethering (P-Selectin), firm adherence (ICAM-1), transmigration of neutrophils (IL-8, PECAM-1), and degranualtion (MDA). The authors found that there was a general upregulation in all of these factors associated with CPB, but there was a substantially less effect in those patients exposed to leukocyte depletion. The authors conclude that the application of leukocyte depletion filtration technology attenuates the very important neutrophil-endothelial interaction, known to be central to the inflammatory response to CPB.The authors are to be congratulated for a performing a very good clinical study, albeit on a small group of patients. Despite the high quality of this research, this study does little to calm the leukocyte depletion controversy. The popular understanding of the major benefit of leukocyte depletion is that this technique removes activated neutrophils from the systemic circulation during CPB, and that this is a desirable characteristic is not in doubt. However, the use of leukocyte filtration remains controversial when viewed from the standpoint of the molecular basis of neutrophil-endothelial interaction, but less controversial in the context of clinical outcome studies. To illustrate this, using MDA as a marker of lipid peroxidation in a much larger study of 80 patients, Scholz and coworkers [1Scholz M. Simon A. Matheis G. et al.Leukocyte filtration fails to limit functional neutrophil activity during cardiac surgery.Inflamm Res. 2002; 51: 363-368Crossref PubMed Google Scholar] found that there was no difference between filter and nonfilter groups, indeed they found that there were greater levels of PMNE and MPO in peripheral venous blood of patients undergoing CPB with the leukocyte filters, but surmised that this was due to degranulation of neutrophils captured by the filters. In an earlier study, Baksaas and colleagues [2Baksaas S.T. Videm V. Mollnes T.E. et al.Leucocyte filtration during cardiopulmonary bypass hardly changed leucocyte counts and did not influence myeloperoxidase, complement, cytokines or platelets.Perfusion. 1998; 13: 429-436Crossref PubMed Scopus (32) Google Scholar] also found no difference between leukocyte-filtered groups when compared with controls in terms of markers of inflammation (MPO, IL-6, complement), and that the filters produced no significant drop in white cell or neutrophil count.Clinical outcome studies tend to tell a somewhat different story. Many clinical outcome studies have shown that the application of leukocyte depleting technology, used in the arterial line of the perfusion circuit, is associated with considerable clinical advantages. Olivencia-Yurvati and associates [3Olivencia-Yurvati A.H. Ferrara C.A. Tierney N. Wallace N. Mallet R.T. Strategic leukocyte depletion reduces pulmonary microvascular pressure and improves pulmonary status post-cardiopulmonary bypass.Perfusion. 2003; 18: 23-31Crossref PubMed Scopus (36) Google Scholar], for example, found that leukocyte depletion was associated with a reduction in pulmonary vascular pressure and an improvement in postoperative pulmonary function. These findings were further enhanced by reduction in intensive care units (ICU) and hospital stay in patients in which leukocyte depletion was used. Our own experience with leukocyte depletion reflects the experiences of others investigating this field. In one brief clinical study (see Stefanou and coworkers [4Stefanou D.C. Gourlay T. Asimakopoulos G. Taylor K.M. Leucodepletion during cardiopulmonary bypass reduces blood transfusion, and crystalloid requirements.Perfusion. 2001; 16: 51-58Crossref PubMed Scopus (28) Google Scholar]), we found absolutely no difference between filtered and unfiltered groups in terms of molecular markers of inflammation (CD11b, MPO, lactoferrin), but we found a significant difference in terms of blood and crystalloid transfusion requirements, and ICU stay, in favor of leukocyte filtration. Indeed our experience with leukocyte depletion indicates that the most significant advantage is to be gained by positioning the leukocyte filter not in the arterial line, but, in the cardioplegia line of the bypass circuit (Samankatiwat and associates [5Samankatiwat P. Samartzis I. Lertsithichai P. et al.Leucocyte depletion in cardiopulmonary bypass a comparison of four strategies.Perfusion. 2003; 18: 95-105Crossref PubMed Scopus (20) Google Scholar]).In summary, I salute the elegant systematic approach to clinical study demonstrated by the authors, but I believe that this study does little to dispel the controversy surrounding the use of leukocyte filters in CPB. However, it may add to the weight of evidence in favor of leukocyte depletion, and would have added even more were the authors to have included indicators of clinical outcome in this study. What is clear, from this report and from the many others in field, is that the mode of action of leukocyte filtration remains uncertain and controversial, but something is happening that seems to benefit patients undergoing CPB, and studies of the nature described in the present study may help shed light on the responsible mechanism(s). This is a very interesting piece of clinical research, focusing on the continued investigation of the clinical efficacy and efficiency of leukocyte filtration technology, applied during routine cardiopulmonary bypass (CPB). The authors focus on molecules thought to be involved in neutrphil-endothelial interaction, in particular the study focused on molecules known to be involved in tethering (P-Selectin), firm adherence (ICAM-1), transmigration of neutrophils (IL-8, PECAM-1), and degranualtion (MDA). The authors found that there was a general upregulation in all of these factors associated with CPB, but there was a substantially less effect in those patients exposed to leukocyte depletion. The authors conclude that the application of leukocyte depletion filtration technology attenuates the very important neutrophil-endothelial interaction, known to be central to the inflammatory response to CPB. The authors are to be congratulated for a performing a very good clinical study, albeit on a small group of patients. Despite the high quality of this research, this study does little to calm the leukocyte depletion controversy. The popular understanding of the major benefit of leukocyte depletion is that this technique removes activated neutrophils from the systemic circulation during CPB, and that this is a desirable characteristic is not in doubt. However, the use of leukocyte filtration remains controversial when viewed from the standpoint of the molecular basis of neutrophil-endothelial interaction, but less controversial in the context of clinical outcome studies. To illustrate this, using MDA as a marker of lipid peroxidation in a much larger study of 80 patients, Scholz and coworkers [1Scholz M. Simon A. Matheis G. et al.Leukocyte filtration fails to limit functional neutrophil activity during cardiac surgery.Inflamm Res. 2002; 51: 363-368Crossref PubMed Google Scholar] found that there was no difference between filter and nonfilter groups, indeed they found that there were greater levels of PMNE and MPO in peripheral venous blood of patients undergoing CPB with the leukocyte filters, but surmised that this was due to degranulation of neutrophils captured by the filters. In an earlier study, Baksaas and colleagues [2Baksaas S.T. Videm V. Mollnes T.E. et al.Leucocyte filtration during cardiopulmonary bypass hardly changed leucocyte counts and did not influence myeloperoxidase, complement, cytokines or platelets.Perfusion. 1998; 13: 429-436Crossref PubMed Scopus (32) Google Scholar] also found no difference between leukocyte-filtered groups when compared with controls in terms of markers of inflammation (MPO, IL-6, complement), and that the filters produced no significant drop in white cell or neutrophil count. Clinical outcome studies tend to tell a somewhat different story. Many clinical outcome studies have shown that the application of leukocyte depleting technology, used in the arterial line of the perfusion circuit, is associated with considerable clinical advantages. Olivencia-Yurvati and associates [3Olivencia-Yurvati A.H. Ferrara C.A. Tierney N. Wallace N. Mallet R.T. Strategic leukocyte depletion reduces pulmonary microvascular pressure and improves pulmonary status post-cardiopulmonary bypass.Perfusion. 2003; 18: 23-31Crossref PubMed Scopus (36) Google Scholar], for example, found that leukocyte depletion was associated with a reduction in pulmonary vascular pressure and an improvement in postoperative pulmonary function. These findings were further enhanced by reduction in intensive care units (ICU) and hospital stay in patients in which leukocyte depletion was used. Our own experience with leukocyte depletion reflects the experiences of others investigating this field. In one brief clinical study (see Stefanou and coworkers [4Stefanou D.C. Gourlay T. Asimakopoulos G. Taylor K.M. Leucodepletion during cardiopulmonary bypass reduces blood transfusion, and crystalloid requirements.Perfusion. 2001; 16: 51-58Crossref PubMed Scopus (28) Google Scholar]), we found absolutely no difference between filtered and unfiltered groups in terms of molecular markers of inflammation (CD11b, MPO, lactoferrin), but we found a significant difference in terms of blood and crystalloid transfusion requirements, and ICU stay, in favor of leukocyte filtration. Indeed our experience with leukocyte depletion indicates that the most significant advantage is to be gained by positioning the leukocyte filter not in the arterial line, but, in the cardioplegia line of the bypass circuit (Samankatiwat and associates [5Samankatiwat P. Samartzis I. Lertsithichai P. et al.Leucocyte depletion in cardiopulmonary bypass a comparison of four strategies.Perfusion. 2003; 18: 95-105Crossref PubMed Scopus (20) Google Scholar]). In summary, I salute the elegant systematic approach to clinical study demonstrated by the authors, but I believe that this study does little to dispel the controversy surrounding the use of leukocyte filters in CPB. However, it may add to the weight of evidence in favor of leukocyte depletion, and would have added even more were the authors to have included indicators of clinical outcome in this study. What is clear, from this report and from the many others in field, is that the mode of action of leukocyte filtration remains uncertain and controversial, but something is happening that seems to benefit patients undergoing CPB, and studies of the nature described in the present study may help shed light on the responsible mechanism(s).