ABSTRACT Objectives: Cardiac surgery with cardiopulmonary bypass provokes systemic inflammatory response, which may cause organ dysfunction. Studies have suggested that pre-operative statin therapy can reduce morbidity and mortality associated with cardiac surgery; the mechanism for this remains unclear. We hypothesise that underlying mechanism of action for these effects of statins is through inhibition of neutrophil transendothelial migration. Methods: We recruited 151 patients undergoing cardiac surgery. Of these 41 patients were on no-statin; 48 patients on low-dose (10 - 30 mg) and 62 patients were on high-dose statin (40 - 80 mg). Ex vivo neutrophil migration was performed on pre-operative blood samples of 90 patients. Of these 90 patients we used 36 patients to assess the levels of TNF-α and sICAM-1. Clinical parameters of total 151 patients were assessed to analyse outcome. Results: Ex vivo neutrophil migration was decreased in high-dose statin group when compared to neutrophils isolated from no-statin or low-dose statin groups (p < 0.001). Serum TNF-α levels were lower in the high-dose statin group (p = 0.002) and sICAM-1 levels were decreased in both low (p = 0.02) and high-dose statin (p = 0.01) groups. Conclusion: Our study demonstrates that high-dose statins reduce ex-vivo transendothelial neutrophil migration, TNF-α and sICAM-1 serum levels suggesting that statins may help in decreasing the post-cardiac surgery morbidity.
Cite this paper
A. Raza, S. Kennedy, Y. Fan, B. Maher, M. Codd, T. Murphy, A. Wood and W. Watson, "Anti Inflammatory Effects of Statins in Cardiac Surgery Patients," World Journal of Cardiovascular Surgery, Vol. 2 No. 3, 2012, pp. 40-47. doi: 10.4236/wjcs.2012.23010.
 L. H. Edmunds Jr., “Inflammatory Response to Cardiopulmonary Bypass,” The Annals of Thoracic Surgery, Vol. 66, No. 5, Suppl. 1, 1998, pp. S12-S16.
 J. R. S. Day and K. M. Taylor, “The Systemic Inflammatory Response Syndrome and Cardiopulmonary Bypass,” International Journal of Surgery, Vol. 3, No. 2, 2005, pp. 129-140. doi:10.1016/j.ijsu.2005.04.002
 N. C. Cavarocchi, M. D. England, H. V. Schaff, P. Russo, T. A. Orszulak, W. A. Schnell Jr., et al., “Oxygen Free Radical Generation during Cardiopulmonary Bypass: Correlation with Complement Activation,” Circulation, Vol. 74, No. 5, Pt. 2, 1986, pp. III130-III133.
 V. Niggli, “Microtubule-Disruption-Induced and Chemotactic-Peptide-Induced Migration of Human Neutrophils: Implications for Differential Sets of Signalling Pathways,” Journal of Cell Science, Vol. 116, Pt. 5, 2003, pp. 813-822. doi:10.1242/jcs.00306
 B. M. Maher, T. N. Dhonnchu, J. P. Burke, A. Soo, A. E. Wood and R. W. G. Watson, “Statins Alter Neutrophil Migration by Modulating Cellular Rho Activity—A Potential Mechanism for Statins-Mediated Pleotropic Effects?” Journal of Leukocyte Biology, Vol. 85, No. 1, 2009, pp. 186-193. doi:10.1189/jlb.0608382
 N. Chalasani, “Statins and Hepatotoxicity: Focus on Patients with Fatty Liver,” Hepatology, Vol. 41, No. 4, 2005, pp. 690-695. doi:10.1002/hep.20671
 The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group, “Prevention of Cardiovascular Events and Death with Pravastatin in Patients with Coronary Heart Disease and a Broad Range of Initial Cholesterol Levels,” The New England Journal of Medicine, Vol. 339, No. 19, 1998, pp. 1349-1357.
 L. L. Clark, J. S. Ikonomidis, F. A. Crawford Jr., A. Crumbley 3rd, J. M. Kratz, M. R. Stroud, et al., “Preoperative Statin Treatment is Associated with Reduced Postoperative Mortality and Morbidity in Patients Undergoing Cardiac Surgery: An 8-Year Retrospective Cohort Study,” The Journal of Thoracic and Cardiovascular Surgery, Vol. 131, No. 3, 2006, pp. 679-685.
 J. S. Pober, “Effects of Tumour Necrosis Factor and Related Cytokines on Vascular Endothelial Cells,” Ciba Foundation Symposium, Vol. 131, 1987, pp. 170-184.
 G. J. Blake and P. M. Ridker, “Novel Clinical Markers of Vascular Wall Inflammation,” Circulation Research, Vol. 89, No. 9, 2001, pp. 763-771. doi:10.1161/hh2101.099270
 J. S. Pober, M. A. Gimbrone Jr., L. A. Lapierre, D. L. Mendrick, W. Fiers, R. Rothlein and T. A. Springer, “Overlapping Patterns of Activation of Human Endothelial Cells by Interleukin 1, Tumor Necrosis Factor, and Immune Interferon,” Journal of Immunology, Vol. 137, No. 6, 1986, pp. 1893-1896.
 A. Rezaie-Majd, G. W. Prager, R. A. Bucek, G. H. Schernthaner, T. Maca, H.-G. Kress, et al., “Simvastatin Reduces the Expression of Adhesion Molecules in Circulating Monocytes from Hypercholesterolemic Patients,” Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 23, No. 3, 2003, pp. 397-403.
 L. M. Blanco-Colio, J. L. Martin-Ventura, E. de Teresa, C. Farsang, A. Gaw, G. Gensini, et al., “Elevated ICAM-1 and MCP-1 Plasma Levels in Subjects at High Cardiovascular Risk Are Diminished by Atorvastatin Treatment. Atorvastatin on Inflammatory Markers Study: A Substudy of Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration,” American Heart Journal, Vol. 153, No. 5, 2007, pp. 881-888. doi:10.1016/j.ahj.2007.02.029
 A. J. Mackarel, K. J. Russell, C. S. Brady, M. X. FitzGerald and C. M. O’Connor, “Interleukin-8 and LeukotrieneB(4), But Not Formylmethionyl Leucylphenylalanine, Stimulate CD18-Independent Migration of Neutrophils Across Human Pulmonary Endothelial Cells in Vitro,” American Journal of Respiratory Cell and Molecular Biology, Vol. 23, No. 2, 2000, pp. 154-161.
 F. Roques, S. A. Nashef, P. Michel, E. Gauducheau, C. de Vincentiis, E. Baudet, et al., “Risk Factors and Outcome in European Cardiac Surgery: Analysis of the EuroSCORE Multinational Database of 19030 Patients,” European Journal of Cardio-Thoracic Surgery, Vol. 15, No. 6, 1999, pp. 816-822.
 J. H. Levy and K. A. Tanaka, “Inflammatory Response to Cardiopulmonary Bypass,” The Annals of Thoracic Surgery, Vol. 75, No. 2, 2003, pp. S715-S720.
 L. M. Fedoruk, H. K. Wang, M. R. Conaway, I. L. Kron and K. C. Johnston, “Statin Therapy Improves Outcomes after Valvular Heart Surgery,” The Annals of Thoracic Surgery, Vol. 85, No. 5, 2008, pp. 1521-1526.
 A. Kinsella, A. Raza, S. Kennedy, Y. Fan, A. E. Wood and R. W. Watson, “The Impact of High-Dose Statin Therapy on Transendothelial Neutrophil Migration and Serum Cholesterol Levels in Healthy Male Volunteers,” European Journal of Clinical Pharmacology, Vol. 67, No. 11, 2011, pp. 1103-1108. doi:10.1007/s00228-011-1062-z
 M. Noutsias, C. Hohmann, M. Pauschinger, P.-L. Schwimmbeck, K. Ostermann, U. Rode, et al., “sICAM-1 Correlates with Myocardial ICAM-1 Expression in Dilated Cardiomyopathy,” International Journal of Cardiology, Vol. 91, No. 2, 2003, pp. 153-161.