Abstract
Rationale
Cardiac surgery presents a risk to all major organs due to activation of the systemic inflammatory response. Patients referred for cardiac surgery are typically older, usually have comorbid conditions, and are thus at higher risk of postoperative multiorgan dysfunction. Patients demonstrating evidence of organ dysfunction require intensive postoperative management. Any means to predict and reduce the inflammatory response mounted postcardiac surgery could translate into a clinical benefit for the patient and reduce the length of stay in intensive care.
Objective
Statins are commonly used to prevent primary and secondary cardiovascular disease through their cholesterol-lowering effects. However, they have been shown to have anti-inflammatory properties, which may help reduce postoperative mortality and morbidity for patients undergoing cardiac surgery. The purpose of this study was to analyze the in vivo effects of high-dose atorvastatin (statin) on ex vivo neutrophil migration in healthy volunteers.
Methods
Thirteen healthy male volunteers consented and were placed on high-dose (40 mg) statin therapy for 2 weeks. At week 0 and week 2, full blood count, liver function, serum cholesterol and creatine kinase were assessed, as was neutrophil migration.
Results
Neutrophil migration of healthy volunteers was significantly reduced after 2 weeks of high-dose statin therapy (p = 0.002), as was serum cholesterol (p <0.001). There was no change in liver function during statin treatment.
Conclusion
Statins have an established role as cholesterol-lowering agents, and this study demonstrates that they also potentially have an anti-inflammatory effect in healthy male volunteers.
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Abbreviations
- ABTS:
-
2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid
- ARDS:
-
Adult respiratory distress syndrome
- CK:
-
Creatine kinase
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- FBC:
-
Full blood count
- FCS:
-
Fetal calf serum
- fMLP:
-
Formyl-methionyl-leucyl-phenylalanine
- HDL:
-
High-density lipoprotein
- HPAEC:
-
Human pulmonary artery endothelial cell
- sICAM:
-
Soluble intercellular adhesion molecule
- LDH:
-
Lactate dehydrogenase
- LDL:
-
Low-density lipoprotein
- LFT:
-
Liver function test
- LPS:
-
Lipopolysaccharide
- MI:
-
Myocardial infarction
- MPO:
-
Myeloperoxidase
- NO:
-
Nitric oxide
- UK:
-
United Kingdom
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Acknowledgments
We thank all our volunteers, without whom this study would not have been possible; the Mater Heart Foundation for financial support; and Pfizer for supplying atorvastatin
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A. Kinsella and A. Raza contributed equally as first authors.
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Kinsella, A., Raza, A., Kennedy, S. et al. The impact of high-dose statin therapy on transendothelial neutrophil migration and serum cholesterol levels in healthy male volunteers. Eur J Clin Pharmacol 67, 1103–1108 (2011). https://doi.org/10.1007/s00228-011-1062-z
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DOI: https://doi.org/10.1007/s00228-011-1062-z