The Effects of Cilostazol on Exercise-induced Ischaemia–reperfusion Injury in Patients with Peripheral Arterial Disease

Autor: Mark E. O'Donnell, Ian S. Young, Stephen A. Badger, M.A. Sharif, Ragai R. Makar, C.V. Soong, Bernard Lee, Jane McEneny
Rok vydání: 2009
Předmět:
Male
Vasodilator Agents
alpha-Tocopherol
Tetrazoles
Walking
Receptors
Tumor Necrosis Factor
law.invention
chemistry.chemical_compound
Randomized controlled trial
law
Prospective Studies
Treadmill
Prospective cohort study
Aged
80 and over
Medicine(all)
Middle Aged
Intercellular Adhesion Molecule-1
beta Carotene
Cilostazol
Peripheral
Interleukin-10
Thromboxane B2
P-Selectin
C-Reactive Protein
Ischaemia–reperfusion injury
Creatinine
Reperfusion Injury
Female
medicine.symptom
Cardiology and Cardiovascular Medicine
medicine.drug
Adult
medicine.medical_specialty
Lipid Peroxides
Urology
Vascular Cell Adhesion Molecule-1
Placebo
Double-Blind Method
Peripheral arterial disease
medicine
Albuminuria
Humans
Aged
business.industry
Interleukin-6
Inflammatory response
Intermittent Claudication
Surgery
chemistry
Ascorbate Oxidase
Claudication
business
Zdroj: European Journal of Vascular and Endovascular Surgery. 37(3):326-335
ISSN: 1078-5884
DOI: 10.1016/j.ejvs.2008.11.028
Popis: sObjectivesCilostazol improves walking distance in peripheral arterial disease (PAD) patients. The study objectives were to assess the effects of cilostazol on walking distance, followed by the additional assessment of cilostazol on exercise-induced ischaemia–reperfusion injury in such patients.MethodsPAD patients were prospectively recruited to a double-blinded, placebo-controlled trial. Patients were randomised to receive either cilostazol 100mg or placebo twice a day. The primary end-point was an improvement in walking distance. Secondary end-points included the assessment of oxygen-derived free-radical generation, antioxidant consumption and other markers of the inflammatory cascade. Initial and absolute claudication distances (ICDs and ACDs, respectively) were measured on a treadmill. Inflammatory response was assessed before and 30min post-exercise by measuring lipid hydroperoxide, ascorbate, α-tocopherol, β-carotene, P-selectin, intracellular and vascular cell-adhesion molecules (I-CAM and V-CAM), thromboxane B2 (TXB2), interleukin-6, interleukin-10, high-sensitive C-reactive protein (hsCRP), albumin–creatinine ratio (ACR) and urinary levels of p75TNF receptor. All tests were performed at baseline and 6 and 24 weeks.ResultsOne hundred and six PAD patients (of whom 73 were males) were recruited and successfully randomised from December 2004 to January 2006. Patients who received cilostazol demonstrated a more significant improvement in the mean percentage change from baseline in ACD (77.2% vs. 26.6% at 6 weeks, p=0.026 and 161.7% vs. 79.0% at 24 weeks, p=0.048) as compared to the placebo. Cilostazol reduced lipid hydroperoxide levels compared to a placebo-related increase before and after exercise (6 weeks: pre-exercise: −11.8% vs. +5.8%, p=0.003 and post-exercise: −12.3% vs. +13.9%, p=0.007 and 24 weeks: pre-exercise −15.5% vs. +12.0%, p=0.025 and post-exercise: −9.2% vs. +1.9%, p=0.028). β-Carotene levels were significantly increased in the cilostazol group, compared to placebo, before exercise at 6 and 24 weeks (6 weeks: 34.5% vs. −7.4%, p=0.028; 24 weeks: 34.3% vs. 17.7%, p=0.048). Cilostazol also significantly reduced P-selectin, I-CAM and V-CAM levels at 24 weeks as compared to baseline (p
Databáze: OpenAIRE
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