BACKGROUND: The mechanisms underlying the ability of cilostazol to improve walking distance in patients with intermittent claudication (IC) are not fully understood, but may be related to its phosphodiesterase type 3 (PDE3) and adenosine uptake inhibition. In the present study the effect of cilostazol on blood flow and interstitial adenosine concentration was compared with that of the PDE3 inhibitor, milrinone, and the adenosine uptake inhibitor, draflazine. METHODS AND RESULTS: Rabbit gastrocnemius muscle blood flow was measured under resting, contracting and ischemic conditions. Interstitial adenosine was sampled by microdialysis. None of the drugs affected tissue blood flow at rest. Blood flow in electrically stimulated muscle was 2- to 3-fold higher in vehicle-, milrinone- and draflazine-treated animals. However, cilostazol caused an 8-fold increase. Ligation of the femoral artery decreased blood flow in the stimulated muscle in all groups to a similar degree. Cilostazol and draflazine increased the dialysate adenosine concentration during the first 10 min of muscle contraction, but had no effect during ischemia, most likely because of the high AMP deaminase activity in skeletal muscle. CONCLUSIONS: Cilostazol increases blood flow in the gastrocnemius muscle during contraction and it is this effect that may be partially responsible for the improved walking distance in IC patients. (Circ J 2010; 74: 181 - 187).
BACKGROUND: The mechanisms underlying the ability of cilostazol to improve walking distance in patients with intermittent claudication (IC) are not fully understood, but may be related to its phosphodiesterase type 3 (PDE3) and adenosine uptake inhibition. In the present study the effect of cilostazol on blood flow and interstitial adenosine concentration was compared with that of the PDE3 inhibitor, milrinone, and the adenosine uptake inhibitor, draflazine. METHODS AND RESULTS:Rabbit gastrocnemius muscle blood flow was measured under resting, contracting and ischemic conditions. Interstitial adenosine was sampled by microdialysis. None of the drugs affected tissue blood flow at rest. Blood flow in electrically stimulated muscle was 2- to 3-fold higher in vehicle-, milrinone- and draflazine-treated animals. However, cilostazol caused an 8-fold increase. Ligation of the femoral artery decreased blood flow in the stimulated muscle in all groups to a similar degree. Cilostazol and draflazine increased the dialysate adenosine concentration during the first 10 min of muscle contraction, but had no effect during ischemia, most likely because of the high AMP deaminase activity in skeletal muscle. CONCLUSIONS:Cilostazol increases blood flow in the gastrocnemius muscle during contraction and it is this effect that may be partially responsible for the improved walking distance in IC patients. (Circ J 2010; 74: 181 - 187).
Authors: Mariana R G A Santos; Andréa C Celotto; Verena K Capellini; Paulo R B Evora; Carlos E Piccinato; Edwaldo E Joviliano Journal: Clinics (Sao Paulo) Date: 2012 Impact factor: 2.365