Comparison of the protective effects of type III phosphodiesterase (PDE3) inhibitor (cilostazol) and acetylsalicylic acid on intestinal microcirculation after ischemia reperfusion injury in mice

Received 3 Apr 2006; first review completed 21 Apr 2006; accepted in final form 12 May 2006ABSTRACT—Antiplatelet therapy has been proposed as the treatment of choice for ischemia/reperfusion injury. The aimof this study is to elucidate the difference in effect between cilostazol (CZ) and acetylsalicylic acid (ASA) onmicrocirculatory disturbance in ischemia/reperfusion injury. Either 10 mg/kg of CZ (n = 14) or 100 mg/kg of ASA (n =14) was administered orally to mice. Thereafter, 20 min of intestinal ischemia, followed by 60-min reperfusion, wasapplied; then, the status of submucosal microcirculation was observed under intravital microscopy. The blood cell countsand organ damage markers were examined in the portal blood. Next, 5 mm of the ileum was excised and was thenhistologically examined. Platelet-leukocyte aggregates were often observed in the postcapillary venules, and thisformation was significantly reduced by both CZ and ASA. The number of adherent leukocytes was significantly lesser inthe CZ-treated mice than in the ASA-treated mice (P G 0.01). The leukocyte number, lactate dehydrogenase, and lactatelevels were best maintained in the CZ-treated mice (P G 0.05). The villus height was best preserved in the CZ-treatedmice. Cilostazol inhibited not only the platelet aggregation but also the leukocyte adhesion to the endothelium, therebyinducing organ protection.KEYWORDS—Platelet, cilostazol, acetylsalicylic acid, ischemia/reperfusion injury, intravital microscopy