Comparison of the protective effects of type III phosphodiesterase (PDE3) inhibitor (cilostazol) and acetylsalicylic acid on intestinal microcirculation after ischemia reperfusion injury in mice.
Antiplatelet therapy has been proposed as the treatment of choice for ischemia/reperfusion injury. The aim of this study is to elucidate the difference in effect between cilostazol (CZ) and acetylsalicylic acid (ASA) on microcirculatory 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, was applied; then, the status of submucosal microcirculation was observed under intravital microscopy. The blood cell counts and organ damage markers were examined in the portal blood. Next, 5 mm of the ileum was excised and was then histologically examined. Platelet-leukocyte aggregates were often observed in the postcapillary venules, and this formation was significantly reduced by both CZ and ASA. The number of adherent leukocytes was significantly lesser in the CZ-treated mice than in the ASA-treated mice (P < 0.01). The leukocyte number, lactate dehydrogenase, and lactate levels were best maintained in the CZ-treated mice (P < 0.05). The villus height was best preserved in the CZ-treated mice. Cilostazol inhibited not only the platelet aggregation but also the leukocyte adhesion to the endothelium, thereby inducing organ protection.
Iba
Toshiaki
T
Department of Surgery, Juntendo Urayasu Hospital, Juntendo University School of Medicine, 2-1-1 Tomioka, Uruyasu, Chiba 279-0021, Japan. iba-jun@umin.ac.jp
Kidokoro
Akio
A
Fukunaga
Masaki
M
Takuhiro
Kitoji
K
Ouchi
Masakazu
M
Ito
Yoshitomo
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D000077407:Cilostazol; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007422:Intestines / Q000098:blood supply* / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008833:Microcirculation; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010976:Platelet Count; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013777:Tetrazoles / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D007770:L-Lactate Dehydrogenase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000077407:Cilostazol; D001241:Aspirin