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Right arrow Extracorporeal circulation

J Thorac Cardiovasc Surg 2005;130:346-350
© 2005 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Phosphodiesterase type 4 inhibitor rolipram inhibits activation of monocytes during extracorporeal circulation

Yukio Sato, MD, PhD a , * , Yuji Hiramatsu, MD, PhD c , Satoshi Homma, MD, PhD c , Makiko Sato, MD b , Shyoko Sato c , Shunsuke Endo, MD, PhD a , Yasunori Sohara, MD, PhD a

a Division of Thoracic Surgery, Department of Surgery, Jichi Medical School, Minamikawachi, Tochigi, Japan
b Department of Medicine, Jichi Medical School
c University of Tsukuba, Institute of Clinical Medicine, Tsukuba, Ibaraki, Japan

Received for publication September 30, 2004; revisions received December 18, 2004; accepted for publication December 23, 2004.

* Address for reprints: Yukio Sato, MD, PhD, Division of Thoracic Surgery, Department of Surgery, Jichi Medical School, 3311-1 Minamikawachi, Kawachi, Tochigi 329-0498, Japan (Email: tcvysato{at}jichi.ac.jp).

OBJECTIVE: Cardiopulmonary bypass is associated with systemic inflammatory response syndrome and risk of multiorgan injury mediated by activated leukocytes. Phosphodiesterase type 4 is the predominant phosphodiesterase isozyme in leukocytes and plays a key role in the regulation of leukocyte activation. The aim of this study was to examine the effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on functional changes of monocytes during simulated extracorporeal circulation.

METHODS AND RESULTS: Simulated extracorporeal circulation was established by recirculating heparinized human blood for 120 minutes on a membrane oxygenator with or without 10 µmol/L of rolipram. L-selectin and CD11b expression of monocytes were measured with flow cytometry. C4d fragment, Bb fragment, C5b-9, and interleukin-6 were measured with enzyme immunoassay. Rolipram reduced the increase in CD11b expression and the decrease in L-selectin expression of monocytes in response to simulated extracorporeal circulation. Rolipram inhibited the increase in C4d fragment and interleukin-6, but it did not affect the increase in Bb fragment or C5b-9.

CONCLUSION: Rolipram inhibited changes in adhesion molecule expression and interleukin-6 release by activated monocytes in simulated extracorporeal circulation. This study suggests that phosphodiesterase type 4 inhibition could be feasible therapeutic strategy to prevent exaggerated inflammatory response and organ injury in patients undergoing cardiopulmonary bypass.






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