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J Thorac Cardiovasc Surg 2003;125:172-177
© 2003 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology (CSP)

Phosphodiesterase type 4 inhibition of activated polymorphonuclear leukocytes in a simulated extracorporeal circulation model

From the University of Tsukuba, Institute of Clinical Medicine, Tsukuba, Japan.

Supported by University of Tsukuba Research Projects.

Received for publication Feb 5, 2002. Revisions requested April 4, 2002; revisions received April 10, 2002. Accepted for publication April 16, 2002. 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 (E-mail: tcvysato{at}md.jichi.ac.jp).

Objectives: Cardiopulmonary bypass is associated with a systemic inflammatory response syndrome and the risk of multiorgan injuries mediated by activated polymorphonuclear leukocytes. Phosphodiesterase type 4 is the predominant phosphodiesterase isozyme in polymorphonuclear leukocytes and plays a key role in the regulation of polymorphonuclear leukocyte activation. The aim of this study was to examine the effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on the functional changes of polymorphonuclear leukocytes by using simulated extracorporeal circulation.
Methods: Simulated extracorporeal circulation was established by recirculating heparinized human blood for 120 minutes on a membrane oxygenator with and without 10 µmol/L rolipram. F-actin content and L-selectin and CD11b expression of polymorphonuclear leukocytes were measured by means of flow cytometry. Polymorphonuclear leukocyte deformability was evaluated with a microchannel array flow analyzer that had a similar diameter as the capillaries. Polymorphonuclear leukocyte elastase was measured with an enzyme immunoassay.
Results: Rolipram reduced the increase of F-actin content of polymorphonuclear leukocytes and the increase of transit time of 100 µL of blood sample through a microchannel. Rolipram reduced the increase of CD11b expression and the decrease of L-selectin expression of polymorphonuclear leukocytes. Rolipram reduced the release of elastase from polymorphonuclear leukocytes.
Conclusion: Rolipram inhibited the deformability change mediated by F-actin assembly, the changes in adhesion molecules, and the release of elastase from activated polymorphonuclear leukocytes in simulated extracorporeal circulation. This study suggests that phosphodiesterase type 4 inhibition could be a feasible therapeutic strategy to prevent the exaggerated inflammatory response related to cardiopulmonary bypass.

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