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Eur J Cardiothorac Surg 2004;25:833-838
© 2004 Elsevier Science NL

Phosphodiesterase type 4 inhibitor prevents acute lung injury induced by cardiopulmonary bypass in a rat model

^a Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
^b Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan
^c Department of Organ Transplantation, National Cardiovascular Center, Osaka, Japan
^d Department of Clinical Engineering, National Cardiovascular Center, Osaka, Japan
^e Department of Surgery, Jichi Medical School, Tochigi, Japan

Received 19 October 2003; received in revised form 20 January 2004; accepted 30 January 2004.

^* Corresponding author. Tel.: +81-6-6833-5012x8379; fax: +81-6-6872-8090
e-mail: msuga{at}ri.ncvc.go.jp

Objectives: Cardiopulmonary bypass (CPB) induces systemic inflammatory response with neutrophil activation and subsequent lung dysfunction. Rolipram, a selective phosphodiesterase type 4 inhibitor, blocks the decrease in levels of cyclic adenosine monophosphate associated with neutrophil activation. Here, we tested the protective effect of rolipram on CPB-induced lung injury in the rat. Methods: Rats were divided into three groups: control (C), rolipram (R) and sham (S). In the C and R groups, animals underwent CPB at a flow rate of 60 ml/kg per min for 60 min followed by another 60-min observation, whereas the S group rats were sustained for 120 min only with median sternotomy and the placement of cannulae for CPB. Rolipram (40 µg/kg per min) was administered to the R group rats by continuous intravenous infusion from 10 min before the establishment of CPB to the end of the experiment. Results: The R and S groups showed significantly higher mean arterial oxygen pressure and lower mean lung wet-to-dry weight ratio compared with those observed in the C group (R: 489±44 or S: 527±55 vs. C: 287±185, and R: 5.0±0.4 or S: 4.7±0.3 vs. C: 5.9±0.5, respectively; P<0.01). Although CD11b expression levels on circulating neutrophils in the C group doubled after CPB, those in the R and S groups remained almost the same (P=0.0008). Intrapulmonary tumor necrosis factor- concentrations (pg/µg protein) in the C group tended to be higher than those observed in the R and S groups (R: 5.2±2.1, S: 5.0±2.1 and C: 8.9±5.4; R vs. C: P=0.09 and S vs. C: P=0.08). Pathological study of lungs revealed that more alveolar hemorrhage and neutrophil accumulation were observed in the C group compared to the R and S groups. Conclusions: These results suggest that rolipram prevents acute lung injury via the inhibition of neutrophil activation during and after CPB in this setting of a rat model.

Key Words: Phosphodiesterase type 4 inhibitor • Cardiopulmonary bypass • Neutrophil activation • Rat